United States
            Environmental Protection
            Agency
              Office of Research and
              Development
              Washington DC 20460
EPA/600/P-95/001bF
April 1996
vvEPA
Air Quality Criteria  for
Particulate Matter
            Volume  II of

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                                    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.
                                         Il-ii

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                                      PREFACE

     On April 30, 1971 (Federal Register, 1971), in accordance with the Clean Air Act (CAA)
Amendments of 1970, the U.S. Environmental Protection Agency (EPA) promulgated the
original primary and secondary National Ambient Air Quality Standard (NAAQS) for particulate
matter (PM).  The reference method for measuring attainment of these standards was the "high-
volume" sampler (Code of Federal Regulations, 1977), which collected PM up to a nominal size
of 25 to 45 //m (so-called "total suspended particulate," or "TSP"). Thus, TSP was the original
indicator for the PM standards.  The primary standards for PM, measured as TSP, were 260
Mg/m3, 24-h average not to be exceeded more than once per year, and 75 //g/m3, annual
geometric mean.  The secondary standard was 150 //g/m3, 24-h average not to be exceeded more
than once per year.
     In accordance with the CAA Amendments of 1977, the U.S. EPA conducted a re-
evaluation of the scientific data for PM, resulting  in publication of a revised air quality criteria
document (AQCD) for PM in December 1982 and a later Addendum to that document in 1986.
On July 1, 1987, the U.S. EPA published final revisions to the NAAQS for PM. The principle
revisions to the 1971 NAAQS included (1) replacing TSP as the indicator for the ambient
standards with a new indicator that includes particles with an aerodynamic diameter less than or
equal to a nominal 10 //m ("PM10"),  (2) replacing  the 24-h primary TSP standard with a 24-h
PM10 standard of 150 //g/m3, (3) replacing the annual primary TSP standard with an annual PM10
standard of 50 //g/m3, and (4) replacing the secondary TSP standard with 24-h and annual PM10
standards identical in all respects to the primary standards.
     The present PM AQCD has been prepared in accordance with the CAA, requiring the EPA
Administrator periodically to review and revise, as appropriate, the criteria and NAAQS for
listed criteria pollutants. Emphasis has been place on the presentation and evaluation  of the
latest available dosimetric and health effects data; however, other scientific data are also
presented to provide information on the nature, sources, size distribution, measurement, and
concentrations of PM in the environment and contributions of ambient PM to total human
exposure.  This document is comprised of three volumes, with the present one (Volume II)
containing Chapters  8 through 11.

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                                  PREFACE (cont'd)

     This document was prepared by U.S. EPA's National Center for Environmental
Assessment-RTF, with assistance by scientists from other EPA Office of Research and
Development laboratories (NERL; NHEERL) and non-EPA expert consultants.  Several earlier
drafts of the document were reviewed by experts from academia, various U.S. Federal and State
government units, non-governmental health and environmental organizations, and private
industry. Several versions of this AQCD have also been reviewed in public meetings by the
Agency's Clean Air Scientific Advisory Committee (CASAC). The National Center for
Environmental Assessment (formerly the Environmental Criteria and Assessment Office) of the
U.S. EPA's  Office of Research and Development acknowledges with appreciation the valuable
contributions made by the many authors, contributors, and reviewers, as well as the diligence of
its staff and contractors in the preparation of this document.
                                         Il-iv

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                   Air Quality Criteria for Particulate Matter


                           TABLE OF CONTENTS


                                 Volume I

 1. EXECUTIVE SUMMARY	 1-1

 2. INTRODUCTION	2-1

 3. PHYSICS AND CHEMISTRY OF PARTICULATE MATTER	3-1

 4. SAMPLING AND ANALYSIS METHODS FOR PARTICULATE MATTER
    AND ACID DEPOSITION	4-1

 5. SOURCES AND EMISSIONS OF ATMOSPHERIC PARTICLES  	5-1

 6. ENVIRONMENTAL CONCENTRATIONS	6-1
    Appendix 6A: Tables of Chemical Composition of Particulate Matter  	6A-1

 7. HUMAN EXPOSURE TO PARTICULATE MATTER: RELATIONS TO
    AMBIENT AND INDOOR CONCENTRATIONS	7-1


                                 Volume II

 8. EFFECTS ON VISIBILITY AND CLIMATE  	8-1

 9. EFFECTS ON MATERIALS 	9-1

10.  DOSIMETRY OF INHALED PARTICLES IN THE RESPIRATORY
    TRACT	 10-1
    Appendix 10A:  Prediction of Regional Deposition in the Human
                 Respiratory Tract Using the International Commission
                 on Radiological Protection Publication 66 Model	10A-1
    Appendix 10B:  Selected Model Parameters	10B-1
    Appendix IOC: Selected Ambient Aerosol Particle Distributions  	10C-1

11.  TOXICOLOGICAL STUDIES OF PARTICULATE MATTER  	 11-1
                                   II-v

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                   Air Quality Criteria for Particulate Matter


                        TABLE OF CONTENTS (cont'd)


                                 Volume III

12.  EPIDEMIOLOGY STUDIES OF HEALTH EFFECTS ASSOCIATED
    WITH EXPOSURE TO AIRBORNE PARTICLES/ACID AEROSOLS	 12-1

13.  INTEGRATIVE SYNTHESIS OF KEY POINTS: PARTICULATE
    MATTER EXPOSURE, DOSIMETRY, AND HEALTH RISKS 	 13-1
    Appendix 13 A:  References Used To Derive Cell Ratings in the Text
                 Tables 13-6 and 13-7 for Assessing Qualitative
                 Strength of Evidence for Particulate Matter-Related
                 Health Effects	13A-1
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                              TABLE OF CONTENTS
                                                                              Page

LIST OF TABLES 	II-xiv
LIST OF FIGURES  	  II-xx
AUTHORS, CONTRIBUTORS, AND REVIEWERS	II-xxix
U.S. ENVIRONMENTAL PROTECTION AGENCY SCIENCE ADVISORY
 BOARD, CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE	  II-xxxv
U.S. ENVIRONMENTAL PROTECTION AGENCY PROJECT TEAM FOR
 DEVELOPMENT OF AIR QUALITY CRITERIA FOR PARTICULATE
 MATTER	II-xxxix
    EFFECTS ON VISIBILITY AND CLIMATE	8-1
    8.1    INTRODUCTION	8-1
          8.1.1    Background	8-1
          8.1.2    Definition of Visibility 	8-3
          8.1.3    Human Vision	8-4
    8.2    FUNDAMENTALS OF ATMOSPHERIC VISIBILITY	8-8
          8.2.1    Geometry of the Atmosphere	8-8
          8.2.2    Illumination of the Atmosphere	8-9
          8.2.3    Optical Properties of the Atmosphere 	8-11
          8.2.4    Multiple Scattering	8-15
          8.2.5    Transmitted Radiance Versus Path Radiance	8-23
          8.2.6    Contrast and Contrast Transmittance as Quantitative
                  Measures of Visibility	8-26
          8.2.7    Contrast Reduction by the Atmosphere	8-27
          8.2.8    Relation Between Contrast Transmittance and Light
                  Extinction	8-33
    8.3    OPTICAL PROPERTIES OF PARTICLES	8-34
          8.3.1    Optical Properties of Spheres  	8-36
          8.3.2    Optical Properties of Fine and Coarse Particles	8-42
          8.3.3    Effect of Relative Humidity on Particle Size	8-44
          8.3.4    Extinction Efficiencies and Budgets  	8-47
    8.4    INDICATORS OF VISIBILITY AND AIR QUALITY	8-51
          8.4.1    Introduction	8-51
          8.4.2    Visual Range from Human Observation 	8-53
          8.4.3    Light-Extinction Coefficient	8-54
          8.4.4    Parameters Calculated from the Light Extinction
                  Coefficient  	8-56
                  8.4.4.1  Visual Range	8-56
                  8.4.4.2  Deciview Haze Index  	8-57
          8.4.5    Light-Scattering Coefficient Due to Particles 	8-57
          8.4.6    Contrast of Terrain Features  	8-60
          8.4.7    Particulate Matter Concentrations	8-61
          8.4.8    Measures of Discoloration	8-63

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                        TABLE OF CONTENTS (cont'd)
                                                                             Page

8.5    VISIBILITY IMPAIRMENT	8-64
       8.5.1    National Patterns and Trends	8-64
       8.5.2    Visibility Monitoring	8-64
               8.5.2.1  Point Versus Sight-Path Measurements	8-64
               8.5.2.2  Instrumental Monitoring Networks	8-65
       8.5.3    Recent Observations  	8-66
8.6    VISIBILITY MODELING	8-73
       8.6.1    Plume Visibility Models  	8-74
       8.6.2    Regional Haze Models  	8-75
       8.6.3    Photographic Representations of Haze	8-79
8.7    ECONOMIC VALUATION OF EFFECTS OF PARTICULATE
       MATTER ON VISIBILITY	8-80
       8.7.1    Basic Concepts of Economic Valuation	8-80
       8.7.2    Economic Valuation Methods for Visibility  	8-81
       8.7.3    Studies of Economic Valuation of Visibility	8-82
               8.7.3.1  Economic Valuation Studies for Air Pollution
                       Plumes  	8-82
               8.7.3.2  Economic Valuation Studies for Urban Haze  	8-84
8.8    CLIMATIC EFFECTS	8-89
       8.8.1    Introduction	8-89
       8.8.2    Radiative Forcing 	8-90
       8.8.3    Solar Radiative Forcing by Aerosols	8-93
               8.8.3.1  Modeling Aerosol Direct Solar Radiative Forcing	8-97
               8.8.3.2  Global Annual Mean Radiative Forcing  	 8-100
       8.8.4    Climate Response 	 8-102
               8.8.4.1  Early Studies	 8-102
               8.8.4.2  Recent Regional Studies 	 8-104
               8.8.4.3  Integrated Global Studies  	 8-106
       8.8.5    Aerosol Effects on Clouds and Precipitation	 8-112
               8.8.5.1  Indirect Solar Radiative Forcing	 8-112
               8.8.5.2  Observational Evidence	 8-116
               8.8.5.3  Modeling Indirect Aerosol Forcing	 8-118
8.9    SUMMARY	 8-120
       8.9.1    Visibility Effects	 8-120
       8.9.2    Climate Change	 8-126
REFERENCES 	 8-128

EFFECTS ON MATERIALS  	9-1
9.1    CORROSION AND EROSION	9-1
       9.1.1    Factors Affecting Metal Corrosion  	9-1
               9.1.1.1  Moisture	9-2
               9.1.1.2  Temperature  	9-5
               9.1.1.3  Formation of a Protective Film  	9-6
       9.1.2    Development of a Generic Dose-Response Function  	9-7

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                           TABLE OF CONTENTS (cont'd)
                                                                               Page

          9.1.3     Studies on Metals 	9-8
                   9.1.3.1  Acid-Forming Aerosols	9-8
                   9.1.3.2  Particles 	9-15
          9.1.4     Paints  	9-17
                   9.1.4.1  Acid-Forming Aerosols	9-17
                   9.1.4.2  Particles 	9-22
          9.1.5     Stone and Concrete	9-22
          9.1.6     Corrosive Effects of Acid-Forming Aerosols and
                   Particles on Other Materials 	9-30
    9.2   SOILING AND DISCOLORATION	9-31
          9.2.1     Building Materials	9-32
                   9.2.1.1  Fabrics 	9-34
                   9.2.1.2  Household and Industrial Paints  	9-34
                   9.2.1.3  Soiling of Works of Art	9-37
    9.3   ECONOMIC ESTIMATES 	9-37
          9.3.1     Methods for Determining Economic Loss from Pollutant
                   Exposure	9-38
          9.3.2     Economic Loss Associated with Materials Damage and Soiling  .... 9-40
    9.4   SUMMARY	9-44
    REFERENCES  	9-46

10.  DOSIMETRY OF INHALED PARTICLES IN THE RESPIRATORY
    TRACT	 10-1
    10.1   INTRODUCTION	 10-1
    10.2   CHARACTERISTICS OF INHALED PARTICLES  	 10-6
    10.3   ANATOMY AND PHYSIOLOGY OF THE RESPIRATORY TRACT 	 10-13
    10.4   FACTORS CONTROLLING COMPARATIVE INHALED DOSE	 10-27
          10.4.1    Deposition Mechanisms  	 10-34
                   10.4.1.1 Gravitational Settling or Sedimentation	 10-35
                   10.4.1.2 Inertial Impaction	 10-36
                   10.4.1.3 Brownian Diffusion	 10-38
                   10.4.1.4 Interception	 10-39
                   10.4.1.5 Electrostatic Precipitation	 10-41
                   10.4.1.6 Additional Factors Modifying Deposition	 10-43
                   10.4.1.7 Comparative Aspects of Deposition	 10-46
          10.4.2    Clearance and Translocation Mechanisms	 10-52
                   10.4.2.1 Extrathoracic Region	 10-53
                   10.4.2.2 Tracheobronchial Region  	 10-55
                   10.4.2.3 Alveolar Region 	 10-56
                   10.4.2.4 Clearance Kinetics 	 10-59
                   10.4.2.5 Factors Modifying Clearance 	 10-66
                   10.4.2.6 Comparative Aspects of Clearance  	 10-70
                   10.4.2.7 Lung Overload  	 10-71
          10.4.3    Acidic Aerosols	 10-73

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                       TABLE OF CONTENTS (cont'd)
                                                                            Page

               10.4.3.1 Hygroscopicity of Acidic Aerosols 	 10-73
               10.4.3.2 Neutralization and Buffering of Acidic Particles	 10-81
10.5  DEPOSITION DATA AND MODELS  	 10-85
      10.5.1   Humans	 10-85
               10.5.1.1 Total Deposition	 10-86
               10.5.1.2 Extrathoracic Deposition 	 10-89
               10.5.1.3 Tracheobronchial Deposition	 10-94
               10.5.1.4 Alveolar Deposition  	 10-97
               10.5.1.5 Nonuniform Distribution of Deposition and Local
                         Deposition Hot Spots  	 10-99
               10.5.1.6 Approaches to Deposition Modeling	  10-101
      10.5.2   Laboratory Animals  	  10-106
10.6  CLEARANCE DATA AND MODELS	  10-119
      10.6.1   Humans	  10-121
      10.6.2   Laboratory Animals  	  10-131
      10.6.3   Species Similarities and Differences  	  10-133
      10.6.4   Models To Estimate Retained Dose	  10-140
               10.6.4.1 Extrathoracic and Conducting Airways	  10-142
               10.6.4.2 Alveolar Region  	  10-145
10.7  APPLICATION OF DOSIMETRY MODELS TO DOSE-RESPONSE
      ASSESSMENT  	  10-146
      10.7.1   General Considerations for Extrapolation Modeling  	  10-147
               10.7.1.1 Model Structure and Parameterization	  10-148
               10.7.1.2 Interspecies Variability	  10-148
               10.7.1.3 Extrapolation of Laboratory Animal Data to
                         Humans	  10-149
      10.7.2   Dosimetry Model Selection	  10-151
               10.7.2.1 Human Model	  10-151
               10.7.2.2 Laboratory Animal Model	  10-154
      10.7.3   Choice of Dose Metrics  	  10-155
               10.7.3.1 Interspecies Extrapolation	  10-156
      10.7.4   Choice of Exposure Metrics  	  10-162
               10.7.4.1 Human Exposure Data  	  10-162
               10.7.4.2 Laboratory Animal Data	  10-163
      10.7.5   Deposited Dose Estimations  	  10-163
               10.7.5.1 Human Estimates  	  10-163
               10.7.5.2 Laboratory Animal Estimates  	  10-194
      10.7.6   Retained Dose Estimates	  10-199
               10.7.6.1 Human Estimates  	  10-199
               10.7.6.2 Laboratory Animal Estimates  	  10-204
      10.7.7   Summary	  10-212
REFERENCES  	  10-218
                                    II-x

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                           TABLE OF CONTENTS (cont'd)
                                                                                Page

    APPENDIX 10A:  Prediction of Regional Deposition in the Human Respiratory
                     Tract Using the International Commission on Radiological
                     Protection Publication 66 Model	10A-1

    APPENDIX 10B:  Selected Model Parameters	10B-1

    APPENDIX IOC:  Selected Ambient Aerosol Particle Distributions	10C-1

11.  TOXICOLOGICAL STUDIES OF PARTICULATE MATTER	 11-1
    11.1   INTRODUCTION	 11-1
    11.2   ACID AEROSOLS  	 11-5
           11.2.1   Controlled Human Exposure Studies	 11-6
                   11.2.1.1 Introduction  	 11-6
                   11.2.1.2 Pulmonary Function Effects of Sulfuric Acid in
                             Healthy  Subjects	 11-9
                   11.2.1.3 Pulmonary Function Effects of Sulfuric Acid in
                             Asthmatic Subjects 	 11-17
                   11.2.1.4 Effects of Acid Aerosols on Airway
                             Responsiveness	 11-32
                   11.2.1.5 Effects of Acid Aerosols on Lung
                             Clearance Mechanisms  	 11-34
                   11.2.1.6 Effects of Acid Aerosols Studied by
                             Bronchoscopy and Airway Lavage 	 11-36
                   11.2.1.7 Human Exposure Studies of Acid Aerosol
                             Mixtures 	 11-37
                   11.2.1.8 Summary and Conclusions  	 11-39
           11.2.2   Laboratory Animal Studies	 11-42
                   11.2.2.1 Introduction  	 11-42
                   11.2.2.2 Mortality	 11-42
                   11.2.2.3 Pulmonary Mechanical Function	 11-43
                   11.2.2.4 Pulmonary Morphology and Biochemistry 	 11-49
                   11.2.2.5 Pulmonary Defenses	 11-55
           11.2.3   Mixtures Containing Acidic Sulfate Particles 	 11-69
    11.3   METALS	 11-76
           11.3.1   Introduction	 11-76
           11.3.2   Arsenic	 11-77
           11.3.3   Cadmium  	 11-82
                   11.3.3.1 Health Effects	 11-83
           11.3.4   Copper  	 11-85
           11.3.5   Iron	 11-87
           11.3.6   Vanadium	 11-89
           11.3.7   Zinc	 11-92
           11.3.8   Transition Metals 	 11-92
           11.3.9   Summary	 11-95

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                       TABLE OF CONTENTS (cont'd)
                                                                           Page

11.4   ULTRAFINE PARTICLES	  11-96
11.5   DIESEL EXHAUST EMISSIONS	  11-102
      11.5.1   Effects of Diesel Exhaust on Humans	  11-103
      11.5.2   Effects of Diesel Exhaust on Laboratory Animals	  11-109
      11.5.3   Species Differences	  11-120
      11.5.4   Effects of Mixtures Containing Diesel Exhaust	  11-122
      11.5.5   Particle Effect in Diesel Exhaust Studies	  11-122
      11.5.6   Gasoline Engine Emissions	  11-124
      11.5.7   Summary  	  11-125
11.6   SILICA 	  11-126
      11.6.1   Physical  and Chemical Properties of Silica	  11-126
      11.6.2   Health Effects of Silica	  11-127
      11.6.3   Differences Between Chemical Forms of Silica	  11-128
      11.6.4   Species Differences	  11-130
11.7   BIOAEROSOLS 	  11-131
      11.7.1   Types of Health Effects Associated with Bioaerosols  	  11-131
               11.7.1.1 Infections  	  11-131
               11.7.1.2 Hypersensitivity Diseases 	  11-132
               11.7.1.3 Toxicoses  	  11-133
      11.7.2   Ambient Bioaerosols	  11-134
11.8   TOXICOLOGY OF OTHER PARTICULATE MATTER	  11-136
      11.8.1   Introduction  	  11-136
      11.8.2   Mortality	  11-137
      11.8.3   Pulmonary Mechanical Function	  11-137
      11.8.4   Pulmonary Morphology and Biochemistry  	  11-141
      11.8.5   Pulmonary Defenses	  11-151
              11.8.5.1  Clearance Function	  11-151
              11.8.5.2  Resistance to Infectious Disease  	  11-154
              11.8.5.3  Immunologic Defense	  11-158
      11.8.6   Systemic Effects	  11-158
      11.8.7   Toxicological Interactions of Other Particulate Matter
              Mixtures	  11-160
              11.8.7.1  Laboratory Animal Toxicology Studies of
                      Particulate Matter Mixtures	  11-160
              11.8.7.2  Human Studies of Particulate Matter Mixtures
                      Other Than Acid Aerosols	  11-166
11.9   PHYSICOCHEMICAL AND HOST FACTORS INFLUENCING PARTICULATE
      MATTER TOXICITY	  11-169
      11.9.1   Physicochemical Factors Affecting Particulate Matter
              Toxicity  	  11-169
      11.9.2   Host Factors Affecting Particulate Matter Toxicity	  11-174

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                      TABLE OF CONTENTS (cont'd)
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11.10  POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS FOR THE EFFECTS
      OF LOW CONCENTRATIONS OF PARTICIPATE
      POLLUTION	  11-179
      11.10.1 Physiological Mechanisms  	  11-179
      11.10.2 Physiological-Particle Interaction  	  11-180
      11.10.3 Pathophysiologic Mechanisms 	  11-181
11.11  SUMMARY AND CONCLUSIONS	  11-185
      11.11.1 Acid Aerosols	  11-185
      11.11.2 Metals	  11-188
      11.11.3 Ultrafme Particles	  11-191
      11.11.4 Diesel Emissions	  11-192
      11.11.5 Silica	  11-193
      11.11.6 Bioaerosols	  11-194
      11.11.7 "Other Paniculate Matter"	  11-194
REFERENCES 	  11-196

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                                  LIST OF TABLES
Number                                                                          Page

8-1       Approximate Distances for Selected Increases in Height of an Initially
          Horizontal Sight Path	8-9

8-2       Relative Importance of Light from Ground, Sky, and Sun in Contributing
          to the Source Function and the Path Radiance When the Absorption is
          Negligible and the Normalized Phase Function Has a Value of 0.4 	8-22

8-3       Long-Term Visibility and Aerosol Databases	8-67

8-4       Short-Term Intensive Visibility and Aerosol Studies	8-70

8-5       Economic Valuation Studies for Air Pollution Plumes	8-83

8-6       Economic Valuation Studies on Urban Haze 	8-85

8-7       Radiative Forcing and Climate Statistics  	 8-111

9-1       Annual Average and Maximum Values of the Hourly Averages for Sulfur
          Dioxide, Nitrogen Oxide, and Ozone and Annual Averages of the Monthly
          Averages of Rain pH at the Five Material Exposure Sites, Based on Data
          Acquired During 1986	9-10

9-2       Average Corrosion Rates for 3003-H14 Aluminum Obtained During the
          National Acid Precipitation Assessment Program Between 1982 and 1987 .... 9-10

9-3       Average Corrosion Rates for Rolled Zinc and Galvanized Steel Obtained
          During the National Acid Precipitation Assessment Program Field
          Experiments	9-14

9-4       Summary of Measured Parameters in Jacksonville, Florida	9-23

10-1      Respiratory Tract Regions	 10-15

10-2      Architecture of the Human Lung According to Weibel's (1963) Model A,
          with Regularized Dichotomy	 10-25

10-3      Morphology, Cytology, Histology, Function, and Structure of the
          Respiratory Tract and Regions Used in the International Commission
          on Radiological Protection Publication 66 (1994) Human
          Dosimetry Model	 10-28

10-4      Deposition Data for Men and Women 	 10-44

10-5      Interspecies Comparison of Nasal Cavity Characteristics	 10-49

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                              LIST OF TABLES (cont'd)
Number                                                                         Page

10-6      Comparative Lower Airway Anatomy as Revealed on Casts 	  10-50

10-7      Acinar Morphometry	  10-51

10-8      Overview of Respiratory Tract Particle Clearance and Translocation
          Mechanisms	  10-53

10-9      Long-Term Retention of Poorly Soluble Particles in the Alveolar
          Region of Nonsmoking Humans  	  10-63

10-10     Fraction of Ventilatory Airflow Passing Through the Nose in
          Human "Normal Augmenter" and "Mouth Breather" 	  10-100

10-11     Regional Fractional Deposition 	  10-111

10-12     Deposition Efficiency Equation Estimated Parameters and 95%
          Asymptotic Confidence Intervals	  10-114

10-13     Comparative Alveolar Retention Parameters for Poorly Soluble
          Particles Inhaled by Laboratory Animals and Humans	  10-135

10-14     Average Alveolar Retention Parameters for Poorly Soluble Particles
          Inhaled by Selected Laboratory Animal Species and Humans 	  10-138

10-15     Physical Clearance Rates	  10-139

10-16     Physical Clearance Rates for Modeling Alveolar Clearance of Particles
          Inhaled by Selected Mammalian Species	  10-146

10-17     Hierarchy of Model Structures for Dosimetry and Extrapolation	  10-149

10-18     Species Comparisons by Miller et al. (1995) of Various Dose Metrics as
          a Function of Particle  Size for 24-Hour Exposures to 150//g/m3	  10-157

10-19     Daily Mass Deposition of Particles from Aerosol Defined in Figure 10C-1
          in the Respiratory Tract of "Normal Augmenter" Adult Male Humans
          Exposed to a Particle Mass Concentration of 50 //g/m3  	  10-164

10-20     Daily Mass Deposition of Particles from Aerosol Defined in Figure 10C-1
          in the Respiratory Tract of "Mouth Breather" Adult Male Humans
          Exposed to a Particle Mass Concentration of 50 //g/m3  	  10-165
                                        II-xv

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                              LIST OF TABLES (cont'd)
Number                                                                         Page

10-21     Daily Mass Deposition of Particles from Philadelphia Aerosol Defined
          in Figure 10C-2a in the Respiratory Tract of "Normal Augmenter" Adult
          Male Humans Exposed to a Particle Mass Concentration of 50 //g/m3	 10-166

10-22     Daily Mass Deposition of Particles from Philadelphia Aerosol Defined
          in Figure 10C-2a in the Respiratory Tract of "Mouth Breather" Adult
          Male Humans Exposed to a Particle Mass Concentration of 50 //g/m3	 10-167

10-23     Daily Mass Deposition of Particles from Phoenix Aerosol Defined in
          Figure 10C-2b in the Respiratory Tract of "Normal Augm enter" Adult
          Male Humans Exposed to a Particle Mass Concentration of 50 //g/m3	 10-168

10-24     Daily Mass Deposition of Particles from Phoenix Aerosol Defined in
          Figure 10C-2b in the Respiratory Tract of "Mouth Breather" Adult
          Male Humans Exposed to a Particle Mass Concentration of 50 //g/m3	 10-169

10-25     Daily Mass Deposition of Aerosol Particles in the Respiratory Tracts
          of "Normal Augmenter" and "Mouth Breather" Adult Male Humans
          Exposed to 50 //g Particles per Cubic Meter  	 10-174

10-26     Extrathoracic Deposition Fractions of Inhaled Monodisperse Aerosols
          in Rats and Human "Normal Augmenter"  and "Mouth Breather"	 10-195

10-27     Extrathoracic Deposition Fractions of Inhaled Poly disperse Aerosols
          in Rats and Human "Normal Augmenter"  and "Mouth Breather"	 10-195

10-28     Tracheobronchial Deposition Fractions of Inhaled Monodisperse Aerosols
          in Rats and Human "Normal Augmenter"  and "Mouth Breather"	 10-195

10-29     Tracheobronchial Deposition Fractions of Inhaled Poly disperse Aerosols
          in Rats and Human "Normal Augmenter"  and "Mouth Breather"	 10-196

10-30     Alveolar Deposition Fractions of Inhaled Monodisperse Aerosols
          in Rats and Human "Normal Augmenter"  and "Mouth Breather"	 10-196

10-31     Alveolar Deposition Fractions of Inhaled Poly disperse Aerosols
          in Rats and Human "Normal Augmenter"  and "Mouth Breather"	 10-196

10-32     Predicted Relative Particle  Mass in Lungs of Adult Male "Normal
          Augmenter" Exposed Chronically to Phoenix Trimodel Aerosol Versus
          Philadelphia Trimodal Aerosol   	 10-202

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                               LIST OF TABLES (cont'd)
Number                                                                          Page

10-33     Fraction of Inhaled Particles Deposited in the Alveolar Region of
          the Respiratory Tract for Rats and Adult Male Humans	  10-204

10-34     Fraction of Inhaled Particles Deposited in the Alveolar Region of
          the Respiratory Tract for Different Demographic Groups	  10-205

10-35     Particle Deposition Rates in the Alveolar Region	  10-205

10-36     Summary of Common and Specific Inhalation Exposure Parameters
          Used for Predicting Alveolar Burdens of Particles Inhaled by
          Rats and Humans	  10-206

10-37     Alveolar Particle Burdens of Exposure to 50 //g/m3 of 1.0-//m Mass
          Median Aerodynamic Diameter Aerosol, Assuming Particle Dissolution-Absorption
          Half-Time of 10, 100, or 1,000 Days	  10-207

10-38     Alveolar Particle Burdens of Exposure to 50 //g/m3 of 2.55-//m Mass
          Median Aerodynamic Diameter Aerosol, Assuming Particle Dissolution-
          Absorption Half-Time of 10, 100, or 1,000 Days	  10-208

lOB-la    Body Weight and Respiratory Tract Region Surface Areas  	10B-2

lOB-lb    Human Activity Patterns and Associated Respiratory Minute
          Ventilation	10B-2

10B-2     Body Weights, Lung Weights, Respiratory Minute Ventilation, and
          Respiratory Tract Region Surface Area for Selected Laboratory Animal
          Species	10B-3

10C-1     Distribution of Particle Count, Surface Area, or Mass in the
          Trimodal Polydisperse Aerosol Defined in Figure 10C-1	10C-3

10C-2a    Distribution of Particle Number in the Trimodal Polydisperse Aerosol
          Defined in Figure  10C-1 	10C-4

10C-2b    Distribution of Particle Surface Area in the Trimodal Polydisperse
          Aerosol Defined in Figure 10C-1	10C-6

10C-2c    Distribution of Particle Mass in the Trimodal Polydisperse Aerosol
          Defined in Figure  10C-1 	10C-8

10C-3     Distribution of Particle Count, Surface Area, or Mass in the Trimodal
          Polydisperse Aerosol for Philadelphia Defined in Figure 10-C-2a	10C-11

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                               LIST OF TABLES (cont'd)
Number                                                                           Page

10C-4a   Distribution of Particle Number in the Trimodal Poly disperse
          Philadelphia Aerosol Defined in Figure 10C-2a	IOC-12

10C-4b   Distribution of Particle Surface Area in the Trimodal Poly disperse
          Philadelphia Aerosol Defined in Figure 10C-2a	IOC-14

10C-4c   Distribution of Particle Mass in the Trimodal Poly disperse
          Philadelphia Aerosol Defined in Figure 10C-2a	IOC-16

10C-5     Distribution of Particle Count, Surface Area, or Mass in the Trimodal
          Poly disperse Aerosol for Phoenix Defined in Figure 10C-2b	10C-18

10C-6a   Distribution of Particle Number in the Trimodal Poly disperse
          Phoenix Aerosol Defined in Figure 10C-2b	10C-19

10C-6b   Distribution of Particle Surface Area in the Trimodal Poly disperse
          Phoenix Aerosol Defined in Figure 10C-2b	10C-21

10C-6c   Distribution of Particle Mass in the Trimodal Poly disperse Phoenix
          Aerosol Defined in Figure 10C-2b	10C-23

11-1      Numbers and Surface Areas of Monodisperse Particles of Unit Density
          of Different Sizes at a Mass Concentration of 10 //g/m3	 11-4

11-2      Controlled Human Exposures to Acid Aerosols and Other Particles	 11-10

11-3      Asthma Severity in Studies of Acid Aerosols and Other Particles  	 11-18

11-4      Pulmonary Function Responses After Aerosol  and Ozone Exposures
          in Subjects with Asthma 	 11-40

11-5      Effects of Acidic Sulfate Particles on Pulmonary Mechanical Function	 11-45

11-6      Effects of Acidic Sulfate Particles on Respiratory Tract Morphology	 11-50

11-7      Effects of Acidic Sulfate Particles on Respiratory Tract Clearance  	 11-57

11-8      Effects of Acid Sulfates on Bacterial Infectivity in Vivo	 11-68

11-9      Toxicologic Effects of Mixtures Containing Acidic Aerosols	 11-71

11-10     Respiratory System Effects of Inhaled Metals on Humans and
          Laboratory Animals	 11-78

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                               LIST OF TABLES (cont'd)
Number                                                                           Page

11-11     Human Studies of Diesel Exhaust Exposure	 11-105

11-12     Short-Term Effects of Diesel Exhaust on Laboratory Animals	 11-110

11-13     Effects of Chronic Exposures to Diesel Exhaust on Survival and
          Growth of Laboratory Animals 	 11-112

11-14     Effects of Diesel Exhaust on Pulmonary Function of Laboratory
          Animals	 11-113

11-15     Histopathological Effects of Diesel Exhaust in the Lungs of
          Laboratory Animals	 11-114

11-16     Effects of Exposure to Diesel Exhaust on the Pulmonary Defense
          Mechanisms of Laboratory Animals	 11-117

11-17     Comparative Inhalation Toxicity Studies with Different Silica
          Polymorphs	 11-129

11-18     Effects of Particulate Matter on Mortality  	 11-138

11-19     Effects of Inhaled Particulate Matter on Pulmonary Mechanical
          Function	 11-139

11-20     Effects of Particulate Matter on Respiratory Tract Morphology	 11-144

11-21     Effects of Particulate Matter on Markers in Lavage Fluid 	 11-148

11-22     Effects of Particulate Matter on Lung Biochemistry	 11-150

11-23     Effects of Particulate Matter on Alveolar Macrophage Function  	 11-152

11-24     Effects of Particulate Matter on Microbial Infectivity  	 11-155

11-25     Effects of Particulate Matter on Respiratory Tract Immune Function	 11-159

11-26     Toxicologic Interactions to Mixtures Containing Non-Acid Aerosol
          Particles	 11-163

11-27     Controlled Human Exposure Studies of Particulate Matter Mixtures
          Other Than Acid Aerosols	 11-167

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                                   LIST OF FIGURES
Number                                                                         Page

8-1       Diagrams showing the definitions of contrast and modulation	8-6

8-2       Spectrum of direct solar rays at the top of the atmosphere and at the
          surface of the earth for various values of the air mass 	8-10

8-3       The approach of radiances in the atmosphere to the equilibrium radiance
          or source function  	8-17

8-4       Data for the ratio of the total flux of skylight F_ incident of the
          earth's to the solar flux F0cos9 on a horizontal surface at the top
          of the atmosphere	8-20

8-5       Illustration of the transmitted radiance and the path radiance for a
          sight path toward a hillside  	8-24

8-6       Nomograms for the estimation of the contrast transmittance in a uniform
          region of the atmosphere and in a nonuniform atmosphere	8-31

8-7       Hour-average values of the modulation transfer and transmittance
          measured in a 2.20-km sight path during the 1987 summer intensive
          of the Southern California Air Quality Study	8-35

8-8a      Light-scattering efficiency factor for a homogeneous sphere with an
          index of refraction of 1.50 as a function of the size parameter
          a = TiDA	8-37

8-8b      Maximum and minimum values for light-scattering efficiency factors for
          homogeneous spheres with indices between 1.33  and 1.50 as a function
          of the normalized size parameter	8-38

8-9       Volume-specific light-scattering efficiency as a function of particle
          diameter Dp 	8-39

8-10      Volume-specific light-scattering efficiency as a function of geometric
          mean particle diameter D^ for log-normal size distributions 	8-41

8-11      Humidogram showing the dependence of the light-scattering coefficient of
          ambient aerosol on the relative humidity 	8-45

8-12      Relative size growth is shown as a function of relative humidity for an
          ammonium sulfate particle at 25 ° C	8-46
                                         II-xx

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                               LIST OF FIGURES (cont'd)
Number                                                                           Page

8-13      Summary of all relative humidity-dependent particle growth factors for
          0.2-//m diameter particles measured in Claremont, California, during the
          Southern California Air Quality Study and at Hopi Point in the Grand
          Canyon National Park during the Navajo Generating Station Visibility
          Study	8-48

8-14      Hypothetical curves showing the effect of nonlinearities on the
          mass-specific light-scattering efficiency	8-52

8-15      Changes in radiative forcing due to increases in greenhouse gas
          concentrations between 1765 and 1990  	8-91

8-16      A schematic diagram  showing the relationship between the radiative
          forcing of sulfate aerosols and climate response	8-93

8-17      Extinction of direct solar radiation by aerosols showing the diffusely
          transmitted and reflected components, as well as the absorbed
          components	8-94

8-18      Global, direct, and diffuse spectral solar irradiance on a horizontal
          surface for a solar zenith angle of 60° and ground reflectance of 0.2	8-96

8-19      Surface measurements of direct, diffuse, and global solar radiation
          expressed as illuminance, at Albany, New York, on August 23, 1992,
          and August 26, 1993  	8-98

8-20      Single scattering albedo of monodispersed spherical aerosols of varying
          radius and three different refractive indices at a wavelength of 0.63 //m  	8-99

8-2la     Annual mean direct radiative forcing resulting from anthropogenic
          sulfate aerosols  	 8-108

8-2Ib     Annual mean direct radiative forcing resulting from anthropogenic
          and natural sulfate aerosols  	 8-108

8-22a     Annual averaged greenhouse gas radiative forcing from increases in
          carbon dioxide, methane, nitrous oxide, and chlorfluorocarbons
          11 and 12, from preindustrial time to the present	 8-110

8-22b     Annual averaged greenhouse gas forcing plus anthropogenic sulfate
          aerosol forcing  	 8-110

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                               LIST OF FIGURES (cont'd)
Number                                                                             Page

8-23      Schematic illustration of the difference between response times of climate
          forcing due to carbon dioxide (heating) and sulfate (cooling) during
          different patterns of global fossil fuel consumption  	  8-113

9-1       Empirical relationship between average relative himidity and fraction
          of time when a zinc sheet specimen is wet	9-4

9-2       Geographic distribution of paint soiling costs	9-42

10-1      Schematic characterization of comprehensive exposure-dose-response
          continuum and the evolution of protective to predictive dose-response
          estimates 	 10-2

10-2      Biological marker components in sequential progression between
          exposure and disease  	 10-4

10-3      Lognormal particle size distribution for a hypothetical poly disperse
          aerosol	 10-9

10-4      These normalized plots of number, surface, and volume (mass)
          distributions from Whitby (1975) show a bimodal mass distribution
          in a smog aerosol	  10-11

10-5      Diagrammatic representation of respiratory tract regions in humans  	  10-16

10-6      Schematic representation of five major mechanisms causing particle
          deposition 	  10-17

10-7      Lung volumes and capacities	  10-23

10-8      Estimated tracheobronchial deposition in the rat lung, via the trachea,
          with no interceptional deposition	  10-40

10-9      Deposition increment data versus particle electronic charge for
          three particle diameters  at 0.3, 0.6, and 1.0 //m 	  10-42

10-10     Total deposition data in children with or during spontaneous breathing
          as a function of particle  diameter	  10-45

10-11     Calculated mass deposition from poly disperse aerosols of unit density
          with various geometric standard deviations as a function of mass median
          diameter for quiet breathing	  10-47

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                               LIST OF FIGURES (cont'd)
Number                                                                             Page

10-12     Major physical clearance pathways from the extrathoracic region and
          tracheobronchial tree	 10-54

10-13     Diagram of known and suspected clearance pathways for poorly soluble
          particles depositing in the alveolar region 	 10-54

10-14     Regional deposition data in rats versus particle size for sulfuric acid
          mists and dry particles	 10-75

10-15     Theoretical growth  curves for sodium chloride, sulfuric acid,
          ammonium bisulfate, and ammonium sulfate aerosols in terms of the
          initial and final size of the particle	 10-76

10-16     Regional deposition of hygroscopic sulfuric acid and control iron
          oxide particles at quiet breathing in the human lung as a function
          of subject age	 10-77

10-17     Distinctions in growth of aqueous ammonium  sulfate droplets of
          0.1 and 1.0 //m initial size are depicted as a function of their initial
          solute concentrations	 10-78

10-18     The initial  diameter of dry sodium chloride particles and equilibrium
          diameter achieved are shown for three relative humidity assumptions 	 10-79

10-19     The initial  dry diameter of three different salts is assumed to be
          1.0 //m	 10-80

10-20     Total deposition data (percentage deposition of amount inhaled) in
          humans as  a function of particle size  	 10-87

10-21     Total deposition as  a function of the diameter  of unit density spheres
          in humans  for variable tidal volume and breathing frequency	 10-88

10-22     Inspiratory deposition of the human nose as a  function  of particle
          aerodynamic diameter and flow rate	 10-91

10-23     Inspiratory extrathoracic deposition data in humans during mouth
          breathing as a function of particle aerodynamic diameter, flow rate,
          and tidal volume  	 10-92

10-24     Inspiratory deposition efficiency data and fitted curve for human
          nasal casts  plotted versus Q'1/8D1/2 (Lmm1)'1/8(cmV1)1/2  	 10-93

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                               LIST OF FIGURES (cont'd)
Number                                                                            Page

10-25     Inspiratory deposition efficiency data in human oral casts plotted
          versus flow rate and particle diffusion coefficient  	 10-95

10-26     Tracheobronchial deposition data in humans at mouth breathing as a
          function of particle aerodynamic diameter	 10-97

10-27     Alveolar deposition data in humans as a function of particle
          aerodynamic diameter  	 10-98

10-28     Percentage of total ventilatory airflow passing through the nasal route
          in human "normal augmenter" and in habitual "mouth breather"  	 10-100

10-29     Local deposition pattern in a bifurcating tube for inhalation and
          exhalation  	 10-102

10-30     Regional deposition fraction in laboratory animals as a function of
          particle size 	 10-107

10-31     Regional deposition efficiency in the rat extrathroacic region versus
          an impaction parameter as predicted by the model of Menache
          et al. (1996)	 10-113

10-32     Comparison of regional deposition efficiencies and fractions for the
          rat  	 10-116

10-33     Experimental deposition fraction data and predicted estimates
          using model of Menache et al. (1996) 	 10-120

10-34     Schematic of the International Commission on Radiological Protection
          Publication 66 (1994) model  	 10-125

10-35     Comparison of regional deposition fractions predicted by the proposed
          National Council on Radiation Protection model with those of the
          International Commission on Radiological Protection Publication 66
          (1994) model  	 10-128

10-36     Comparison of regional deposition fractions predicted by the proposed
          National Council on Radiation Protection model with those of the
          International Commission on Radiological Protection Publication 66
          (1994) model  	 10-129
                                         II-xxiv

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                               LIST OF FIGURES (cont'd)
Number                                                                            Page

10-37     Comparison of regional deposition fractions predicted by the proposed
          National Council on Radiation Protection model with those of the
          International Commission on Radiological Protection Publication 66
          (1994) model   	 10-130

10-38     Compartments of the simulation model used to predict alveolar burdens
          of particles acutely inhaled by mice, hamsters, rats, guinea pigs,
          monkeys, and dogs	 10-132

10-39     Schematic showing integration of inhalability with deposition efficiency
          functions 	 10-171

10-40     Daily mass deposition in tracheobronchial and alveolar regions for
          normal augmenter versus mouth breather adult males using International
          Commission on Radiological Protection Publication 66 (1994) minute
          volume activity patterns	 10-172

10-41     Daily mass deposition in tracheobronchial and alveolar regions for
          normal augmenter versus mouth breather adult males using
          International Commission on Radiological Protection Publication 66
          (1994) minute volume activity patterns  	 10-173

10-42     Deposition fraction in each respiratory tract region as predicted by the
          International Commission on Radiological Protection Publication 66
          (1994) model	 10-177

10-43     Daily mass particle deposition rates for 24-hour exposure at 50 //g/m3
          in each respiratory tract region as predicted by the International
          Commission on Radiological Protection Publication 66 (1994) model	 10-178

10-44     Respiratory tract deposition fractions and PM10 sampler collection
          versus mass median aerodynamic diameter with two different geometric
          standard deviations 	 10-181

10-45     Respiratory tract deposition fractions and PM10 or PM2 5 sampler
          collection versus mass median aerodynamic diameter with two
          different geometric standard deviations  	 10-182

10-46     Respiratory tract deposition fractions and PM10 or PM2 5 sampler
          collection fractions versus mass median aerodynamic diameter
          with two different geometric standard deviations	 10-183
                                         II-XXV

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                               LIST OF FIGURES (cont'd)
Number                                                                             Page

10-47     Schematic illustration of how ambient aerosol distribution data were
          integrated with respiratory tract deposition efficiency or sampler
          efficiency to calculate deposition in respiratory tract regions or mass
          collected by sampler  	  10-185

10-48     Mass deposition fraction in normal augmenter versus mouth breather
          adult male with a general population minute volume activity pattern
          predicted by the International Commission on Radiological Protection
          Publication 66 (1994) model and the mass collected by PM10 or PM2 5
          samplers for Philadelphia aerosol	  10-186

10-49     Mass deposition fraction in normal augm enter versus mouth breather
          adult male with a general population minute volume activity pattern
          predicted by the International Commission on Radiological Protection
          Publication 66 (1994) model and the mass collected by PM10 or PM2 5
          samplers for Phoenix aerosol	  10-187

10-50     Fractional number deposition in each respiratory tract region for
          normal augmenter versus mouth breather adult male with a general
          population activity pattern as predicted by the International Commission
          on Radiological Protection Publication 66 (1994) model for an exposure
          to the Philadelphia aerosol	  10-188

10-51     Number of particles deposited per day in each respiratory tract region
          for normal augmenter versus mouth breather adult male with a general
          population activity pattern predicted by the International Commission
          on Radiological Protection Publication 66 (1994) model for an exposure
          to the Philadelphia aerosol at a concentration of 50 //g/m3	  10-189

10-52     Fractional number deposition in normal augmenter versus mouth
          breather adult male with a general population activity pattern predicted
          by the International Commission on Radiological Protection
          Publication 66 (1994) model for an exposure to the Phoenix aerosol	  10-191

10-53     Number of particles deposited per day in each respiratory tract region
          for normal augmenter versus mouth breather adult male with a general
          population activity pattern predicted by the International Commission
          on Radiological Protection Publication 66 (1994) model for an exposure
          to the Phoenix aerosol at a concentration of 50 //g/m3  	  10-192

10-54     Predicted extrathoracic deposition fractions versus mass median
          aerodynamic diameter of inhaled monodisperse aerosols or polydisperse
          aerosols for humans and rats for the extrathoracic region, the
          tracheobronchial region, and the alveolar region   	  10-197

                                         II-xxvi

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                               LIST OF FIGURES (cont'd)
Number                                                                            Page

10-55     Particle mass retained in the lung versus time predicted by the
          International Commission on Radiological Protection Publication 66
          (1994) model, assuming dissolution-absorption half-times of 10, 100,
          and 1,000 days for the accumulation, intermodal, and coarse modes,
          respectively, of continuous exposures to Philadelphia and Phoenix
          aerosols at 50 //g/m3	  10-201

10-56     Specific lung burden versus time predicted by the International
          Commission on Radiological Protection Publication 66 (1994) model,
          assuming dissolution-absorption half-times of 10, 100, and 1,000 days
          for the accumulation, intermodal, and coarse modes,  respectively, of
          continuous exposures to Philadelphia and Phoenix aerosols at
          50 Mg/m3 	  10-203

10-57     Predicted retained alveolar dose in normal augmenter human or in a
          rat for exposure at 50 //g/m3 to 1.0-//m mass median aerodynamic
          diameter monodisperse aerosol, assuming a dissolution-absorption
          half-time of 10, 100, or 1,000 days  	  10-210

10-58     Predicted retained alveolar dose in a normal augmenter human or in a
          rat for exposure at 50 //g/m3 to 2.55-//m mass median aerodynamic
          diameter polydisperse aerosol, assuming a dissolution-absorption
          half-time of 10, 100, or 1,000 days  	  10-211

10-59     Predicted alveolar region retained dose ratios in rats
          versus humans for chronically inhaled exposure at 50 //g/m3
          to 1.0-//m mass median aerodynamic diameter (MMAD) monodisperse
          and 2.55-//m MMAD polydisperse aerosols, assuming a dissolution-
          absorption half-time of 10, 100, or 1,000 days	  10-213

10A-1     Nasal deposition efficiency measured in adult Caucasian males during
          normal breathing and data on extrathoracic deposition when  particles
          are inhaled and exhaled through a mouthpiece	10A-5

10A-2     Comparisons of the "fast cleared" fraction of lung deposition measured
          at the GSF Frankfurt Laboratory with the tracheobronchiolar deposition
          predicted by the theoretical model of Egan et al. (1989)	10A-8

10A-3     Comparisons of the "slow cleared" fraction of lung deposition measured
          at the GSF Frankfurt Laboratory with the alveolar deposition predicted
          by the theoretical model of Egan et al. (1989) 	10A-9
                                        II-xxvii

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                               LIST OF FIGURES (cont'd)
Number                                                                           Page

10A-4    Comparison of fractional deposition measured by Foord et al. (1978) and
          Emmett and Aitken (1982) in different subjects with values given by the
          International Commission on Radiological Protection Publication 66
          (1994) lung model	10A-12

10A-5    Comparison of total respiratory tract deposition of submicron-sized
          alumino-silicate particles measured by Tu and Knutson (1984) in two
          subjects, with the values calculated as a function of particle
          diameter by Egan et al. (1989)	10A-14

10A-6    Comparison of the distributions of total respiratory tract deposition
          measured in 20 different subjects breathing spontaneously at rest or
          breathing at a controlled rate at rest	10A-15

10A-7    Experimental data on deposition efficiency of the tracheobronchial
          region and fractional deposition in the alveolar region for the
          large group of subjects studied at New York University	10A-17

10B-1    Daily minute volume pattern for male demographic groups	10B-4

10B-2    Daily minute volume pattern for female demographic groups  	10B-5

10B-3    Daily minute volume pattern for demographic groups for children	10B-6

10C-1    An example of histogram display  and fitting to log-normal functions for
          particle-counting size distribution data	10C-2

10C-2    Impactor size distribution measurement generated by Lundgen et al.
          with the Wide Range Aerosol Classifier: Philadelphia and Phoenix  	10C-10

11-1      Mean plus or minus standard error of the mean specific airway
          resistance before and after a 16-minute exposure for nine subjects who
          inhaled low relative-humidity (RH) sodium chloride (NaCl),  low-RH
          sulfuric acid (H2SO4), and high-RH H2SO4 aerosols at rest, and six
          subjects who inhaled low-RH NaCl and low-RH H2SO4 aerosols
          during exercise	  11-29

11-2      Decrements in forced expiratory volume in one second following
          6.5-hour exposures on two  successive days  	  11-38

11-3      Asthmatic subjects	  11-41

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                   AUTHORS, CONTRIBUTORS, AND REVIEWERS
                CHAPTER 8. EFFECTS ON VISIBILITY AND CLIMATE
Principal Authors

Dr. Harshvardhan—Purdue University, Department of Earth and Atmospheric Sciences,
W. Lafayette, IN 47907-1397

Dr. Willard Richards—Sonoma Technology, Inc., 5510 Skyline Blvd., Santa Rosa, CA 95403
Contributors and Reviewers

Dr. Michael A. Berry—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Beverly Comfort—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Adarsh Deepak—Science and Technology, 101 Research Drive, Hampton, VA 23666

Dr. Derrick Montaque—University of Wyoming, Department of Atmospheric Sciences,
P.O. Box 3038, University Station, Laramie, WY  82071

Dr. Joseph P. Pinto—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Joseph Sickles—National Exposure Research Laboratory (MD-80A), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. William E. Wilson—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
                      CHAPTER 9. EFFECTS ON MATERIALS
Principal Authors

Ms. Beverly Comfort—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. Fred Haynie—300 Oak Ridge Road, Cary, NC 27511
                                       II-xxix

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               AUTHORS, CONTRIBUTORS, AND REVIEWERS (cont'd)
Contributors and Reviewers

Dr. Michael A. Berry—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Edward Edney—National Exposure Research Laboratory (MD-84), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. Douglas Murray—TRC Environmental Corporation, 5 Waterside Crossing, Windsor,
CT 06095

Dr. John Spence—National Exposure Research Laboratory (MD-75), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. John Yocom—Environmental Consultant, 12 Fox Den Road, West Simsbury, CT 06092
                CHAPTER 10.  DOSIMETRY OF INHALED PARTICLES
                           IN THE RESPIRATORY TRACT
Principal Authors

Dr. Anthony C. James—ACJ and Associates, 129 Patton Street, Richland, WA  99352-1618

Ms. Annie M. Jarabek—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Paul E. Morrow—University of Rochester Medical Center, School of Medicine and
Dentistry, Rochester, NY 14614

Dr. Richard B. Schlesinger—New York University, Department of Environmental Medicine,
550 First Avenue, New York, NY 10016

Dr. Morris Burton Snipes—Inhalation Toxicology Research Institute, Lovelace Biomedical and
Environmental Research Institute, Albuquerque, NM  87185-5890

Dr. C.P. Yu—State University of New York, Department of Mechanical and Aerospace
Engineering, Buffalo, NY  14260-4400
                                       II-XXX

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               AUTHORS, CONTRIBUTORS, AND REVIEWERS (cont'd)
Contributors and Reviewers

Dr. William J. Bair—Battelle, Pacific Northwest Laboratories, Kl-50, P.O. Box 999,
Richland, WA  99352

Dr. Lawrence J. Folinsbee—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Timothy R. Gerrity—Veterans Administration, Acting Deputy Director, Medical Research,
810 Vermont Avenue, NW, Washington, DC 20420

Dr. Judith A. Graham—National Exposure Research Laboratory (MD-75), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. Raymond A. Guilmette—Inhalation Toxicology Research Institute, Lovelace Biomedical
and Environmental Research Institute, Inc., P.O. Box 5890, Albuquerque, NM 87185

Dr. F. Charles Hiller—University of Arkansas for Medical Science, 4301 W. Markham,
Little Rock, AR 72212

Dr. Wolfgang G. Kreyling—GSF, Institute for Inhalation Biology, Ganghferstr,
40 Unterschleissheit, Germany D-85716

Dr. Ted Martonen—National Health and Environmental Effects Research Laboratory (MD-74),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Ms. Margaret G. Menache—Duke University Medical Center, Center for Extrapolation
Modeling, P.O. Box 3210, First Union Plaza/Suite B-200, Durham, NC  27710

Dr. Gunter Oberdorster—University of Rochester, Department of Environmental Medicine,
575 Elmwood Avenue, Rochester, NY 14642

Dr. Robert F. Phalen—University of California—Irvine, Department of Community and
Environmental Medicine, Air Pollution Health Effects Laboratory, Irvine, CA  92717-1825

Dr. Otto G.  Raabe—University of California—Davis, Institute of Toxicology and Environmental
Health, Old Davis Road, Davis, CA  95616

Dr. Sid Soderholm—National Institute for Occupational Safety and Health, 1095 Willowdale
Road, Morgantown, WV 26505

Dr. Magnus Svartengren—Karolinska Institute of Huddinge University Hospital, Department of
Occupational Medicine,  S-141  86Hugginge, Sweden
                                        II-xxxi

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               AUTHORS, CONTRIBUTORS, AND REVIEWERS (cont'd)
       CHAPTER 11. TOXICOLOGICAL STUDIES OF PARTICIPATE MATTER
Principal Authors

Dr. Lawrence J. Folinsbee—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC  27711

Dr. Mark Frampton—University of Rochester Medical Center, Pulmonary Disease Unit,
601 Elmwood Avenue, Rochester, NY 14642-8692

Dr. Rogene Henderson—Lovelace Biomedical and Environmental Research Institute,
Inhalation Toxicology Research Institute, Albuquerque, NM 87105

Ms. Annie M. Jarabek—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC  27711

Dr. James McGrath—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC  27711

Dr. Gunter Oberdorster—University of Rochester, Department of Environmental Medicine, 575
Elmwood Avenue, Rochester, NY 14642

Dr. Richard B. Schlesinger—New York University, Department of Environmental Medicine,
550 First Avenue, New York, NY 10016

Dr. David B. Warheit—Haskell Laboratory, E.I. Du Pont de Nemours, P.O. Box 50, Elkton
Road, Newark, DE  19714
Contributors and Reviewers

Dr. Daniel L. Costa—National Health and Environmental Effects Research Laboratory
(MD-82), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Kevin E. Driscoll—The Miami Valley Laboratories, Procter & Gamble Company, P.O. Box
538707, Cincinnati, OH  45253-8707

Dr. Don Dungworth—6260 Cape George Road, Port Townsend, WA 98368

Dr. Gary Foureman—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Donald Gardner—P.O. Box 97605, Raleigh, NC 27624-7605

                                      II-xxxii

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               AUTHORS, CONTRIBUTORS, AND REVIEWERS (cont'd)
Contributors and Reviewers (cont'd)

Dr. Andy Ohio—Duke University Medical Center, Division of Pulmonary Medicine and
Critical Care Medicine, P.O. Box 3177, Durham, NC  27710

Dr. Jeff Gift—National Center for Environmental Assessment (MD-52), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. Judith A. Graham—National Exposure Research Laboratory (MD-75), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. Lester D. Grant—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Daniel Guth—National Center for Environmental  Assessment (MD-52), U.S. Environmental
Protection Agency, Research Triangle Park, NC 27711

Dr. Jack Harkema—Michigan State University, Department of Pathology, College of Veterinary
Medicine, Veterinary Medical Center, East Lansing, MI 48824

Dr. Gary Hatch—National Health and Environmental Effects Research Laboratory (MD-82),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Michael T. Kleinman—University of California—Irvine, Department of Community and
Environmental Medicine, Irvine, CA 92717-1825

Dr. Dennis Kotchmar—National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Gunter Oberdorster—University of Rochester, Department of Environmental Medicine
575 Elmwood Avenue, Rochester, NY 14642

Dr. Mary Jane Selgrade—National Health and Environmental Effects Research  Laboratory (MD-
92), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Jeff Tepper—Genetech, Inc., Pulmonary Research, 460 Point San Bruno  Boulevard,
South San Francisco, CA 94080-4990

Dr. Hanspeter Witschi—University of California—Davis, Laboratory for Energy-Related Health
Research, Davis, CA 95616

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                   U.S. ENVIRONMENTAL PROTECTION AGENCY
                            SCIENCE ADVISORY BOARD
                  CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE

              PARTICIPATE MATTER CRITERIA DOCUMENT 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 Jacobson—Boyce Thompson Institute, Tower Road, Cornell University, Ithaca,
NY 14853

Dr. Philip Hopke—Clarkson University, Box 5810, Pottsdam, NY 13699-5810

Dr. Joseph Mauderly—Inhalation Toxicology Research Institute, Lovelace Biomedical and
Environmental Research Institute, P.O. Box 5890, Albuquerque, NM 87185

Dr. Paulette Middleton—Science and Policy Associates, 3445 Penrose Place, Suite 140,
Boulder, CO 80301

Dr. James H. Price, Jr.—Research and Technology Section, Texas Natural Resources
Conservation Commission, P.O. Box 13087, Austin, TX  78711-3087


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. Petros Koutrakis—Harvard School of Public Health, 665 Huntington Avenue, Boston,
MA 02115
                                      II-XXXV

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                   U.S. ENVIRONMENTAL PROTECTION AGENCY
                            SCIENCE ADVISORY BOARD
                  CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
                                      (cont'd)
Consultants (cont'd)

Dr. Kinley Larntz—Department of Applied Statistics, University of Minnesota, 352 COB,
1994 Buford Avenue, St. Paul, MN 55108-6042

Dr. Allan Legge—Biosphere Solutions, 1601 llth Avenue, N.W., Calgary, Alberta T2N 1H1,
Canada

Dr. Daniel Menzel—Department of Community and Environmental Medicine, University of
California—Irvine, 19172 Jamboree Boulevard, Irvine, CA 92717-1825

Dr. William R. Pierson—Energy and Environmental Engineering Center, Desert Research
Institute, P.O. Box 60220, Reno, NV 89506-0220

Dr. Jonathan Samet—Johns Hopkins University, School of Hygiene and Public Health,
Department of Epidemiology, 615 N. Wolfe Street, Baltimore, MD 21205

Dr. Christian Seigneur—Atmospheric and Environmental Research, Inc., 6909 Snake Road,
Oakland,  CA  94611

Dr. Carl M. Shy—Department of Epidemiology, School of Public Health, University of North
Carolina,  CB #7400 McGravran-Greenberg Hall, Chapel Hill, NC 27599-7400

Dr. Frank Speizer—Harvard Medical School, Channing Laboratory, 180 Longwood Avenue,
Boston, MA 02115

Dr. Jan Stolwijk—Epidemiology and Public Health, Yale University, 60 College Street,
New Haven, CT 06510

Dr. Mark J. Utell—Pulmonary Disease Unit, Box 692, University of Rochester Medical Center,
601 Elmwood Avenue, Rochester, NY 14642

Dr. Warren White—Washington University, Campus Box 1134, One Brookings Drive,
St. Louis, MO 63130-4899
                                      II-xxxvi

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                   U.S. ENVIRONMENTAL PROTECTION AGENCY
                            SCIENCE ADVISORY BOARD
                  CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE
                                      (cont'd)
Designated Federal Official

Mr. Randall C. Bond—Science Advisory Board (1400), U.S. Environmental Protection Agency,
401 M Street, S.W., Washington, DC 20460

Mr. A. Robert Flaak—Science Advisory Board (1400), U.S. Environmental Protection Agency,
401 M Street, S.W., Washington, DC 20460
Staff Assistant

Ms. Janice M. Cuevas—Science Advisory Board (1400), U.S. Environmental Protection
Agency, 401 M Street, S.W., Washington, DC 20460
Secretary

Ms. Lori Anne Gross—Science Advisory Board (1400), U.S. Environmental Protection Agency,
401 M Street, S.W., Washington, DC 20460

Ms. Connie Valentine—Science Advisory Board (1400), U.S. Environmental Protection
Agency, 401 M Street, S.W., Washington, DC 20460
                                      II-xxxvii

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                   U.S. ENVIRONMENTAL PROTECTION AGENCY
         PROJECT TEAM FOR DEVELOPMENT OF AIR QUALITY CRITERIA
                           FOR PARTICIPATE MATTER
Scientific Staff

Dr. Lester D. Grant—Director, National Center for Environmental Assessment (MD-52),
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Michael A. Berry—Deputy Director, National Center for Environmental Assessment, (MD-
52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Dr. Dennis Kotchmar—Project Manager, Medical Officer, National Center for Environmental
Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC
27711

Ms. Beverly Comfort—Deputy Project Manager/Technical Project Officer, Health Scientist,
National Center for Environmental Assessment (MD-52), U.S. Environmental Protection
Agency, Research Triangle Park, NC 27711

Dr. Lawrence J. Folinsbee—Chief, Environmental Media Assessment Group, National Center
for Environmental Assessment (MD-52), U.S. Environmental Protection Agency, Research
Triangle Park, NC 27711

Dr. A. Paul Altshuller—Technical Consultant, National Center for Environmental Assessment
(MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (Retired)

Dr. Robert Chapman—Technical Consultant, Medical Officer, National Center for
Environmental Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle
Park, NC 27711

Mr. William Ewald—Technical Project Officer, Health Scientist, National Center for
Environmental Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle
Park, NC 27711

Mr. Norman Childs—Chief, Environmental Media Assessment Branch, National Center for
Environmental Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle
Park,NC 27711 (Retired)

Dr. Judith A. Graham—Associate Director for Health, National Exposure Research Laboratory
(MD-77), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
                                      II-xxxix

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                   U.S. ENVIRONMENTAL PROTECTION AGENCY
         PROJECT TEAM FOR DEVELOPMENT OF AIR QUALITY CRITERIA
                            FOR PARTICIPATE MATTER
                                       (cont'd)
Scientific Staff (cont'd)

Ms. Annie M. Jarabek—Technical Project Officer, Toxicologist, National Center for
Environmental Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle
Park, NC 27711

Dr. Allan Marcus—Technical Project Officer, Statistician, National Center for Environmental
Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC
27711

Dr. James McGrath—Technical Project Officer, Visiting Senior Health Scientist, National
Center for Environmental Assessment (MD-52), U.S. Environmental Protection Agency,
Research Triangle Park, NC  27711

Dr. Joseph P. Pinto—Technical Project Officer, Physical Scientist, National Center for
Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC
27711

Ms. Beverly Tilton—Technical Project Officer, Physical Scientist, National Center for
Environmental Assessment (MD-52), U.S. Environmental Protection Agency, Research Triangle
Park,NC 27711 (Retired)

Dr. William E. Wilson—Technical Consultant, 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

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

Ms. Diane H. Ray—Program Analyst, National Center for Environmental Assessment
(MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
                                        II-xl

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                  U.S. ENVIRONMENTAL PROTECTION AGENCY
         PROJECT TEAM FOR DEVELOPMENT OF AIR QUALITY CRITERIA
                           FOR PARTICIPATE MATTER
                                      (cont'd)
Technical Support Staff (cont'd)

Ms. Eleanor Speh—Office Manager, Environmental Media Assessment Branch, National Center
for Environmental Assessment (MD-52), U.S. Environmental  Protection Agency, Research
Triangle Park, NC 27711

Ms. Donna Wicker—Administrative Officer, National Center for Environmental Assessment
(MD-52), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

Mr. Richard 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

Mr. Donald L. Duke—Project Director, 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. 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. Terri D. Ragan—Personal Computer Technician, ManTech Environmental Technology,
Inc., P.O. Box 12313, Research Triangle Park, NC 27709

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                  U.S. ENVIRONMENTAL PROTECTION AGENCY
         PROJECT TEAM FOR DEVELOPMENT OF AIR QUALITY CRITERIA
                           FOR PARTICIPATE MATTER
                                      (cont'd)
Document Production Staff (cont'd)

Mr. Derrick Stout—Local Area Network System Administrator, 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
Technical Reference Staff

Ms. Ginny M. Belcher—Bibliographic Editor, ManTech Environmental Technology, Inc.,
P.O. Box 12313, Research Triangle Park, NC 27709

Mr. Robert D. Belton—Bibliographic Editor, Information Organizers, Inc.,
P.O. Box 14391, Research Triangle Park, NC 27709

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. 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

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         8.  EFFECTS ON VISIBILITY AND CLIMATE
8.1   INTRODUCTION
     Visibility is the yardstick by which the layman measures air quality every day. Air
pollutants can change the way he sees the world.  The air pollutant that makes the largest
contribution to visibility impairment is usually fine particulate matter, more specifically the
accumulation mode, -0.3 to 1.0 //m diameter (see Chapter 3).
     The primary objective of the visibility discussion in this chapter is to present the technical
basis for understanding the linkage between air pollution, especially particulate matter, and
visibility.  This linkage can be used to (1) evaluate the visibility effects of different levels for the
primary standards for particulate matter concentrations designed to protect public health and (2)
evaluate the need for a secondary standard designed to reduce visibility impairment.
     The visibility sections of this chapter are complementary to recent reviews of visibility
published by the National Research Council (National Research Council, 1993), the National
Acid Precipitation Assessment Program (Trijonis et al., 1991), and the U.S. EPA (U.S.
Environmental Protection Agency, 1995e). Little of the information in those reviews has been
presented again here, with the result that this review does not attempt to present a fully
comprehensive overview of the effect of particulate matter on visibility. Instead, the visibility
sections of this chapter focus on presenting additional information relevant to the consideration
of visibility protection that does not appear in the prior reviews.

8.1.1    Background
     In August 1977, Congress amended the Clean Air Act (CAA) to establish as a national
goal "the prevention of any future and remedying of any existing impairment of visibility in
mandatory Class I Federal areas, which impairment results from manmade air pollution" (Title I
Part C Section 169A; 42 U.S.C. 7491).  Class I areas include many national parks and
wilderness areas, especially in the western portion of the United States.  These areas were
generally large national parks and federal wilderness areas and included all national parks in
existence on August 7, 1977. The visibility protection provisions of section  169A
                                          3-1

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required the U.S. Environmental Protection Agency (EPA) to establish a regulatory program to
assure reasonable progress toward this national goal. In 1980, the EPA established regulatory
requirements under section 169A to address Class I protection from visibility impairment that
could be reasonably attributed to major stationary air pollution sources. At that time, regulatory
action on regional haze (pollution transported long distances from a multitude of sources) was
deferred until better scientific tools were developed. The 1977 Amendments also included
provisions requiring applicants for new major source permits to assess the potential for their
projects to cause adverse impacts on the air quality-related values, including visibility, in nearby
Class I areas.
     The mandate to protect visibility in national parks and wilderness areas led to the
development of the Interagency Monitoring of Protected Visual Environments (IMPROVE), a
cooperative visibility monitoring network managed and operated by federal land management
agencies, the U.S. EPA, and State air quality organizations (Malm et al., 1994: Sisler et al.,
1993). The 1977 CAA amendments also (a) led to major visibility research studies, such as (1)
the Visibility Impairment due to Sulfur Transformation and Transport in the Atmosphere
(VISTTA) study (Blumenthal et al., 1981); (2) the Subregional Cooperative Electric Utility, and
the Department of Defense, National Park Service,  and Environmental Protection Agency Study
(SCENES) (Mueller et al., 1986); and (b) included the requirement to  control  sulfur dioxide
(SO2) emissions from the Navajo Generating Station, which is near the Grand Canyon National
Park (56 FR 38399,  1991).
     The CAA was amended in 1990 by adding section 169B, which  authorized the EPA (a) to
conduct research on regional visibility impairment and (b) to establish the Grand Canyon
Visibility Transport Commission (GCVTC) for the  assessment of appropriate  actions under
section 169A for protecting the Grand Canyon from regional visibility impairment caused by
man-made sources.  This charge was expanded by the U.S. EPA to include the 15 other Class I
parks and wilderness areas on the Colorado Plateau. Work is now being performed to assess the
scientific and technical data,  studies, and other available information pertaining to adverse
impacts on visibility from projected growth in emissions from sources located in the region. The
U.S. EPA has also initiated a tracer study to evaluate the effects of emissions from the Mohave
Power Project on visibility in the Grand Canyon National Park and other Class I areas in the
Colorado Plateau. Because of these events, a major portion of
                                          8-2

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the funding for visibility research during the last two decades has been directed toward
protecting pristine and scenic areas.
     Interest in protecting visibility in urban areas has a much longer history and is strong at the
present time. Smoke in European cities, especially London, has been a concern for centuries.
Many of the modern advances in the understanding of atmospheric fine particles were made
during the 1969 Pasadena Smog Experiment (see, for example, Whitby et al., 1972), which was
followed by the Aerosol Characterization Experiment (ACHEX) sponsored by the California Air
Resources Board (Hidy et al., 1980).  The continuing interest in urban visibility is indicated in
the list of short-term intensive visibility and aerosol studies summarized by the National Acid
Precipitation Assessment Program (NAPAP) report on visibility (Trijonis et al., 1991) and
discussed later in this chapter. Many of the studies focused on urban visibility.
     Visibility impairment carries significant social and economic costs, which are discussed
below.
     Particulate matter also affects climate by increasing the absorption of solar radiation within
the atmosphere and by increasing the fraction of solar radiation reflected into space (Charlson et
al., 1992). The first effect causes heating within the atmosphere, especially where the
concentrations of light-absorbing particles  are elevated, and the second  effect causes a cooling of
the Earth.  This cooling counteracts the heating caused by the greenhouse effect of gases that
absorb infrared radiation.

8.1.2   Definition of Visibility
     The National Research Council's Committee on Haze in National Parks and Wilderness
Areas said, "Visibility is the degree to which the atmosphere is transparent to visible light."
(National Research Council,  1993).  Section 169A of the 1977 CAA Amendments (42 U.S.C.
7491) and the 1979 Report to Congress (U.S. Environmental Protection Agency,  1979) define
visibility impairment as a reduction in visual range and atmospheric discoloration. Equating
visibility to the visual range is consistent with historical visibility measurements at airports,
where human observers recorded the greatest distance at which one of a number of pre-selected
targets could be perceived.

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     Visibility may also be defined as the clarity (transparency) and color fidelity of the
atmosphere. Transparency can be quantified by the contrast transmittance of the atmosphere.
This definition of visibility is consistent with both (1) the historical records based on human
observation of the perceptibility of targets, which include both the longest duration and most
widespread records now available, and (2) the definition of visibility recommended by the
National Research  Council (National Research Council, 1993).
     Air pollution can also alter the colors of the atmosphere and the perceived colors of objects
viewed through the atmosphere. A complete quantification of visibility should include a
measure of the color changes caused by the atmosphere. Such measures have been included in
plume visibility models (e.g., Latimer et al., 1978), but there is no consensus on the best
parameter to quantify color changes caused by air pollution from many sources.
     Visibility is an effect of air quality and, unlike the particulate matter concentration, it is not
a property of an element of volume in the atmosphere.  Visibility can be defined only for a sight
path and depends on the illumination of the atmosphere and the direction  of view.  The factors
that control this dependence are described in the succeeding sections of this chapter.

8.1.3    Human Vision
     Vision results from the human response to the electromagnetic radiation that enters the eye.
Therefore, this presentation of the theory of visibility begins with a brief outline of the relevant
properties of human vision.
     The eye is most sensitive to green wavelengths, near 550 nm, and can perceive radiation
between approximately 400 and 700 nm. The sensitivity of the eye is greatly diminished near
the longest and shortest visible wavelengths.  When measurements or calculations  at only one
wavelength are used to characterize visibility, it is customary to select a wavelength between  500
and 550 nm because these wavelengths are in the middle of the visible spectrum and the eye is
most sensitive in this range.
     The retina of the eye contains two types of receptor cells, rods and cones. The rods, used
for nighttime vision, are not capable of perceiving color and are most concentrated in the parts
of the retina used for peripheral vision.  Rods are most sensitive at a wavelength of 510 nm and
are insensitive to wavelengths longer than about 630 nm. The foveal pit, which
                                           8-4

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subtends an angle of about 1 degree, contains only cones, which are used for daytime color
vision. There are no rods in approximately the central 2 degrees of the field of view. As a
result, a faint light is best detected at night by looking in a slightly different direction. On the
other hand, visual acuity is greatly diminished in peripheral vision. For example, at normal
levels of illumination, text which is quite readable becomes unreadable when the direction of
view is displaced by a few degrees so that the image of the text no longer falls on the fovea.
      Human vision has a dynamic range of about 1012 cd/m2 (candelas per square meter).
Radiation becomes perceptible to the completely dark adapted eye at levels of about 10"6 cd/m2.
Cones begin to be activated at levels of about 10"3 cd/m2, the rods cease to function at about 125
cd/m2, and light levels above 106 cd/m2 cause the observer to be uncomfortable and to feel
blinded.  The visibility regulations are usually interpreted as addressing daytime visibility, which
is provided by the cones and is called photopic vision.
      Contrast is widely used as a measure of the perceptibility of faint objects because of the
following property of human vision. Weber's law, sometimes called Fechner's law or the
Weber-Fechner law, states that for a wide range of luminance levels, to be just noticeably
brighter,  one patch of light must exceed the luminance of another by a constant fraction.  Figure
8-1 and Equation 8-1 illustrate the definition of the contrast, C, of an object (target) of radiance,
I, viewed against a background of radiance, Ib
                                                                                  (8-1)
Figure 8-1 also illustrates the definition of modulation, M, of a sine wave with maximum and
minimum radiances, lmaK and 1^, respectively

             M=(In,ax-In,1n)/(In,ax+In,1n) •                                     (8-2)
If the average radiance of the sine wave is indicated by Ib, then Equation 8-2 can be written
                    M = (Imax-Ib)/Ib                                            (8-3)
                                           3-5

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         10

         9-

         8-
       « 6
       u
       « 5
       •o
       « 4
       tt ^

         3-
         2

         1
          m
      Target
      radiance

        I.
Background '
 radiance   ^
                                    "
           UJ
                  23456789  10
                     Position in Scene
                                            a_
                                            b
         10
       „
       o
9-

8-

7-

6-

5-
       a
       1 4^
       Of
         3-

         2-

         1 -

         0
Maximum
radiance
Minimum
radiance

  'min
   345678
    Position in Scene
                                                Modulation ='max^'|min
a_
b
                                 1/2(l
                                 /j2V'
                        + 1  )
                      max  'mm'
                                              10
Figure 8-1.  Diagrams showing the definitions of contrast and modulation. If the
          background radiance in the definition of contrast is equated to the average
          radiance in the definition of modulation, the definitions have the same
          mathematical form.

Source:     Richards (1990).
                                  8-6

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which is identical in form to Equation 8-1. This transformation allows contrast and modulation
to be used interchangeably in visibility calculations.  It is shown below that the average radiance
or background radiance in Equations 8-1 and 8-3 plays a key role in visibility calculations.
     The accommodation of the eye, and its ability to perceive contrasts, changes in response to
the general light level. The above definitions of contrast and modulation assume that the eye is
accommodated to the background radiance. The effects of the accommodation of the eye can be
experienced by first viewing objects in a relatively dark room, then going outside into bright
daylight and viewing the same objects through an open window. Radiance differences that were
perceptible when the eye was accommodated to those radiances become imperceptible when the
eye becomes accommodated to a much greater radiance.
     The perception of discoloration in the atmosphere depends on the properties of human
color vision. Studies with color matches have shown that color vision is three dimensional.  For
example, images on color television or computer monitors are made up of red, green, and blue
dots. All colors that the screen is capable of displaying can be specified by three numbers that
quantify the intensity of the light from each of the three phosphors. For purposes of determining
color matches, it is possible to characterize colors by these three numbers, X, Y, and Z, which
are called tristimulus values.  Colors that have the same tristimulus values will appear to match.
In 1931, the Commission Internationale de 1'Eclairage (CIE, or International Commission for
Illumination) adopted a standard method of calculating these numbers from the spectrum of the
light reflected from an object.
     The perception of color depends on illumination and setting. For example, when there is a
brilliant sunset, a white picket fence will appear to be white, but will be distinctly yellow in a
color photograph. A nitrogen dioxide (NO^) containing plume appears to be yellow against a
blue sky even when a photograph or spectral measurement shows that the plume is blue, but less
blue than the surrounding sky.  The eye correctly perceives that a yellow gas is present in the
plume. Spectral measurements have shown that the "Denver brown cloud" is a neutral gray
(Waggoner etal., 1983).
     These properties of human vision been described and explained by MacAdam (1981).  The
eye tends to perceive the lightest and brightest object in a scene as white, and to determine the
color of other objects by comparison.  For example, water clouds are typically
                                          3-7

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present in the sky above Denver.  Spectral measurements show that they are blue compared to
the color of sunlight, but the eye perceives them as white. The urban haze is not as blue as the
water clouds in the sky, and by comparison, appears yellow or brown.
     Because of this property of human vision, plume visibility models calculate the spectral
radiance and tristimulus values of a "reference white." This reference is then used in the color
calculations in the models.
8.2    FUNDAMENTALS OF ATMOSPHERIC VISIBILITY
     This section presents a simple, complete, and reasonably accurate theory of daytime
visibility for approximately horizontal sight paths. This theory provides the linkage between the
nature and concentration of particulate matter in the atmosphere and visibility.

8.2.1    Geometry of the Atmosphere
     The atmosphere is an extremely thin layer on the surface of the Earth, and all of its
physical properties have  strong vertical gradients.  Half the mass of the atmosphere is at altitudes
below 5.7 km (18,700 ft) mean sea level. The average of the equatorial and polar radii  of the
Earth is 6,370 km (3958  mi). Thus, most of the mass of the atmosphere is within a shell having
a thickness 0.09% of the radius of the Earth.
     The atmosphere is thin enough compared to the radius of the Earth that its curvature can be
neglected in most optical calculations. This is not the case for sight paths that are horizontal or
nearly so (Malm, 1979).  Because of the curvature of the Earth, a sight path that is initially
horizontal will have an altitude that increases with distance.  Table  8-1 gives the approximate
distances for selected increases in height above ground level. Sight paths longer than
approximately 100 km (60 mi) are always subject to  substantial changes in the properties of the
atmosphere over the length of the sight path because of the changes in altitude. The atmosphere
rarely has uniform optical properties over distances greater than a few tens of kilometers, even at
a constant height above ground.  Tabulations of air quality or visibility data that report visual
ranges much greater than 100 km are based on assumptions that cannot be valid in the Earth's
atmosphere.

-------
     TABLE 8-1. APPROXIMATE DISTANCES FOR SELECTED INCREASES IN
              HEIGHT OF AN INITIALLY HORIZONTAL SIGHT PATH
Height
(m)
300
1,000
2,000
3,000
4,000

(ft)
1,000
3,280
6,560
9,840
13,120
Distance
(km)
62
113
160
196
226

(mi)
39
70
99
122
140
     Optical calculations for the Earth's atmosphere are simplified if it is assumed that the Earth
is flat and the atmosphere is horizontally uniform. Except for horizontal, or nearly horizontal,
sight paths, it is an excellent approximation to neglect the Earth's curvature. An initially
horizontal sight path above a curved Earth can be simulated in the calculations for a flat Earth by
a sight path approximately 1.5 degrees above the horizontal sight path (Bergstrom et al., 1981).
This angle depends on the vertical profile of the atmospheric haze,  and can be calculated from an
analytic expression in Latimer et al. (1978).
     The variation in the optical properties of the atmosphere in the vertical dimension has
received little attention in visibility monitoring and data reporting.  Interest in the effects of
particulate matter on climate forcing is causing a rapid expansion of the available information on
haze aloft (see Section 8.8).
8.2.2    Illumination of the Atmosphere
     Illumination of the atmosphere and factors affecting illumination of the sight path will
affect visibility and visibility observations.  Figure 8-2 shows the spectrum of the direct solar
rays at the top of the atmosphere. Much of solar energy is in the visible wavelength range.
Figure 8-2 also shows the spectra at the surface of the Earth for increasing amounts of
atmospheric attenuation as the sun moves lower in the sky.
                                          8-9

-------
T   2,250
 E
,f  2,000
 E
 ^  1,750
 o
 .§  1,500
 •o
 ra
 |  1,250
       o  1,000
       Q.
      (O
      I    750
       o
      J    500
       u
      Q    250
                           n      r
                                                    n      r
                            Extraterrestrial
                                               O3=0.35cm(NTP)
                                                HO = 2 cm
                                                a = 1.3
                     0.5
                                                                2.5
                                 1.0          1.5          2.0
                                     Wavelength, |jm
Figure 8-2.  Spectrum of direct solar rays at the top of the atmosphere and at the surface
            of the Earth for various values of the air mass (m). The air mass equals 1 for
            an overhead sun and increases in proportion to the mass of atmosphere
            between the observer and the sun as the sun moves lower in the sky.  The
            aerosol optical depth is m P A"K, where A is the wavelength in /j,m.
Source: Duffie and Beckman (1991).
     The data in Figure 8-2 show that the atmospheric attenuation is greater at the shorter
visible wavelengths than the longer visible wavelengths. This is because light scattering by air
molecules depends inversely on the fourth power of the wavelength (as expressed in Equation 8-
5). The greater atmospheric light scattering at the shorter wavelengths causes the blue sky in
daytime and the familiar red and yellow colors at dawn and sunset. These color changes occur
naturally, and are very great.  They are much greater than would be caused by typical amounts
of NO2 in haze layers.
                                        8-10

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     On a clear day, 80 to 90% of the visible solar radiation reaches the surface of the Earth
without being scattered or absorbed when the sun is high in the sky.  At the surface, a variable
fraction is reflected upwards, so the atmosphere is illuminated both from above and below.  The
fraction of the radiation incident on the surface of the Earth that is reflected is known as the
surface reflectance or the albedo.  Both visibility and visibility observations are affected by
clouds in the viewing background or overhead.  The effects of clouds are readily apparent and
are very great.  The illumination of a terrain feature or the atmosphere in a sight path can change
by a factor of 10 or more in a few minutes as clouds pass overhead. Very dark terrain can reflect
only one tenth as much radiation as snow-covered terrain.
     The derivations in the following subsections show that visibility is determined both by the
illumination of the sight path and by the air quality in the sight path. The effects of the
illumination are great enough and variable enough that it is not appropriate to omit them from
quantitative discussions of visibility.

8.2.3    Optical Properties of the Atmosphere
     The fate of the solar radiation that enters the Earth's atmosphere is determined by the
geometry and optical properties of the atmosphere and the Earth's surface. This  section presents
definitions of the atmospheric optical properties that affect visibility and also presents data for
the optical properties of gases. Data for the optical properties of particles are presented in
Section 8.3. All of these optical properties are functions of the wavelength of light.
     The atmosphere is a turbid medium, which both scatters and absorbs light. A ray of light
passing through the atmosphere is weakened by both of these processes. The distance-rate of
energy loss is proportional to the radiance of the ray, and the proportionality constant is the
light-extinction coefficient, oext, which has units of length"1. The light-extinction coefficient is
the sum of the light-scattering coefficient, oscat, and the light-absorption coefficient, oabs, which
are the proportionality constants for energy loss from the ray caused by scattering and
absorption, respectively.
     The light-extinction coefficient can be further divided into coefficients for the following
components:
                                           8-11

-------
     oag, light absorption by gases,
     osg, light scattering by gases,
     oap, light absorption by particles, and
     osp, light scattering by particles.
Because of their different origins and composition, atmospheric particles are frequently divided
into coarse and fine particles (see Chapters 3 and 6). The corresponding division of osp is
     osfp, light scattering by fine particles and
     oscp, light scattering by coarse particles.
These components of the light-extinction coefficient are related as follows:
            °~ext = °abS + °~Scat
            °~Scat =
               = °Sfp
                                                                                    (8-4)
     Light scattering by gases is also known as Rayleigh scattering, and the coefficient can be
calculated from the equation
 sg
    = 16.51(p/1013.25  mb)(273.15  K/Dx^4-07  Mm                          (8-5)
where p and t are the ambient pressure and temperature and the wavelength, A, is in micrometers
(Edlen, 1953; Penndorf, 1957).  Equation 8-5 was obtained by fitting values reported by
Bodhaine (1979). At modest elevations and daytime temperatures, the coefficient for light
scattering by gases has a value near 10 Mm"1 (or 0.01 km"1) at a wavelength of 550 nm. This
corresponds to an attenuation of a ray of green light in particle-free air of 1% per kilometer.
     Light absorption by gases is predominantly caused by NO2, and typically accounts for a
few percent of the total light extinction in urban atmospheres.  It is typically negligible in
                                          8-12

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remote areas. Nitrogen dioxide absorbs blue light more strongly than other visible wavelengths,
and thus contributes to the yellow or brown appearance of urban hazes.
     Ozone (O3) absorbs ultraviolet light strongly and, in the visible range, has a weak
absorption at green wavelengths. The absorption in the green wavelength could cause
perceptible effects only if the O3 concentration were much greater than 0.2 ppmv in a long sight
path through a very clean atmosphere. These conditions are quite improbable.
     The optical properties of particles are complicated enough that all of Section 8.3 is devoted
to a summary of current knowledge. The remaining discussions in this section make use of that
information as if it were presented here.
     The appearance of the atmosphere, especially near the horizon, is affected by the relative
importance of light scattering and absorption, which is measured by the single scattering albedo,
(»)„
  O'
            = ascat/aext =  ^cat/Kcat  +  aabs > •                                 (8-6)
When there is no light absorption, co0 = 1. As light absorption increases, the single scattering
albedo becomes smaller, and hazes and the horizon sky become darker. Typical values for co0
range between 0.8 and 1.0, even in smoke from fires.
     When the direction of travel of radiation is changed by light scattering, the redirected
radiation is not evenly distributed into  all possible angles.  The angular distribution of the
scattered light is described by the phase function. This function was named by astronomers, and
an example of its use is provided by the phases of the moon. The moon scatters light back
toward the sun more strongly than in other directions, so the moonlight is strongest when the
moon is full.  Measuring the light from the moon during the progression from  a new moon to a
full moon would provide data for the phase function of the moon. The scattering angle is the
angle through which radiation is deflected by the scattering process. This angle is near 0 degrees
for a new moon and is 180 degrees for a full moon.  (The infinitesimal deflection of radiation
that passes near the moon is neglected  in this discussion.)
     The phase function for the scattering of unpolarized light by clear air (Rayleigh scattering)
is
                                          8-13

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               P(e)  = (3/4) (l + cos2e)                                        (8-7)
where 6 is the scattering angle.  This function is normalized so that the integral from 0 to TT
radians equals 2.
n
 P(e)sinede =  2
                    f
This normalization is customarily used for all phase functions, and causes the integral over all
scattering angles to equal 47i.
     The optical depth, T, associated with a distance in a turbid medium is equal to the definite
integral of the light-extinction coefficient over that distance
                   T  =
                                                               (8-9)
where dx is the element of distance and oext is the average of the light-extinction coefficient over
the distance x.  The transmittance, T, for a ray of light that passes through a medium of optical
depth is

                         T = e ~T .                                                 (8-10)

When distances in the atmosphere are specified in terms of the optical depth, the phase function
and the single scattering albedo provide all the information about the optical properties of the
atmosphere required for visibility calculations.  As mentioned above, these quantities must be
known as a function of wavelength.
                                          8-14

-------
     Polarization has not been included.  If polarization were included, radiances would be
described by the Stokes vector and the phase function would be replaced by a phase matrix. In
general, polarization effects are small enough that they can be neglected when considering the
effects of air quality on visibility. However, polarization effects are readily apparent, and can be
used to infer information about air quality (White, 1975).
     Visibility is affected by atmospheric refraction (Minnaert, 1954). Those effects are often
important, but are not discussed in any depth here because they are not closely linked to air
quality. Atmospheric refraction causes mirages and looming, i.e., causes sight paths to be bent
so the apparent positions of objects are displaced from their actual position. The refraction
associated with thermal turbulence causes the stars to twinkle at night and distant objects to
shimmer in the daytime. In general, an effort is made to eliminate the effects of atmospheric
refraction from measurements and analyses to determine the effects of air quality on visibility.
     This subsection has listed all the optical properties of the atmosphere that must be known
to understand and calculate atmospheric visibility. With the inclusion of the absorption
spectrum of NO2 (Davidson et al., 1988),  this section also presents all the required optical data
for gases. The necessary optical data for particles are discussed in Section 8.3.

8.2.4    Multiple Scattering
     The term, multiple scattering, is used when light is scattered more than once in a turbid
medium. Light passing through a turbid medium transmits energy, and this process is known as
radiative transfer. (Convective and conductive transfer  of energy are also possible.) The
equation that governs the light intensities, and hence the radiative transmission of energy in a
turbid medium, is known as the equation  of radiative transfer. Obtaining solutions of this
equation for the Earth's atmosphere requires a knowledge of the optical properties of the
atmosphere listed in Section 8.2.3 as a function of position and also a knowledge of the
boundary conditions.  The boundary conditions at the top of the atmosphere are (1) the
atmosphere is  illuminated  by the solar radiation, and (2) radiation that leaves the top of the
atmosphere does not return. The boundary condition at the bottom of the atmosphere is specified
by the bidirectional reflectance of the Earth's surface. The reflectance albedo
                                           8-15

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indicates the fraction of the radiation incident on the Earth's surface that is reflected, and the
bidirectional reflectance specifies both this fraction and the angular distribution of the reflected
light as a function of the angle of incidence.
     The equation of radiative transfer can be written

                  dl/dx = -oext(l - Ie)                                         (8-n)


where dl/dx is the rate of change with distance x of a ray of radiance I and Ie is the source
function. All of these quantities (except the distance x) are functions of the wavelength.
     Middleton used the name equilibrium radiance for the source function. This name conveys
the idea that the radiance of a ray always tends toward the "equilibrium" value as the ray
progresses through the atmosphere.  Also, if the radiance of a ray is equal to the source function,
its value will not change with distance in the atmosphere.  These properties are represented in
Figure 8-3, which Middleton adapted from Hugon (1930).  The rate of approach to the
"equilibrium" is determined by the light-extinction coefficient.  When the light-extinction
coefficient has high values, e.g., in a fog, radiances approach the source function (equilibrium
radiance) in short distances.
     When the optical depth defined in Equation 8-9 is used in place of distance x in Equation
8-11, the equation of radiative transfer becomes

                     dl/Ch =  Ie- I .                                             (8-12)


This equation focuses attention on the source function.  An intuitive understanding of the
properties of radiation in the Earth's atmosphere must be based on an understanding of the
source function and the factors that determine its value.
     For horizontal sight paths, the  horizon sky radiance typically provides a reasonable
estimate of the source function. If the surface of the Earth were perfectly flat and the
atmosphere and its illumination were perfectly uniform, the sight path into the horizon sky
                                           8-16

-------
           B
         B,
                 Equilibrium
Figure 8-3.  The approach of radiances in the atmosphere to the equilibrium radiance or
            source function.
Source: Middleton (1952).
would be limited in length by the atmospheric extinction.  The curves in Figure 8-3 indicate that
in this case, the horizon sky radiance would be equal to the source function. In the real world,
the horizon sky radiance provides a good estimate of the source function if the light-extinction
coefficient is great enough that the curvature of the Earth and nonuniformities of the atmosphere
can be neglected for distances with an optical depth approaching a value of 3.  This condition
can be satisfied in fogs or moderate hazes. In practice, the greatest errors in equating the source
function to the horizon sky radiance are due to variations in the optical properties of the
atmosphere and its illumination along the sight path toward the horizon and beyond.
     Further insight into the properties of the source function can be obtained from the equation
of radiative transfer. When the radiance of a ray is equal to the source function, the radiance
does not change as the ray is propagated. In this case, the removal of energy
                                          8-17

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from the ray by light extinction is balanced by scattering of light into the direction of the ray.
This balance is expressed by the equation

                           o-eA = (osca/47i) Jj (Q') P (Q,Q') dQ'.                     (8-13)

The left side indicates the removal of energy by extinction per unit distance.  The right side
indicates the addition of energy by scattering per unit distance. The quantity, I(Q'), specifies the
strength of the illumination of the path of the ray by radiation from the angle Q'.  The quantity
(oscat/47i)P(Q,Q') describes the amount of this illumination scattered into the direction of the ray.
The phase function for scattering of radiation from the direction Q' of the illumination into the
direction Q of the ray is P(Q,Q').  Because this function is normalized (see discussion of
Equation 8-8), it is necessary to multiply by the light-scattering coefficient, which specifies the
strength of the light scattering.  The factor of 471 results from the conventions used in the
normalization of the phase function.  The integration extends over all angles.
     Dividing both sides of Equation 8-13 by the light-extinction coefficient and using Equation
8-6 gives

                             Ie = ((O0/47i)   l (Q') P (Q,Q') dQ'                        (8-14)
which is the customary form of the equation for the source function. All the complications of
radiative transfer calculations are contained in this equation.  The value of the source function at
each point in the atmosphere depends on the illumination at that point, which is affected by all
the nearby surroundings.
     Equation 8-14 can be simplified by making some reasonable, but not strictly valid,
assumptions. The purpose of this simplification is to derive a formula that shows the dominant
factors that affect the source function for an approximately horizontal  sight path.  This formula
can then be used to develop an intuition for the factors that control visibility in the atmosphere
and also to perform simple, approximate visibility calculations.
                                           8-18

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     The first assumption is that the skylight is perfectly diffuse, i.e., that the radiance of the
sky is the same in all directions. The second assumption is that the light reflected from the
surface of the Earth is also perfectly diffuse. Richards et al. (1983) and Richards (1988) showed
that these assumptions permit the integration in Equation 8-14 to be divided into integrations
over each of two hemispheres to obtain

         Ie=(co0/4n)[2F+ + 2F_ + FsP(Q,Qs)]                                (8-15)


where co0 is the single scattering albedo defined in Equation 8-6, F+ is the flux of diffuse light
reflected upward from the Earth's surface, F. is the flux of diffuse skylight incident on the Earth's
surface, Fs is the direct solar flux on the sight path measured normal to the solar rays, and
P(Q,QS) is the phase function for the scattering of radiation from the direction Qs of the solar
rays into the direction Q of the line of sight. Near the surface of the Earth, Equation 8-15 can be
simplified by the relationship

                   F+ = a(F_ + FSCOS9)                                         (8-16)


where a is the diffuse reflectance albedo of the Earth's surface and 6 is the angle between the
sun's rays and the normal to the Earth's surface. It is known that the assumptions used to derive
Equations 8-15 and 8-16 are not strictly valid; the radiance reflected from the Earth's surface is
not perfectly diffuse (Gordon, 1964), the skylight is also not perfectly diffuse, and these
assumptions are worst when the sun is near the horizon.
     The use of Equations 8-15 and 8-16 requires data for the flux of diffuse skylight. Figure 8-
4 provides the necessary information for a broad range of cases in which the sky is cloud free.
The curves in Figure 8-4 were calculated using the data and calculation methods in Richards et
al. (1986). The atmosphere is represented by four layers of different composition. The
composition and optical properties of the top three layers are kept constant. The curves in
Figure 8-4 show the effects of increasing amounts of haze in the
                                          8-19

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    0.50
    0.40
 8  °-30
    0.20
to
    0.10
    0.00
                   0.1 = Haze layer optical depth
         10
30                 50
        Solar zenith angle (deg)
70
90
Figure 8-4.  Data for the ratio of the total flux of skylight F_ incident of the earth's surface
            to the solar flux F0cos0 on a horizontal surface at the top of the atmosphere.
            These data are a function of the solar zenith angle and the optical depth of the
            haze layer, which is the bottom of four layers used to represent the
            atmosphere.
Source: Richards et al. (1986).
bottom layer of the atmosphere.  The amount of haze is measured by the optical depth, defined
in Equation 8-9.
     The aerosol in the bottom layer is composed of fine, coarse, and carbon particles with the
same physical and optical properties as the bottom haze layer described by Richards et al.
(1986).  The relative volume concentrations of fine, coarse, and carbon aerosol are 46, 51, and
3%, respectively. The relative contributions to the light-extinction coefficients are 75, 12.5, and
12.5%, respectively.  These proportions were kept constant as the total aerosol concentration was
changed to vary the optical depth of the haze, uh.
     The ordinate in Figure 8-4 is the total flux of skylight incident on the Earth's surface
divided by the total flux of sunlight incident on a horizontal surface at the top of the
                                          8-20

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atmosphere, F0cos6.  Equation 8-10 can be used to relate the solar flux at the Earth's surface, Fs
to the solar flux at the top of the atmosphere
                         •Oe
where T3 is the optical depth of the top three layers of the atmosphere used in the calculations
(Richards et al., 1986). The optical depth is equal to 0.50, 0.134, and 0.079 at wavelengths of
370, 550, and 650 nm, respectively.  These fluxes are for surfaces normal to the solar rays.
     Equations 8-15 and 8-16 can be used to evaluate the relative roles of the factors that
determine the source function, and hence the horizon sky radiance and path radiance (defined
below). The role of the single scattering albedo defined in Equation 8-6 is immediately
apparent; light absorption darkens the horizon sky by an amount proportional to the decrease in
the single scattering albedo.  The relative importance of (1) the direct solar radiation,
(2) skylight, and (3) light reflected from the ground can also be evaluated.  Table 8-2 presents
data showing that light reflected from the ground always makes a significant contribution to the
source function, and that  sometimes this contribution is dominant. Past reviews of the optics of
visibility have not adequately recognized the role of light reflected from the surface of the Earth.
Mariners have long known that land over the horizon can be detected by the change in color of
the horizon sky (U.S. Naval Oceanographic Office, 1966).
     These calculations are simplified in the case of a uniformly overcast sky.  In this case, the
direct solar flux on the sight path measured normal to the solar rays, Fs, in Equations 8-15 and 8-
16 is equal to zero, and these equations can be combined to obtain

                 Ie= (co0/2n) (1 +a)F_                                        (8-18)

where F. is the downward flux of diffuse light from the cloud layer. The ratio of the source
function to the downward flux depends on the single scattering albedo and the diffuse
reflectance albedo.
                                          8-21

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   TABLE 8-2.  RELATIVE IMPORTANCE OF LIGHT FROM GROUND, SKY, AND
             SUN IN CONTRIBUTING TO THE SOURCE FUNCTION AND
      THE PATH RADIANCE WHEN THE ABSORPTION IS NEGLIGIBLE AND
           THE NORMALIZED PHASE FUNCTION HAS A VALUE OF 0.4.

                                                    Percentage of Source Function or Path
                                                       Radiance Due to Light from the
Conditions
                                  Ratio of Source
   Ground      Ratio of Sky        Function to
 Reflectance  Light to Sunlight   Sunlight Flux (%]
      a             F/F.            1001/F.
                                            Ground
Sky
Sun
0.10
0.15
0.20
0.40
0.80
0.10
0.15
0.20
0.40
0.80
0.10
0.10
0.10
0.10
0.10
0.20
0.20
0.20
0.20
0.20
6.53
7.40
8.28
11.78
18.78
8.28
9.23
10.19
14.01
21.65
26.83
35.48
42.31
59.46
74.58
23.08
31.03
37.50
54.55
70.59
24.39
21.51
19.23
13.51
8.47
38.46
34.48
31.25
22.73
14.71
48.78
43.01
38.46
27.03
16.95
38.46
34.48
31.25
22.73
14.71
F. = the flux of diffuse light incident on the Earth's surface.
a = diffuse reflectance albedo.
Ie = source function for a ray of radiance.
Fs = the direct solar flux on the sight path measured normal to the solar rays.

Source: Richards (1988).
     The equations in this section provide the basis for the radiative transfer calculations
required to understand visibility as defined by the clarity (transparency) and color fidelity of the
atmosphere (see Section 8.1.2).
     The equations apply to a single wavelength; radiative transfer calculations must be
performed for a representative series of wavelengths for a complete description of visibility.
However, it would be compatible with current practice to perform these calculations only for one
wavelength of green light, such as 500 nm or 550 nm, to determine the visibility.  When

addressing  practical problems, it is essential to adequately address the strong temporal and
spatial variations in the illumination and the optical properties of the atmosphere.
                                          8-22

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8.2.5    Transmitted Radiance Versus Path Radiance
     The appearance of a distant object is determined by light from two sources. One source is
the light reflected from the object itself.  This reflected light is attenuated by scattering and
absorption as it travels through the atmosphere toward the observer. The portion that reaches the
observer is the transmitted radiance, It. These processes are illustrated in the top panel in Figure
8-5, where an observer looks at a distant hillside illuminated by direct sunlight, diffuse skylight,
and light reflected from the surrounding terrain.  The horizontal black bar indicates the light
reflected from the hillside into the sight path.  The small arrows pointing away from this bar
indicate that some light is scattered into other directions.  The decrease in the transmitted
radiance with distance along the sight path caused by scattering and absorption is indicated by
the horizontal bar becoming narrower as the distance increases.
     The other source of light seen by the observer is the intervening atmosphere.  During the
daytime, the sight path is illuminated by the direct rays of the sun, diffuse skylight, light that has
been reflected from the surface of the Earth, etc.  This is indicated in the bottom panel of
Figure 8-5 by the small arrows pointing toward the sight path.  Some of this illumination is
scattered by the air and particulate matter in the sight path toward the observer.  The horizontal
bar in the lower panel indicates the path radiance, Ip, which is an accumulation of this light
scattered into the sight path. The width of the horizontal bar indicates that the path radiance has
a value of zero at the start of the sight path at the hillside and increases  with increasing distance
along the sight path. Not all of the light scattered into the sight path reaches the observer.  Some
is absorbed and some is scattered into other directions as indicated by the small  arrows pointing
away from the sight path. Because the path radiance arises in the atmosphere, it is sometimes
referred to as air light.  The radiance seen by the observer looking at the hillside is the sum of
the transmitted radiance and the path radiance.
     The transmitted radiance carries the information about the object; this is the radiance
which tells us what the object looks like.  The path radiance only carries information about the
intervening atmosphere and is often quite featureless.  In a dense fog, the transmitted radiance
from nearby objects can be seen, but the transmitted radiance from more distant

-------
                                                        Transmitted
                                                         Radiance
                                                      Path Radiance
Figure 8-5.  (A) Illustration of the transmitted radiance and (B) the path radiance for a
            sight path toward a hillside.
objects is completely overwhelmed by the path radiance, i.e., the light scattered by the fog.
Distant objects are lost in the white (or gray) of the fog.
     Visibility is determined by the competition between the transmitted radiance and the path
radiance. The effects of this competition can be observed anytime the sun is low in the sky.
Distant hillsides viewed toward the sun appear to be silhouettes; all details on their surface are
lost in the haze.  The reason is that the hillsides are in a shadow and, therefore, are dark. Only a
small amount of light is reflected from them, so the transmitted radiance is small and is easily
overwhelmed by the path radiance. Hillsides at a similar distance viewed looking away from the
sun clearly show the details of trees, gullies, grass patches, etc. A large amount of light is
reflected from these hillsides because they are sunlit, so the transmitted radiance is large.  These
effects can also be observed when portions of a scene
                                          8-24

-------
are shadowed by clouds and adjacent portions are sunlit.  Cloud shadows on the atmosphere
decrease the path radiance and improve the ability to see distant objects, but shadows on the
objects themselves decrease the transmitted radiance and make it more difficult to see details in
those objects. With practice, a discerning observer can visually evaluate the separate effects of
the transmitted radiance and the path radiance on the appearance of a scene.
     The remainder of this subsection presents a mathematical description of these effects. The
radiance transmitted from an object at a distance x is equal to the initial radiance, I0, of that
object (measured at the object) multiplied by the transmittance, T, of the atmosphere in the sight
path (see Equation 8-10).


                      It=IoT=Ioe"T                                            (8-19)

In general, the value of the light-extinction coefficient will not be uniform over the sight path,
and this should be accounted for in the calculation of the optical depth (see Equation 8-9).
     The completely general calculation of the path radiance requires solving the equation of
radiative transfer for the atmosphere. However, if the illumination and optical properties of the
atmosphere were uniform over the sight path, the path radiance could be calculated from the
equation

                      Ip=Ie(l-T).                                            (8-20)


Equations 8-19 and 8-20 are typically used to calculate photographic images that show the
effects of haze (see, for example, Equations 1 and 2 in Molenar et al., 1994).  With rare
exceptions, the calculations used to generate photographic images assume that the atmosphere is
uniform.
     The apparent radiance, I, is the radiance that enters the eye of an observer or the aperture
of a measurement instrument, and is the sum of the transmitted and path radiance.
                                          8-25

-------
                                                                                  (8-21)
The radiances from these two sources must be considered in all visibility calculations.  As stated
above, it is the competition between the transmitted radiance and the path radiance that
determines the visibility.
     Because of the role  of the path radiance in determining visibility, and because the path
radiance is strongly influenced by the illumination of the sight path, daytime visibility is
inextricably linked to the illumination of the atmosphere. A knowledge of the atmospheric
optical properties alone (e.g., the value of the light-extinction coefficient) is not adequate to
predict the visibility.  These ideas are quantified in the next section, where contrast and contrast
transmittance are used as measures of visibility.

8.2.6    Contrast and Contrast Transmittance as  Quantitative Measures of
         Visibility
     It is  standard practice in science to define numerical scales that can be used to quantify
observations. Because of the properties of human vision described in Section 8.1.3, contrast
provides a numerical scale that can be used to quantify visibility. When investigating the ability
to perceive faint objects, the use of contrast to quantify visibility is based directly on Weber's
law and experiments with perception thresholds (see, for example, Blackwell, 1946).  Contrast is
defined in Equation 8-1 in Section 8.1.3.
     The  contrast of a distant object is determined by its initial contrast, C0, and the contrast
transmittance of the atmosphere,  C/C0.  The definition of contrast transmittance is analogous to
the definition of the transmittance.  If C is the apparent contrast, i.e., the observed or measured
contrast at the end of the  sight path, and C0 is the  initial  contrast, i.e., the contrast at the start of
the sight path, then

          Contrast transmittance =  C/C0.                                (8-22)
                                          8-26

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Modulation is defined in Equation 8-2 in Section 8.1.3. If M is the apparent modulation and M0
the initial modulation, then

            Modulation transfer = M/M0.                                   (8-23)
As indicated by Equation 8-3, modulation and contrast can be used interchangeably. Similarly,
contrast transmittance and modulation transfer can be used interchangeably. The more familiar
contrast and contrast transmittance are used in this chapter.
     The contrast transmittance of the atmosphere in the sight path to a distant object largely
determines whether or not that object can be perceived.  Thus, the quantitative calculation of
contrast transmittance plays a key role in the investigation of the perceptibility of distant objects.
At these distances, the contrast transmittance of the atmosphere and the apparent contrast of the
object can be used to quantify visibility. If these parameters are used for objects at all  distances,
then the same numerical scales can be used to quantify the visibility of objects at all distances.
     The National Park Service used contrast measurements to quantify visibility for
approximately a decade beginning in the late 1970s. This monitoring method is continued in the
use of photographs and video images to characterize visibility.  Computer-generated
photographs are often used to demonstrate the visual effects of haze, and they are generated by
calculating the contrast transmittance of the atmosphere  and the contrast of objects in the scene.

8.2.7    Contrast Reduction by the Atmosphere
     Because of the quantitative relationship between visibility and contrast reduction by the
atmosphere, the investigation of the effect of the atmosphere on apparent contrasts has a long
history, which has been reviewed by Middleton (1952).  An early result was obtained by
Haecker (1905), who showed that radiance differences are attenuated by the atmosphere to the
same degree as the radiance of a single ray. For example, if two objects at the same distance
with initial radiances I10 and I2o are viewed through the same sight path, Equations 8-19 and 8-21
give the result that the difference in the apparent radiances is
                                          8-27

-------
                                                                                 (8-24)
For the same sight path, the two path radiances have the same value, and therefore have no effect
on the radiance difference.  Also, the optical depth is the same for both sight paths. This result is
valid regardless of the uniformity of the atmosphere and the illumination.  If human perception
were controlled by radiance differences instead of radiance ratios (as in the formula for
contrasts), optical calculations for visibility analyses would have been greatly simplified.
     Equation 8-24 applies to any two adjacent objects viewed through sight paths close enough
together to have the same optical depths and path radiances. In the following derivation, this
equation is applied to a case in which an object with initial radiance, I0, is viewed against a
background with initial radiance, Ibo. The definition of contrast in Equation 8-1 and contrast
transmittance in Equation 8-22 can be combined to obtain

        C/C0=[(I-Ib)/Ib]/[I0-Ibo]/Ibo] .                               (8-25)


Replacing I - Ib by the right-hand side of Equation 8-24 and using Equation 8-19 gives the result

               C/C0=Iboe-VIb=Ibt/Ib.                                      (8-26)


In other words, the contrast transmittance of the atmosphere is the transmitted radiance of the
background, Ibt, divided by the apparent radiance of the background, Ib.  The role of the path
radiance is made more apparent by writing Equation 8-26 as
                                                                                 (8-27)
                                          8-28

-------
where the apparent radiance of the background is equal to the sum of the background transmitted
radiance and the path radiance.  Equations 8-26 and 8-27 are completely general and contain no
assumptions about the uniformity of the atmosphere or its illumination. They are included in the
paper of Duntley et al. (1957), which contains an excellent overview of contrast reduction by the
atmosphere.
     Exactly the same derivation can be performed using the modulation defined in Equation 8-
3 and modulation transfer defined in Equation 8-23 instead of contrast and transmittance. The
result is

                  M/M0=Ib/(Ibt + Ip)                                        (8-28)


where Ib is now the average radiance  of the sine wave instead of the background radiance used in
the definition of contrast. Equations  8-27 and 8-28 are identical in form and in interpretation.
     Equations 8-19 and 8-21 can be used to show the dependence of contrast transmittance and
modulation transfer on the variables T, Ibo, and Ie in cases where the atmosphere and the
illumination are uniform over the length of the sight path
             C/C0=IboT/[IboT + Ie(l-T)]
             M/M0=IboT/[IboT + Ie(l-T)]                                   (8'29)
The dependence of the T on the average light-extinction coefficient for the sight path is given by
Equations 8-9 and 8-10.
     Koschmieder (1924) derived a simple equation for the contrast of distant objects viewed
against the horizon sky. He assumed that the radiance of the background horizon sky at the
target initial background radiance is the same as at the apparent background radiance, with the
result that Equation 8-26 becomes
                                         8-29

-------
                                                                                  (8-30)
This assumption would be valid if the atmosphere and its illumination were uniform, which
accounts for the long list of assumptions often associated with discussions of Equation 8-30
(Malm, 1979; U.S. Environmental Protection Agency, 1979). Only the one assumption above is
necessary, and that assumption could be valid in a nonuniform atmosphere.  If it is further
assumed that the target is black, so that C0 = -1, Equation 8-30 becomes
                                                                                  (8-31)
but this assumption is not necessary if the value of C0 is measured or can be estimated with
sufficient accuracy (see, for example, Malm et al., 1982).  The average value of the light-
extinction coefficient for the sight path is equal to the optical depth divided by the length of the
sight path (see Equation 8-9). Equation 8-31 can be used to estimate the average value of the
light-extinction coefficient from only a measurement of the apparent contrast of a dark object
against the sky and the distance to the object.  However, the assumptions used in the derivation
of Equation 8-31 are generally not satisfied, with the result that the values of the light-extinction
coefficient obtained from it may not be appropriate when illumination along the sight path is not
uniform (White and Macias,  1987).
     The nomogram in Figure 8-6A provides an instructive visualization of the factors that
determine the visibility.  In this figure, the abscissa is a linear measure of the light transmittance
or light extinction. This is a  change from Figure 8-3, where the abscissa is linear in distance.
This change causes the curves for radiances in a uniform atmosphere to be  straight lines instead
of exponential curves.
     The lines at the left side of Figure 8-6 A show the radiances measured at the target.  The
initial radiance of the background (used in the calculation of contrast) measured at the target is
Ibo.  The path radiance is equal to zero. As the distance from the target increases, the initial
radiance  of the background and the transmittance decreases linearly towards zero. By definition,
this line is always straight. With increasing distance, the path radiance (air light) typically
increases. If the atmosphere were uniform, Equation 8-20 could be used to
                                          8-30

-------
                                     Transmittance (%)
                        100      80      60      40      20
                                       40     60
                                       Extinction (%)
80
100
                                    Transmittance (%)
                        100     80      60      40     20
                               20      40      60     80
                                      Extinction (%)
       100
Figure 8-6.  (A) Nomogram for the estimation of the contrast transmittance in a uniform
            region of the atmosphere; (B) Nomogram for the estimation of contrast
            transmittance in a nonuniform atmosphere.  In a nonuniform atmosphere, the
            curve representing the path radiance will typically not be a straight line.

Source: Richards (1990).
                                        8-31

-------
calculate the path radiance, and the values would form a straight line as in Figure 8-6A.  When
the distance from the target becomes sufficiently great (which is possible in the Earth's
atmosphere only for relatively large values of the light-extinction coefficient, the transmitted
radiance becomes zero and the path radiance becomes equal to the source function, as at the right
edge of the figure. This condition is easily observed in dense fogs.
     The apparent radiance is equal to the sum of the transmitted and path radiances, and is
shown by the upper line in the figure.  The contrast transmittance can be calculated at any place
in the figure by drawing a vertical line between the x-axis and the apparent radiance. The
contrast transmittance is the fraction of the line due to the transmitted radiance. These fractions
are illustrated by the shaded portions of the vertical lines in Figure 8-6 A.
     This nomogram  shows how the relative values of the initial background radiance used to
calculate contrast and  the source function interact with the transmittance of the sight path to
determine the contrast transmittance of a sight path, i.e., the visibility.  When the initial
background radiance is small  compared to source function, the transmitted radiance rather
quickly becomes a small part  of the apparent radiance, and the visibility in that sight path is
rapidly degraded by increasing light extinction.  However, if the initial background radiance is
much larger than source function, as is the case for  snowcapped mountains, the transmitted
radiance is not so quickly dominated by the apparent radiance as the light extinction in the sight
path increases.  Sometimes, snowcapped peaks at a distance appear to float in the sky because
the transmitted radiance from the dark mountainsides below the snow line is completely
dominated by the path radiance, making the dark mountainsides invisible.
     The initial and apparent background radiances may be assigned to different parts of the
scene in different calculations. If the contrast of an object against the horizon sky is to be
calculated, the background is  the horizon sky. When the horizon sky radiance  is approximately
equal to the source function, initial background radiance is approximately equal to the source
function. However, if the contrast of a feature on a hillside, such as a tree or a rock, is to be
calculated, then the background is the hillside.  In this case, it is necessary to determine the ratio
of the initial radiance of the hillside to the source function. In cases where the horizon sky
radiance is approximately equal to the source function, this ratio is equal to the initial contrast
used in contrast teleradiometry. Data for these initial  contrasts have been tabulated for a range
of types of ground cover and illumination (Malm et al.,
                                           8-32

-------
1982). These data provide an acceptable basis for estimating values of the background initial
radiance/source function when measurements are not available.
     The nomogram for a nonuniform atmosphere is shown in Figure 8-6B. Because the source
function varies along the sight path, the path radiance does not vary linearly with the light
extinction.  This is indicated by the curve in Figure 8-6B. Regardless of the form of the curve
for the path radiance, the apparent radiance is the sum of the transmitted and path radiances and
the contrast transmittance is the transmitted radiance divided by the apparent radiance.
Therefore, the calculations represented in the nomogram remain exactly valid for any curve
representing the dependence of the path radiance on the fraction of the initial radiance removed
by light extinction along the sight path. If the curve for the path radiance is properly calculated,
the relations shown by the nomogram in Figure 8-6B are exact and contain no approximations.

8.2.8    Relation Between Contrast Transmittance and Light  Extinction
     The light-extinction coefficient determines the transmittance of a sight path (see Equations
8-9 and 8-10). The nomogram in Figure  8-6A shows that the transmittance provides a
reasonable estimate of the contrast transmittance only when the initial radiance of the
background is approximately equal to the source function (or equilibrium radiance). The only
situation where this approximation is reliable enough to be useful is for a target viewed against
the horizon sky when it is hazy enough that the horizon sky radiance is approximately  equal to
the source function.  The southern and eastern United States have many days that are hazy
enough to satisfy this criterion, so the use of the light-extinction coefficient as a measure of
visibility frequently gives a satisfactory indication of the perceptibility of targets against the sky
in those locations. However, the light-extinction coefficient may not provide a satisfactory
indication of the perceptibility of features viewed against other backgrounds (e.g., trees on a
hillside),  because the radiances of other backgrounds will not, in general, be approximately equal
to the source function.
     Data for both the transmittance and modulation transfer of a sight path were measured
during the Southern California Air Quality Study (SCAQS) (Richards, 1989) and  are shown in
Figure 8-7. Modulation and modulation transfer were used to present these data because the
white and black pattern of the target were more like the sine wave pattern in Figure 8-1
                                          8-33

-------
than the pattern in that figure used to define contrast. It is shown in Equation 8-28 that the
modulation transfer is mathematically equivalent to the contrast transmittance.  It is apparent that
the data for modulation transfer in Figure 8-7 are poorly  correlated with the sight path
transmittance. In particular, when the sight path transmittance was 50%, the modulation transfer
varied from 5 to 70%. When the modulation transfer was 5%, the target was barely perceptible.
A modulation transfer of 70% corresponds to the visibility for a 30-km (19-mi) sight path
through particle-free air under conditions where the Koschmieder equation is valid. Thus, at the
same value of the light-extinction coefficient, the visibility ranged from excellent to nearly
obscured. However, the inability  of the light-extinction coefficient to represent the perceived
visibility of any specific scene does not affect its ability to characterize the visual effects on a
sensitive scene caused by the combination of air pollutants and relative humidity. The data
points in Figure 8-7 are scattered in the vertical direction, and do not tend to cluster along  a
simple relationship between modulation transfer and transmittance.
     The lack of correlation between modulation transfer and light extinction in Figure 8-7
shows that the light-extinction coefficient does not, in the general case, provide a reliable
quantitative measure of the visibility and specifically not under conditions of varying
illumination.  When using airport  visibility data to estimate values for the light-extinction
coefficient, it is common practice  to select only midday data.  This practice minimizes variations
in the illumination of the atmosphere, and would reduce  the variability of the data in plots such
as Figure 8-7.
     On the other hand, the light-extinction coefficient is an optical property of each point in the
atmosphere and is closely linked to air quality. It also plays a key role in radiative transfer
calculations.  However, although the light-extinction coefficient is a key input to visibility
calculations, it does not, by itself,  provide a reliable quantitative measure of the degree to which
the atmosphere is transparent to visible light under varying illuminations.
8.3    OPTICAL PROPERTIES OF PARTICLES
     The 1978 report on the technical basis for visibility protection in Class I areas that was
prepared for the Council on Economic Quality stated, "From a scientific and technical point of
view, the optical effects of particles are also the best understood and most easily measured
                                           8-34

-------
22    20
                               Deciview Haze Index
                          18          16          14
12     10   8   6 4 0
                  i-i-
     10     20     30     40     50     60     70     80     90
                          Transmittance (%)
                                                                                100
Figure 8-7.  Hour-average values of the modulation transfer and transmittance measured
            in a 2.20-km sight path during the 1987 summer intensive of the Southern
            California Air Quality Study.  These data show that the modulation transfer
            (and contrast transmittance) are poorly correlated with the light-extinction
            coefficient. At 50% transmittance (oext = 315 Mm *), the visibility ranged
            from excellent to nearly obscured.  The scale at the top shows the value of the
            deciview haze index, an index of haze that is scaled to correspond to
            properties of human vision.

Source: Richards (1989).
effects of air pollution." (Charlson et al., 1978). There was much truth in that statement, but
since then, significant advances have been made in the understanding of the physical, chemical,
and optical properties of fine particulate matter. At the present time, this is an active area of
research and an area where significant future advances can be expected.
                                        8-35

-------
8.3.1    Optical Properties of Spheres
     Fine particles, which are typically the dominant cause of visibility impairment, are small
enough in comparison with the wavelength of visible light that their optical properties are nearly
the same as those of homogeneous spheres of the same volume and average index of refraction.
This approximation is good enough that by far the greatest uncertainty in using light-scattering
equations for homogeneous spheres to calculate the optical properties of fine particles is due to
uncertainties in their size distribution. Uncertainties in the index of refraction, due to  lack of
knowledge of the detailed particle composition, is the next greatest source of uncertainty in these
calculations.
     These assertions are supported by an example from the pigment industry.  Titanium
dioxide (TiO2), the universally used white pigment, has a size distribution similar to atmospheric
fine particles. Titanium dioxide particles are crystalline, and therefore have angular shapes.
Titanium dioxide is birefringent, i.e., has different indices of refraction for different directions in
the crystal. The size distribution of TiO2 samples can be estimated by measuring the size of
1000 particles in an electron micrograph. Alternatively, it can be estimated by measuring the
light-extinction coefficient as a function of wavelength for a dilute suspension and comparing
the result with theoretical curves calculated assuming the particles were homogeneous spheres.
It was found that one light-extinction spectrum gave a better estimate of the size distribution
determined from repeated counts of 1000 particles than did one count of 1000 particles
(Richards,  1973). A knowledge of the size distribution is  key to calculating the optical
properties of fine particles.
     The equations for calculating the optical properties of homogeneous spheres in the size
range of atmospheric particles are known as the Mie equations (Mie, 1908), but Lorenz, Debye,
and others made substantial contributions to this theory (Kerker, 1969). The only inputs to these
calculations are the particle-size parameter a = 7iD/A, where D is the particle diameter and A is
the wavelength of light,  and the ratio of the index of refraction of the particle to the index of
refraction of the medium surrounding the particle. For collections of particles, it is assumed that
there is no phase coherence in the scattering by neighboring particles, so that the intensity of the
light scattered by an ensemble of particles is the sum of the intensities scattered by the individual
particles. Therefore, the optical properties of atmospheric particles are calculated by
representing the aerosol  particle-size  distribution by a
                                           8-36

-------
histogram, performing Mie calculations for each particle-size bin in the histogram, weighting the
results by the amount of aerosol in each bin, and calculating the sum.
     The output of the Mie calculations includes efficiency factors for extinction, scattering, and
absorption, Qext, Qscat, and Qabs, respectively. These factors give the fraction of the incident
radiation falling on a circle with the same diameter as the particle that is either scattered or
absorbed, only scattered, or only absorbed, respectively. Figure 8-8A shows the scattering
efficiency factor for  a sphere with an index of refraction of 1.5 as a function of the size
parameter, a.  Many fine aerosol particles have an  index of refraction near this value. Because
of diffraction, all particles with an index of refraction of 1.5 and a size parameter larger than
about 1.6 scatter more radiation than falls on the geometrical  cross section of the particle.  The
scattering efficiency factor tends toward a value of 2.0 for large particles.
4.5 J
4.0 I—

3.5 j-
3.0 i
0 C i
a2-5!
2.0 I
1.5J-
1.0 j
0.5 j-


	 f 	 I 	 u&l 	 i 	
	 1 	 | 	 | 	 ! 	 ! 	 	 1 	 1 	 i 	 i 	 J
f llii 1 f f i i
__! Tdtal iMJU^L^^ennqJJoeiTidieniL^.
! I I/ I V\ i I i i i !FoifR = l!50i i i i
' ' UL™! lV~~~ !
	 i 	 a 	 i 	 E 	 i 	
! I/I I I \ I
I I/Ill *\L
	 j 	 | 	 I 	 ! 	 ! 	 f\
r: : : t
	 j 	 w 	 , 	 	 	 	 	 j 	 j 	 j 	 j 	
LI* ! ^A i i - Lrk^U i i
jr. i r%iy
	 i 	 l 	 l 	 i^Yl 	
	 L^d 	 t 	 t 	 I 	 ht 	 i 	 i 	 t 	 t 	
fl I i i f~~~~j I i i i i
i_y j j i i i 1 j [[ii
~i r\i i
! ! l^-'l- —


                                                                 :LQ
             012345 6 7  8  9101112131415161718192021222324252627282930
                                                a
Figure 8-8a.  Light-scattering efficiency factor for a homogeneous sphere with an index of
              refraction of 1.50 as a function of the size parameter a =
Source: Penndorf (1958).
     The major oscillations and ripples in the curve in Figure 8-8A are typical. The data in
Figure 8-8B show that when the size parameter is scaled by the index of refraction minus 1,
scattering efficiency factors for a range of indices of refraction fall in a narrow range of
efficiency factors. The index of refraction range extends from water (n = 1.33) to a reasonable
value for dry fine particulate matter (n = 1.5). For example, Hering and McMurry (1991) found
that calibration of an optical particle counter with oleic acid, with an
                                           8-37

-------
                                        6789
                                          (p/2) = oc(n -1)
                                                         10   11   12   13   14
                                                                               15
Figure 8-8b.  Maximum and minimum values for light-scattering efficiency factors for
              homogeneous spheres with indices of refraction between 1.33 and 1.50 as a
              function of the normalized size parameter.
Source: Penndorf (1958).
index of refraction of 1.46, gave better results than did calibration with polystyrene latex
spheres, with an index refraction of 1.59, for monodisperse samples of Los Angeles aerosol
obtained from a differential mobility analyzer. Thus, within the range of indices of refraction
that most commonly occur in atmospheric fine particles, the  results of Mie calculations can be
scaled to account for the effect of the index of refraction.
     Figure 8-9 shows the same data as in Figure 8-8b, except that the scattering efficiency
factor Q was multiplied by the cross section of the sphere to  obtain the scattering cross section
and divided by the volume of the sphere to obtain the volume-specific light-scattering efficiency
factor, Ev, in units of jim"1. A wavelength of 550 nm was assumed in these calculations.
Multiplying the values of the light-scattering efficiency factor by the  aerosol volume
concentration (in units of |im3/cm3) gives the value of light-scattering coefficient, osp, (in units
of Mm"1) for these particles. Thus, the curves in Figure 8-9 gives the light-scattering coefficient
for a unit concentration of aerosol if all particles have the same diameter and index of refraction.
     Dividing the curves in Figure 8-9 by the density of the  particulate material (in units of
g/cm3) gives the mass-specific light-scattering efficiency, £„, (in units of m2/g).  Multiplying the
values of the mass-specific light-scattering efficiency by the  aerosol mass concentration (in units
of |ig/m3) gives the value of the light-scattering coefficient (in units of Mm"1) for these particles.
Thus, the mass-specific light-scattering efficiency for water,  which has an
                                           8-38

-------
                         12345
                              Particle Diameter (|jm)

Figure 8-9.  Volume-specific light-scattering efficiency as a function of particle diameter
            Dp. The calculations were performed for the indicated indices of refraction
            and a wavelength of 550 nm.  For large particle diameters the scattering
            efficiencies tend toward a value of 3/Dp. Mass-specific light-scattering
            efficiencies (in units of m2/g) can be obtained by dividing the values of the
            curves by the particle density (in units of g/cm3).
index of refraction of 1.33 and a density of 1.0, is shown by the curve for n = 1.33 in Figure 8-9.

Ammonia salts have a density near 1.75 g/cm3 and an index of refraction near 1.5, so the mass-

specific light-scattering efficiency for these compounds can be obtained by dividing the curve

for n = 1.5 in Figure 8-9 by 1.75 g/cm3.  The maximum value for mass-specific light-scattering

efficiency for both water and ammonia salts is close to 6 m2/g.

     The particle diameter at the maximum light-scattering efficiency for green light with a

wavelength of 550 nm is approximately given by the relationship
                                          8-39

-------
                     = 0.28/(n - l)|jm                                          (8-32)
although the exact value depends on the ripples in the curve.  This formula gives a diameter of
0.85 jim for an index of refraction of 1.33 and a diameter of 0.56 jim for an index of refraction
of 1.5. Most fine aerosol particles are smaller, so it is generally true that processes which tend to
increase the size of fine particles tend to increase their scattering efficiency. The absorption of
water at high humidity is an example of such a process.
     The Mie equations can also be used to calculate the efficiency factors for light absorption
by particles. The results of these calculations contain significant uncertainties because (1) the
imaginary component of the refractive index of the particles is usually not accurately known,
and (2) light-absorbing particles are frequently chained agglomerates that do not have a spherical
shape. In some aerosol particles, light absorption is caused by elemental carbon particles coated
with chemical species that absorb light much less strongly (see,  for example, Husar et al., 1976).
For these reasons, the theoretical calculation of the strength of light absorption by atmospheric
particles is significantly less reliable than the calculation of light scattering.
     Computer codes are available for calculating the light scattering and light absorption by
particles composed of a spherical core and a concentric shell (Toon and Ackerman, 1981;
Appendix B of Bohren and Huffman, 1983; Kerker and Aden, 1991).  These codes  are used to
determine the optical properties of particles with a solid core and a liquid shell, which can be
formed by the absorption of water at high humidities by particles that contain insoluble species.
A core-and-shell particle can also be formed by condensation and coagulation of materials of
one refractive index on pre-existing particles that have a different refractive index.
     The data for the volume-specific light-scattering efficiency for particles of one size in
Figure 8-9 can be made more useful by averaging the values for log-normal size distributions.
Results from such calculations are presented in Figure 8-10. As before, the calculations are
performed for a wavelength of 550 nm. A value of 2.0 was used for the sigma of the log-normal
size distributions, and the scattering efficiency was calculated as a function of the geometric
mean diameter, D^.  For water, the index of refraction is 1.33 and
                                          8-40

-------
                      Geometric Mean Diameter Dgv (|jm)

Figure 8-10.  Volume-specific light-scattering efficiency as a function of geometric mean
             particle diameter Dgv for log-normal size distributions. The calculations
             were performed for the indicated indices of refraction, a wavelength of
             550 nm, and size distributions with a sigma of 2.0. Mass-specific light-
             scattering efficiencies (in units of m2/g) can be obtained by dividing the
             values of the curves by the particle density (in units of g/cm3).
the maximum volume-specific scattering efficiency of 4.1 jim"1 occurs at a geometric mean

diameter of 0.74 jim. For the index of refraction of 1.5, the maximum volume-specific

scattering efficiency of 6.2 jim"1 occurs at a geometric mean diameter of 0.53 jim. If these

particles had a density of 1.75, then the maximum mass-specific scattering efficiency would be

3.5 m2/g. The curves in Figure 8-10 show that the scattering efficiency increases rapidly

                                        8-41

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with increasing particle size in the 0.2- to 0.4-|im-diameter range. The accumulation-mode
aerosol is typically in this size range.  Therefore, the uptake of water by aerosol particles can
cause significant increases in the light-scattering coefficient.
     Computer codes to calculate the optical properties of log-normal size distributions of
homogeneous spheres can be obtained from the U.S. Environmental Protection Agency Support
Center for Regulatory Air Models (SCRAM) by calling 919-541-5742 and downloading the files
for the PLUVUE II plume visibility model. The FORTRAN source code is in the file
RNPLUVU2.ZIP, code compiled for Intel 386- or 486-compatible computers is in the file
RUNPLUVU.ZIP, and the manual is in PLVU2MAN.ZIP. These codes are available at no
charge, and the program MIETBL.EXE calculates the normalized phase function and the
efficiencies for light scattering, absorption, and extinction. These codes will run on any personal
computer with enough speed, memory, and hard drive space to run Microsoft Windows®. If the
parameters of the log-normal size distribution and the index of refraction can be satisfactorily
estimated, these codes will generate all the information on the optical properties of particles
required for the calculations described in Section 8.2.
     Coarse particles in the atmosphere are large enough that the effects caused by their non-
spherical shape can be detected (see, for example, Holland and Gagne, 1970; Wiscombe and
Mugnai, 1988). However, in most actual cases, the dominant uncertainty in using the Mie
equations to calculate the optical properties of coarse particles  in the atmosphere is due to
uncertainties in their size distribution. Therefore, obtaining data for particle-size distributions is
more important than determining the shape of coarse particles in the atmosphere.

8.3.2   Optical Properties of Fine  and Coarse Particles
     Field measurements of the optical properties of fine and coarse particles have produced
results compatible with the theoretical results described above.  The mass-specific light-
scattering efficiency is usually used to report these results. The mass-specific light-scattering
efficiency (in units of m2/g)  multiplied by  the particle concentration, c, (in units of |ig/m3) is
equal to the light-scattering coefficient for particles (in units of Mm"1).  For these units, no
                                          8-42

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conversion factor is required. As discussed above, the value of the mass-specific light-scattering
efficiency is different for different particle-size fractions.
     White et al. (1994) determined the value of Efp, the scattering efficiency for particles
smaller than 2.5-|im diameter, at two sites in the desert southwest and obtained values of 2.4 and
2.5 m2/g.  These experiments were unique in that both  the light scattering and particulate-mass
concentration measurements were made with a 2.5-|im-diameter cutpoint.  The relative humidity
was generally low, so these values are appropriate for dry particles.
     In the same experiments, White et al. (1994) also determined the value of Ecp, the
scattering efficiency for coarse particles, and obtained  values that ranged from 0.34 to 0.45 m2/g.
Earlier, White and Macias (1990) obtained an estimate of 0.4 m2/g.  Watson et al.  (1991) also
obtained a value of 0.4 m2/g. One of the first determinations of the scattering efficiency for
coarse particles was by Trijonis and Pitchford (1987), who obtained the value of 0.6 m2/g.  In all
cases, these authors estimated that the integrating nephelometer responds to approximately half
the light scattered by coarse particles (White et al., 1994), so the scattering efficiency for coarse
particles observed by the nephelometer would be approximately 0.2 m2/g.  This is mentioned
here to provide assurance that the values of the scattering efficiency for coarse particles near 0.4
m2/g are not biased by the failure of nephelometers to detect light scattered at angles near 0 and
180 degrees.
     A review article by Waggoner et al. (1981) indicates that at moderate or low humidities,
the mass-specific light-scattering efficiency, measured by a nephelometer without a size-
selective inlet, was equal to 3.1 ± 0.2 m2/g using the fine-particle mass concentration.  A good
correlation was obtained even though the nephelometer measurements included both coarse and
fine particles because of the small scattering efficiency of coarse particles.  The nephelometer
response to all particles reported by White et al. (1994) was 2.8 and 3.1  m2/g times the fine-
particle mass concentration at their two sites.
     As a general rule, the above values of mass-specific light-scattering efficiencies can be
used at moderate to low humidities. The effect of water uptake by particles at high humidities is
discussed in Section 8.3.3.
     Widely varying mass-specific scattering efficiencies can be observed near sources, in
plumes, and in cases where particle formation occurred in clouds and fog. Particles formed in
power station plumes in clean areas can be quite small. For example, during the Navajo
                                           8-43

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Generating Station Visibility Study (NGSVS), a pulse of SO2 and sulfate from the station was
observed at Hopi Point, 100 km from the source.  Mie calculations based on the measured size
distribution of the sulfate formed in the plume indicated a light-scattering efficiency for
ammonium sulfate of 1.2 m2/g, and this result agreed with the value determined from the
integrating nephelometer readings and the sulfate concentrations determined by filter sampling
(Richards et al., 1991). Closer to the source, the sulfate formed in the plume was in still smaller
particles with an even smaller light-scattering efficiency (Richards et al., 1981).
     Larger light-scattering efficiencies for fine particles have been observed when significant
numbers of the particles are in the 0.5- to 1.0-|im size range. The measurements of John et al.
(1990) provide an example of data for particles in this size range. Secondary particles in this
size range are the result of heterogeneous gas-to-particle conversion in fogs or clouds (Meng and
Seinfeld, 1994).  However, heterogeneous particle formation in fogs or clouds does not always
produce large particles.  Events in which large amounts of sulfate were rapidly formed in clouds
were observed in the NGSVS, and these typically produced sulfate with a smaller mean diameter
than the background aerosol (Richards et al., 1991).
     Because of the strong dependence of both the light-scattering efficiency and settling
velocity of coarse particles on particle size, it would be expected that the light-scattering
efficiency of coarse particles in an air parcel would vary with time. In cases where coarse
particles are not being added to the air parcel, the light-scattering efficiency of the coarse
particles would increase with time.
     The  great majority of light absorption by particles is caused by elemental carbon (Rosen et
al., 1978, Japar et al., 1986).  Determinations of the mass-specific light-absorption efficiency of
elemental  carbon gives values in the range of 9 to 10 m2/g (Japar et al., 1984; Adams et al.,
1989). A  value of 9 m2/g has been used in recent studies of urban haze with satisfactory results
(Watson et al., 1988, 1991).

8.3.3   Effect of Relative Humidity  on Particle Size
     Water in the atmosphere exists in both the particle and vapor phases. Great reductions in
visibility occur when water condenses to form fog or clouds. Water is also present in all
                                          8-44

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ambient particles, even on relatively clear days. The increase in the amount of water in the
particle phase that occurs at high relative humidity (RH) has a significant effect on visibility.
     The effect of water has been understood for many decades, and was one of the key areas of
investigation in the Aerosol Characterization Experiment (ACHEX) in California in the 1970s
(Hidy et al., 1980). Figure 8-11 shows a summary of Humidogram data measured in several
parts of the United States.  These data were obtained by comparing the integrating nephelometer
signal from an ambient aerosol sample conditioned to 30-% RH with the signal from the same
aerosol conditioned to a higher RH (Covert et al.,  1980). The increase in light scattering with
increasing RH is due to two factors: (1) the  absorption of water by the aerosol particles
increases the volume of the particle phase, and (2) the absorption of water increases the size of
the aerosol particles, which increases the light-scattering efficiency of most particles.
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     Ammonium salts are an aerosol component that contribute to the absorption of water at
high RH. Figure 8-12 shows the relative diameter of a pure ammonium sulfate particle as a
function of RH. At humidities above the deliquescence point of 80%, the particle is a liquid
solution, the higher the RH, the more dilute the solution and the larger the particle.  When the
RH is below 80%, the particle is a dry ammonium sulfate crystal at equilibrium. If the RH of
the air surrounding liquid ammonium sulfate decreases through the deliquescence RH, it is
necessary for a crystal to nucleate for the conversion from liquid to solid to occur.  For pure
solutions, this can require either tens of minutes to hours or the reduction of the RH far below
the deliquescence point.  Thus in  ambient air deliquescence particles frequently exist in a non-
equilibrium state, containing water even though the RH is below the deliquescence point.
    2.4

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     Ambient particles are always a mixture of chemical compounds. Different salts have
different deliquescence points, and some aerosol components, such as sulfuric acid and perhaps
some organic compounds, have water absorption properties represented by a smooth curve.
Therefore, a typical sample of ambient aerosol shows a smooth dependence of light scattering on
RH, as shown in Figure 8-11. Figure 8-13 shows data from experiments that can detect the
change in size of individual particles in response to a change  in RH.  These data show that the
ambient particles in the Los Angeles Basin tended to fall either in a more hygroscopic class,
presumably containing inorganic salts and acids, and a less hygroscopic class, which may be
predominantly composed of primary organic species (McMurry and Stolzenburg, 1989).  The
particles in the desert Southwest tended to grow more with increasing RH, suggesting that
ammonium salts are present in most fine particles (Zhang et al., 1993, 1994) and that the organic
compounds in the particles are more oxidized (Saxena et al.,  1995).
     The RH of the atmosphere is nonuniform in both space  and time, so the ambient aerosol is
continually subjected to cycles of RH.  Radiational cooling increases the RH at night near the
surface of the Earth, and this tends to increase the haze in the early morning. Also, atmospheric
convection frequently cycles the aerosol particles through clouds during the day.  Rood et al.
(1989) have shown that hysteresis like that shown in Figure 8-12 exists in the atmosphere, so it
is reasonable to  believe that the ambient particles are commonly on the upper curve, which
represents the properties of the particles that have recently been exposed to high values of RH.
     Data for the dependence of the particle size of the ambient aerosol on RH have also been
obtained by cascade impactor measurements in urban and rural environments, and are in
reasonable agreement with the Humidogram in Figure 8-11.  Good examples of this type of
measurement appear in a report by Watson et al. (1991) and papers by Zhang et al. (1993, 1994).
A more detailed discussion of the effects of RH on the size distribution of ambient particles is
given in Chapter 3.

8.3.4   Extinction Efficiencies and Budgets
     The attribution of visibility impairment to emission sources can proceed through a series of
steps in which the following are determined in sequence:  (1) emissions,
                                         8-47

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                       (a)       Ratio of DMA2 to DMA1 Diameters versus RH
                                      SCAQS; DMA1 Size = 0.2um

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                          o More Hygroscopic Particles
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        10    20   30    40   50   60   70
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Figure 8-13.  Summary of all relative humidity-dependent particle growth factors for
              0.2 /u,m diameter particles measured (a) in Claremont, CA during the
              SCAQS and (b) at Hopi Point in the Grand Canyon National Park during
              the Navajo Generating Station Visibility Study.

Source: McMurry and Stolzenburg (1989); Zhang et al. (1993).
(2) composition of the atmosphere, (3) optical properties of the atmosphere, (4) optical
properties of sight paths, and (5) visibility. In principle, the effects of selected emissions can be
determined by performing the above analysis steps with and without those emissions.
                                            8-48

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     This section addresses the calculation of the optical properties of the atmosphere from a
knowledge of its composition. This is an essential step in the source attribution of visibility
impairment.  This calculation is also useful in understanding current visibility conditions.
Portions of this calculation proceed through simple addition.  Section 8.2.3 showed how the
optical properties of the atmosphere can be represented as the sum of the components of light
extinction.  It also indicated that the light-scattering coefficient for particles can be represented
as the sum of the scattering by coarse and fine particles. Operationally, the separate
contributions of coarse and fine particles to the light-scattering coefficient can be determined by
using instruments with size-selective inlets.
     It would be convenient if the light-scattering coefficient for fine and coarse particles, osfp
and oscp, could each be represented as the sum of the light scattering by the chemical constituents
of those particles. Then the components of light extinction could be calculated from
                        a
sfP = EEjCj                                               (8-33)
where Ej is the light-scattering efficiency of fine-particle species j whose concentration is Cj and
the sum includes all species. Unfortunately, there is no theoretical basis for such a
representation, because the light-scattering efficiency depends strongly on the particle size, and
changing the atmospheric concentration of one chemical species can change the size distribution
of the other particulate species (White, 1986; Sloane, 1986; Sloane and White, 1986).
      Simple additive calculations can be justified theoretically only in the hypothetical case of
an externally mixed aerosol, in which each particle contains only one chemical species.  In this
case,  the contribution of each chemical species to light extinction can be determined by summing
the contributions of the particles of each species. The calculation in Equation 8-33 can be
performed on either a particle volume or particle mass basis. The mass basis is customarily used
because aerosol mass concentrations are more easily monitored, so most ambient data are for
particulate mass concentrations.
      In practice, useful approximations exist that allow the estimation of light extinction by
ambient particles from the aerosol composition.  White (1986) showed that it made little
                                           8-49

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difference in the calculated optical properties of an aerosol mixture to assume either that the
chemical species are externally mixed, as described above, or internally mixed. In an internally
mixed aerosol, all particles in a stated particle-size cut have the same composition, i.e., they each
have the same proportions of all chemical species. This finding has been confirmed by other
authors, including Lowenthal et al. (1995). Lowenthal et al. (1995) showed that for an internally
mixed aerosol, it made little difference whether each particle was assumed to be homogeneous,
or assumed to be composed of a core of insoluble species and a shell of species that form a
solution at high humidities. Thus, useful estimates of the aerosol optical properties can be
constructed by assigning extinction efficiencies to chemical species, multiplying the ambient
concentrations by the efficiencies, and summing the results.
     Two key inputs to this estimation are (1) estimates of the size of the (dry) particles and (2)
estimates of the water uptake associated with each chemical species with increasing RH.  If it is
known that the chemical species were mostly formed in homogeneous (i.e., dry) photochemical
reactions, then it can be assumed that most particles are in a size mode with a diameter in the
0.2- to 0.3-|im size range (see, for example, Meng and  Seinfeld, 1994; John et al.,  1990).
However,  in locations where particle formation is active, the particle-size distribution can be
shifted toward smaller particle sizes. If it is known that most particles were formed
heterogeneously (i.e., in liquid particles), then the particle size is less certain. John et al.  (1990)
observed that the droplet mode particles formed in the Los Angeles Basin typically had a mean
size near 0.7 jim. Sulfur particle-size distributions measured in the NGSVS show that droplet
mode particles formed in a relatively clean environment could have a mean size near 0.2-|im
diameter (Richards et al., 1991).  Small particles are formed when only a small amount of
parti culate matter is formed in each cloud drop. The effects of water uptake on light extinction
are discussed in Section 8.3.3.
     When designing control strategies to improve visibility, it is necessary to estimate the
change in light extinction that would result from a change in the atmospheric composition.
It would be convenient if Equation 8-34 could be  used  for this calculation.
                                                                                  (8-34)
                                          8-50

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However, as illustrated by the hypothetical curves in Figure 8-14, the light-scattering efficiency
of fine particle species j is typically not a linear function of the species concentration.
Therefore, the value of the light-scattering efficiency for fine particles to be used in
Equation 8-33 to calculate the contribution of species j to light scattering when its concentration
has the value indicated by point a, (shown by the slope of the dashed line through the origin), is
typically different from the value of the light-scattering efficiency of fine particle species j to be
used in Equation 8-34 to calculate the change in the contribution to light scattering when the
concentration is reduced from point a to point b (shown by the slope of the dotted line that
passes through points a and b).
     The literature contains data for extinction efficiencies defined both ways, so the reader
should maintain an awareness of this distinction. Lowenthal et al. (1995) have published an
analysis of the sensitivity of light-extinction efficiencies to the methods and assumptions used in
their calculation and have presented values calculated using different assumptions.
     Light-extinction budgets have the objective of estimating the fraction of the total light
extinction contributed by each chemical species. Because the  chemical species in particles do
not scatter light independently, light-extinction budgets are somewhat arbitrary. Budgets can be
calculated from estimated extinction efficiencies and measured species concentrations using
Equation 8-33, but the values  obtained depend on the assumptions used.  Many tabulations of
light-extinction efficiencies and budgets have been published.   Some of the more recent data and
reviews are in the National Acid Precipitation Assessment Program report (Trijonis et al., 1991),
a separate publication of some of those data (White, 1990), a summary of IMPROVE data
(Malm et al., 1994), and a review of light-extinction calculation methods and the results from
their application to data from recent field studies (Lowenthal et al., 1995).
8.4    INDICATORS OF VISIBILITY AND AIR QUALITY
8.4.1  Introduction
     Air quality standards to protect human health designate an indicator, which is the
atmospheric constituent (such as O3) whose concentration is regulated. The standards also
specify a concentration level and a form. The form specifies such variables as the averaging
                                          8-51

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                                0.5          1.0          1.5
                              Concentration of Species j (jjg/m3)
2.0
Figure 8-14.  Hypothetical curves showing the effect of nonlinearities on the mass-specific
             light-scattering efficiency. The bold curve shows the contribution of species j
             to the light-scattering coefficient as a function of the concentration of species
             j. The slope of the dashed curve gives the mass-specific light-scattering
             efficiency to be used in Equation 8-33 for the species concentration at point
             a. The slope of the dotted curve gives the efficiency to be used in Equation 8-
             34 when the species concentration changes from point a to point b.
time and the number of times the average concentration may exceed the concentration level of
the standard in a specified length of time. Indicators are selected on the basis of their linkage to
the human health of populations, and the levels are set based on data for the health of classes of
sensitive individuals.
     A similar approach is also useful when considering visibility standards; some property of
the atmosphere related to visibility must be selected as  an indicator. Factors which may be
considered in making this selection include (1) the linkage between the indicator and
                                         8-52

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visibility, (2) the cost and feasibility of monitoring the indicator to determine compliance with
the standard as well as progress toward achieving the standard, (3) the nature and severity of the
interferences inherent in the available monitoring methods, (4) the relationship between the
visibility indicator and indicators for other air quality standards, and (5) the usefulness of
monitoring data in analyses which have the purpose of determining the optimum control
measures to achieve the standard.
     Even though contrast and contrast transmittance provide numerical scales that can be used
to quantify visibility, they are not suitable indicators of visibility for regulation of visibility
protection based on air quality. Visibility is strongly affected by the illumination of the sight
path, which is largely determined by natural processes that are not subject to regulation.
Visibility is also affected by meteorological conditions, such as very high humidity,
precipitation, and fog,  which are also not subject to regulation.  Furthermore, the derivations
presented above show that complex calculations are required to relate contrast  and contrast
transmittance to air quality.
     A secondary standard to protect visibility has the objective of setting an air quality
standard that ensures visibility protection. Therefore, it is appropriate to select an indicator more
closely linked to air quality than to visibility. In this case, the indicator would  not be closely
linked to the visibility  along a specific sight path at a specific time. Instead, the indicator would
be linked to the distribution of visibilities observed as a function of the value of the indicator.
The level of the  standard could be set to protect sensitive views under specified illumination
conditions.  This relationship between the indicator and visibility is similar to that for standards
set to protect human health.
     The following sections discuss parameters that could be used as indicators for regulation of
visibility protection based on air quality.

8.4.2    Visual Range from Human  Observation
     The use of visual range from human observation as an indicator of visibility is listed here
for historical reasons.  The National Weather Service is discontinuing the observations at
airports, so the number of locations at which observations are being made is now declining
rapidly.  In 1989, the California Air Resources Board changed the standard for visibility
                                           8-53

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reducing particles, replacing the observation of visual range with an instrumental measurement
(VanCuren, 1989a,b).
     There is a long history of recording the most distant target that can be perceived, or
alternatively, whether or not a distant target can be perceived. For example, Husar et al. (1981)
cited data from visibility observations at the Blue Hill Observatory in Massachusetts that
extended from the 1880s to the 1950s. During recent decades, visibility at all major airports
throughout the United States has been recorded hourly during the daytime by human
observation.  These data have been used to determine visibility trends in the United States as
well as the spatial distribution of current visibility conditions (see, for example, Trijonis et al.,
1991; Husar and Wilson, 1993). No other visibility measurement provides an historical record
for the United States of comparable usefulness.
     The advantages of human observations of visibility are: (1) they provide a direct measure
of the visibility as defined in Section 8.1.2, (2) no special equipment is required, and (3)
manpower requirements are minimal if an observer is already present for other reasons.  The
disadvantages are: (1) the results depend on the observer and the available visibility targets, and
(2) in general, the data are poorly related to air quality.  However, the linkage to air quality can
be improved by using only midday observations not influenced by meteorological effects such as
fog, precipitation, or very high humidities.
     Middleton (1952) reports data from experiments in which photometric measurements were
made in parallel with routine visibility observations. There was a wide range in the measured
contrasts of the targets selected by the observers to indicate the visual range. These data
document only one source of uncertainty in human observations.

8.4.3    Light-Extinction Coefficient
     The light-extinction coefficient is the parameter most frequently used by the air quality
community to characterize visibility because it is  closely linked to air quality. The advantages of
using the light-extinction coefficient are that it is: (1) an intensive property of the atmosphere
(i.e., a property of an element of volume of the atmosphere),  (2) closely linked to air quality, (3)
can be directly measured by a commercially available instrument, and (4) is a key input for the
radiative transfer calculations needed to calculate the visibility.
                                           8-54

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     The light-extinction coefficient can be directly measured by a transmissometer (Molenar et
al., 1990, 1992) or it can be estimated by measuring the components of light extinction listed in
Equation 8-4 (dry scattering and absorption, or ambient scattering and absorption) and
calculating the sum  (see, for example, Malm et al., 1994; Richards, 1995). There are several key
disadvantages of using the transmissometer to monitor the light extinction coefficient. These
disadvantages include: (1) transmissometer measurements respond to meteorological effects
such as fog and precipitation, and (2) the commercially available transmissometer is difficult to
calibrate and maintain. For example, the optical windows need to be cleaned frequently. It is a
further disadvantage of transmissometer measurements that the measurement error is large
compared to the effects of air pollution when the atmosphere is very clear.
     The effects of meteorological conditions on light extinction can be very great; they
frequently completely obscure the sight path. In applications such as airport runway control,
where visibility is the  prime concern, it is appropriate to include these  effects in the monitoring
data. However, when the effect of air quality on visibility is the prime concern, it is important to
remove meteorological effects from the monitoring data.  This is recognized by the IMPROVE
protocols for processing transmissometer data. Measurements made at relative humidities above
90% are flagged because they may be affected by meteorological effects such as fog, clouds, or
precipitation  (Blandford, 1994). It is standard practice to exclude these data from statistical
summaries (Mercer, 1994).  However, it is nearly impossible to remove these effects to a
satisfactory degree because it is nearly impossible to distinguish between  snow flurries or rain
showers on the one hand or puffs of haze on the  other. Subjective judgement enters into the
flagging of transmissometer data.  Furthermore, particle formation is often enhanced at high
humidity, so failing  to collect visibility-related air quality data at high humidities is a significant
omission (Richards, 1994).
     The value of the light-extinction coefficient calculated from the sum of its components
listed in Equation 8-4  could be used in place of transmissometer measurements as an indicator of
visibility. In this case, it is an option to exclude the contribution of gases to the light-extinction
coefficient and to include only the contribution of particles.  Light scattering by gases can be
omitted because it is nearly constant and cannot be regulated. Light absorption by gases can be
omitted because it is primarily due to NO2, whose concentrations
                                          8-55

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are (1) already subject to regulation, and (2) typically too small outside urban areas to have a
significant effect on visibility.  If such calculations use the ambient scattering, the light-
extinction coefficient, as is the case with transmissometer measurements, will be strongly
dependent upon the relative humidity and so will not be a good indicator of air quality. If the air
sample is dried the light-extinction coefficient will be a better indicator of air quality but a
poorer indicator of visibility.
     In 1989, the California Air Resources Board adopted a standard for visibility reducing
particles that is calculated from the sum of the light-scattering coefficient for particles and the
light-absorption coefficient for particles. Light scattering by particles is measured by a heated,
enclosed integrating nephelometer (see Section 8.4.5) and light absorption by particles is
measured with a tape sampler (VanCuren, 1989a,b).

8.4.4   Parameters Calculated From the Light-Extinction Coefficient
8.4.4.1  Visual Range
     The visual range can be calculated from a measurement of the light-extinction coefficient
at a point by assuming (1) that the atmosphere and the illumination over the sight path is
uniform and (2) the threshold contrast is 2%. Then, for a black target, the left side of Equation
8-31 has the value -0.02 and Equation 8-9 can be used to obtain

               Visual Range = 3.91/oext                                     (8-35)
which is known as the Koschmieder equation. This equation is useful when the value of the
light-extinction coefficient is large enough that the visual range is small enough for the
assumptions to be valid. The assumptions are quite questionable for visual ranges larger than 10
to 20 km, and invalid for visual ranges greater than about 100 km (see Section 8.2.1).
     In addition, the use of visual range calculated from a point measurement of the light-
extinction coefficient is useful  as an indicator of visibility related to air quality. It does,
however, have the same disadvantages as associated with the use of transmissometer
measurements of light-extinction coefficients listed in Section 8.4.3.
                                          8-56

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8.4.4.2  Deciview Haze Index
     The deciview haze index, dv, was proposed by Pitchford and Malm (1994) to provide an
indicator of haze that is scaled to correspond to the properties of human vision.  It is calculated
from the light-extinction coefficient for green light by the equation

              dv  = 101og10(oext/10 Mm-1)                                     (8-36)


This index has a value of zero, approximately 10 Mm"1 at sea level, where the light-extinction
coefficient has the value for particle-free air (see Equation 8-5) and increases by one unit for
each 10% increase in the value of the light-extinction coefficient.  The logarithmic scaling is
similar to that of the decibel scale, which is also related to human perception.
     As described in Section 8.2.8 and the above sections, the light-extinction coefficient is
closely linked to air quality. Therefore, the deciview haze index is similarly a measure of haze,
and is closely related to air quality.  The scale at the top of Figure 8-7 indicates that for a given
sight path, the deciview haze index is linked to the visibility only in the range of light-extinction
values that correspond to sight path transmittances between roughly 20 and 80%.  Outside this
range, changes in the deciview haze index have a greatly decreased effect on visibility. For
example, increases in the deciview haze  index will not change the appearance of features that are
already  completely obscured by haze.
     The deciview haze index is well suited for presenting data for spatial and temporal  trends
of haze. It is not influenced by the many factors unrelated to air quality that affect visibility, and
it is scaled to approximately linearize the relationship between human perception and the haze
index. However, its use as an indicator of visibility has the disadvantages associated with the
use of transmissometer measurements of light-extinction coefficients listed in Section 8.4.3.

8.4.5    Light-Scattering Coefficient Due to Particles
     There are several advantages to using the light-scattering coefficient for particles as an
indicator of visibility effects.  They include: (1) it is the component of the light-extinction
                                           8-57

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coefficient primarily responsible for visibility impairment; (2) it is closely linked to fine particle
concentrations; (3) a number of monitoring methods and commercial instruments are available;
(4) the cost of implementing the monitoring methods and maintaining measurement instruments
is competitive with those for other indicators; (5) accurate instrument calibration methods are
available; (6) interferences can be reduced to an acceptable level and are as well understood as
for any other indicator; (7) it is typically measured continuously; and (8) commercial
instruments are available that are either designed to include or designed to exclude
meteorological effects.
     There is a linkage between the light-scattering coefficient for particles and visibility
because the dominant cause of visibility impairment is light scattering by particles.  The
components of the light-extinction coefficient other than the coefficient for light scattering by
particles are the coefficient for light scattering by gases, which is nearly constant, and the
coefficient for light absorption by gases and particles. Light absorption does not contribute to
the path radiance, and under some circumstances, decreases it significantly.  Therefore, under
some lighting conditions, light absorption does not degrade visibility as effectively as does light
scattering. In extreme cases, the addition of absorption to the sight path has no effect on
visibility (e.g., sun glasses), or can even increase the apparent contrast of bright objects viewed
against the horizon sky by darkening the background sky and thereby increasing the initial
contrast (Dessens, 1944; Middleton, 1952). On the other hand, increasing the light-scattering
coefficient for particles always decreases the transmitted radiance and increases the path
radiance, so it always impairs visibility, which depends on the competition between the
transmitted radiance and path radiance. However, athough the light-absorption coefficient is not
significant to visibility impairment for every scene as is the light-scattering coefficient, the light-
absorption component of the light-extinction coefficient is important in  overall  visibility
impairment.
     The available monitoring instruments include: (1) the enclosed integrating nephelometer
(Ahlquist and Charlson, 1967), (2) the open integrating nephelometer (Molenar et al., 1992),
and (3) forward scatter visibility monitors (see, for example, National Oceanic and Atmospheric
Administration, 1992). The  enclosed nephelometer can be fitted with a size-selective inlet,
which  excludes the large particles that cause meteorological interferences and provides control
over the particle-size fraction that is sampled (White et al., 1994; Richards,
                                           8-58

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1994). Enclosed nephelometers that use an incandescent lamp heat the sample a few degrees,
but this heating can be less than 1 °C in nephelometers that use a flashlamp.  Sample heating
reduces the RH of the sample air, which causes absorbed water to evaporate from particles in the
sample chamber.
     The California Air Resources Board Method V for monitoring ambient concentrations of
visibility-reducing particles uses an enclosed nephelometer that is deliberately heated to
minimize the effects of high humidities on the monitoring data (VanCuren, 1989a,  1989b). This
drying of the aerosol particles is similar to the drying which occurs when filter samples are
conditioned to a standard humidity before being weighed in the laboratory.
     Open nephelometers were designed to reduce the heating of the sample to a fraction of a
degree, and to admit a broad  range of particle sizes (Molenar et al., 1992).  Therefore,  open
nephelometers respond to meteorological effects such as fog and snow.  The standard
IMPROVE protocol flags open nephelometer data influenced by meteorological effects and
excludes them from some the statistical presentations of the data (Cismoski, 1994). The
difficulties associated with this data flagging are the same as those for flagging light-extinction
coefficient data listed in Section 8.4.3.
     Forward scatter meters  have been selected by the National Weather Service to replace
human observers for visibility measurements at airports (National Oceanic and Atmospheric
Administration, 1992).  The sample volume is in the open air, so the instrument responds to
meteorological effects as well as air quality effects.  This instrument is significant because it is
in use at approximately 600 locations as of the end of 1995, and additional installations are
planned.  Data from this instrument have the potential to provide a database for the evaluation of
spatial and temporal trends in the light-scattering coefficient for particles that is more useful than
the historical records of visual range at airports.  However, this will require a change in the way
data are archived by the National Weather Service because current practice is to report all
visibilities greater than 10 mi in one bin.
     The cost of most instruments to measure the light-scattering coefficient for particles is in
the range of typical monitoring instruments. They operate for long periods of time unattended,
but do require routine lamp replacement and occasional cleaning.
     Integrating nephelometers can be accurately calibrated with gases of varying scattering
coefficients (see, for example, Bodhaine, 1979; Ruby and Waggoner,  1981). These
                                          8-59

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calibrations are applicable to the measurement of light scattering by fine particles. Because
integrating nephelometers are blind to light scattered near 0 and 180 degrees, their response to
particles in the 2.5- to 15-|im-diameter range is roughly half the correct value (White et al.,
1994). This property of nephelometers, known as the truncation error, has been quantified
(Ensor and Waggoner, 1970; Heintzenberg and Quenzel, 1973; Heintzenberg, 1978; Hasan and
Lewis, 1983; White et al., 1994).
     The measurement of the light-scattering coefficient has the potential to be an indicator for
health effects as well as visibility effects. Enclosed nephelometer readings are highly correlated
with the mass of fine particles collected on a filter (see, for example, Waggoner et al., 1981).
The correlation between nephelometer readings and the mass concentration of fine particles is
improved by using the same size selective inlet on both the nephelometer and filter sampler
(White et al., 1994). Filter samples are typically equilibrated to a standard RH before being
weighed. The correlation between nephelometer readings and mass concentrations measured by
filter can be improved minimizing the occurrence of high RH in the nephelometer scattering
chamber. This can be accomplished by heating the sample air a few degrees, as in the California
Air Resources Board Method V (VanCuren, 1989a,b) or by passing the air sample through a
dryer that removes water. Heating the air sample has the potential to volatilize particulate
species other than water.

8.4.6   Contrast of Terrain Features
     Data for the contrast of terrain features provides a direct measure of the visibility.
In current practice, the contrasts of features in a scene are most commonly monitored
photographically and determined by film densitometry (Johnson et al., 1985).
     Because of the close relationship to visibility, contrast measurements were used by the
National Park Service when instrumental visibility monitoring in Class I areas began in the late
1970s (Malm, 1979). A teleradiometer was used to measure the contrast of a distant terrain
feature against the horizon sky.
     When contrasts and background radiances are measured at both ends of the sight path,
Equations 8-26  and  8-9 can be used to accurately determine the average light-extinction
coefficient of the atmosphere in the sight path. These measurements are rarely made. It is more
common to assume that the background radiances are equal at each end of the sight
                                          8-60

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path (Malm, 1979) to estimate the initial contrast (Malm et al., 1982) and to calculate the
average light-extinction coefficient from Equations 8-30 and 8-9. Values of the light-extinction
coefficient calculated by this method have been found to be unreliable (White and Macias,
1987). For this reason, the National Park Service has discontinued making instrumental contrast
measurements in favor of the direct measurement of the light-extinction coefficient or the light-
extinction coefficient due to particles.
     The contrast monitoring data provide a direct measure of the visibility, which is affected
by many factors other than the air quality (see Section 8.2.9). Sections 8.2.5 through 8.2.8
provide the methods for calculating contrasts and contrast transmittances from air quality data.
It is expected that improvements in these calculation methods will lead to, increasing emphasis
on the contrasts of terrain features and contrast transmittances for specific sight paths as
measures of visibility. The calculation methods presented in this chapter can be used to
calculate contrasts of terrain features when the air quality and land-use data are available and the
skies are either reasonably  free of clouds or are uniformly overcast.

8.4.7    Particulate Matter Concentrations
     The fine-particle concentration could be used as an indicator of visibility because (1) the
data cited below show that the coefficient for light-scattering by  particles is closely linked to the
mass concentration  of fine  particles, and (2) the coefficient for light-scattering by particles is the
component of light  extinction primarily responsible for visibility impairment. This alternative
would be attractive  if fine particle concentrations were monitored to determine compliance with
a primary air quality standard because no additional monitoring would be required to determine
compliance with a visibility standard. The calculation methods presented in Sections 8.2 and  8.3
could be used to relate the visibility (as measured by contrast and contrast transmittance) to the
fine-particle concentration  for purposes of evaluating various options for the level and form of a
fine-particle standard designed to protect visibility.
     A number of studies report data for the relationship between the coefficient for light-
scattering by particles (as measured by an integrating nephelometer) and the fine-particle
concentration. Most of these studies report correlation coefficients of 0.9 or greater.  Early
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results were reported by Waggoner and Weiss (1980), who measured correlation coefficients
greater than 0.95 at Mesa Verde, CO, and at industrial, residential, and rural sites in the Pacific
Northwest.  The nephelometer measurements were made using an enclosed nephelometer
without a size selective inlet and with some sample heating caused by the lamp. Dichotomous
samplers with a 3 //m cutpoint were used to collect fine particles on teflon or Nuclepore
substrates.  No  special precautions were taken in the filter sampling to prevent the evaporation or
collection of semi-volatile species. The mass-specific light-scattering efficiencies determined
from regression analysis of the data from each of the five sites ranged from 2.9 to 3.2 m2/g.
These data were also reported by Waggoner et al. (1981).
     The results of Koenig et al. (1993) are of interest because pulmonary function changes in
children were associated with integrating nephelometer readings in Seattle, WA. The studies
were conducted during two winter heating seasons in areas affected by wood smoke.  The year
following these studies,  PM2 5 samples collected at pre-set time intervals over 1-week periods
from January 17 to December 12, 1991, were compared with integrating nephelometer
measurements averaged over the sample collection times. Regression analysis gave a mass-
specific light-scattering  efficiency of 4.9 m2/g, which is larger than typically observed, and a
regression coefficient of 0.97.
     The results of White et al. (1994) are of interest because size-selective inlets with cutpoints
of 2.5 and 15 //m were used  on both the integrating nephelometer and the filter sampler. As in
the previous studies, the nephelometer sample chamber was heated by the lamp.  The samples
were collected in  a desert climate in northern Arizona.   As described in Section 8.3.2, the mass-
specific light-scattering  efficiency of particles that pass the 2.5 //m cutpoint at two sites was 2.8
and 3.1 m2/g and the correlation coefficients were 0.86 and 0.84.
     Integrating nephelometer readings are not as well  correlated with total suspended
particulate concentrations (Waggoner et al., 1981) or with particle concentrations measured with
a 15 //m cutpoint (White et al., 1994).  The reasons are  (1) fine particles have mass-specific
light-scattering efficiencies 5 to 10 times greater than the efficiencies of coarse particles, (2) the
integrating nephelometer responds to roughly half the light scattered by coarse particles (White
et al., 1994), and (3) the relative amounts of coarse and fine particles in the atmosphere are
typically quite variable.  Therefore, the coefficient for light-scattering
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by particles is much less closely linked to the PM10 concentration than to the fine-particle
concentration, making PM10 less satisfactory as an indicator of visibility than the fine-particle
concentration.

8.4.8    Measures of Discoloration
     The 1977 Clean Air Act Amendments define visibility impairment as a reduction in the
visual range or atmospheric discoloration.  Color calculations have been included in plume
visibility models (see,  for example, Latimer et al., 1978), and quantitative color measurements
have been made for urban hazes (e.g., Waggoner et al., 1983). Less emphasis has been placed
on the color of regional hazes.  A brief review of methods for specifying the colors of hazes
appears in the National Acid Precipitation Assessment Program report on visibility (Trijonis et
al., 1991).
     For plume visibility analyses, the most commonly used parameter is the color difference
AE(L*a*b*) between the apparent spectral radiances for a sight path with and without the
plume.  The equations for calculating this parameter are presented in an EPA workbook (U.S.
Environmental Protection Agency, 1988).  It is the intent of these equations to linearize the
human perception of color differences, so color differences with equal values of AE(L*a*b*) are
equally perceptible. It was also an intent of these equations to assign a AE(L*a*b*) value of
unity to color differences that were just perceptible when presented as  two, side-by-side, uniform
areas of color that each subtended angles of a few degrees or more.  For plume visibility
analyses, the threshold for the perception of color differences is greater than for color patches
separated by a sharp edge because of the diffuse edges of the plume. It also depends on the
apparent angle subtended by the plume, i.e., the apparent width of the  plume (U.S.
Environmental Protection Agency, 1988).
     The apparent color of an urban or regional haze depends on the element of the scene used
by the human visual system as a reference white (MacAdam,  1981). Water clouds in the sky
typically have spectra that are strong in the blue.  If such water clouds  are used as the reference
white for color perception, hazes that have a more neutral spectrum (Waggoner et al., 1983) can
appear yellowish or brown by comparison. Thus, an analysis of haze colors requires an analysis
of both the spectral radiance of the haze and the spectral radiance of the elements of the scene
used by the observer as the reference white (MacAdam, 1981).
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8.5   VISIBILITY IMPAIRMENT
8.5.1    National Patterns and Trends
     National patterns and historical visibility trends are summarized in the National Acid
Precipitation Assessment Program report by Trijonis et al. (1991). They were also reviewed in
the National Research Council report prepared by the Committee on Haze in National Parks and
Wilderness Areas (National Research Council, 1993). Data for spatial and temporal patterns of
haze measured by the IMPROVE (Interagency Monitoring of Protected Visual Environments)
protocol in Class I areas, mostly in the western United States, have been summarized by Sisler et
al. (1993) and Malm et al. (1994).
     Patterns and trends in visibility are closely linked to patterns and trends in particulate
matter concentrations, which are reviewed in Chapter 6 of this  document.  Because of the close
linkage to data appearing elsewhere in this document and the availability of good, current
reviews in publications of the federal government, the data for  visibility patterns and trends are
not summarized again here.

8.5.2    Visibility Monitoring
     Visibility observations have long been made as part of weather observations. Since the
advent of aviation, visibility observations have routinely been made  at airports.  The 1977
Amendments to the Clean Air Act generated a need for visibility and air quality monitoring to
determine the visibility conditions in Class I areas and a need to monitor progress toward the
national goal of eliminating man-made air pollution in Class I areas.
     A recent report summarizes current visibility monitoring  activities (U.S Environmental
Protection Agency, 1995e).  The following sections give additional information which
supplements the information  in the U.S Environmental Protection Agency report.

8.5.2.1 Point Versus Sight Path Measurements
     The monitoring methods used in visibility studies can be  divided into point measurements,
which measure properties of the atmosphere at the sampler inlets, and path measurements, which
determine the optical properties of a sight path through the atmosphere. This distinction is
blurred only in mobile or airborne sampling,  where the sampler inlets can be moved through a
sight path.

                                         8-64

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     Visibility, by definition, is linked to sight paths and can be quantified only after a sight
path is specified.  Sight path measurements, such as human observations of the visual range, the
instrumental measurement of the contrast of distant terrain features, or contrasts measured from
photographs provide a direct measure of the visibility.
     Most air quality measurements measure the air quality at the sampler inlets. This is
typically true of trace gas monitors, aerosol filter samplers, and optical monitors such as the
integrating nephelometer.  Some remote sensing instruments measure air quality parameters,
such as trace gas concentrations or light extinction, for a sight path. However, the sight paths for
these instruments are typically short enough that the measurements are more appropriately
classified as point measurements rather than sight path measurements.
     The Optec Transmissometer is an example of a remote sensing instrument that typically
produces data that can be classified as a point measurement.  To conserve electric power in
remote locations,  the IMPROVE protocol for the transmissometer calls for collecting data for 10
min each hour.  For typical wind velocities, the spatial and temporal averaging resulting from a
10-min measurement each hour for a sight path a few  kilometers in length is comparable to the
hour-average data continuously measured at a sampler inlet.  An exception to this classification
occurs when the transmissometer sight path is strongly slanted, with the result that different
layers in a stable atmosphere may  be sampled. An example is the transmissometer with one end
of the sight path at Hopi Point on the rim of the Grand Canyon and the other end of the sight
path at Indian Gardens within the Canyon.
     When air quality measurements made at a point  satisfactorily represent the conditions in
the  surrounding region, the methods in Section 8.2 can be used to calculate the visibility from
the  air quality data.  Uncertainties  in the representativeness of the air quality data should be
evaluated when estimating the uncertainties in the visibility calculations.

8.5.2.2  Instrumental Monitoring Networks
     According to present plans, the largest instrumental visibility monitoring network in the
United States will be operated by the National Oceanic and Atmospheric Administration and
cooperating agencies to measure airport visibility.  The primary purpose of this network is to
provide real-time data for runway  visibility to aid in controlling airport operations.  The
visibility measurements are one component of the Automated Surface Observing System
                                          8-65

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(ASOS) and are made by the Belfort Visibility Sensor (National Oceanic and Atmospheric
Administration, 1992).  This instrument uses a flash lamp to illuminate a volume of open air and
a sensor to measure the scattering of visible light at angles near 40 degrees. The signals from the
visibility sensor have been calibrated by comparison with transmissometer measurements during
episodes of haze, fog, rain, snow, etc., and a calibration curve is used to convert the sensor
readings to units of light extinction and visual range. Between 400 and 600 installations are now
operating.
     The IMPROVE is the largest network that includes both visibility and air quality
measurements. Most sites are operated by the National Park Service, but sites are also operated
by the U.S. Forest Service and other agencies. Data are being collected using the IMPROVE
protocols at more than 40 sites, most of which are in or near federal Class I areas (Malm et al.,
1994; Sisler et al., 1993; U.S. Environmental Protection Agency, 1995e).
     The Clean Air Status and  Trends Network (CASTNET), which is no longer in operation,
included the CASTNET Visibility Network, which had nine sites, primarily in the eastern United
States (U.S. Environmental Protection Agency, 1995e).  The California Air Resources Board
operates integrating nephelometers (to measure light scattering by visibility-reducing particles)
at approximately 16 sites and tape samplers (to measure light absorption by particles) at nearly
40 sites (VanCuren,  1989a,b). Data from many of these sites are used when forecasting
agricultural burn days.  Other monitoring activities are listed in a recent U.S. Environmental
Protection Agency report  (U.S.  Environmental Protection Agency, 1995e) and in Tables 8-3 and
8-4 adapted from the National Acid Precipitation Assessment Program report (Trijonis et al.,
1991).

8.5.3    Recent Observations
     This section briefly summarizes results presented in selected papers published since the
U.S. Environmental Protection Agency review was prepared (U.S. Environmental Protection
Agency, 1995e).
     Vasconcelos et al. (1994)  examined data from Subregional Cooperative Electric Utility,
Department of Defense, National Park Service, and EPA Study (SCENES) conducted from  1984
to 1989 in the area surrounding the Grand Canyon.  Aerosol concentrations showed
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                                            TABLE 8-3.  LONG-TERM VISIBILITY AND AEROSOL DATA BASES
Study/Data Base
Air Sheds
Period
Type of Data"
Purpose of Study
Comments
References
National and Regional Networks
Analyses of National
Weather Service (NWS)
Airport Visibility Data
Rural and urban
airports all over the
nation.
19 18 to present
Human estimates of prevailing
visibility mainly in support of
aircraft operations
To assess visibility trends;
Assessment of the role of
meterology on visibility
impairment.
Quality varies from site to site;
natural causes of visibility
impairment (rain, snow, fog)
included in data.
Trijonis (1979,
1982a,b); Sloane
(1982 a,b, 1983);
Patterson et al.
(1980);Husarand
Patterson (1984)
       Interagency Monitoring of Twenty remote
       Protected Visual
       Environments
       (IMPROVE)
locations nationwide,
though primarily in the
West.
                       1987 to present    Aerosol and visibility; PM10     To establish baseline values and  Employs "state-of-art" methods     Joseph et al. (1987)
                  and fine particle mass.  Fine
                  particle elements, ions, organic
                  and light absorbing carbon.
                  aext> a,P, and asp and
                  photography.
                             identify existing impairment in
                             visibility protected federal Class
                             I areas.
                               for long term routine monitoring.
                               Operated jointly by U.S. EPA four
                               federal land managers.
                                 Sisler et al. (1993)
                                 Malmetal. (1994)
OO
       Eastern Fine Particle
       Visibility Network
       National Park Service
       Network (NFS)
       SCENES
Five eastern rural
locations.
About 37 remote
locations nationwide,
though primarily in the
west.
1988-89 five sites;  Aerosol and visibility; fine      A research monitoring program   An U.S. EPA operated network.      Handler (1989)
after 1989 two     particle elements organic and   to provide information needed to  Sites are collocated with other air
sites              soot carbon.  aext, alp, and alg,   quality support development of a  monitoring programs.
                  and photography.              secondary fine particle standard.
1987 to present
Seventeen sites
started in 1987.
                                Eleven rural and remote  1984-1989
                                southwestern locations.
Aerosol & visibility; 17 sites
operated with IMPROVE
measurements. Other have
some subset of the IMPROVE
measurements.
Aerosol and visibility; PM15
and fine particle mass,
elements, organic and light
carbon at most sites. aext or a^
and asg, and photography at
most sites.
To document visibility and
aerosol levels and to identify
sources of visibility impairment
measurements in NFS.
Represents the longest period of
record for visibility and aerosol
monitoring at remote locations.
Joseph etal. (1987)
                                                                      To document levels and causes   This cooperative research program  McDade and
                                                                                                      of visibility impairment in
                                                                                                      northern Arizona and southern
                                                                                                      Utah.
                                                                                                    included several intensive and
                                                                                                    special studies.  An ambitious
                                                                                                    quality assurance protocol
                                                                                                    identified many monitoring method
                                                                                                    difficulties which new techniques
                                                                                                    ultimately solved.
                                                                                                               Tombach (1987)
       Western Regional Air
       Quality Study (WRAQS)
Eleven nonurban
locations in the western
U.S.
1981-1982         Aerosol and visibility; PM15
                  and fine particle mass,
                  elements, ion.
                             To document bacground levels
                             of visibility and related aerosols,
                             organic and elemental carbon.
                             asg and a^, observed visual
                             range and photography.
                               Represents the highest times
                               resolution for routinely collected
                               filter samples (two four-hour
                               samples each day).
                                 Maciasetal. (1987)

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                     TABLE 8-3 (cont'd). LONG-TERM VISIBILITY AND AEROSOL DATA BASES
oo
oo
Study/Data Base
National Air Surveillance
Network (NASH)

Inhalable Particle Network
(IP Network)



Sulfate Regional
Experiment (SURE)


Eastern Regional Air
Quality Studies (ERAQS)




Ohio River Valley Study





Harvard School of Public
Health's Six Cities Study



Air Sheds Period
Urban & rural areas of 1975 to present
U.S.

Urban and rural areas June 1979 to
of U.S. Evans (84) present
Rodes and Evans (85)


Nonurban areas of 1 977- 1 978
eastern U.S. (9 Class I
sites and 45 Class II
sites)
Nine nonurban areas in 1978-1979
northeastern U.S. SURE
Class I sites.



Three rural sites in May 1980-August
Ohio River Valley. 1981




Portage, WI; Topeka, Spring 1979
KS; Kingston, TN;
Watertown, MA;
St. Louis, MO;
Steubenville, OH
Type of Data"
Aerosol only; TSP ions, and
some elements.

Aerosol only; fine and coarse
aerosol mass, PM15 mass,
elements, and ions (every
fourth sample).

Aerosol only; TSP, fine and
coarse aerosol mass, ions and
elements.

Aerosol and visibility; TSP,
fine and coarse aerosol mass,
ions, elements, asg and a^, aext,
and photography.


Aerosol only; fine and coarse
aerosol mass and elements.




Aerosol and visibility; fine and
coarse aerosol mass, elements,
SO,', a!g and a^.


Purpose of Study
Air quality monitoring.


Characterize inhalable particles.




Sulfate characterization pollutant
source characterization


To characterize visibility (at two
sites only) and air quality in the
northeastern U.S. region.



Characterization of fine and
coarse aerosols in the region.




Mass and elemental
characterization of aerosol and
their temporal variations to
assess health effects of air
pollution.
Comments
No size-fractioned data;
collected only once every six
days; artifact on filter possible.
Discrepancy exists between
PM15 and IP mass (sum of fine
and coarse). Screening of the
data required to remove invalid
data points (-25%).
Class I sites operated for 18
months continuously; Class II
sites operated for one month
every season for a total of six.
The only long-term instrumental
visibility data set generated in
the eastern U.S. Visibility
monitored only at 2 sites;
intercomparison of visibility
measurement methods made.
Portion of aerosol composition
was not accounted for due to
limitations in XRF analysis used.
A long-term daily monitoring of
aerosol in rural areas of the Ohio
River Valley.
Portion of aerosol composition
was not accounted for due to
limitations in XRF analysis used.


References
Shah et al. (1986)
Mueller and Hidy
(1983)
Paceetal. (1981)
Watson etal. (1981)



Mueller and Hidy
(1983)


Mueller and Watson
(1982)
Tombach and Allard
(1983)


Shaw and Paur (1983)





Spengler and Thurston
(1983)




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                            TABLE 8-3 (cont'd).  LONG-TERM VISIBILITY AND AEROSOL DATA BASES
oo
vo
Study/Data Base
RESOLVE





Air Sheds
Seven remote sites in
the California Mojave
Desert



Period Type of Data"
1983-1985 Aerosol and visibility; PM10 and fine
particle mass, elements, organic and
elemental carbon, aext, a^ and asg, alp
and (7^, and photography.


Purpose of Study
To document levels and identify
causes of visibility impairment in
the R-2508 military air space.



Comments
DOD sponsored study to
provide information
needed to limit future
additional degradation of
military testing by
visibility impairment.
References
Blumenthal et al.
(1987)




Single Air Shed Studies
Great Smoky Mountain
National Park Visibility
and Air Quality Study
(TVA)




Regional Air Pollution
Study (RAPS)

Portland Aerosol
Characterization Study
(PACS)
Great Smoky
Mountain National
Park





100 km region around
St. Louis, MO

Two rural and four
urban areas in
Portland, OR
1980-1983 Aerosol and visibility; fine and coarse
aerosol mass and elements; a^ and asg
and aext; photography.





1974-1977 Aerosol only; fine and coarse mass,
SO4", elements.

July 1977-April Visibility and aerosol; fine and coarse
1978 mass, TSP, ions, elements, a^ and asg.

Characterize visibility and aerosol.







Develop and evaluate regional air
quality models.

Aerosol characterization source
apportionment.

Because of instrument
problems, teleradiometer
data were lost. Total
particulate matter mass
only estimated in some
cases. PIXE analysis
could not provide some
major elemental data.
Comparison of Hi-Vol and
dichotomous samplers.

Significant role of
carbonaceous aerosols
recorded.
Valente and
Reisinger(1983)
Reisinger and
Valente (1984,
1985)



Jaklevic et al. (1981)
Altshuller (1982,
1985)
Copper and Watson
(1979)
Shah et al. (1984)
     ^Visibility data include light scattering and light extinction measurements using integrating nephelometer, teleradiometers, cameras, and human observers.




     Adapted from: Trijonis et al. (1991).

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                                    TABLE 8-4.  SHORT-TERM INTENSIVE VISIBILITY AND AEROSOL STUDIES
Study/Data Base
Air Sheds
Period
Type of Data"
Purpose of Study
Comments
References
Rural Studies
Allegheny Mountain Studies
Shenandoah Valley Studies
Rural Allegheny
Mountain site
Rural Shenandoah
Valley
24 July- 11 Aug 1977
and Aug 1993
15 July- 15 Aug 1980
Visibility and aerosol; TSP,
fine and coarse aerosol mass,
ions, elements, a^ and asg.
Visibility and aerosol; fine and
coarse aerosol mass, ions,
Characterization of visibility and
SO4" in the region.
To characterize visibility and
aerosol in the rural eastern U.S.
Filter artifact investigated;
no size fractionated data in
1977.
Since three different groups
performed the study,
Pierson et al.
(1980a,b)
Stevens et al. (1984)
Weiss et al. (1982)
                                                                              elements, aext, human estimates
                                                                              of visibility.
                                                                                                      intercomparability of data    Ferman et al. (1981)
                                                                                                      possible.                   Wolff etal. (1983)
       Great Smoky Mountain
       Study (EPA)
Great Smoky Mountain  20-26 Sept 1978
National Park
                      Aerosol and gaseous
                      pollutants; fine and coarse
                      aerosol mass and elements.
                                                                                                          Characterize aerosol in a rural
                                                          Comparison of day and
                                                          night aerosol data made.
                                                       Stevens et al. (1980)
       Research Triangle Park      Rural Research         8 June - 3 Aug 1979
       Visibility Study             Triangle Park, NC
                                            Visibility and aerosol; fine and
                                            coarse aerosol mass, elements,
                                            a,,,, and am and a „.
                                                   Characterize visibility and
                                                   aerosol in the region.
                                                          Comparison of different
                                                          visibility measurement
                                                          methods studies.
                                                       Dzubay and Clubb
                                                       (1981)
OO     Louisiana Gulf Coast Study   Gulf Coast
       Atlantic Coastal Study
Lewes, DE
                      8 Aug - 7 Sept 1979
1-31 Aug 82, 25 Jan-
28 Feb 1983
Visibility and aerosol; fine and
coarse aerosol mass, ions,
elements, a^ and a!g.

Visibility and aerosol; fine and
coarse aerosol mass and
chemistry, a and a
                                                   Investigation of sources of O3
                                                   and haze.
Air quality and sources of haze.
                             Calibration errors of MRI
                             1550 integrating
                             nephelometer applied to
                             data.
Wolff etal. (1982)
Wolff etal. (1985a)
       Pacific Northwest Regional   Twenty-six rural and    May - Nov 1984
       Aerosol Mass Apportionment remote locations in
       (PANORAMAS)            Washington, Oregon,
                                 and Idaho
                                            Visibility and aerosol; fine
                                            particle mass, elements, and
                                            ions. aext, alp, alg, and
                                            photography.	
                                                   To document the levels and
                                                   sources of summer visibility
                                                   impairment in the Northwest.
                                                          This cooperative monitoring  Core et al. (1987)
                                                          program identified smoke as
                                                          a major contributor to
                                                          visibility impairment.	

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                               TABLE 8-4 (cont'd).  SHORT-TERM INTENSIVE VISIBILITY AND AEROSOL STUDIES
       Study/Data Base
                               Air Sheds
                                                   Period
                                     Type of Data*
                                                                  Purpose of Study
                                                                                                                               Comments
                                                                                                                                                             References
                                                            Rural Studies
       California Aerosol
       Characterization Study
       (ACHEX)
Fourteen southern    July- Nov 72, July  Aerosol and visibility TSP, fine  Characterization of urban
California cities      - Oct 73           and coarse aerosol mass, ions,   aerosols in California.
                                     elements, a „ and 
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                         TABLE 8-4 (cont'd). SHORT-TERM INTENSIVE VISIBILITY AND AEROSOL STUDIES
oo
I

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substantial seasonal variation but little systematic diurnal variation. Aerosol composition, but
not total concentration, depended strongly on ambient relative humidity, with crustal materials
augmented at low humidities and sulfates augmented at high humidities.  Total fine-particle
concentrations showed the expected strong correlation with light scattering, but the aerosol
composition was essentially the same on clear days and hazy days.
     Saxena et al. (1995) analyzed data for particle growth as a function of RH and particle
composition to evaluate the effect of organic compounds on water uptake. They analyzed the
data from which the examples in Figure 8-13  were taken. They compared the observed water
content with the water content expected to be associated with the inorganic fraction, and found
that the aggregate hygroscopic properties of inorganic particles were altered substantially when
organic compounds are also present.  The alterations can be positive or negative. For the
nonurban location near the Grand Canyon, organics enhance water absorption by inorganics.  In
the RH range of 80 to 88%, organics account for 25 to 40% of the total water uptake, on
average.  For the urban location in the Los Angeles Basin, the net effect of organics is to
diminish water absorption of the inorganics by 25 to 35% in the RH range of 83 to 95%.
8.6    VISIBILITY MODELING
     Three types of models are discussed in this section:  plume models; regional haze models;
and models for photographic representation of haze. Plume visibility models and regional haze
models are source models which simulate the transport, dispersion, and transformation of
chemical species in the atmosphere.  Plume models use the resulting air quality data to calculate
the values of parameters related to human perception, such as contrast and color difference.
Regional haze models currently calculate aerosol species concentrations and the light-extinction
coefficient. Models for the photographic representation of haze use air quality data as an input,
and perform the optical calculations required to create images that represent the visual effects of
the air quality.
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8.6.1    Plume Visibility Models
     As part of the 1977 amendments of the Clean Air Act (Section 169 A to Part C) of Title I),
the U.S. Environmental Protection Agency sponsored the development of the plume visibility
model (PLUVUE) to be used during the preparation of a permit application to determine
whether or not a proposed new facility would cause visibility impairment in a class I area
(Latimer et al., 1978; Johnson et al., 1980; White et al., 1985).  Plume visibility models estimate
the value of optical parameters related to human perception, such as contrast and color
differences.  The calculated values for these parameters are then compared with perception
thresholds to determine whether or not the plume would be perceptible in each simulated case
(U.S. Environmental Protection Agency, 1988; Latimer, 1988).
     Other plume visibility models have been developed by the Los Alamos National
Laboratory (Williams et al., 1980, 1981), Environmental Research and Technology, Inc. (Drivas
et al., 1981), and the University of Washington (Eltgroth and Hobbs, 1979). Additional citations
for these models and a comparison of results from PLUVUE and the other models with
experimental data have been reported by White et al. (1985). The PLUVUE model (PLUVUE I)
has been refined, now known as PLUVUE II (Seigneur et al., 1983; Seigneur et al., 1984)  and
has been evaluated (White et al., 1986).
     To minimize the cost of visibility analyses in cases where a full plume visibility analysis is
not necessary, the U.S. Environmental Protection Agency sponsored the development of a
visibility screening model, VISCREEN (U.S. Environmental Protection Agency, 1988). When
used for Level-1 analyses, default values are used for most input data to evaluate the visibility
effects of a worst case scenario.  If necessary, a Level-2 analysis is performed with more realistic
values for the input data. If these screening analyses indicate a potential for visible effects, a full
Level-3 analysis must be performed with a plume visibility model.
     It is anticipated that an improved version of the PLUVUE II plume visibility model  will
be available on the U.S. Environmental Protection Agency's Support Center for Regulatory Air
Models bulletin board in 1995.
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8.6.2    Regional Haze Models
     The primary sources of anthropogenically induced, regional visibility degradation (also
referred to as regional haze) measured as light extinction, are fine particles in the atmosphere. In
the eastern United States, these anthropogenic particles are composed primarily of sulfate
compounds, organic compounds, and to a much lesser extent nitrate compounds. These are
important constituents in other areas of the United States as well; their relative importance,
however, changes.  For example, in some areas of the Pacific Northwest, organic aerosols are as,
or more, important than sulfate aerosols. In some parts of Southern California, nitrate aerosols
are the dominant species.
     Sulfate aerosols are mostly formed from SO2 emissions, which are predominantly due to
fuel combustion. The sources of organic aerosols can be both natural and anthropogenic.
Organic aerosols may be primary, emitted directly from a source, or secondary products of
chemical reactions which occur in the atmosphere during transport and dispersion downwind
from the source. The processes which lead to their formation are not altogether well understood.
     For the purposes of calculating regional visibility degradation due to specific sources of air
pollution, the primary focus has been on the contribution to light extinction of fine particles of
sulfate and nitrate compounds. Once these particles are formed, their size  can change, and thus
their light scattering efficiency, due to changes in the RH of the atmosphere.  In order to account
for the contribution for light extinction of either sulfate or nitrate compounds, the mass of these
constituents and the RH of the atmosphere in  which these particles reside must be known.  The
calculations of the extinction due to primary fine particles are assumed to be non-hygroscopic.
     Depending on the modeling situation, regional haze assessment can involve one to several
sources, or it can involve a multitude of sources spanning several states. The first situation
(involving isolated source impacts) most often arises within the context of assessing air quality
impacts on Class I wilderness areas,  which often involve transport of 50 km or more.  The
second situation (involving nationwide or regional impact assessments) most often arises within
the context of assessing the impacts of new or existing air quality regulations.  The modeling
requirements for regional-scale multiple-source haze models are nearly identical to the modeling
requirements for simulations of regional-scale multiple-source fine
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particle impacts. Hence, the Eulerian-based grid models currently under development to support
fine particle impact assessments will be relied upon to provide a means for assessing large-scale
multiple-source haze impacts. Middleton (1996) described the findings of such a modeling
effort; the Denver Air Quality Modeling Study (DAQMS). The Denver Air Quality Model was
designed to apportion sources of visibility degradation and to evaluate the benefits of future
emission controls in the Denver Metropolitan area. The results of the study demonstrated an
association between visibility and air quality issues in the Colorado Front Range area. As this
latter modeling is still under development, the following discussion summarizes recent efforts to
improve the Lagrangian-based modeling products available for characterizing isolated source
impacts involving long-range transport and  dispersion.
     A requirement of the CAA concerns air pollution impacts of proposed new sources on
federal Class I areas and prevention of significant deterioration. The Class I areas (e.g., national
parks, national wilderness areas, and other areas of special national value) are the responsibility
of Federal Land Managers.  The responsibility for prevention of significant deterioration is
shared with U.S. Environmental Protection  Agency and the States. However, the air quality
assessment for proposed new sources often  involves the simulation of air transport and
dispersion over large distances (greater than 50 km).  This creates a problem since Lagrangian-
based simulation methods capable of reliably handling the complex transport and dispersive
process unique to such long-range transport assessments have not been  developed as yet to a
point where guidance can be offered on how to apply these methods routinely (see section 7.6.2
of the Guideline on Air Quality Modeling, 40 CFR Appendix W to Part 51).
     To address the joint responsibilities of various governmental agencies involved, a
memorandum of understanding was established in November 1991 which formed a working
group,  known as the Interagency Workgroup for Air Quality Modeling. The purpose of the
working group was to foster cooperation among the U.S. Environmental Protection Agency, the
U.S. Forest Service, the Fish and Wildlife Service, the National Park Service, and selected State
representatives. The goal was to foster development of applied mathematical  modeling
techniques needed by Federal Land Managers, and others, to make informed
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decisions regarding the protection of federal Class I areas, especially within the context of
assessing individual source impacts.
     A two phased approach was devised (U.S. Environmental Protection Agency, 1992), given
(1) the immediate need for guidance on modeling techniques for impact assessments involving
regional scale (greater than 50 km) transport, (2) the complexity of applicable modeling systems
and data bases, and (3) the spatial scales and potential numbers of sources for consideration.
The first phase involved a review of available modeling techniques and construction of an
interim recommendation for use by concerned technical and regulatory communities until such
time that more permanent guidance could be offered. The second phase involved development,
testing and application of state-of-the-art meteorological processors and dispersion modeling
systems, to establish a basis for enhancement and perhaps replacement of the Phase I interim
recommendations..
     Following a series of model comparison and sensitivity analyses, a technical review was
completed of meteorological data processing and dispersion modeling systems (U.S.
Environmental Protection Agency, 1993b).  This served as the basis for the Phase I interim
recommendations. These findings facilitated use of the MESOPUFF II system (U.S.
Environmental Protection Agency, 1994) within established national guidance provided in the
Guideline on Air Quality Modeling.  For the purposes of assessing regional haze impacts, the
light extinction is estimated using 3- to 24-h concentration averages for the sulfate and nitrate
compounds. The use of longer-period concentration averages to compute a light extinction
coefficient  (inverse of visual range) provides a pragmatic surrogate for assessing visibility
degradation and avoids the overwhelming complications introduced when one attempts to invoke
a line  of sight visibility assessment for an actual vista.
     The interim  recommendations were applied in simulating pollutant impacts  on the
Shenandoah National Park to provide further technical information on the strengths and
weaknesses of the available modeling systems (U.S. Environmental Protection Agency, 1995a).
These results demonstrated that sources beyond 100 km might be expected to contribute and
should not be arbitrarily excluded from assessments. They also demonstrated that such
assessments are currently best accomplished on a case-by-case basis using expert judgement.
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     The technical work associated with phase II involves:  (1) testing and assessment of
possible benefits to be achieved through the use of state-of-the-art mesoscale meteorological
(MM) processors employing four dimensional data assimilation (FDDA); (2) development of a
state-of-the-art Lagrangian puff modeling system; and (3) testing of the developed modeling
methods. Following completion of these technical efforts, an update to the Guideline on Air
Quality Modeling can be proposed describing the modeling methods to be routinely accepted for
characterization of long-range transport and dispersion from isolated sources.
     The first step was addressed by initiating an analysis, in which MM-FDDA meteorological
model was used to develop an hourly characterization of meteorological conditions (on a 80-km
resolution) for an entire one-year period for the contiguous United States, northern Mexico and
southern Canada. It was shown that MM-FDDA meteorological models could be applied
operationally. Use of sophisticated meteorological processors provides a means for realistic
characterization of long-range transport trajectories.
     The second step involved enhancement of an advanced modeling system, entitled
CALPUFF, capable of processing mesoscale meteorological data and capable of addressing
dispersive processes of a regional nature. The modeling system was evaluated demonstrating the
benefits of MM-FDDA meteorological data in characterizing long-range pollutant trajectories.
Simulated trajectories were successfully compared to results from a field study involving
transport to 1000 km downwind (U.S. Environmental Protection Agency, 1995b).  The
CALPUFF system was incorporated into a user-friendly windows-based environment with an
on-line electronic user's guide (U.S. Environmental Protection Agency 1995c,d).
     Previous evaluation results of puff dispersion models for transport distances of 30 to 100
km (Carhart et al., 1989), have illustrated the difficulty in characterizing the transport trajectory,
but have seen a bias on the order of 30% on average towards overestimating the magnitude of
the maximum surface concentration values. One of the findings of the trajectory comparisons
(U.S. Environmental Protection Agency, 1995b), was that Lagrangian puff dispersion modeling
involving transport of 200 km or more will underestimate the horizontal extent of the dispersion,
thereby overestimate surface concentration values if delayed shear enhancement of dispersion
(Moran and Pielke, 1994) is not addressed. In anticipation that CALPUFF will likely find
widespread use in a variety of situations, a puff splitting algorithm was added to CALPUFF.
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However, there remains a need to determine how best to invoke this algorithm for improved
characterization of surface concentration values.
     The third  step towards providing enhanced guidance on methods for characterizing long-
range dispersion for individual sources has been initiated by placing the CALMET/CALPUFF
modeling system on the Support Center for Regulatory Models electronic bulletin board system
for testing.  Currently, this stage of the process must primarily rely on volunteer efforts from the
public at large.  It is hoped these efforts will prove successful in resolving the remaining
technical issues, and that an update to the modeling guidance can be drafted for comment and
review late in 1997.

8.6.3    Photographic Representations of Haze
     Photographs are frequently used to illustrate visibility conditions.  However, it is difficult
to take a series of photographs of an actual scene under known, uniform conditions to illustrate
the effects of various intensities of haze. Therefore, computer-generated photographs have been
used for this purpose.  Examples of this use of photographs appear at the back of the National
Acidic Precipitation Assessment Program  report on visibility (Trijonis et al., 1991). The current
status of photographic representations of haze has been described by Molenar et al. (1994) and
Eldering et al. (1993).
     A photograph is taken on a very clean, cloud-free day and scanned to generate an initial
image.  The most  laborious step is the creation of a distance map, which assigns a distance to
each element in the scene.  The estimated value of the light-extinction coefficient when the
photograph was taken is used to calculate the initial radiances for each element in the scene.  The
horizon sky radiance can be used to estimate the source function in the calculations for the clean
day.
     The equations to generate images showing the effects of haze must calculate the value of
the source function appropriate for the haze represented. Larson et al. (1988) have shown that
the common practice of using the horizon  sky radiance in the clean photograph as an estimate of
the source function produces distorted results.  Radiative transfer calculations can be used to
derive the source function from the haze composition (Molenar et al., 1994; Eldering et al.,
1993). Equations 8-19 and 8-20 are used to calculate the radiances presented in the
photographic images.
                                          8-79

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     The use of photographic models for representation of haze requires many  approximations.
The softening of shadows caused by the diffuse lighting when it is hazy is neglected, and it is
usually assumed that the haze is uniformly distributed throughout the scene. Photographs also
have the limitation that they are expensive to produce, so are typically used to illustrate only a
few conditions. Often, the selected conditions are idealized,  so the full range of conditions that
occur in a scene are not represented.
8.7   ECONOMIC VALUATION OF EFFECTS OF PARTICULATE
      MATTER ON VISIBILITY
     The effects of particulate matter on visibility were described in previous sections of this
chapter and are hazes and reductions in visual range in all of the United States. This section
discusses the available economic evidence concerning the value of preventing or reducing these
types of effects on visibility.  The following brief summary of economic estimation methods and
available results is derived from the document, Air Quality Criteria for Oxides of Nitrogen (U.S.
Environmental Protection Agency, 1993a). A comprehensive study on the economic impact of
visibility impairment on national parks and wilderness areas and the cost of controls is currently
being conducted by the Grand Canyon Visibility Transport Commission.

8.7.1   Basic Concepts of Economic Valuation
     Studies on the economic impact of visibility degradation have mainly focused on consumer
activities, specifically on the individuals response to the aesthetic aspects.  Studies on the effects
of visibility degradation on commercial activities are limited.  However, airport operations may
be affected by visibility degradation, but available evidence suggests that the economic
magnitude of the effects of haze on commercial operations probably is very small. Based on a
1985 report by the U.S. Enviromental Protection Agency the percentage of the visibility
impairment incidents sufficient to affect air traffic activity might be attributable, at least in part,
to manmade air pollutants (possibly 2% to 12% in summer in the eastern United States).
                                         8-80

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     That people notice changes in visibility conditions and that visibility conditions affect the
well-being of individuals has been verified in scenic and visual air quality rating studies
(Middleton et al., 1983; Latimer et al., 1981; Daniel and Hill, 1987), through the observation
that individuals spend less time at  scenic vistas on days with lower visibility (MacFarland et al.,
1983), and through use of attitudinal surveys (Ross et al.,  1987).

8.7.2    Economic Valuation Methods for Visibility
     Two main economic valuation methods have been used to estimate dollar values for
changes in visibility conditions in various  settings: (1) the contingent valuation method (CVM),
and (2) the hedonic property value method. Both methods have important limitations, and
uncertainties surround the accuracy of available results for visibility. Ongoing research
continues to address important methodological issues, but at this time some fundamental
questions remain unresolved (Chestnut and Rowe, 1990a; Mitchell and Carson, 1989; Fischhoff
and Furby, 1988; Cummings et al., 1986).  See Fischhoff and Fauby (1988), Kahneman and
Knetsch (1992), Rowe and Chestnut (1982),  Mitchell and Carson (1989), and Cummings et al.
(1986) for details on these methods and its usefulness in economic valuations.
     The CVM involves the use of surveys to elicit values that respondents place on changes in
visibility conditions.  The most common variation of the CVM relies on questions that directly
ask respondents to estimate their maximum willingness to pay (WTP) to obtain or prevent
various changes in visibility conditions based on photographs and verbal descriptions, and  some
hypothetical payment mechanism, such as a general price  increase or a utility bill increase.
     Among the fundamental issues concerning the adequacy of CVM for estimating visibility
values are (1) the ability of researchers to present visibility conditions in a manner relevant to
respondents and to design instruments that can elicit unbiased values; and (2) the ability of
respondents to formulate and report values with acceptable accuracy.  Another important issue in
CVM visibility research concerns the ability of respondents to isolate values related to visibility
aesthetics from other potential benefits of  air pollution control such as protection of human
health.
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     The hedonic property value method uses relationships between property values and air
quality conditions to infer values for differences in air quality. The approach is used to
determine the implicit, or "hedonic," price for air quality in a residential housing market, based
on the theoretical expectation that differences in property values that are associated with
differences in air quality will reveal how much households are willing to pay for different levels
of air quality in the areas where they live. This approach uses real market data that reflect what
people actually pay to obtain improvements in air quality in association with the purchase of
their homes.  Hedonic property value studies provide estimates of total value for all perceived
impacts resulting from air pollution at the residence, including health, visibility, soiling, and
damage to materials and vegetation. The most important limitation is the difficulty in isolating
values for visibility from other effects of air pollution at the residence.

8.7.3    Studies of Economic Valuation of Visibility
     Economic studies have estimated values for two types of visibility effects  potentially
related to particulate matter and NOX: (1) use and non-use values for preventing the types of
plumes caused by power plant emissions, visible  from recreation areas in the southwestern
United States; and (2) use values of local residents for reducing or preventing increases in urban
hazes in several different locations.

8.7.3.1    Economic Valuation Studies for Air  Pollution Plumes
     Three CVM studies have estimated on-site use values for preventing an air pollution plume
visible from recreation areas in the southwestern United States (Table 8-5). One of these studies
(Schulze et al.,  1983) also estimated total preservation (use and non-use) values held by visitors
and non-visitors for preventing a plume at the Grand Canyon. The plumes in all three studies
were illustrated with actual or simulated photographs showing a  dark, thin plume across the sky
above scenic landscape features, but specific measures such as contrast and thickness of the
plume were not reported. The estimated on-site use  values for the prevention or elimination of
the plume ranged from about $3 to $6 (1989 dollars) per day  per visitor-party at the  park. A
potential problem common to all of these studies  is the use of daily entrance fees as  a payment
vehicle.
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                     TABLE 8-5. ECONOMIC VALUATION STUDIES FOR AIR POLLUTION PLUMES
oo
I
oo
Study
Schulzeetal. (1983)


MacFarland et al.
(1983)
Brookshire et al.
(1976)

Location
of Plume
Grand Canyon
National Park


Grand Canyon
National Park
Glen Canyon
National
Recreation Area
(Lake Powell)

Study Subjects
Urban residents
who have visited
or plan to visit
Grand Canyon
Urban residents
in Denver, Los
Angeles,
Chicago,
Albuquerque;
visitors and non-
visitors
Park visitors
Nearby residents
and lake visitors

Year of
Interviews Type of Value
1980 Daily use value
at park per
household
1980 Monthly
preservation
value per
household

1980 Daily use value
at park per
visitor-party
(household)
1 974 Daily use value
at recreation
area per visitor-
party
(household)

Valuation
Method3
Contingent
valuation, direct
WTP question
Contingent
valuation, direct
WTP question

Contingent
valuation, direct
WTP question
Contingent
valuation, direct
WTP question

Payment Mean Results
Vehicle ($ 1989)
Daily park $6. 17 per day at
entrance fee park per household
Monthly utility $5.31 per month
bill increase per household

Daily park $2.84 per day at
entrance fee park per visitor-
party (household)
Daily entrance Visitors: $3. 32 per
fee day additional to
prevent visible
plume
Residents: $2.21
per day additional
to prevent visible
plume
    aWTP = Willingness to pay.

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     The Schulze et al. (1983) study suggest that on-site preservation values for preventing a
plume at the Grand Canyon every day, based on 1.3 million visitor-parties of about three people
per party, would be about $8 million.  Based on their results, the implied preservation value for
preventing a visible  plume most days (the exact frequency was not specified) at the Grand
Canyon would be about $5.7 billion each year when applied to the total U.S. population.
However, Chestnut and Rowe (1990b) reported that the Schulze et al. (1983) preservation value
estimates for haze at national parks in the Southwest are probably  overstated by a factor of two
or three and the same probably applies to the preservation value estimates for plumes.

8.7.3.2   Economic Valuation Studies for Urban Haze
     Six economic studies concerning urban haze caused by air pollution are summarized in
Table 8-6. The implicit values obtained for a 10% change in visual range are reported in Table
8-6 to allow a comparison of results across  the studies.  Values for a 10% change are shown to
illustrate the range of results across the different studies. These estimates are based on a model
developed for comparison purposes that assumes economic values are proportional to the
percentage change in visual range.  Values  for a 20% change, for example, would be about twice
as large as those shown for a 10% change, given the underlying comparison model.  Each of
these studies relied on a reasonably representative sample of residents in the study area, such that
a range of socioeconomic characteristics and of neighborhood pollution levels was included in
each sample.
     The first five studies in Table 8-6 all focused on changes in urban hazes with fairly
uniform features that can be described as changes in visual range.  The sixth study (Irwin et al.,
1990) focused on visual air quality in Denver, where a distinct edge to the haze is often
noticeable, making visual range a less useful descriptive measure because it would vary
depending on the viewpoint of the individual and whether the target was in or above the haze
layer. The studies conducted in Denver and in the California cities are likely to have a higher
NOX component than in the eastern cities.
     Both of the CVM studies in California asked respondents to consider health and visual
effects but used different techniques to have respondents partition the total values. They found
that, on average, respondents attributed about one-third to one-half of their total values
                                          8-84

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                                     TABLE 8-6.  ECONOMIC VALUATION STUDIES ON URBAN HAZE
       Study
   Location
 Year
Valuation Method3
Payment Vehicle
Presentation/Definition
of Change in Visibility
   Implied Mean Annual
 WTPa for a 10% Change in
       Visual Range
	($ 1989)	
                                                             PARTI. UNIFORM URBAN HAZE
       Western Cities
       Loehman et al.
       (1981)
San Francisco       1980     Contingent valuation,    Monthly utility bill
                            direct WTP question    increases
                                                       Change in frequency
                                                       distribution illustrated
                                                       with local photos for
                                                       3 levels of air quality
                                                                    $106 per household
       Brookshire et al.       Los Angeles        1978      Contingent valuation,    Monthly utility bill
       (1982)                                             direct WTP question    increases
                                                                         Change in average
                                                                         visibility illustrated with
                                                                         local photos for 3 levels
                                                                         of air quality	
                                                                                $10 per household
oo
i
oo
       Trijonis et al. (1984)
San Francisco

Los Angeles
1978-79    Hedonic property
           value
1978-79    Hedonic property
           value
                                           Light extinction based on
                                           airport visibility data
                                           Light extinction based on
                                           airport visibility data
                                             $208-231 per household

                                             $112-226 per household
       Eastern Cities
       Tolleyetal. (1986)
Chicago;
Atlanta;
Boston;
Mobile;
Washington,
D.C.;
Miami;
Cincinnati
 1982     Contingent valuation,
           direct WTP question
                     Monthly payment
                     for visibility
                     improvement
                     program
                    Change in average
                    visibility illustrated with
                    Chicago photos for levels
                    of air quality
                        $8-51 per household

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                                TABLE 8-6 (cont'd).  ECONOMIC VALUATION STUDIES ON URBAN HAZE
       Study
   Location
Year
Valuation Method3
Payment Vehicle
Presentation/Definition
of Change in Visibility
   Implied Mean Annual
 WTPa for a 10% Change in
      Visual Range
	($ 1989)	
                                                       PART I (cont'd). UNIFORM URBAN HAZE
      Rae (1984)
Cincinnati
1982     Contingent valuation,
         direct WTP question
                    Monthly payment
                    for visibility
                    improvement
                    program
                   Change in average
                   visibility illustrated
                   with Chicago photos
                   for 3 levels of air
                   quality
                       $48 per household
PART H. URBAN HAZE WITH BORDER
Irwin et al. (1 990) Denver
1 989 Contingent valuation,
direct WTP question
General higher
prices each year
1-step change in
7-point air quality
Preliminary results
indicate mean annual WTP
oo
I
oo
                                                                       scale, illustrated with
                                                                       photos
                                                                            of about $ 100 per
                                                                            household for a 1-step
                                                                            change in the 7-point
                                                                            scale, with about one-third
                                                                            of the value attributed to
                                                                            visibility alone
     aWTP = Willingness to pay.

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to aesthetic visual effects.  In spite of many similarities in the approaches used, the CVM results
for San Francisco are notably higher than for Los Angeles when adjusted to a comparable
percentage change in visual range.  One potentially important difference in the presentations was
that Loehman et al. (1981) defined the change in visibility as a change in a frequency
distribution rather than simply a change in average conditions. This type of presentation is more
realistic but more complex; and it is unclear how it may affect responses relative to presentation
of a change in the average.  It is possible that the distribution presentation might elicit higher
WTP responses because it may focus respondents' attention on the reduction in the number of
relatively bad days (and on the increase in the number of relatively good days), whereas the
associated change in the average may not appear as significant.  The implied change in average
conditions in the Loehman et al. (1981) San Francisco study was considerably smaller than that
presented in the Brookshire et al. (1982) Los Angeles study, which may have also resulted in a
higher value when adjusted to a comparable size change in average visual range because of
diminishing marginal utility (i.e., the first incremental improvement is expected to be worth
more than the second).
     The California studies in Los Angeles and San Francisco provide some interesting
comparisons because two different estimation techniques were applied for the same locations.
Property value results for changes in air quality for both cities were found to be higher than
comparable values (for changes in total air quality) obtained in the CVM studies.  This is as
expected given the theoretical underpinnings of each estimation method, although Graves et al.
(1988) have reported that subsequent analysis of the property value data revealed that the
estimates are more variable than the original results suggest. These property value results are
not reported here because they are for changes in air pollution indices that are not tied to visual
air quality.
     The property value study results reported in Table 8-6 from Trijonis et al. (1984) were
estimated using light extinction as the measure of air quality. However,  as discussed in the
previous section on the hedonic property value method, these estimates are still likely to include
perceived benefits to human health for reductions in air pollution as well as values for visual
aesthetics. Consistent with this expectation, the results for a 10% change in light extinction are
higher than the CVM results for visual range changes for the same cities. Respondents in several
CVM studies have reported that,  on average, they would attribute to
                                          8-87

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visibility aesthetics about one-fourth to one-half of their total WTP for improvements in air
quality. This would imply that the Trijonis et al. (1984) results may reflect $25 to $100 for a
change in visibility alone.
     The results for the uniform urban haze studies in cities in the eastern United States fall
between the respective CVM results for the California cities. The changes in visual range
presented in these studies were similar to those presented in the Los Angeles study. In all of the
eastern studies respondents were simply asked to consider only the visual effects when
answering the WTP questions. This approach is now considered to be inadequate (Irwin et al.,
1990; Carson et al.,  1990).
     McClelland et al. (1991) conducted a mail survey in 1990 in Chicago and Atlanta.
Residents were asked what they would be willing to pay to  have an improvement in air quality,
which  amounted to about a 14% improvement in annual average visual range. Respondents
were then asked to say what percentage of their response was attributable to concern about
health  effects, soiling, visibility, or other air quality effects.  Respondents, on average, attributed
about 20% of their total WTP to visibility. The authors conducted two analyses and adjustments
on the  responses.  One was to estimate and eliminate the potential selection bias resulting from
non-response to the WTP questions (including what has been called protest responses). The
other was to account for the potential  skewed distribution of errors caused by the skewed
distribution of responses (the long tail at the high end). Both of these adjustments caused the
mean value to decrease. The annual average household WTP for the designated visibility
improvement was $39 before the adjustments and $18 after the adjustments.  This adjusted mean
value implies about $13 per household for a 10% improvement in visual range. This is at the
low end of the range of estimates shown in Table 8-6. If peer-review of this research effort
confirms the appropriateness of the study design and analysis, the results suggest that greater
confidence should be placed in the lower end of the range of results shown in Table 8-6 because
this study represents  an improvement in approach over the other eastern-cities studies.
     Irwin et al. (1990) have reported preliminary results for the Denver study (Part II, Table 8-
6).  Comparison of these preliminary results with results from other studies is difficult because
the photographs used to illustrate different levels of air quality were not tied to visual range
levels.  Instead, they  were rated on a seven-point air quality scale by the

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respondents, who were then asked their maximum WTP for a one-step improvement in the scale.
This study reports some important methodological findings.  One of these is confirmation that
simply asking respondents to think only about visibility results in higher WTP responses for
visibility changes than when respondents are asked to give WTP for the change in air quality and
then to say what portion of that total they would attribute to visibility only. The latter approach
produced a mean WTP estimate for a one-step change in visibility that was about one-half the
size of the mean WTP estimate given when respondents were simply asked to think only about
visibility. This may result from the effect of budget constraints on marginal values (the
respondent has less to spend on visibility when he also is buying health); however, the authors
express the concern that some, but not all, of the value for health may be included in the
response when respondents are told to think only about visibility.  They recommend that
respondents be asked to give total values for changes in urban air quality and then be asked to
say what portion is for visibility.
8.8    CLIMATIC EFFECTS
8.8.1  Introduction
     Aerosols of submicron size in the atmosphere can affect the Earth's climate directly
through the absorption of radiation and indirectly by modifying the optical properties and
lifetime of clouds (perturbation of the radiative field). Perturbation of the radiation field
generally is expressed as a radiative forcing, which is the change in average net radiation at the
top of the troposphere because of a change in solar (shortwave) or terrestrial (longwave)
radiation (Houghton et al., 1990). Note that it is the net effect at the top of the troposphere (i.e.,
the tropopause) that forces climate, and not the change at the surface, because the surface and
troposphere are intimately coupled through atmospheric energy exchange processes such as dry
and moist convection (Ramanathan et al., 1987). The radiative forcing due to aerosols is
negative (i.e., aerosols have a cooling effect through the enhanced reflection of solar energy).
This is in contrast to radiatively active trace ("greenhouse") gases associated with industrial and
agricultural activities,  which produce a positive longwave radiative forcing (i.e., "greenhouse"
gases cause a warming of the earth-troposphere system).  A large fraction of atmospheric
paniculate matter is of anthropogenic origin, the chief
                                          8-89

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sources being the emission of sulfur-containing aerosols by industry and the large-scale burning
of biomass.

8.8.2  Radiative Forcing
     There is now little doubt that long-lived, optically thick, aerosol layers may have modified
the Earth's climate in the past. Geologic evidence suggests that there have been episodic
injections of massive amounts of material into the Earth's atmosphere as a result of the impact of
large asteroids or comets. The diminution of solar radiation reaching the surface has been
suggested as the most likely cause of mass extinctions of species at the Cretaceous-Tertiary
boundary (Alvarez et al., 1980) and also in the Late Devonian (Claeys et al., 1992). The
possibility of a similar climatic catastrophe following a nuclear war has also been raised (Turco
et al., 1983, 1990). However, these are examples of massive injections of paniculate matter that
result in extremely large radiative forcings. Current interest is focused on much more modest
injections of materials that form thin aerosol layers in the troposphere. Although the radiative
effects are smaller and have been generally ignored in climate model simulations (Hansen and
Lacis, 1990), recent studies have estimated that they are not negligible and that their radiative
forcing may be comparable (but opposite in sign) to the radiative effects of increased greenhouse
gas emissions (Wigley, 1991; Charlson et al., 1992; Penner et al., 1992). Because there is so
much concern regarding greenhouse gas-induced climate change, the study of this potential
opposite  effect of industrial emissions is expected to be quite intense in the near future (Penner
etal., 1994).
     To  appreciate what is at issue here, it is necessary to understand the concept of radiative
forcing.  Averaged globally and annually, about 240 watts per meter squared (W m"2) of solar
energy is absorbed by the earth-atmosphere system (Hartmann, 1994).  This  must be balanced by
an equal  emission of thermal energy back to space for equilibrium. A change in average net
radiation at the tropopause, because of a change in either solar or terrestrial radiation, perturbs
the system and this perturbation is defined as the radiative forcing. In response to this
perturbation, the climate system will try and reach a new equilibrium state. For example, the
increase in longwave opacity of the atmosphere resulting from enhanced concentrations of
greenhouse gases such as carbon dioxide (CO2) and methane (CH4) is a positive radiative  forcing
because it leads to a reduction in outgoing thermal
                                          8-90

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radiation. For equilibrium, given that there is no change in solar input, the temperature of the
surface-troposphere system must increase. The individual contributions to this positive forcing,
since pre-industrial times, is shown in Figure 8-15 (Houghton et al., 1990). Carbon dioxide is
the single most important contributor with a radiative forcing of 1.50 W m"2 for the period 1765
to 1990. The total for all greenhouse gases attributable to anthropogenic sources is 2.45 W m"2.
                        CFCs & HCFCs
                        STRATH2O
                    D  N20
                    D  CH2
                        CO,
           1750
  \
1800
  \       '      \
1850         1900
      Year
  r
1950
2000
Figure 8-15.  Changes in radiative forcing (W m 2) due to increases in greenhouse gas
             concentrations between 1765 and 1990. Values are changes in forcing from
             1765 concentrations.
Source: Houghton et al. (1990).
     Human activity has also led to an increase in the abundance of tropospheric aerosols,
primarily as a result of enhanced SO2 emission, but also from biomass burning.  This aerosol
                                         8-91

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layer produces a radiative forcing by perturbing the amount of solar energy that is absorbed by
the earth-atmosphere system.  By increasing the amount of solar energy reflected by the planet,
aerosols produce a direct radiative forcing. They can also force the climate system indirectly by
modifying the microphysical properties of clouds, primarily by reducing the effective drop size
of water clouds.  Both the direct and indirect radiative forcing of aerosols are negative (i.e., in
response to this perturbation, the planet will cool).
     Aerosols in the stratosphere have been implicated in the loss of O3 through heterogeneous
chemistry involving chlorine compounds (Hoffman and Solomon, 1989; Schoeberl  et al., 1993;
Hoffman et al.,  1994). Although the chlorine is primarily of anthropogenic origin, the enhanced
concentrations of aerosols are a result of volcanic eruptions.  Anthropogenic SO2 does not
change the stratospheric aerosol burden appreciably. Therefore, this effect of aerosols is not
relevant to this discussion.
     The succeeding sections of this chapter are devoted to the estimation of aerosol radiative
forcing. Translating this forcing into a climate response requires the incorporation of the forcing
into a climate model.  The model simulations,  of course, are only as reliable as the models,
which typically incorporate numerous feedbacks in the climate system that are only represented
to some degree of approximation. There are certainly many feedbacks missing from current
climate models, and it is quite possible that some feedbacks have been modeled quite
incorrectly.  Moreover, the radiative forcing due to anthropogenic aerosols needs to be estimated
separately from that due to naturally occurring aerosols in order to evaluate the impact of human
activity. The relationship between these aspects of the problem is shown in Figure 8-16.
     As has been mentioned, the radiative forcing due to aerosols is opposite in sign to that due
to greenhouse gases, but the degree of offset in forcing may not translate into offsetting climatic
consequences. We can only judge these by studying model simulations.  Also, it must be kept in
mind that climate variations occur in the absence of radiative forcing as a result of interactions
between the atmosphere, oceans, and the various elements of the land surface such as snow
cover and vegetation.
                                          8-92

-------
                    Natural Sulfate
                Anthropogenic Sulfate
                                   Sulfate Aerosols
            Direct radiative forcing through
            reduction in surface insolation
            and increase in atmospheric
            solar absorption
                 Indirect radiative forcing
                 through modification of
                 cloud and haze
                 microphysical properties
             Feedbacks in the
             climate system
CLIMATE RESPONSE
Figure 8-16. A schematic diagram showing the relationship between the radiative forcing
             of sulfate aerosols and climate response.
Source: Harshvardhan (1993).
8.8.3  Solar Radiative Forcing by Aerosols
     Aerosol radiative forcing results from enhanced reflection of solar energy which enters the
top of the Earth's atmosphere as a collimated beam of infinite width, but is subsequently
scattered and absorbed to some degree even on the clearest day.  Figure 8-17 shows this process
schematically. Throughout the troposphere molecules, constituting the atmosphere, scatter
sunlight by Rayleigh scattering (see the discussion of visibility for the definition of Raleigh
scattering), which is highly wavelength dependent. In the lower troposphere, sunlight is
scattered by aerosols or haze and absorbed by aerosols and water vapor. Because the aerosol
loading is quite variable, this component of aerosol scattered solar radiation is also variable.
     The degree to which a layer of particles scatters solar radiation is primarily determined by
the nondimensional parameter referred to as the scattering optical depth of the layer, TX,
                                          8-93

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                                                    Backscatter
                                                    Absorption
                                                    Diffuse
Figure 8-17. Extinction of direct solar radiation by aerosols showing the diffusely
             transmitted and reflected components, as well as the absorbed components.
which in turn is the column integrated volume scattering coefficient for particles, osp (units are
km"1,  see sections on visibility for details).  Because the scattering coefficient for particles
depends on wavelength, the attenuation of the direct beam of sunlight is also wavelength
dependent. This spectral behavior is usually expressed by the proportionality
                                                                                  (8-37)
where A is the wavelength in micrometers Cam). The exponent, a, is the turbidity parameter
introduced by Angstrom (1964) and varies between 0.5 and 1.5 for aerosols (Twomey, 1977).
For particles that are very small compared to the wavelength (Rayleigh scattering), a = 4, and
for relatively larger particles, such as cloud drops, a = 0.    The downwelling portion  of the
radiation scattered by molecules and aerosols forms diffuse skylight whereas the unattenuated
beam of solar radiation is said to be the directly transmitted or beam radiation.  The upwelling
portion of scattered radiation, together with energy reflected by the surface, is the diffuse
reflection of the earth-atmosphere system. It is the perturbation in this
                                          8-94

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component of radiant energy by enhanced aerosol loadings that constitutes the radiative forcing
to the system by aerosols.  The sum of directly and diffusely transmitted solar energy is the
global solar radiation incident on a surface.
     Figure 8-18, from Iqbal (1983), shows computations of the spectral distribution of a solar
energy incident on a horizontal surface for a solar zenith angle of 60° (air mass = 2) and
standard clear conditions.  The atmosphere contains 350 Dobson units of ozone (O3), 2 ppt/cm of
water vapor, and a nonabsorbing aerosol layer corresponding to a surface visibility of 28 km.
The ground reflectance is 0.2.  Some features  of Figure 8-18 are worth noting. Virtually all
solar radiation at wavelengths less than 0.29 //m is removed by O3 absorption. Rayleigh
scattering by molecules is the predominant source of the diffuse radiation at shorter wavelengths,
but the contribution falls off very dramatically with increasing wavelength because of the
inverse fourth power dependence. Aerosol scattering contributes to the diffuse component at
visible and near-infrared wavelengths. Absorption by the strong water vapor bands is quite
evident in the near-infrared.
     An increase in the optical depth of aerosols results in  a decrease in the direct beam
radiation, which could be substantial, but the downwelling portion of the enhanced scattered
radiation compensates for this to a large extent.  This  is illustrated in Figure 8-19, which shows
surface measurements of direct, diffuse, and global solar radiation, made using a multifilter
rotating shadowband radiometer (Harrison and Michalsky,  1994; Harrison et al.,  1994) at
Albany, NY, on two clear days in August of 1992 and 1993. The total atmospheric optical depth
in 1992 was influenced by the eruption of Mt. Pinatubo in June 1991. Although the volcanic
aerosols were in the stratosphere, their effect on direct and diffuse transmitted radiation is
similar to that due to tropospheric aerosols.  The quantity plotted is  the spectral irradiance
convolved with the average human eye response that peaks at 550 nm and falls to zero at 400
and 700 nm.  The main feature of the plot is the substantial difference in direct and diffuse
radiation, but quite similar global irradiances.  Close inspection shows that on the hazier day (in
1992), the global transmitted radiation was somewhat less (i.e., the volcanic aerosol  caused a
negative radiative forcing to the earth-atmosphere system by increasing the planetary albedo).
Locally, tropospheric aerosol optical
                                           8-95

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            1,000
           E
          g
750  -
           o>
           o
          •o
          m
          ± 500 -
           o
           0)
           Q.
          CO
           n
          4-1
           C
           O
           N
250
                0.29  0.5
                      1.0           1.5
                        Wavelength (|jm)
Figure 8-18.  Global, direct, and diffuse spectral solar irradiance on a horizontal surface
              for a solar zenith angle of 60° and ground reflectance of 0.2.  Atmospheric
              conditions are visibility, 28 km; water vapor, 2 ppt/cm.; ozone, 350 Dobson
              units.
Source: Iqbal (1983).
depths are much larger than the stratospheric optical depth and one would expect a more obvious
diminution of global transmitted radiation than is shown here.
     Figure 8-19 is for the spectrally integrated irradiance. Within the solar spectrum,
wavelengths are affected to different degrees by the presence of aerosols. In particular there
have been some studies on the effect of aerosols on transmitted UV to the surface.  This an
important consideration, especially for UV-B (280 nm 
-------
the sky and the layer is above the absorption region.  The process responsible for this is single
scattering which changes the direction of the incident radiation such that there is a shorter path
through the absorbing layer and more is transmitted to the ground.  However, when the sun is
high in the sky or the scattering layer is below the absorbers this effect does not occur.
     For tropospheric aerosols, the net effect is a reduction in global irradiance at all
wavelengths similar to the total energy shown in Figure 8-19. Frederick et al. (1989) have
calculated the  expected change in Robertson-Berger meter readings from 1969 to 1986 for
34.5°N based  on changes in column ozone as reported by Watson et al. (1988). They compared
ratios with and without an aerosol layer of optical depth 0.1 independent of wavelength in the
lowest 2 km for  1986 only. For clear atmospheres, the ratio changed from 1.02 without the
aerosol to 0.92 with the aerosol indicating that the effect on UV-B transmission of the depletion
in column ozone from 1969 to 1986 could be compensated by a concomitant increase in
particulate matter. Measurements made at Barcelona, Spain, by Lorente et al. (1994) show that
the UV-B at the surface is reduced by 37% during the most polluted days and UV-A is reduced
by 30% compared to the clearest days. By reflecting some UV back to space,  tropospheric
aerosols actually decrease  the irradiance of this flux to the surface.

8.8.3.1    Modeling Aerosol  Direct Solar Radiative Forcing
     Some basic aspects of scattering and absorption by small particles typically present in
aerosol layers  govern the sign and magnitude of the direct radiative forcing by aerosols. These
properties are  discussed in Section 8.2 of this chapter. The reflectance of an aerosol layer is
chiefly determined by the optical depth, single scattering albedo, co^, and some measure of the
scattering phase function.  The single scattering albedo, the ratio of the light-scattering
coefficient and the light-extinction coefficient, is a measure of the absorptance of the aerosol
layer. Related quantities are the specific extinction and specific scattering coefficients, tyext and
tyscap which are defined as  the coefficients per unit mass in units of m2g"1. The phase function
determines the probability that incident radiation will scatter into a particular direction  given by
the scattering angle measured from the forward direction of the incident radiation.
                                          8-97

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  100

   90

   80

t? 70
_3
2  60
                        o>
                        u
                           50
                        E
                        =  40
                           30

                           20

                           10
                                                           Direct
                             6:00  8:00   10:00  12:00 2:00   4:00  6:00
                             AM              NOON             PM
                                           Local Time
Figure 8-19.  Surface measurements of direct, diffuse, and global solar radiation expressed
              as illuminance, at Albany, NY, on August 23,1992, and August 26,1993.
Source: Harrison and Michalsky (1994).
     At visible wavelengths, the optical depth of tropospheric aerosols ranges from less than
0.05 in remote, pristine environments to about 1.0 near the source of copious emissions (Weller
and Leiterer, 1988). The optical depth decreases quite rapidly with increasing wavelength if the
layer is composed of fine particles as can be seen from Equation 8-37.  Aerosol layers, therefore,
tend to be fairly transparent at thermal wavelengths and their radiative forcing is confined to
solar wavelengths. Because there are strong water vapor absorption bands in the solar near-
infrared (see Figure 8-20), the dominant effect of tropospheric aerosols is in the visible
wavelengths. Harshvardhan (1993) has shown that, to the first order, the change in the  albedo
with the addition of a thin aerosol layer over a surface of reflectance, Rx, is
                                           8-98

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                                                            m = 1.53-0.0011
                                                            m = 1.53-0.011
                                                            m = 2.0-0.641
       0.01                      0.1                       1.0                       10
                                       Radius (|jm)
Figure 8-20.  Single scattering albedo of monodispersed spherical aerosols of varying
             radius and three different refractive indices at a wavelength of 0.63 /j,m.
Source:  Harshvardhan (1993).
               AR « R a(l -  R J2 - 2A R
                      a        b         a b
(8-38)
where Ra and Aa are the reflectance and absorptance, respectively, of the aerosol layer. The
perturbation, AR, will be positive when
             (1 - con)/co  R < (1 - RJ2/2Re
(8-39)
where P is the average backscatter fraction and can be computed from the scattering phase
function. A positive value for the change in albedo implies a negative solar radiative forcing
because the planetary albedo increases and less solar energy is absorbed by the earth-atmosphere
system.
                                          8-99

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     From Equation 8-39, it is obvious that the sign of the forcing will be determined to a large
extent by the single scattering albedo. At visible wavelengths, most constituents of tropospheric
aerosols, with the exception of elemental carbon, are nonabsorbing and co^ =1.0 (Bohren and
Huffman,  1983) so that the change in albedo will be positive. Aerosols with absorbing
components can be modeled as equivalent scatterers of refractive index, m = n - ik, with the
imaginary index being a measure of particle absorption. Figure 8-20, shows the computed
values of single scattering albedo at a wavelength of 0.63 //m for single particles of varying
radius. The three separate curves are for aerosols composed of carbon (m = 2.0 - 0.64/') and two
models of sulfate aerosols containing absorptive components.  Given the properties of an aerosol
layer, the change in albedo can be computed from Equation 8-38.  To calculate the radiative
forcing, one must also include the effects of other atmospheric constituents such as molecular
scattering, stratospheric O3,  water vapor absorption, and, most importantly, cloud cover.

8.8.3.2 Global Annual Mean Radiative Forcing
     Charlson et al. (1991)  calculated the global mean radiative forcing due to anthropogenic
aerosols by making the following assumptions. They assumed that the perturbation would be
exceedingly small over cloudy areas  because cloud optical depths are one to two orders of
magnitude greater than aerosol optical depths (Rossow and Schiffer, 1991).  For nonabsorbing
aerosols, they found that the change in planetary albedo could be expressed as
                                         c)  (1  -  Rs2)
                                                                                 (8-40)
where T is the transmittance of the atmosphere above the aerosol layer and Nc is the global mean
cloud fraction. The planetary mean radiative forcing is then
                                    AFR  =  ARpS0/4
                                                                                 (8-41)
                                         8-100

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where SJ4 is the annual global mean insolation of the earth-atmosphere system (Hartmann,
1994) with S0 being the solar constant, which equals to 1,370 W m"2.  For the generally accepted
values of T = 0.71, Nc = 0.6, Rx = 0.15 and P = 0.3, Charlson et al. (1991)
                                      AFR  = 30.OT
                                                                                    (8-42)
obtained such that for u, the optical depth at visible wavelengths ranging from 0.05 to 0.10, the
direct solar radiative forcing is 1.5 to 3.0 W m"2, a value comparable to the long-wave radiative
forcing of all the anthropogenic greenhouse gases (Section 8.8.2).
     The above estimate was refined by Charlson et al. (1992) in which the anthropogenic
sulfate aerosol burden was actually related to the source strength  of anthropogenic SO2, the
fractional yield of emitted SO2 that reacts to produce sulfate aerosol and the sulfate lifetime in
the atmosphere. The scattering properties of the sulfate aerosol were also modeled in terms of a
relative humidity  factor that accounts for the increase in particle size associated with
deliquescent or hygroscopic accretion of water with increasing RH.  The relationship between
optical depth and the areal mean column burden of anthropogenic sulfate aerosol, Bsulfate, is

                                   T = Xsulfate f(RH) Bsdfate                             (8-43)

where Xsulfate is the molar scattering cross section of sulfate at a reference low RH (30%) and
f(RH) is the relative humidity factor. The sulfate burden, is related to SO2 emissions and sulfate
lifetime.  For an emission rate of 90 x 1012 g of sulfur per year, a  yield fraction of 0.4, a sulfate
lifetime of 0.02 years (7 days) and the molar scattering cross section of sulfate of 500 n^mol"1
(corresponding to specific extinction coefficient of 5 m^"1), Charlson et al. (1992) estimated that
AF^ = 1.0 W m"2,  with an uncertainty factor of 2, which perhaps should be more considering that
the uncertainty in the specific extinction coefficient alone is higher (Hegg et al., 1993, 1994;
Anderson et al., 1994).
     The above is an estimate for the forcing  due to industrial emissions. Another
anthropogenic source of aerosols is biomass burning. Penner et al. (1992) have estimated
                                          8-101

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that the radiative forcing due to this activity could be as much as 0.9 W m"2, which is comparable
to the sulfate forcing.  One difference is that the smoke produced is somewhat  absorbing and the
atmosphere would experience a positive forcing of 0.5 W m"2. Estimates of the global forcing
due to biomass burning are even more uncertain than those for sulfate because  of the sparsity of
data on the relevant radiative properties of biomass aerosols.

8.8.4  Climate Response
8.8.4.1  Early Studies
Global Background Aerosols
     The role of aerosols in modifying the Earth's climate through solar radiative forcing has
been a topic of discussion for many decades. Modeling studies assumed a climatological
background  distribution of aerosols such as that of Toon and Pollack (1976). Two simple types
of climate models were used to calculate the effects of aerosols on climate:  (1) the radiative-
convective model, which resolves radiative perturbations in an atmospheric column, and (2) the
energy balance model, which allows for latitudinal dependence, but parameterizes all processes
in terms of the surface temperature.  A typical study was that of Charlock and Sellers (1980)
who used an enhanced one-dimensional radiative-convective model that included the effects of
meridional heat transport  and heat storage.  The model was run with and without a prescribed
aerosol layer of visible optical depth equal to 0.125 for conditions representative of 40° and 50°
N latitude.  The annual mean surface temperature with aerosols was 1.6 °C lower than that for
the aerosol-free run.
     Coakley et al. (1983) were the  first to use an energy balance model to compute the
latitudinally dependent radiative forcing for the Toon and Pollack (1976) aerosol distribution,
including the effects of absorbing components. Even for moderately absorbing aerosols (m= 1.5
- 0.01/'), the solar radiative forcing was negative, except in the 80° to 90° N latitude belt, which
has a very high surface albedo. Here the criterion given by Equation 8-31 is not satisfied and the
change in albedo is negative  (i.e., the solar radiative forcing is positive).  The model results
showed global mean surface temperature decreases ranging from 3.3 °C for nonabsorbing
aerosols to 2.0 °C for the  absorbing aerosols.  The maximum temperature drop was at polar
latitudes  even for the absorbing layer because advective processes responded to the aerosol-
                                         8-102

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induced cooling at low- and middle-latitudes.  Other two-dimensional model studies have
confirmed this basic picture (Jung and Bach, 1987).

Regional and Seasonal Effects
     Apart from global studies, there have been several programs devoted to ascertaining the
effects of aerosols on regional and seasonal scales. An example is the radiative effect of aerosols
in the Arctic (Rosen et al.,  1981). A field experiment, the Arctic Gas and Aerosol Sampling
Program, was conducted in 1983 (Schnell, 1984). It was determined that aerosols had a
substantial absorbing component. The study by MacCracken et al. (1986) used both one- and
two-dimensional climate models to evaluate the climatic effects.  They found that the initial
forcing of the surface-atmosphere system is positive for surface albedos greater than 0.17, and
the equilibrium response of the one-dimensional radiative-convective model showed surface
temperature increases of 8  °C. Infrared emission from the warmer atmosphere was found to be
an important forcing agent of the surface. The two-dimensional model was run through the
seasonal cycle and had an interactive cryosphere. Peak warming occurred in May, a month later
than the peak radiative forcing, as a result of earlier snow melt.

Massive Aerosol Loads
     In the 1980s, there were several studies related to what became known as the "nuclear
winter" phenomenon (Turco et al., 1983) (i.e., the climatic consequences of widespread nuclear
war).  Modeling efforts ranged from radiative-convective models (Cess et al., 1985) to three-
dimensional general circulation models (GCM) (Thompson et al., 1987; Ghan  et al., 1988), and
mesoscale models (Giorgi and Visconti, 1989) with interactive smoke generation and removal
processes and fairly detailed smoke  optics.  A review of modeling efforts has been made by
Schneider and Thompson (1988) and Turco et al. (1990). The latter study summarized the best
estimates of possible reduction in surface temperature from the smoke lofted into the atmosphere
during the initial acute phase.
     General Circulation Model studies (Thompson et al., 1987; Ghan et al., 1988) indicate that
for a July smoke injection, the average land temperatures over the latitude zone from 30° to 70°
N, over a 5-day period, would decrease by 5 °C for smoke of optical depth equal to 0.3, but
could decrease by 22 °C for large loadings of optical depth equal to
                                         8-103

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3.0.  However, the temperature in the interior of land masses could drop by as much as 30 °C.
The temperature perturbations for smoke injections in other seasons are smaller.  At lower
latitudes, the cooling is moderated by the delay in smoke transport (assuming initial injection in
high northern latitudes), and the more humid climate. Model studies also indicate a dramatic
decrease in rainfall over land and a failure of the Asian monsoon (Ghan et al., 1988).

8.8.4.2  Recent Regional Studies
     There have been more recent studies of possible climatic effects resulting from severe
aerosol loading on regional scales. The Arctic haze problem has been investigated extensively.
Blanchet (1989, 1991), using a GCM, studied the effects of increasing aerosol loads north of
60° N.  Although the solar heating rate in the troposphere increased quite dramatically, the
temperature did not rise substantially. The positive forcing of 0.1 to 0.3 Kday"1 resulted in  a
decrease in the meridional heat flux. Quite importantly, the simulated cloud cover in the
experiment was altered sufficiently to produce changes in net radiative fluxes at the top were
locally an order of magnitude greater than the initial forcing. This implies that it may be very
difficult to identify climate change effects due to aerosols alone. Another effect of aerosols at
high latitudes that has the potential for affecting climate is the change in surface albedo due to
deposition of soot. This was studied by Vogelmann et al. (1988) with respect to the nuclear
winter problem. They found that the cooling due to smoke aerosol could be moderated
somewhat by the "dirty" snow at very high latitudes.
     Several studies have examined the effect of smoke from forest fires on climate. Since
these are natural phenomena, it is important to understand their effects in order to place
anthropogenic effects in context. Evidence of substantial  climatic effects is present only when
the smoke loading is substantial. For example, Robock (1988) examined the situation in
northern California where a subsidence inversion trapped smoke in mountain valleys for several
days in  September 1987.  One station recorded an anomaly in the maximum temperature of
-20  °C. Veltischev et al. (1988) analyzed data covering the period  of major historical fires in
Siberia, Europe, and Canada. They estimated that the optical depth of
                                         8-104

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smoke following fires in Siberia in 1915 was about 3.0 and surface temperature dropped by
5 °C.
     Other studies have also shown a relationship between smoke and surface temperature.
Robock (1991) studied the smoke from Canadian fires in July 1982. He compared forecasted
temperatures with observations and found that regions of negative anomaly were well correlated
with the smoke layer. Westphal and Toon (1991) used a mesoscale model with interactive
smoke physics and optics to simulate the smoke plume and its meteorological effects.  They
calculated the albedo of the smoke-covered area to be 35%, and the resulting surface cooling
was 5 °C.
     Perhaps the most extensive recent investigation of the possible climatic effects of heavy
aerosol burdens was the study of the Kuwait oil fires in 1991. Several modeling studies were
undertaken. Browning et al. (1991) simulated the  smoke plume with a long-range dispersion
model and concluded that the smoke would remain in the troposphere and not be lofted into the
stratosphere where the residence  time would be much longer. They estimated a maximum
temperature drop of 10 °C beneath the plume, within about 200 km (i.e., only a regional, not
global climatic effect). Bakan et al. (1991) used a GCM with an interactive tracer model to
simulate the plume dispersion and climatic effects. The maximum  temperature drop was
estimated to be about 4 °C near the source.  The local and regional nature of the effect was
confirmed during a field experiment undertaken in May/June, 1991. The smoke from the oil
fires had insignificant global effects because (1) particle emissions  were less than expected, (2)
the smoke was not as black as expected, (3) the smoke was not carried high in the atmosphere,
and (4) the smoke had a short atmospheric residence time (Hobbs and Radke, 1992).
     The study of severe events  such as those described above is useful for investigating model
response since such strong forcings usually provide unambiguous climate response signals.  The
simulated climate response to the more modest radiative forcing due to the distribution of natural
and usual anthropogenic sulfate or smoke aerosols is well within the internal model variability.
However, an estimate of the magnitude of possible effects can be obtained by model simulations
that integrate the chemistry, optics, and meteorology of anthropogenic aerosols.
                                        8-105

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8.8.4.3 Integrated Global Studies
     Ideally, one should study the problem in an integrated manner, in which the emissions of
sulfate precursors are tracked globally and the radiative forcing of the resulting aerosols
computed locally in space and time. A further step would be to let the radiative response impact
climate interactively.  This latter step could be carried out by a GCM coupled to an oceanic
model. Recent studies have accomplished various elements in this scenario.
     Global three-dimensional models of the tropospheric sulfur cycle consider emission,
transport, chemistry, and removal processes for both natural and anthropogenic sources. The
primary natural source is dimethylsulfide (DMS), which is released by oceanic phytoplankton
(Nguyen et al., 1983;  Shaw, 1983; Charlson et al., 1987). The DMS reacts in air to form sulfate
aerosols.  Anthropogenic emissions are over land, especially in the heavily industrialized areas
of the Northern Hemisphere.  Examples of such sulfur cycle models are the Lagrangian model of
Walton et al. (1988) and Erickson et al. (1991), known as the GRANTOUR model, and the
Eulerian transport model of Langner and Rodhe (1991) and Langner et al. (1992), known as the
MOGUNTIA model.  Both models use prescribed mean winds, typically obtained from GCM
simulations, to provide monthly mean concentrations of sulfate aerosols.
     With such detailed input, it is possible to construct global maps of the radiative forcing due
to sulfate and compare the magnitude with that due to greenhouse gases. Kiehl and Briegleb
(1993) carried out such a study using the monthly mean  sulfate abundances from the
MOGUNTIA model.  For meteorological parameters,  they used  1989 monthly mean temperature
and moisture fields data from the European Center for Medium Range Weather Forecasting.
Vertical distributions  of clouds were taken from a GCM simulation using the National Center for
Atmospheric Research Community Climate Model (CCM2) since such detailed observations are
lacking. However, attempts were made to adjust the total cloud cover to correspond to
observations.
     The radiative forcing was calculated by Kiehl and Briegleb using an 18-band 5-Eddington
model in the shortwave and a 100 cm"1 resolution band model in the longwave, which includes
the contributions due  to trace gases such  as CH4, NO2, and chlorofluorocarbons. The  optical
properties of sulfate aerosol were calculated spectrally using the refractive indices for 75%
sulfuric acid (H2SO4)  and 25% water (H2O) and an
                                         8-106

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assumed log-normal size distribution that has a geometric mean diameter by volume of 0.42 //m.
The specific extinction coefficient of the dry particles was found to be a very strong function of
wavelength, decreasing from 10 m2g"1 at 0.3 //m to less than 2.0 n^g"1 at 1.0 //m.  This is
significant in interpreting the computed forcing when comparisons are made with earlier studies
that used a constant value for the specific extinction coefficient.
     The value of the specific extinction coefficient depends on the size distribution of the
aerosols but that also affects the phase function such that changes in the coarse particle or fine
particle mode do not greatly affect the total radiative forcing (Kiehl and Briegleb, 1993). This is
because the extinction cross section has a sharp maximum for particles that are of the same
dimension as the wavelength and falls off rapidly for smaller and larger particles (Covert et al.,
1980).
     The direct radiative forcing is  calculated by adding the sulfate burden to the model and
computing the change in absorbed solar radiation.  Figures 8-2la and 8-2Ib, from Kiehl and
Briegleb (1993)  show the annual mean direct solar radiative forcing resulting from
anthropogenic sulfate aerosols (global mean = -0.28 W m"2) and anthropogenic plus natural
sulfate (global mean =  -0.54 W m"2).  The patterns are similar to those obtained earlier by
Charlson et al. (1991),  but the magnitude is roughly half.  Most of the  difference is  due to the
assumption of a constant value of 5.0 m2g"1 for the  specific extinction coefficient in the earlier
study, but there was also a difference in the phase function used. Therefore, assumptions
regarding radiative properties were able to account for all the differences.  Points to note in the
figure are the local concentrations of anthropogenic forcing and particularly the hemispheric
asymmetry in the forcing, even when natural sulfate is included. Although the southern
hemisphere is largely ocean, the direct forcing due  to natural sulfate is substantial only in the
clear oceanic areas since, in the presence of clouds, the additional sulfate effect is minimal.
     To place the role of anthropogenic sulfate in perspective, Kiehl and Briegleb (1993)
compared the direct radiative forcing with that of increasing greenhouse gases from preindustrial
times to the present. The greenhouse gas forcing is calculated by computing the spatial
distribution of the change in the net longwave flux  at the tropopause for the trace gas increases
from the preindustrial period to the present. The annual averaged results for
                                          8-107

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                                 ,-2\
       Annual Mean Forcing (W rrr)
                                                       anthropogenic sulfate aerosols

        -2.5    -2.0    -1.5     -1.0    -0.5     0
Figure 8-21a.  Annual mean direct radiative forcing (W m"2) resulting from anthropogenic
               sulfate aerosols.
Source: Kiehl and Briegleb (1993).

       Annual Mean Forcing (W m"2)
                                            anthropogenic plus natural sulfate aerosols
        -3.0   -2.5   -2.0   -1.5   -1.0   -0.5    0
Figure 8-21b.  Annual mean direct radiative forcing (W m"2) resulting from anthropogenic
               and natural sulfate aerosols.

Source: Kiehl and Bnegleb (1993).
                                         8-108

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greenhouse gases alone and in combination with anthropogenic sulfate are shown in
Figure 8-22a and 8-22b, respectively. The greenhouse gas forcing is, of course, positive and is
the greatest in the clear regions over the land and oceanic deserts. The global annual mean is 2.1
W m"2. When the negative forcing of aerosols is added, the global annual mean direct radiative
forcing due to anthropogenic activities is 1.8 W m"2. However, locally, there are regions where
the anthropogenic sulfate forcing cancels the greenhouse forcing.
     The forcing is simply an initial perturbation. Because the sulfate forcing  is in the
shortwave and felt primarily at the surface (for nonabsorbing aerosols), a coupled atmospheric-
oceanic climate model is required to determine the effect on climate. Taylor and Penner (1994)
have used the GRANTOUR model to provide the sulfate input to a GCM (CCM1), which was
coupled to a 50 m mixed-layer ocean model with sea ice and a specified meridional oceanic heat
flux.
     To assess the anticipated patterns of climate response to anthropogenic emissions of both
SO2 and CO2, Taylor and Penner performed four 20-simulated-year integrations in which the
atmospheric CO2 concentration was fixed at either the preindustrial level (275 ppm) or the
present day concentration (345 ppm). Anthropogenic sulfur emissions, corresponding to 1980,
were either included or excluded. Table 8-7 summarizes their annual average results. The
global  average anthropogenic sulfate forcing was found to be -0.95 W m"2; more than three
times larger than calculated by Kiehl and Briegleb (1993). The differences in the annual
anthropogenic sulfate forcing value in the two studies is due partially to the sulfate chemistry in
the model used by Taylor and Penner, (1994).  For example, there is a stronger seasonal cycle
with enhanced northern hemisphere concentrations in summer.  The remainder may be
contributed to the use of a constant specific scattering coefficient (8.5 n^g"1 at 0.55 //m) instead
of the RH-dependent model used by Kiehl and Briegleb (1993). As noted earlier, the value of
the specific scattering coefficient chosen could be a gross overestimate and, therefore the values
of the sulfate forcing shown in Table 8-7 are probably much too high.
     Some noteworthy features of Table 8-7 are that the combined CO2 and sulfate forcing is
not linearly additive and there is a pronounced asymmetry in the climate response in the two
hemispheres. What is clear is that the anthropogenic sulfate is expected to reduce somewhat the
anticipated warming resulting from the increased emission of greenhouse gases, especially
                                         8-109

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                                ,-2\
       Annual Mean Forcing (W m )
                        greenhouse

        0.50    1.0     1.5     2.0    2.5     3.0

Figure 8-22a.  Annual averaged greenhouse gas radiative forcing (W m"2) from increases
              in CO2, CH4, N2O, CFC-11, and CFC-12 from preindustrial time to the
              present.
Source:  Kiehl and Briegleb (1993).

       Annual Mean Forcing (W m"2)
greenhouse plus anthropogenic sulfate
                      •<:-:--:-::--:::f::-:--:-:::-^




                               '
      m

       -0.50   0   0.50  1.0   1.5   2.0   2.5   3.0
Figure 8-22b. Annual averaged greenhouse gas forcing plus anthropogenic sulfate aerosol
              forcing (W m"2).

Source: Kiehl and Bnegleb (1993).
                                         8-110

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                                            TABLE 8-7.  RADIATIVE FORCING AND CLIMATE STATISTICS
oo
Case
Northern Hemisphere
Preindustrial
Present-day CO2
Present-day sulfate
Combined CO2 and sulfate
Observed climate statistics
Southern Hemisphere
Preindustrial
Present-day CO2
Present-day sulfate
Combined CO2 and sulfate
Observed climate statistics
Global average
Preindustrial
Present-day CO2
Present-day sulfate
Combined CO2 and sulfate
Observed climate statistics
AF
(W m'2)


1.26
-1.60
-0.34



1.25
-0.30
0.95



1.26
-0.95
0.31

(°C)

12.5
14.5
11.3
13.0
14.9

12.5
14.8
11.7
13.6
13.5

12.5
14.6
11.5
13.3
14.2
(Ac)


1.9
-1.2
0.5



2.3
-0.8
1.1



2.1
-1.0
0.8

P
(mm d'1)

3.40
3.48
3.36
3.43
2.6

3.54
3.61
3.48
3.56
2.7

3.47
3.55
3.42
3.49
2.7
AP
(mm d'1)


0.09
-0.04
0.03



0.08
-0.06
0.02



0.08
-0.05
0.02

C

56.6
55.0
56.9
55.8
58.9

62.4
61.1
63.1
62.1
65.6

59.5
58.0
60.0
58.9
62.2
AC


-1.7
0.3
-0.9



-1.3
0.7
-0.3



-1.5
0.5
-0.6

SI

4.87
4.13
5.54
4.85
4.4

6.64
4.39
7.24
5.40
4.5

5.76
4.26
6.39
5.13
4.5
ASI


-0.74
0.67
-0.02



-2.26
0.59
-1.24



-1.50
0.63
-0.63

     AF = radiative forcing; Ts = surface temperature; P = precipitation; C = cloud cover; SI = sea ice coverage.




     Source:  Taylor and Penner (1994).

-------
in the Northern Hemisphere. On a regional scale, Taylor and Penner (1994) found that the
strongest response was in the polar regions associated with an increase in sea ice. Note that the
change in sea ice coverage, (AST), in the northern hemisphere is essentially zero as the sulfate
completely cancels the CO2 effect. Also, the greatest cooling is found over broad regions of the
Northern Hemisphere continents where all the sulfur emission is occurring.  However, the
maximum cooling is not over Europe where the maximum radiative forcing occurs, but further
north, and associated with changes in sea ice.

Comparative Lifetimes of the Forcing
               One extremely important aspect in comparing the effects of CO2 and sulfur
emissions is the disparate lifetimes of the forcing mechanisms. The residence times of trace
gases that result in a positive longwave forcing of the climate system is from decades to a
century or more (Houghton et al., 1990).  On the other hand, the cycling time for sulfate in the
troposphere is only about a week (Langner and Rodhe, 1991), which is dependent on the
frequency of precipitation removal (Charlson  et al., 1992). Therefore, any changes in industrial
emission patterns  will  be reflected immediately in the sulfate forcing, but the concentration of
CO2 and the accompanying forcing will continue to rise for more than a century even  if
emissions were kept constant at present levels.  See Figure 8-23.
               One could infer from the above discussion that sulfate emissions are providing
some amelioration of greenhouse warming, and that a curtailment of such emissions might result
in enhanced global warming. However, given the uncertainties in present estimates of the
effects of aerosols, especially the fact that many feedbacks are not fully included, it would be
premature to base any  decisions on these current discussions of the possible effects of aerosols
on climate.

8.8.5    Aerosol Effects on Clouds and Precipitation
8.8.5.1   Indirect Solar Radiative Forcing
Cloud Microphysical Properties
               A substantial portion of the solar energy reflected back to space by the earth
system is due to clouds.  The albedo (i.e., reflectivity) of clouds, in turn, depends to a large
extent on the optical thickness,  which is the column integrated light-extinction coefficient  (see
                                         8-112

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                   o
                   10
                   3
                   .Q
                   E
                   o
                   o
                   in
                   a
                   o
          Growth phase
Levelling-off
  phase
Reduction phase
                                          Time
Figure 8-23.
                                          Time
Schematic illustration of the difference between response times of climate forcing due to CO2
(heating) and sulfate (cooling) during different patterns of global fossil fuel consumption.
Source: Charlson et al. (1991)


Section 8.8.3). The light-extinction coefficient is related to the size distribution and number
concentration of cloud droplets.  Because these cloud droplets nucleate on aerosols, it is to be
expected that changes in aerosol loading could affect cloud albedo, particularly that marine
stratiform clouds.  Because of their effect on the Earth's radiative energy budget, marine status
and stratocumulus cloud systems are likely to influence climate and climate change.  Their high
albedo compared with ocean background provide a large negative shortwave forcing which is
not compensated in thermal wavelengths because of their low altitude (Randall et al.,  1984).
Recent studies by Ramanathan et al. (1995) and Cess et al. (1995) indicate that more solar
radiation is being absorbed by clouds in cloudy atmospheres than originally believed. This
finding has, however, not been confirmed.
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     Stephens (1994) gave the volume light-extinction coefficient of a cloud of spherical
polydispersed drops ranging in size as:
Jext
                  = n     n(r)Qext  (r)r2dr                                     (8-44)
where n(r) represents the size distribution and is the number concentration per unit volume per
unit radius increment and Qext is the extinction efficiency factor (see Section 8.3.1) which
approaches the value of 2.0 for drops that are large relative to the wavelength.  At visible
wavelengths, this limit for the extinction efficiency factor is satisfied by cloud drops that are
typically 10 //m in radius.  Therefore,
    a
      ext
                             n(r)r2dr.                                          (8-45)
The mass concentration of water in clouds, called the liquid water content, M (in kg"3), is
proportional to the total volume of liquid water in a unit volume of air. This may be written as
                        r
                         max
                   M-  f  n(r)r3dr                                           (8-46)
because the volume of each cloud drop is (4/3) TT r3.  Comparing Equations 8-45 and 8-46, one
can see that
                       oext <* M/re                                               (8-47)

where r is the effective radius, defined as the ratio
                                         8-114

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                        r
                         max
                         /  n(r)r3dr
                  re =  7^	•                                          (8-48)
                         max
                         /  n(r)r 2dr
                        r •
                         mi n

For identical meteorological conditions, the liquid water content will be the same in two cloud
layers that are composed of droplets of different effective radius. If other paramaters remain the
same, the light-extinction coefficient will increase as the effective radius decreases (Equation 8-
47).  Therefore, if the geometric depth of two cloud layers is the same and the column amount of
liquid water is the same, the cloud with more numerous, but smaller drops, will have a larger
optical depth  and a higher albedo.  This sets the stage for a potentially important indirect effect
of anthropogenic aerosols on the Earth's radiation balance. As suggested by Twomey (1974),
the addition of cloud nuclei by pollution can lead to an increase in the solar radiation reflected
by clouds, a negative radiative forcing that is in addition to the direct radiative forcing discussed
in Section 8.8.3.
     Another radiative consequence of pollution is the emission of elemental carbon, which can
be incorporated into clouds and increase the absorptance at visible wavelengths at which pure
water is nonabsorbing.  This mechanism decreases the single scattering albedo of the cloud
material (see Figure 8-20), causing a decrease in the reflectance of the layer.  There are,
therefore, two competing mechanisms, but Twomey et al. (1984) assessed the relative
magnitudes of the two effects based on observations of clean and polluted air in Arizona, and
concluded that increases in albedo from increases in cloud droplet concentration would dominate
over the absorption effect.

Cloud Lifetimes
     Another possible indirect effect of aerosols on clouds and precipitation is that of increased
cloud condensation nuclei (CCN), the inhibition of precipitation (Albrecht, 1989;  Twomey,
1991). Cloud condensation nuclei can be either hygroscopic or deliquescent, having large light
scattering efficiency due to hygroscopic growth. With more droplets, coagulative growth, which
is the mechanism of water removal in liquid water clouds, will be hindered.  This will  result in
                                          8-115

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longer residence times for clouds and a higher mean albedo time, which, again, is indirect
negative solar radiative forcing.
     There is some observational evidence that cloud amounts have increased during the recent
decades. Henderson-Sellers (1986, 1989) has analyzed surface based meterological observations
from several stations in the United States and Canada. There is coherent increase in cloud
amount in all seasons between 1900 and 1982 with most of the increase occuring between 1930
and 1950. Attribution of this increase to anthropogenic causes is very difficult.  The possibility
of jet contrails playing a role has been mentioned by Changnon (1981) but this would not
explain the increase in the 1930-1950 time frame. Warren et al. (1988) have also noted a
positive trend in the total cloud amount and also for all classes of clouds globally over the
oceans. An increase in aerosol concentration is compatible with an increase in cloud lifetimes
for low level  clouds so there is a plausible link between these observations and anthropogenic
activities but nothing definitive can be said at the moment.

Cloud Chemistry
     Novakov and Penner (1993) pointed out that anthropogenic activity could modify the
nucleating properties of anthropogenic sulfate. It has already been mentioned that carbon black
influences the direct radiative forcing. The presence of carbon black and other organics can also
alter the hygroscopic properties of sulfate aerosols. For instance, the condensation of
hydrophobic organics onto preexisting sulfate particles may render these inactive as CCN. On
the other hand, the condensation of sulfuric acid vapor on a hydrophobic organic aerosol may
convert it to a hydrophilic particle.  Because the indirect radiative forcing depends on the ability
of sulfate to nucleate, organics may enhance or diminish the potential indirect radiative forcing.

8.8.5.2  Observational Evidence
     The relationship between the availability of CCN and cloud droplet size distribution has
been a subject of research in cloud physics for decades.  It has been known, for instance, that
continental clouds are composed of far more numerous, but smaller drops than maritime clouds
(Wallace and Hobbs, 1977). The more difficult question is whether the additional
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contribution to CCN by anthropogenic activities has increased the reflectance of clouds over
large areas of the Earth. If so, this would be an additional indirect radiative forcing attributable
to sulfate emissions.
     The most dramatic evidence of such an indirect effect (albeit on a small scale) is the
observation of "ship tracks" in marine stratocumulus (Conover, 1966; Coakley et al., 1987).
These are visible in satellite images as white lines against a gray background and follow the path
of ships that have been emitting effluents.  King et al. (1993) reported the first radiation and
microphysics measurements on ship tracks obtained from a research aircraft as it flew within
marine stratocumulus clouds off California. Comparing the flight track with satellite images,
they were able to locate two distinct ship tracks in which they measured enhanced droplet
concentration, and liquid water contents, greater than in the surrounding clouds.  They also
derived the effective radius of the cloud drops and found that there was a significant decrease
within the ship tracks.  The radiation measurements were consistent with increased optical
depths in the ship tracks.  The increased liquid water content is compatible with the suppression
of drizzle as a result of slower coagulative growth (Albrecht,  1989), an indirect aerosol effect.
     Twomey (1991) estimated that the visible reflectance of clouds, R, is affected by cloud
droplet concentration, N, according to the following relationship for a fixed liquid water content,
M
                      dR)      R(l-R)
                            ~-                                                      (8-42)
The parameter, dR/dN, the susceptibility, is a measure of the sensitivity of cloud reflectance to
changes in microphysics (Platnick and Twomey, 1994). It has a maximum value atR = 0.5 and
is inversely proportional to the cloud droplet concentration such that when the cloud droplet
concentration is low as in marine clouds, the susceptibility is high. It is, therefore, not surprising
that emissions from ships can influence cloud albedo.
     To determine whether the indirect effect of aerosols on clouds is detectable on a global
scale, Schwartz (1988) compared cloud albedos in the two hemispheres and also historic changes
in surface temperature from preindustrial times. The sulfate signal is expected in
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both:  cloud albedos in the Northern Hemisphere should be higher, and the rate of greenhouse
warming should be slower. The results of his study were inconclusive in that no inter-
hemispheric differences were found. However, more recent studies suggest some influence of
sulfate emissions.
     Falkowski et al. (1992) showed that cloud albedos in the central North Atlantic Ocean, far
from continental emission sources, were well correlated with chlorophyll in surface waters.
These correspond to higher ocean productivity and DMS emissions, indicating that natural
sources of sulfate emission can influence cloud albedo.  More substantial evidence of the effect
of sulfate aerosol has been presented by Han et al. (1994) who made a near-global survey of the
effective droplet radii in liquid water clouds by inverting satellite visible radiances obtained
from advanced very-high-resolution radiometer (AVHRR) measurements. Han et al. (1994)
found systematic differences between the effective radius of continental clouds (global mean
effective radius = 8.5 //m) and maritime clouds (global mean effective radius =11.8 //m), which
is the expected result based on differences in CCN concentrations. In addition, they found
inter-hemispheric differences in the effective radius over both land and ocean. Northern
Hemisphere clouds had smaller effective radii, the difference being 0.4 //m for ocean and
0.8 //m for land. However, Southern Hemisphere clouds tended to be optically thicker, which
explains why Schwartz (1988) was unable to detect inter-hemispheric albedo differences.

8.8.5.3   Modeling Indirect Aerosol Forcing
     If the appropriate radiative properties of aerosols are known, it is fairly straightforward to
model the direct solar radiative forcing of aerosols (Section 8.8.3) and estimate possible climatic
responses (Section 8.8.4).  Calculations of the indirect forcing of aerosols, on the other hand, is
much more difficult since several steps are involved and the uncertainty at each level is high.
Charlson et al. (1992) proposed that enhancements in albedo would occur only for marine
stratocumulus clouds and for a uniform global increase of droplet concentration of 15% in only
these clouds, the global mean solar radiative forcing would be -1.0 W m"2, which is comparable
to  the direct forcing (Section 8.8.4) and of the same sign. The greatest uncertainty in this
estimate is the degree that cloud droplet number concentration is enhanced by increasing
emissions.  The uncertainty has been estimated by Kaufman et al.
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(1991) to be at least a factor of 2. Leaitch and Isaac (1994) have addressed this issue based on
their observations of the relationship between cloud droplet concentrations and cloud water
sulfate concentrations.  They find that the assumptions in Kaufman et al. (1991) are within
reasonable bounds. The Scientific Steering Committee for the International Global Aerosol
Program concluded that the uncertainties involved in determining the indirect effects of aerosols
on the Earth's radiation balance are so great that no formal value can be given at this time
(Hobbs, 1994).
     The indirect forcing has been included in climate model simulations by Kaufman and Chou
(1993) who used a zonally averaged multilayer energy balance model and by Jones et al. (1994)
who used a GCM.  Kaufman and Chou (1993) modeled the competing effects of enhanced
anthropogenic emissions of CO2 and SO2 since preindustrial times. They concluded that SO2 has
the potential of offsetting CO2-induced warming by 60% for present conditions and 25% by the
year 2060 given the Intergovernmental Panel on Climate Change BAU (business as usual)
scenario of industrial growth (Intergovernmental Panel on Climate Change, 1994). They also
found a small inter-hemispheric difference in climate response, with the Northern Hemisphere
cooler than Southern Hemisphere by about -0.2 °C.
     Jones et al. (1994) used a GCM with a prognostic cloud scheme and a parameterization of
the effective radius of cloud water droplets that links effective radius to cloud type, aerosol
concentration and liquid water content. The parameterization is based on extensive aircraft
measurements. The distribution of column sulfate mass loading was obtained from the model of
Langner and Rodhe (1991) separately  for natural and anthropogenic sources. Simulated
effective radius distributions of low-level clouds showed land-ocean contrasts and also inter-
hemispheric differences as observed by Han et al. (1994).  The indirect forcing due to
anthropogenic sulfate was estimated by performing a series of single-timestep calculations with
the GCM. For present conditions, the mean northern hemisphere forcing was calculated to be
-1.54 W m"2 and the southern hemisphere forcing was -0.97 W m"2. This is comparable to the
estimates of Charlson et al. (1992) and Kaufman and Chou (1993) and substantially larger than
the direct forcing estimates of Kiehl and Briegleb (1993).  The combined direct and indirect
forcing is more than half the total positive forcing of greenhouse gas emissions. It should be
noted that the indirect effect is greatest when the atmosphere is very clean and so, in principle,
could saturate with time.  The direct effect is
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linear with emissions and may dominate in the future. In any case, the negative forcing of
sulfate aerosols must be considered in any overall estimate of the total anthropogenic effect on
climate.
8.9  SUMMARY
8.9.1  Visibility Effects

     This chapter presents (1) an overview of the effects of particulate matter on visibility, and
combines information from this chapter and other recent reviews by the National Research
Council (NRC), the National Acid Precipitation Assessment Program (NAPAP), and
Environmental Protection Agency (U.S. EPA) and (2) a discussion on the effects of particulate
matter on climate.
     Several definitions of visibility have been noted in this chapter,  and they are generally
consistent with each other. Section 169A of the 1977 Clean air Act Amendments (42 U.S.C.
7491) and the U.S. EPA 1979 Report to Congress defined visibility impairment as a reduction in
visual range and atmospheric discoloration. The National Research Council's Committee on
Haze in National and Wilderness Areas said, "Visibility is the degree to which the atmosphere is
transparent to visible light."  These definitions indicate that visibility  is determined by the clarity
(or transparency)  and color fidelity of the atmosphere.  Visibility can be numerically quantified
by equating it with the contrast transmittance of the atmosphere.  This quantification is
consistent with both (1) the use of visual range to quantify visibility, and (2) the definition
recommended by  the NRC.
     All evaluations of visibility have focused on daytime visibility as perceived by  a human
observer looking through one or more  sight paths in the Earth's atmosphere.  Weber's Law
indicates that if an object is just perceptible, the brightness of the object differs from the
brightness of its surroundings by a constant fraction, i.e.,  a constant percentage of the
surrounding brightness.  A perception threshold of 2% brightness change is most commonly
used, but 5% is sometimes used in visibility analyses. Either contrast or modulation  can be used
to quantify changes in brightness.  Weber's law is not exact, so perception thresholds depend on
the viewing conditions.  The eye is the most sensitive to objects that subtend an angle of
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approximately 1/3 degree, is somewhat less sensitive to objects that subtend larger angles, and
becomes rapidly less sensitive as the size of the object is decreased below a subtended angle of
0.1 degree. Many factors, such as the brightness level and the pattern of brightness surrounding
the object being viewed can affect the perception threshold. The contrast threshold of 2%
generally applies to objects that subtend an angle between 0.1  and 1.0 degree and are viewed
against uniform backgrounds.
     The atmosphere is a very thin layer on the Earth and has strong vertical gradients. Because
of these gradients and the curvature of the Earth, the properties of the atmosphere exhibit
substantial variations in sight paths longer than roughly 100 km. The visual range is the greatest
distance at which a dark target can be perceived against the horizonal sky. Because of the non-
uniformities in the atmosphere, the visual range provides a meaningful characterization of the
Earth's atmosphere  only for haze levels that cause the visual range to be much less than 100 km.
     A sight path through the atmosphere is illuminated by direct sunlight, diffused skylight,
and light reflected by the Earth's surface. An observer looking through the atmosphere sees
light from two sources: (1) the light reflected from the object or terrain feature being viewed that
is transmitted through the sight path to the observer, and (2) the light scattered by the
atmosphere into the line of sight and then transmitted to the observer. These are known as the
transmitted radiance and the path radiance (air light), respectively.
     Visibility is determined by the competition between the transmitted radiance and the path
radiance.  The transmitted radiance carries all of the information about the nature of the object
being viewed. When this radiance is dominant, the features of the object can be easily perceived
and the visibility is good.  The path radiance contains information only about the uniformity of
the intervening atmosphere, and no information about the object being viewed.  When the path
radiance is dominant, it tends to obscure the object.  These effects are easily seen by viewing
objects at various distances in a dense fog, but can also be seen on a clear day if sight paths of
sufficient length are available.
     The transmitted radiance is attenuated by light extinction. The strength of that attenuation
is quantified by the light-extinction coefficient, which describes the rate of energy loss with
distance from a beam of light. The light-extinction coefficient for green light in particle-free air
(Raleigh scattering) is 1% per km, or 0.01 km"1. Extinction coefficients are
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most often measured in units of inverse megameters (Mn"1), and in these units the extinction
coefficient for clean air is 10 Mn"1.
     Light extinction is caused by light scattering and light absorption by particles and gases.
In visibility analyses it is useful to consider each of these separate contributions to the light-
extinction coefficient; the coefficients for light absorption by gases (oag), light scattering by
gases (osg), light absorption by particles (oap), and light scattering by particles (osp). Because of
their different origins and composition, atmospheric particles are frequently divided into coarse
and fine particles.  The  corresponding division of coefficients for light scattering and absorption
then becomes, the coefficient for light-scattering and light-absorption by fine particles (osfpand
o^p) and the coefficient for light scattering and light-absorption by coarse particles (oscp and oacp).
The components of the  light-extinction coefficient are related as follows:
            °~ext = °abS + °~Scat
            °ab=
            °~Scat =
            °Sp = °Sfp + ascp

            °ap = °~afp + aacp
Light scattering by gases (Raleigh Scattering) is nearly constant, but decreases with increasing
altitude.  Light absorption by gases is almost entirely due to NO2, and is typically significant
only near NO2 sources, e.g., in or downwind of urban areas or in plumes.  Light absorption by
particles is principally caused by elemental carbon. Light scattering by particles is typically the
most important component of light extinction in causing visibility degradation. Further
discussion of this component of light extinction appears below.
     If the average light-extinction coefficient and path length are known, the light
transmittance of a sight path can be calculated. Thus, the effect of light extinction on the
transmitted radiance is easily quantified.
     The calculation of the path radiance is much more difficult.  It requires a knowledge if (1)
the illumination of the sight path at each point along its length, (2) the light scattering properties
of the atmosphere at each point, and (3) the transmittance of the atmosphere
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between each point and the observer.  The illumination is affected by the clouds in the sky, the
haze that contributes to diffuse skylight, and the variations of the reflectance of the Earth's
surface under the sight path. Light scattering and light absorption contribute differently, because
light absorption does not contribute to the scattering of light into the sight path. Thus, a given
amount of light extinction due to light absorption causes less visibility impairment than the same
amount of light extinction due to light scattering.  Because of the differing effects of scattering
and absorption and the highly variable effects of the illumination, the path radiance is not closely
linked to light extinction.  As a result, the visibility for a specific sight path under specific
illumination conditions is not closely linked to the light-extinction coefficient.
     All of these effects can be mathematically simulated, and a simple theory for these
simulations is present in the text.  The theoretical  development includes the equations used to
generated photographs showing the visual effects with various amounts of haze. For simple
situations, e.g., a cloud-free sky and uniform haze, photographic simulation are quite realistic.
Examples appear in the National Acid Precipitation Assessment Program study. These
photographs, and other comparisons, indicated that the relationship between air pollution and
visibility is well understood.
     As previously stated, the most important component of light extinction in causing visibility
degradation is typically light scattering by particles. Except in dust storms or during fog, snow,
or rain, most light scattering by particles is caused by  fine particles, i.e. the accumulation mode,
-0.3 to 1.0 //m diameter.  Coarse particles typically have a light-scattering efficiency 5 to 10
times less that the  efficiency of fine particles. Coarse  particles can have important visibility
effects in dusty or desert areas, but fine particles dominate the visibility effects in most of the
eastern United States.
     The light-scattering efficiency of particles is a maximum for particles with a diameter
approximately equal to the wavelength of visible light. For a single particle, the maximum in
light-scattering efficiency occurs at a diameter approximately equal to

                  D = 0.28/(n-l)//m
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where n is the index of refraction of the particulate matter. This formula gives a diameter of
0.85 /u,m for an index of refraction of 1.33 (e.g. water) and a diameter of 0.56 //m for an index of
refraction of 1.5, which is larger than typical for ambient aerosol mixtures. Most fine particles
have smaller diameters. Therefore, processes that increase the particle size of fine particles tend
to increase the light-scattering efficiency of the particles.
     Coagulation of nuclei particles, which can be smaller that 0.1 //m in diameter, in the
atmosphere will increase their light-scattering efficiency. Particles in the 0.2 to 0.3 //m in
diameter range are small enough that their light-scattering efficiency is roughly half that of
particles with the optimum  size.  Particles in this range coagulate very slowly, so they tend to
maintain their size in the atmosphere as long as they are not processed by clouds or fog.
Heterogenous processes in clouds and fogs can form particles in any size range, but these
processes are the dominant source of particles with a diameter near 0.7 //m, which is near the
optimum size for light scattering. Particles in this size range are frequently observed in air
samples processed by clouds or fog.
     The dominant chemical components of fine parti culate matter are sulfates, organic species,
nitrates, crustal species, and elemental carbon.  Sulfates and organic species dominate visibility
impairment in the eastern United States, and nitrates and organic species are dominant in many
western urban areas as well as the California Central Valley during winter months. Crustal
species are important contributors in dry areas, especially when these areas are farmed.
Elemental carbon is most important in urban areas, and in Phoenix, AZ can contribute about
one-third of the light extinction during some episodes.
     Water uptake, which occurs when hygroscopic aerosol is exposed to elevated humidities,
increase light scattering by two mechanisms: (1) the mass concentration of parti culate matter is
increased, and (2) the increase particle size causes the light scattering efficiency to increase.
Thus, the materials present before the water uptake makes a larger contribution to light
scattering because they are now a component of larger particles. The overall effect on increasing
humidity on light scattering by particles was quantified nearly 20 years ago, but current research
is greatly increasing the detailed understanding of the response of aerosol particles to changing
humidities and the relationship of this response to the chemical composition of the particles.
Humidity effects generally become important at relative humidities between 60 and 70%, and
increase the light scattering by a factor of 2  at
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approximately 85% relative humidity.  The light scattering increase rapidly with relative
humidity when the humidity exceeds 90%.
     Potential indicators for a visibility and air quality include: (a) fine particle mass and
composition, or only fine particle mass; (b) light scattering by dried ambient particles; (c) light
scattering by particles under ambient conditions; (d) light extinction calculated from separate
measurements of dry scattering and absorption or ambient scattering and absorption; (e) light
extinction measured directly; and (f) contrast transmittance of a sight path.
     The selection of an indicator should consider such factors as (1) the linkage between the
indicator and visibility, (2) the cost and feasibility of monitoring the indicator to determine both
compliance with the standard and progress toward achieving the standard, (3)  the nature and
severity of the interferences inherent in the available monitoring methods, (4)  the relationship
between the visibility indicator and indicators for other air quality standards, and (5) the
usefulness of monitoring data in analyses which have the purpose of determining the optimum
control measures to achieve the standard.
     In general there is an inverse relationship between an indicator's ability to characterize air
quality and its ability to characterize visibility.
     There is general agreement in the technical community that contrast transmittance would
not be a suitable indicator for regulatory purposes.  It is affected by too many  factors other than
air quality, such as cloud shadows, precipitation, fog, etc. Therefore, only the other indicators
merit consideration.
     Visibility has value to individual  economic agents primarily through its impact upon the
activities of consumers. Most economic studies of the effects of air pollution  on visibility have
focused on the aesthetic effects to the individual, which are, at this  time, believed to be the most
significant economic impacts of visibility degradation caused by air pollution  in the United
States. It is well established that people notice those changes in visibility conditions that are
significant enough to be perceptible to the human observer, and that visibility  conditions  affect
the well-being of individuals.
     One way of defining the impact of visibility degradation on the consumer is to determine
the maximum amount the individual would be willing to pay to obtain improvements in
visibility or prevent visibility degradation. Two economic valuation techniques have been used
to estimate willingness to pay for changes in visibility: (1) the
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contingent valuation method, and (2) the hedonic property value method.  Both methods have
important limitations, and uncertainties exist in the available results. Recognizing these
uncertainties is important, but the body of evidence as a whole suggests that economic values for
changes in visibility conditions are probably substantial in some cases, and that a sense of the
likely magnitude of these values can be derived from available results in some instances.
Economic studies have estimated values for two types of visibility effects potentially related to
particulate air pollution: (1) use and non-use values for preventing the types of plumes caused
by power plant emissions, visible from recreation areas in the southwestern United States; and
(2) use values of local residents for reducing or preventing increases in urban hazes in several
different locations.

8.9.2  Climate Change
     Aerosols of submicron size in the Earth's atmosphere perturb the radiation field. There is
no doubt that anthropogenic aerosol emissions, primarily sulfur oxides, have the potential to
affect climate; the question is by how much. There are two chief avenues through which
aerosols impact the radiation budget of the Earth. The direct effect is that of enhanced solar
reflection by the cloud-free atmosphere. Since aerosols, even those containing some absorptive
component,  are primarily reflective, their impact is felt as a negative radiative forcing (i.e., a
cooling) on the climate system. Although there is some uncertainty in the global distribution of
such aerosols and in the chemical and radiative properties of the aerosols, the radiative effects
can still be modeled within certain bounds.  Estimates of this forcing range from -0.3 W m"2 to
about twice that value for current conditions over pre-industrial times.
     The indirect forcing results from the way in which aerosols affect cloud microphysical
properties. The most important is the effective radius of cloud droplets, which decrease in the
presence of higher concentrations of Cloud Condensation Nuclei (CNN) since more nucleating
sites are available for droplets to form.  This effect is most pronounced when the concentration,
N, is very low, and clouds are moderately reflective.  Other effects are the enhancement of cloud
lifetimes and also changes in the nucleating ability of CCN through chemical changes. Although
estimates of the indirect effect are uncertain by at least a factor of 2, but perhaps much more, it
appears to be potentially more important than the direct
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effect. Taken together, on a global mean basis, anthropogenic emissions of aerosols could have
offset substantially the positive radiative forcing due to greenhouse gas emissions. High priority
should be given to acquiring the measurements needed to quantifying these effects with greater
accuracy.
     The one crucial difference between aerosol forcing and greenhouse (gas) forcing is the
atmospheric lifetime of aerosols and gases and hence, forcing. The aerosol forcing is fairly
localized, whereas the greenhouse forcing is global.  One should, therefore, expect
inter-hemispheric differences in the forcing and perhaps climate response.  However, climate
models are not currently at the level of sophistication needed to determine  climate response
unambiguously.  With few exceptions, global observations of surface temperature can not
separate natural and anthropogenic causal mechanisms.
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                     9.  EFFECTS ON MATERIALS
     The deposition of airborne particles on the surface of building materials and culturally
important articles (e.g., statuary) can cause damage and soiling, thus reducing the life usefulness
and aesthetic appeal of such structures (National Research Council, 1979; Baedecker et al.,
1991).  Furthermore, the presence of particles on surfaces may also exacerbate the physical and
chemical degradation of materials that normally occur when these materials are exposed to
environmental factors such as wind, sun, temperature fluctuations, and moisture. Beyond these
effects, particles, whether suspended in the atmosphere, or already deposited on a surface,  also
adsorb or absorb acidic gases from other pollutants like sulfur dioxide (SO2) and nitrogen
dioxide (NO2), thus serving as nucleation sites for these gases. The deposition of "acidified"
particles on a susceptible material surface is capable of accelerating chemical degradation  of the
material.  Therefore, concerns about effects of particles on materials are relate both to impacts
on aesthetic appeal and physical damage to material surfaces, both of which may have serious
economic consequences. Insufficient data are available regarding perception thresholds with
respect to pollutant concentration, particle size, and chemical composition to determine the
relative roles these factors play in contributing to materials damage.
     This chapter briefly discusses the effects of particle exposure on the aesthetic appeal  and
physical damage to different types of building materials.  This chapter also discusses the effects
of dry deposition of acid forming gases on economically  important materials.  For more detailed
discussion of the effects of acid gases on materials, see the 1991 National Acid Precipitation
Assessment Program report (Baedecker et al., 1991).
9.1   CORROSION AND EROSION
9.1.1    Factors Affecting Metal Corrosion
     The mechanisms controlling atmospheric corrosion of metals have been thoroughly
discussed in the National Acid Precipitation Assessment Program (Baedecker et al., 1991).  In
summary, metals undergo corrosion in the absence of pollutant exposure through a series of
physical, chemical, and biological interactions involving moisture, temperature, oxygen, and
                                          9-1

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various types of biological agents.  In addition to these environmental factors, atmospheric
pollutant exposure may accelerate the corrosion process. Pollutant-induced corrosion arises
from complex interactions of the pollutant with the metal surface and the metal corrosion film.
In the absence of moisture, there would be limited pollutant-induced or nonpollutant-induced
corrosion.
     The atmospheric corrosion of most metals is a diffusion-controlled electrochemical
process.  For an electrochemical reaction to take place, there must exist an electromotive force
between points on the metal surface; a mechanism for charge transfer between the electronic
conductors; and a conduction path between the cathode and anode reaction centers (Haynie,
1980). The rate of corrosion is still, however, dependent upon the deposition rate and nature of
the pollutant (discussed in Chapter 3 of this document); the variability in the electrochemical
reactions; the influence of the metal protective corrosion film; the effects of the pollutant
coupled with the amount of moisture present (time-of-wetness; relative humidity) (Zhang et al.,
1993; Pitchford and McMurry,  1994; Li et al., 1993); the presence and concentration of other
surface electrolytes; and the orientation of the metal surface.
     The principal form of atmospheric metal corrosion is the uniform corrosion of the metal
surface.  Other forms of corrosion include pitting, grain-boundary corrosion, and stress-
corrosion cracking.

9.1.1.1 Moisture
     The formation of a moisture layer (condensation) on the metal surface is dependent upon
precipitation in the form of rain, fog, mist, thawing snow and sleet, and dew.  The moisture layer
provides a medium for conductive paths for electrochemical reactions and a medium for water
soluble air pollutants.
     A moisture layer may also form as the result of the reaction of adsorbed water with the
metal surface or protective corrosion film, deposited particles and salts from the reaction of the
metal surface, and deposited particles with reactive gases.  Of particular importance is the
production of hydrated corrosion products that increase the absorption rate of moisture.  The
presence of these hygroscopic salts can drastically decrease the critical relative humidity,
resulting in large amounts of moisture on the metal surface.
                                           9-2

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     When the temperature of a metal is below the ambient dew point, water condenses on the
metal surface.  Whether or not the metal reaches the temperature at which condensation occurs
varies with heat transfer between ground and metal and between air and metal. Condensation
occurs when the relative humidity adjacent to the surface exceeds a value in equilibrium with the
vapor pressure of a saturated solution of whatever salts are on the surface. The solution may
contain corrosion products, other hygroscopic contaminants, or both.  Temperature, wind,
sunshine, and night sky cover then become factors in establishing corrosion rates, since they
determine whether there will be sufficient dew condensation.
     The first evidence of ambient relative humidity-dependent atmospheric corrosion was
demonstrated by Vernon (1931, 1935). Vernon showed a dramatic increase in weight gain in
magnesium and iron samples when the relative humidity exceeded certain values (critical
relative humidities) in the presence of SO2. More recently, researchers have shown particle size
related effects based on relative humidity (Pitchford and McMurry, 1994).  A more detailed
discussion on the water content of atmospheric aerosols and its dependence on relative humidity
appears in Chapter 3 of this document.
     According to Schwartz (1972), the corrosion rate of a metal could increase by 20% for
each increase of 1% in the relative humidity  above the critical relative humidity value.  It is
evident that relative humidity has a considerable influence on the corrosion rate, as established in
laboratory trials by Haynie and Upham (1974) and Sydberger and Ericsson (1977). Although
these experimental results do not support the exact rate predicted by Schwartz (1972), they do
indicate that the corrosion rate of steel increases with increasing relative humidity.
     Since average relative humidity is calculated from the relative humidity distribution, an
empirical relationship exists between average relative humidity and the fraction of time some
"critical humidity value " (minimum concentration of water vapor required for corrosion to
proceed) is exceeded, assuming a relatively constant standard deviation of relative humidity
(Mansfeld and Kenkel, 1976;  Sereda, 1974). The fraction of time that the surface is wet must be
zero when the average relative humidity is zero and unity when the average relative humidity is
100%. According to Haynie (1980), the following equation is the simplest single-constant first-
order curve that can be fitted to observed data:

-------
                 f = (1 - k)/(100 - k)RH
(9-1)
where
      f = fraction of time relative humidity exceeds the critical value,
      RH = average relative humidity, and
      k = an empirical constant less than unity.
      Haynie (1980) analyzed and fitted, by the least-squares method, ten quarter-year periods of
relative humidity data from St. Louis International Airport to this equation. The fraction of time
the relative humidity exceeded 90% gave a value of 0.86 for k.  This fraction and the data points
are plotted in Figure 9-1.
                      1.0
                      0.9
                      0.8
                   |  0-7
                   £
                   3  0.6
                   o>
                   E
                   K  0.5
                   i^
                   o
                   o  0.4
                   o
                   £  0.3
                      0.2
                      0.1
                            10   20  30  40   50   60  70   80   90   100
                                 Average Relative Humidity, percent
Figure 9-1.  Empirical relationship between average relative humidity and fraction of time
             when a zinc sheet specimen is wet.
Source: Haynie (1980).
Time-of-Wetness Sensors
     Time-of-wetness sensors, sensors that detect moisture using an electrochemical cell, have
been developed to better determine critical relative humidities. The first of these
                                            9-4

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sensors, developed by Sereda (1958) and Tomashov (1966), measured voltage and current
changes across galvanic cells.  More recently, Mansfeld and Vijaykumar (1988) reported a
technique that uses single metal electrodes for detection of moisture and measurement of the
corrosion rate.
     Haynie and Stiles (1992) evaluated the Mansfeld type Atmospheric Corrosion Rate
Monitor (ACRM) with 19 mo of exposure in an hourly monitored field  environment. Duplicate
sensors were exposed each at 30° and 90°  C.  The distribution of measured currents were
bimodal for all sensors with definite minimums at around a cell resistance of 1065 ohms between
wet and dry modes.  Thus, the  sensors can be used to measure time-of-wetness with good
reproducibility between sensors exposed at the same time in the same manner. An analysis of
variance of the results revealed statistically significant differences between exposure months and
angles but not between sensors. Also, there was a significant interaction between month and
exposure angle. From these results it was concluded that the sensors are sensitive enough to
detect changes with time that are not associated with the primary effects of surface temperature
or air moisture content. The magnitude of the dew point/surface temperature difference when a
surface becomes wet changes with time, possibly as corrosion products  and pollutant
concentrations change on the surface. Exposure angle affects time-of-wetness by changing the
surface temperature.  The surface temperature is related to the relative sun angle and the angle
with respect to the night sky. The angle affects radiant heat transfer. This effect was observed
as an interaction between seasonal change and exposure angle. Further  analysis of the
magnitude of the sensor responses when they were wet and comparing the results with weight
loss data and model predictions indicated that they were measuring cell  resistance rather than
polarization resistance (Haynie and Stiles,  1992).

9.1.1.2 Temperature
     Few recent studies were found on the effects of temperature on the corrosion process, and
earlier studies (Guttman and Sereda, 1968; Barton,  1976; Haynie et al.,  1976; Guttman, 1968;
Haynie and Upham,  1974; Harker et al., 1980) disagree on the role temperature plays in the rate
of corrosion.  How temperature affects the corrosion rate of metal was probably best explained
by Haynie (1980). He reported that the rate of metal corrosion is diffusion-
                                          9-5

-------
controlled, and that under normal temperature conditions, effects on the rate of corrosion would
likely not be observed. A decrease in temperature would raise the relative humidity but decrease
diffusivity. When the temperature reaches freezing, a decrease in the overall corrosion rate
occurs because diffusion has to take place through a solid (Haynie, 1980;  Biefer, 1981; Sereda,
1974). Available recent studies on the effects of temperature on metal corrosion are discussed
below in various subsections on pollutant-induced corrosion of various specific metals.

9.1.1.3  Formation of a Protective Film
     The rust layer on steel is somewhat protective against further corrosion, though far less so
than the corrosion layer  on zinc and copper. The content of soluble compounds in rust limits its
protection of steel. Rust samples analyzed by Chandler and Kilcullen (1968) and Stanners
(1970) contained 2 to 2.5% soluble SO;;" and 3 to  6% total SO;;". The outer rust layer contained a
small amount (0.04 to 0.2%) of soluble SO;;", compared with 2% in the inner rust layer.  The
concentration of insoluble SO;;" was fairly uniform throughout the rust layers.
     The composition of the rust layer has led to studies of the corrosion protective properties of
rust as a function of exposure pattern (Nriagu, 1978;  Sydberger, 1976). Steel samples initially
exposed to low concentrations of sulfur oxides (SOX) and then  moved to sites of higher SOX
concentrations corroded at a slower rate than did samples continuously exposed to the higher
concentrations. Exposure tests started in summer showed slower corrosion rates during the first
years of exposure than those started in winter.
     The long-term corrosion rate of steel appears to depend on changes in the composition and
structure of the rust layer. During the initiation period, which varies with the SO2 concentration
and other accelerating factors, the rate of corrosion increases with time (Barton, 1976).  Because
it is porous and non-adherent, the rust initially formed offers no protection and may accelerate
corrosion by retaining hygroscopic sulfates and chlorides, producing a micro-environment with a
high moisture content. This is consistent with the concept of sulfate nests discussed by Kucera
and Mattsson (1987).  After the initiation stage, the corrosion rate decreases as the protective
properties of the rust layer improve. Satake and Moroishi (1974) relate this slowing down to a
decrease in the porosity  of the rust layer.
                                           9-6

-------
During a third and final stage, corrosion attains a constant rate and the amount of SO^" in rust is
proportional to atmospheric SO2 concentrations.  The quantitative determination and subsequent
interpretation of corrosion rates becomes difficult if it is not known how long the metal has had
a surface layer of electrolyte.  Variations in the "wet states" occur with relative humidity,
temperature, rain, dew, fog, evaporation, wind, and surface orientation. Capillary condensation
in rust can be related to the minimum atmospheric moisture content that allows corrosion to
occur (i.e., critical relative humidity). Centers of capillary condensation of moisture on metals
can occur in cracks, on dust particles on the metal surface, and in the pores of the rust
(Tomashov, 1966).

9.1.2 Development of a Generic Dose-Response Function
     There are several factors that are important in the corrosion process. First, the rate of
corrosion is decreased in the absence of moisture (moisture layer). Secondly, the deposition rate
of a pollutant is more important in determining the rate of corrosion than  the pollutant
concentration. Lastly, the protective corrosion layer may be affected by either dry or wet
deposition.  A generic semi-theoretical model has been developed that takes into account these
factors (Edney et al., 1986; Haynie, 1988; Haynie et al., 1990; and Spence et al.,  1992). The
model is based on the relative rates of the competing processes of buildup and dissolution of
protective corrosion product films. It is a mathematical function that expresses the relationship
between corrosion and environmental factors.  The general form of the equation is:
                    C = btw+a/(Dc/dtw)                                            (9-2)

or a transcendental form:
               C = btw + a(l - exp[-Bc/a])/b                                       (9.3)

where C is the amount of corrosion, tw is time-of-wetness, a is a film diffusivity term, and b is a
film dissolution rate. The last two terms  are associated with the conditions of the environment
and the corrosion product film. For long-term exposures, the exponential term approaches zero
and the film reaches a steady state thickness.  The equation simplifies to the linear form:
                                          9-7

-------
                       C = btw + a/b.                                               (9.4)
It is in determining the magnitude of the term b that the effects of pollution on corrosion can be
analyzed.  More detailed discussion of a generic dose-response function comparing metal
corrosion in the absence of pollution and acidic dry deposition of acidic aerosols appears in
Baedecker et al. (1991).

9.1.3    Studies on Metals
9.1.3.1 Acid-Forming Aerosols
Ferrous Metals
     Ferrous metals include iron, steel, and steel alloys. Stainless steels, incorporating
chromium, molybdenum,  and nickel, are highly corrosion resistant because of the protective
properties of the oxide corrosion film; however, in more polluted areas, the oxide corrosion film
becomes less protective. Based  on early studies,  reported in the National Acid Precipitation
Assessment Program report (Baedecker et al., 1991), most steels are susceptible to corrosion
from pollutant exposure unless covered by an organic or metallic covering. The rate of
corrosion was related to the amount of SO2 in the atmosphere, showing increasing rates of
corrosion with increasing concentrations of SO2.  The rate of corrosion was also found to depend
on the deposition rate of SO2.
     A recent report by Butlin et al. (1992a) also demonstrated that the corrosion of mild steel
and galvanized steel was SO2-dependent.  These researchers monitored the corrosion of steel
samples by SO2 and ozone (O3) under artificially fumigated environmental conditions, and NO2
under natural conditions.  The natural meteorological conditions of the areas were unaltered.
Annual average SO2 concentrations ranged from  2.1 //g/m 3 in a rural area to 60 //g/m3 in one of
the SO2-fumigated locations. Annual average NO2 concentrations ranged from 1.5 //g/m3 in the
most rural area to 61.8 //g/m3 in the most polluted area.  They found that corrosion of the steel
samples was more dependent on the long-term SO2 concentration and was only minimumly
affected by nitrogen oxides (NOX).
                                           9-8

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Aluminum and Aluminum Alloys
     Aluminum is generally considered corrosion resistant, but when exposed to very high SO2
concentrations and relative humidities above 50%, aluminum will corrode rapidly, forming a
hydrated aluminum sulfate.  When aluminum is exposed to low concentrations of acid sulfate
particles, a protective aluminum oxide film is formed.
     Early evaluations of the effects of SO2 exposure on aluminum indicated that corrosion of
aluminum by SO2 was exposure-dependent and insignificant, based on loss of metal thickness
(Haynie, 1976; Fink et al.,  1971). However,  Haynie (1976) reported SO2 exposure-related loss
in bending strength in the aluminum samples.
     In a more recent study, Butlin et al. (1992a) reported that aluminum corrosion was
insignificant in SO2-spiked environments.  The aluminum samples were exposed under natural
environmental conditions (29 sites) for up to 2 years.  The corrosion was greater and often more
patchy on the underside of some of the metal samples.  The authors attributed the increased
corrosion on the underside  of some samples to the lack of pollutant washoff by rain and an
increased concentration of particulate matter (dust) in those test areas.
     Aluminum alloy 3003-H14 was exposed to various acid forming aerosols and particles as
part of the National Acid Precipitation Assessment Program (Baedecker et al., 1991).
Aluminum samples were exposed at 5 sites (Newcomb, NY, Chester, NJ, Washington, DC,
Steubenville, OH, and Research Triangle Park, NC). Corrosion after 60 mo of exposure, as
measured by weight loss, was more than three times greater at the industrial site (NJ) than at
rural sites.  Parti culate matter concentrations ranged from 14 //g/m3 in NY to 60 //g/m3 in OH
and DC.  The concentration ranges for other pollutants at the 5 sites appears in Table 9-1. Even
at the industrial site the corrosion rate was very low at a factor of about 10 less than for
Galvalume (aluminum-zinc). The exposure time and the average corrosion rate by site is listed
in Table 9-2.

Copper and Copper Alloys
     Graedel et al. (1987) studied the chemical composition of patinas exposed in the greater
New York area for from 1 to 100 years and compared the results  with estimated dry and wet
deposition of pollutants between 1886 and 1983.  They concluded that the long-term corrosion
of copper was not controlled by deposition of pollutants, but rather, it was more
                                          9-9

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   TABLE 9-1. ANNUAL AVERAGE AND MAXIMUM VALUES OF THE HOURLY
        AVERAGES FOR SULFUR DIOXIDE (SO2), NITROGEN OXIDE (NOX),
   AND OZONE (O3) AND ANNUAL AVERAGES OF THE MONTHLY AVERAGES
         OF RAIN pH AT THE FIVE MATERIAL EXPOSURE SITES, BASED
                        ON DATA ACQUIRED DURING 1986a
                                                                       Particulate
         SO7 (ppb)           NO7 (ppb)             O, (ppb)           Matter (//g/tn3)
Site
NC
DC
NJ
NY
OH
Avg.
2±4
12±9
6±7
2±3
15±17
Max.
45
91
87
29
450
Avg.
14±9
28±12
14±10
2±2
19±11
Max.
65
91
98
21
98
Avg.
25±21
17±16
30±20
30±14
19±17
Max.
99
99
114
99
94
Avg.
35
60
30
14
60
Avg.
4.33
4.10
4.16
4.28
3.90
aThe ± errors are estimates of one standard deviation on a single hourly average based on the dispersion of the
data.

Source: Baedecker et al. (1991).
      TABLE 9-2. AVERAGE CORROSION RATES FOR 3003-H14 ALUMINUM
    OBTAINED DURING THE NATIONAL ACID PRECIPITATION ASSESSMENT
                        PROGRAM BETWEEN 1982 AND 1987
Site
NC
DC
NJ
NY
OH
Exposure Time (y)
5
5
5
5
1
Average Corrosion Rate (//m/y)
0.036
0.069
0.106
0.036
0.056
Source: Baedecker et al. (1991).
likely controlled by the availability of copper to react with deposited pollutants.  The patina, that
is mostly basic sulfate, is not readily dissolved by acids and thus provides significant protection
for the substrate metal. However, according to Simpson and Horrobin (1970), the formation of

these basic copper salts can take as long as 5 or more years and will vary with the concentration
of SO2 or chloride particles, the humidity, and the temperature.
                                        9-10

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     Butlin et al. (1992a) reported an average rate for copper corrosion of 1 ± 0.2 //m/y in 19 of
29 sites evaluated.  In areas where there was above average SO2, mass loss ranged from 1.5 to
1.75 //m/y. The lowest recorded mass loss was 0.66 //m/y in an area with low precipitation and
low SO2. The maximum pit depth over a 2-year period was 63 //m.
     Meakin et al. (1992) reported on the atmospheric degradation of monumental bronzes.
They measured ion concentrations in rain run off from brigade markers at the Gettysburg
National Military Park as well as rain samples. There was a very strong correlation between
copper and sulfate ions with a regression coefficient not significantly different from the
stoichiometric value for cupric sulfate. There appeared to be little  correlation between the
acidity of the run off and the acidity of the rain fall on the markers. Dry deposition between rain
events was concluded to dominate the soluble corrosion of the bronze.
     Because of the complexity of the patina formation, few damage functions have been
reported and most of those that have been  reported were based on short-term data when the
patina had not developed.  Corrosion rates of 0.5 to 1 //m/y have been predicted by these
equations.  However, the values greatly over estimate long-term damage and would be
misleading in an economic assessment.
     Although limited to 5 years of exposure, the National Acid Precipitation Assessment
Program study (Baedecker et al., 1991; Cramer et al., 1989) may be useful in evaluating the
affects of SO2 on copper because it analyzed 110 Cu soluble corrosion data with components of
the previously discussed generic damage function. The average total corrosion rate between
3 and 5  years was about 1 //m/y but the soluble portion was less than a third of that which could
be statistically attributed to SO2. The resulting coefficient for the product of SO2 times the time-
of-wetness was 0.18 cm/s which has the units of a deposition velocity.  This term may be
multiplied by a stoichiometric conversion  factor to get a corrosion  rate. With SO2 expressed in
mg/m3 and time-of-wetness in years, the conversion  factor for//m/y of Cu to cupric sulfate is
0.035. The coefficient is 0.0063 and for an average concentration of 20 mg/m3 of SO2 the
resulting corrosion rate is 0.126 //m/y of wetness.  If the surface is  wet only a quarter of the
time, the corrosion rate attributable to SO2 is around 0.03 //m/y. If the patina color has aesthetic
value, and SO2 accelerates the formation, then, in the case of Cu, the presence of SO2 may be
beneficial.
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Zinc and Galvanized Steel
     In the presence of moisture and oxygen, zinc will form an initial corrosion product of zinc
hydroxide. Carbon dioxide (CO2) in the atmosphere further reacts with this film to form basic
zinc carbonates.  This corrosion product is insoluble in neutral environments but dissolves in
both strong acids and strong bases.  Zinc is electrochemically more active than iron. Coating
steel with  zinc provides a protection to the steel substrate against atmospheric corrosion.
     Many studies conducted on the corrosive properties of zinc and zinc products are
extensively evaluated in the National Acid Precipitation Assessment Program report (Baedecker
et al., 1991).  Two of the studies, conducted over a 20-year period, showed zinc corrosion rates
of 0.22 to  7.85 //m/y from 1931 to 1951 and 0.6 to 3.6 //m/y from 1957 to 1977 (Anderson,
1956; Showak and Dunbar, 1982).  State College, PA was the only site common to both studies.
The corrosion rates were 1.13 and  1.2 //m/y.
     Harker et al. (1980) examined the variables controlling the corrosion of zinc by SO2 and
sulfuric acid (H2SO4).  Experimental conditions were selected from the following ranges:

     Temperature                                   12to20°C
     Relative humidity                              65 to  100%
     Mean flow velocity                            0.5 to 8 m/s
     Sulfur dioxide concentration                    46 to 216 ppb
     Sulfate aerosol mass concentration                1.2 mg/m3
     Aerosol size distribution                        0.1 to 1.0 //m

     The  factors controlling the rate of corrosion were found to be relative humidity, pollutant
flux, and the chemical form of the pollutant. Corrosion occurred only when the relative
humidity was greater than 60%. The deposition velocities were 0.07 cm/s for 0.1 to 1.0 ppm
H2SO4 aerosols and 0.93 cm/s for SO2 at a friction velocity of 35 cm/s. The results indicate that
SO2-induced corrosion of zinc proceeds at a rate approximately a factor of two greater than that
for the equivalent amount of deposited H2SO4 aerosol. Temperature did not appear to be a
controlling factor within the range 12 to 20 °C.
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     Edney et al. (1986) conducted controlled environmental chamber experiments on
unexposed galvanized steel panels to determine the rate at which SO2 deposits to fresh test
panels and the fate of the deposited compound.  During exposure, dew was periodically
produced on some of the panels.  After exposure, samples were washed with sprays of different
pH levels to simulate acidic wet deposition.  The runoff samples were analyzed for corrosion
product ions.
     In the absence of dew, deposited SO2 was absorbed. With dew present, the absorption rate
increased substantially.  At a chamber flow rate of 3 m/s, the flux of SO2 to the panel surfaces
was directly proportional to the air concentration and the regression slope represents a deposition
velocity of 0.9 cm/s.  A linear regression slope between zinc and sulfate in the runoff was 1.06,
which is consistent with a stoichiometric reaction.
     The National Acid Precipitation Assessment Program (Baedecker et al., 1991; Cramer et
al., 1989) included zinc and galvanized steel panels in its field exposure experiments in
Newcomb, NY, Newark, NJ, Washington, DC, Research Triangle Park, NC, and Steubenville,
OH.  The NC and OH sites were the only two of the 5 sites that had covers and spray devices set
up to separate the effects of wet and dry deposition of pollutants. Air quality, meteorological
parameters, and rain chemistry were determined at all sites. Runoff samples were collected and
analyzed for both ambient rain and the deionized water spray.
     In general, the rolled zinc corrosion rates were larger than those found for the galvanized
steel panels, most likely because of a protective chromate treatment that had been factory applied
to the galvanized steel. The deposition of SO2 was one of several corrosion contributing factors.
The concentrations of SO2 at the different sites varied by as much as a factor of 10, but the
corrosion rates were within a factor of 2 (see Table 9-3).  Pollutant concentrations at the 5
exposure sites appear in Table 9-1.
     At the NC and OH sites, exposed samples of both zinc and galvanized steel corroded more
than similar samples exposed to the clean simulated rain. Although SO2 levels were higher at
the OH site, the deionized water spray samples corroded about the same at both sites.  This
result, together with high levels of particles at the industrial OH site, may indicate that much of
the deposited SO2 was neutralized by dry deposited alkaline particles.
     Cramer et al. (1989) did a preliminary analysis of the soluble fraction of the total zinc
corrosion with respect to the model of the generic damage function.  The multiple regression
                                          9-13

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       TABLE 9-3. AVERAGE CORROSION RATES FOR ROLLED ZINC AND
            GALVANIZED STEEL OBTAINED DURING THE NATIONAL
     ACID PRECIPITATION ASSESSMENT PROGRAM FIELD EXPERIMENTS
Average Corrosion Rate (//m/y)
Site
NC
DC
NJ
NY
OH
Exposure Time (y)
5
5
5
5
1
Rolled Zinc
0.81
1.27
1.32
0.63
1.33
Galvanized Steel
0.73
0.71
0.99
0.63
0.99
Source: Baedecker et al. (1991)


analysis gave significant coefficients for SO2, hydrogen ions (If), and CO2 in precipitation. The
coefficient for SO2 was not significantly different from stoichiometric for both the rolled zinc
and the chromated galvanized steel. Most of the zinc corrosion product was soluble.  Haynie
et al. (1990) have calculated the solubility of basic zinc carbonate in equilibrium with water
containing CO2.  Zinc solubility is very temperature dependent due to the strong inverse
dependence of CO2 solubility in water, leading to increased dissolution of the corrosion products
as the ambient temperature decreases.
     In the study reported by Butlin et al. (1992a), galvanzied steel was found to  corrode at a
rate of 1.45 //m/y (high precipitation, low SO2) to 4.25 //m/y (high SO2). Galvanized steel
samples from the area of low rainfall and low SO2 had a corrosion rate of 1.53 //m/y.
Metallographical evaluation of the galvanized steel samples showed only superficial corrosion
with no  penetration of the zinc coating.
     The various factors that contribute to the corrosion of zinc and galvanized steel are
discussed in more detail in terms of the model of the generic damage function in Spence and
Haynie (1990), Haynie et al. (1990), and  Spence et al. (1992).  The combined terms of the long-
term form of the model are:
                 C=F+Cd+CRA+CRC                                         (9-5)

where C is total corrosion in //m, F is the equivalent thickness of zinc remaining in the insoluble
corrosion product film and, at steady state, is equal to a/b, Cd is the corrosion
                                         9-14

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associated with deposition of SO2 both in wet and dry periods, and CRC is the corrosion due to
rain acidity (H+ and dissolved CO2).  The SO2 contribution, Cj, is expressed as follows:
          Cd = 0.045 Vd(S02)tw + 1.29 x 10 4ArN                                   (9-6)

where,
     Cd = zinc corrosion, //m
     Vd = deposition velocity (wind speed, shape, and size dependent), cm/s
     SO2 = ambient SO2 concentration, mg/m3.
     A,. = ratio of actual to apparent surface area
     N = number of times surface is dry during the exposure period.
     The first additive term represents corrosion from the dry deposition of SO2 during periods
of wetness caused by condensation (dew), and the second term is the corrosion associated with
the adsorption of a monolayer of SO2 during periods of dryness.
     In the absence of sufficient data to accurately determine each of the terms, Haynie et al.
(1990), and Spence et al. (1992) have applied assumed values for flat galvanized specimens
(different sizes), large sheets, and wire with reasonable success. More recently, Cramer and
Baker (1993) have applied the generic damage function to predict the expected life of the
restored tin plated roof of Monticello. Thus, the model can be used to assess the economic
effects of atmospheric corrosion on several metals, especially zinc.

9.1.3.2 Particles
     Only limited  information is available on the effects of particles alone on metals. Goodwin
et al. (1969) reported damage to steel, protected with a nylon screen, exposed to quartz particles.
The damage did not, however, become substantial until the particle size exceeded 5 //m.  Barton
(1958) found that dust contributed to the early stages of metal corrosion. The  effect of dust was
lessened  as the rust layer formed. Other early studies also indicated that suspended particles can
play a significant role in metal corrosion.  Sanyal and Singhania (1956) wrote that particles,
along with other cofactors and SO2, promoted the corrosion of metals in India. Yocom and
Grappone (1976) and Johnson et al. (1977) reported that moist air containing both particles and
SO2 resulted in a more rapid  corrosion rate than air polluted with SO2 alone. Russell (1976)
stated that particles serve as points for
                                          9-15

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the concentration of active ionic species on electrical contact surfaces, thereby increasing the
corrosion rate of SOX.  However, other studies have not established a conclusive statistical
correlation between total suspended particulates (TSP) and corrosion, possibly due to data
limitations (Mansfeld, 1980; Haynie andUpham,  1974; andUpham, 1967; Yocom andUpham,
1977).
     Edney et al. (1989) reported on the effects of particles, SO2, NOX, and O3  on galvanized
steel panels exposed under actual field conditions in Research Triangle Park, NC, and
Steubenville, OH, between April 25 and December 28, 1987.  The panels were  exposed under
the following conditions:  (1) dry deposition only; (2) dry plus ambient wet deposition; and (3)
dry deposition plus deionized water. The average concentrations for SO2 (in ppb) and
particulate matter (in //g/m3) was 22 ppb and 70 //g/m3 and <1 ppb and 32 //g/m3 for
Steubenville and Research Triangle Park, respectively. By analyzing the runoff from the steel
panel the authors concluded that the dissolution of the steel corrosion products for both sites was
likely the result of deposited gas phase SO2 on the metal surface and not parti culate sulfate.
     Dean and Anthony (1988) investigated the atmospheric corrosion of unstressed wrought
aluminum alloys at three sites representing industrial, marine, and coastal-industrial
environments.  After 10 years of exposure, degradation was measured by several means.  They
reached the following  conclusions: (1) a sooty industrial environment is far more damaging than
a warm, salt-laden seacoast atmosphere, (2) by far the most noticeable effect of prolonged
atmospheric exposure  is loss of ductility in susceptible alloys, and (3) sacrificial cladding
completely eliminates  ductility loss.
     Walton et al. (1982) performed a laboratory study of the direct and synergistic effects of
different types of particles and SOX on the corrosion of aluminum, iron, and zinc.  The four most
aggressive species were salt and salt/sand from marine or deiced locations, ash  from iron
smelters, ash from municipal incinerators, and coal mine dusts. Fly ashes of various types were
less aggressive.  Coal ash with SOX did promote corrosion but oil fly ash was relatively
noncorrosive.  This suggests that catalytic species in the ash promote the oxidation of SOX and
the presence of SOX alone is not sufficient to accelerate corrosion. Other laboratory studies of
metal corrosion provide considerable evidence that the catalytic effect is not significant and that
atmospheric corrosion rates are dependent on the
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conductance of the thin-film surface electrolyte and that the first-order effect of contaminant
particles is to increase solution conductance, and, hence corrosion rates (Skerry et al., 1988a,b;
Askey etal., 1993).

9.1.4    Paints
     Paints, opaque film coatings, are by far the dominant class of manmade materials exposed
to air pollutants in both indoor and outdoor environments.  Paints are used as decorative
coverings and protective coatings against environmental elements on a variety of finishes
including woods, metals, cement, asphalt, etc.
     Paints primarily consists of two components: the film forming component and the
pigments. Paints undergo natural weathering processes from exposure to environmental  factors
such as sunlight (ultraviolet light), moisture, fungi, and varying temperatures.  In addition to the
natural weathering from exposure to environmental factors, evidence exists that demonstrates
pollutants affect the durability of paint (National Research Council, 1979).
     Paint failure may be manifested by two general degradation modes.  The first involves the
paint surface and includes paint discoloration, chalking, loss of gloss, and erosion.  Paint erosion
can be measured by loss of thickness of the paint layer. The second is degradation at the
paint/substrate interface, which can be manifested as loss of adhesion leading to blistering and
peeling.
     In paint formulas, the ratio of pigments to film formers is important to the overall
properties of gloss, hardness, and permeability to water. If the amount of film former is too low,
soiling is increased and the paint may lose the film flexibility needed for durability and become
brittle.

9.1.4.1 Acid-Forming Aerosols
     Paint films permeable to water are also susceptible to penetration by SO2 and SO^"
aerosols. Baedecker et al. (1991) reviewed about twenty papers (1958 to 1985) dealing with
solubility and permeability of SO2 in paints and polymer films. Permeation and adsorption  rates
varied by as much as several orders of magnitude depending on formulation.  They concluded
that unpigmented polymer films have a large range of permeabilities but that the polymers used
in paint formulations generally do not form barriers to SO2 either in the
                                          9-17

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gaseous state or in solution as sulfurous acid.  Although 20% of the absorbed SO2 was retained
in alkyd/melamine and epoxide films and probably reacted with the polymer, there appears to be
little degradation to the polymer itself from SO2 at low concentrations.  Absorption is inhibited
by pigments; those pigments that can catalyze the oxidation of SO2 and scavenge the resulting
sulfate ions can limit the penetration even more than can typical pigments.
     Concentrations of SO2 found in fog or near industrial sites can increase the drying and
hardening times of certain kinds of paints. Holbrow (1962) found that the drying time of
linseed, tung, and certain castor oil paint films increased by 50 to 100% on exposure to 2,620 to
5,240 //g/m3 (1 to 2 ppm) SO2.  The touch-dry and hard-dry times of alkyl and oleoresinous
paints with titanium dioxide pigments were also reported to increase substantially; however, the
exposure time of the wet films was not reported. Analysis of the dried films indicated that SO2
chemically reacted with the drying oils, altering the oxidation-polymerization process.  No
studies have been reported  on the effects of SO2 on the drying of latex paints.
     Spence et al. (1975) conducted a controlled exposure study to determine the effects of
gaseous pollutants on four classes of exterior paints: oil-base house paint, vinyl-acrylic latex
house paint,  and vinyl and acrylic coil coatings for metals. The house paints were sprayed on
aluminum panels. The coil coating panels were cut from commercially painted stock. Recorded
paint thickness was oil-base paint film, 58 //m; acrylic latex, 45 //m; vinyl coil coating, 27 //m;
and acrylic coil coating, 20 //m. Temperature, humidity, and SO2, (78.6 and 1,310 //g/m3), NO2
(94 and 940  //g/m3), and O3 (156.8 and 980 //g/m3) exposures were controlled.  Each exposure
chamber had a xenon arc lamp to provide ultraviolet radiation. A dew/light cycle was included;
light exposure time was followed by a dark period during which coolant circulated through racks
holding the specimens, thereby forming dew on the panels. Each dew/light cycle lasted 40 min
and consisted of 20 min of darkness with formation of dew, followed by 20 min under the xenon
arc.  The total exposure time was 1,000 h.  Damage was measured after 200 h, 500 h, and  1,000
h by loss of both weight and film thickness. In evaluating the data, loss of weight was converted
to equivalent loss of film thickness.
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     Visual examination of the panels coated with oil-base house paint revealed that all
exposure conditions caused considerable damage. The erosion rate varied from 28.3 to 79.14
//m/y, with an average of 60 //m/y.  The investigators concluded that SO2 and relative humidity
markedly affected the rate of erosion of oil-base house paint. The presence of NO2 increased the
weight of the paint film. A multiple linear regression on SO2 concentration and relative
humidity yielded the following relation:

                            E= 14.3 +  0.0151 SO2 +0.388 RH                        (9-7)

where
     E = erosion rate in //m/y,
     SO2 = concentration of SO2 in //g/m3, and
     RH = relative humidity in percent.
The authors reported the 95% tolerance limits on 99% of the calculated rates to be ±44 //m/y.
     Blisters formed on the acrylic latex house paint at the high SO2 levels.  The blisters
resulted from severe pitting and buildup of aluminum corrosion products on the substrate. The
paint acted as a membrane retaining moisture under the surface and excluding oxygen that would
passivate the aluminum. The vinyl coating and the acrylic coating are resistant to SO2. The
visual appearance of the vinyl coil coating showed no damage. The average erosion rate was
low, 3.29 //m/y. The average erosion rate for a clean air exposure was 1.29 //m/y.  The acrylic
coil coating showed an average erosion rate of 0.57 //m/y (Spence et al., 1975).
     A study of the effects of air pollutants on paint, under laboratory controlled conditions,
was conducted by Campbell et al. (1974).  The paints studied included oil and acrylic latex
house paints,  a coil coating, automotive refmish, and an alkyd industrial maintenance coating.
These coatings were exposed to clean air,  SO2  at 262 and 2,620 //g/m3, and O3 at 196 and 1,960
Mg/m3. Light, temperature, and relative humidity were controlled.  In addition, one-half of the
coatings were shaded during the laboratory exposures. Similar panels (half facing north) were
exposed at field sites in Leeds, ND; Valparaiso, IN; Research Center, Chicago, IL; and Los
Angeles, CA.
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     The laboratory exposure chamber operated on a 2-h light-dew cycle (i.e., 1 h of xenon
light at 70% relative humidity and a temperature of 66 °C followed by 1 h of darkness at 100%
relative humidity and a temperature of 49 °C). Coating erosion rates were calculated after
exposure periods of 400, 700, and 1,000 h.  Erosion rates for samples exposed to the lowest
exposure concentrations were not significantly different from values for clean air exposures due
to the high variability of the data.  The erosion rates on the shaded specimens were significantly
less than the unshaded panel results; panels facing north were also less eroded. At the highest
exposure concentrations, erosion rates were significantly greater than controls for both
pollutants, with oil-base house paint experiencing the largest erosion rate increases, latex and
coil coatings moderate increases, and the industrial maintenance coating and automotive refmish
the smallest increases (Yocom and Grappone, 1976; Yocom and Upham, 1977; and Campbell
et al., 1974). Coatings that contained extender pigments, particularly calcium carbonate
(CaCO3), showed the greatest erosion rates from the SO2 exposures. Results of field exposures
also support these conclusions (Campbell et al., 1974).
     Haynie and Spence (1984) evaluated data on two house paints that were exposed for up to
30 mo at 9 environmental monitoring sites in the St. Louis, MO area.  The paints were
formulated with and without CaCO3 and applied to stainless steel panels. Multiple regression
analysis of mass loss versus the environmental variables revealed no statistical differences
associated with SO2.
     Hendricks and Balik (1990) evaluated the effects of SO2 on free films of paint and the latex
polymer for one of the paints and established diffusion coefficients for SO2 in the various
formulations. Pigments, as well as fillers such as CaCO3, were found to decrease the diffusion
coefficient. A latex polymer desorbed all SO2 when placed in a vacuum but an alkyd retained
approximately 15 to 20% SO2 even after several days. Xu and Balik (1989, 1990) concluded
that the gas had reacted with the polymer in the paint. They also determined quantitatively the
rate of CaCO3 removal from paints exposed to different pH levels of sulfurous acid or distilled
water (weak carbonic acid). The rates of dissolution were dependent on acid strength but
removal was complete for all acids. The mass loss was 27%. A similar paint without CaCO3
lost only 7%.
     Patil et al. (1990) reported that certain combinations of SO2/H2O/UV light (high SO2
levels) had detrimental effects when they were evaluating various techniques for measuring
                                          9-20

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film degradation. Mechanical properties were dominated by cross-linking. While SO2 had little
effect when dry, there was considerable chain scissioning when exposed wet. Sanker et al.
(1990) found that after exposing the polymer to SO/UV light that there was a decrease in
carbonyl signal associated with the acrylate group, whereas no decrease in carbonyl signal was
associated with samples exposed to UV light alone. They reported a synergistic effect on
polymer degradation between UV light and SO2 under both wet and dry conditions.
     Edney  (1989) and Edney et al. (1988, 1989) measured the chemical composition of runoff
from painted red cedar and zinc panels exposed at field sites in Raleigh, NC, and Steubenville,
OH, and in controlled chambers. Acidic gases such as SO2 and nitric acid dissolved alkaline
(CaCO3 or ZnO) components in the paint.
     Williams et al. (1987) demonstrated that weathering of wood prior to painting decreases
the adhesion of paint. Significant decreases in paint adhesion were noted in panels weathered
for 4 weeks and those weathered for 16 weeks had about a 50% decrease in adhesive strength.
In similar studies, it was shown that acid treatment of specimens during weathering increased the
rate of surface deterioration; the rate of wood weathering increased by as much as 50% when it
was exposed to sulfurous, sulfuric, or nitric acids (Williams, 1987, 1988).
     As part of the National Acid Precipitation Assessment Program, Davis et al. (1990) studied
the effects of SO2 on oil/alkyd systems on steel using a custom designed exposure chamber in
which a dew cycle could be simulated. Energy dispersive X-ray microscopy scans were made
across primer/paint cross-sections. Samples were exposed to 1 ppm  SO2 at 90 to 95% relative
humidity, and thermally cycled (12-h dew cycle followed by 12-h drying period) or the chamber
was maintained at a constant temperature.  Controls were exposed under similar conditions but
without SO2.  All samples gained weight after 7 days of exposure. The greatest weight gain was
noted in the cyclic samples (30 to 40% more than those samples maintained under constant
temperatures). After 28 days to cyclic (dew/drying) conditions samples exposed to SO2 had
rusted scribe marks while the controls showed only light rust.
     As the  specimens were exposed in the chamber, the tensile strength decreased significantly
and the locus of failure shifted from within the coating system to the primer-metal interface.
The relationship of tensile strength to metal/primer failure was
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approximately linear, suggesting that the decrease in tensile strength was dominated by a loss or
weakening of adhesion between the substrate and the primer (Davis et al., 1990).

9.1.4.2 Particles
     Several studies suggest that particles serve as carriers of other more corrosive pollutants,
allowing the pollutants to reach the underlying surface or serve as concentration sites for other
pollutants (Cowling and Roberts, 1954).
     Reports have indicated that particles can damage automobile finishes.  In an early study,
staining and pitting of automobile finishes was reported in industrial areas. The damage was
traced to iron particles emitted for nearby plants (Fochtman and Langer, 1957). General Motors
conducted a field test to determine the effect of various meteorological events, the  chemical
composition of rain and dew, and the ambient air composition during the event, on automotive
paint finishes.  The study was conducted in Jacksonville, FL. Painted (basecoat/clearcoat
technology) steel panels were exposed for varying time periods, under protected and unprotected
conditions. Damage to paint finishes appeared as circular, elliptical, or irregular spots, that
remained after washing. Using scanning electron microscopy (high magnification) the spots
appeared as crater-like deformities in the paint finish.  Chemical analyses of the deposit
determined calcium sulfate to be the predominant species. It was concluded that calcium sulfate
was formed on the paints surface by the reaction of calcium from dust and sulfuric acid
contained in rain or dew. The damage to the paint finish increased with increasing days of
exposure (Wolff et al.,  1990). Table 9-4 contains the atmospheric pollutants and their
concentrations during the study.
     The formulation of the paint will affect the paint's durability under exposure to varying
environmental factors and pollution; however, failure  of the paint system results in the need for
more frequent  repainting and additional cost.

9.1.5    Stone and Concrete
     Air pollutants are known to damage various building stones. Some of the more susceptible
stones are the calcareous stones, such as limestone, marble and carbonated cemented stone. The
deterioration of inorganic building materials occurs initially through surface weathering.
Moisture and salts are considered the most important factors in building
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             TABLE 9-4.  SUMMARY OF MEASURED PARAMETERS
                              JACKSONVILLE, FLORIDA
                             (Statistics based on 8-h samples)
IN
Variable
Fine particulatesd (//g/m3)
Particulate matter6 (//g/m3)
Total suspended particulates (//g/m3)
Fine sulfatesf (//g/m3)
Sulfates6 (Mg/m3)
Sulfur dioxide (//g/m3)
Fine ammonium (//g/m3)
Fine organic carbon (//g/m3)
Organic carbon6 (//g/m3)
Fine elemental carbon (//g/m3)
Elemental carbon6 (//g/m3)
Fine calcium (ng/m3)
Calcium (ng/m3)
Fine silica (ng/m3)
Silica6 (ng/m3)
Potassium6 (ng/m3)
Titanium6 (ng/m3)
Iron6 (ng/m3)
Total nitrates (//g/m3)
Nitric acid (//g/m3)
Fine nitrates (//g/m3)
Nitrogen oxide (ppb)
Nitrogen dioxide (ppb)
Oxone (maximum) (ppb)

Meanb
22.2
38.7
55.8
6.9
7.7
6.7
2.5
2.0
4.4
1.3
1.8
284.0
3,572.0
132.0
995.0
348.0
42.0
421.0
1.3
0.7
0.6
3.1
8.8
48.0
Overall3
Standard
Deviation
11.0
15.9
22.2
4.6
4.9
9.8
1.5
1.3
2.8
1.1
1.8
224.0
3,850.0
214.0
909.0
140.0
38.0
388.0
1.3
1.2
0.3
4.0
5.9
20.2

Maximum6
58.2
89.8
129.2
18.1
18.9
56.6
7.8
6.4
12.9
5.4
8.5
1,145.0
21,073.0
1,797.0
6,572.0
920.0
237.0
3,090.0
8.4
7.8
1.5
19.2
32.3
93.0
aOverall = combination of three daily 8-h samples.
bMean daily ozone maximum.
°Maximum ozone concentration over the study period.
d<2.5 ^m.
ePM10 variables.
f<2.5 ^m.

Source:  Wolff et al. (1990).
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material damage.  Many researchers believe that the mechanism of damage from air pollution
involves the formation of salts from reactions in the stone; subsequently, these surface salts
dissolve in moist air and are washed away by rainfall. Luckat (1977) reported good  correlation
with stone damage and  SO2 uptake. Riederer (1974) and Niesel (1979) reported that stone
damage is predominantly associated with relative humidity >65% and freeze/thaw weathering.
Still other researchers suggest that microorganisms must also be considered in order to quantify
damage to building materials due to ambient pollutant exposure (Winkler, 1966; Riederer, 1974;
Krumbein and Lange, 1978; Eckhardt, 1978; Hansen, 1980).  Sulfur chemoautotrophs are well
known for the damage they can cause to inorganic materials.  These microorganisms (e.g.,
Thiobacillus) convert reduced forms of sulfur to H2SO4  (Anderson, 1978) and the presence of
sulfur oxidizing bacteria on exposed monuments has been confirmed (Vero and Sila, 1976).  The
relative importance of biological, chemical, and physical mechanisms, however, have not been
systematically investigated. Thus, damage functions definitely quantifying the relationship of
pollutant concentrations to stone and concrete deterioration are not available in the literature.
     Baedecker et al. (1991) reviewed the published literature on calcareous stones and
concluded that the most significant damage to these stones resulted from the exposure to natural
constituents of nonpolluted rain water; carbonic acid from the reaction of CO2 with rain reacts
with the calcium in the  stone. Based on the work conducted by the National Acid Precipitation
Assessment Program, 10% of chemical weathering of marble and limestone was caused by wet
deposition of hydrogen  ions from all acid species.  Dry deposition of SO2 between rain events
caused 5 to 20% of the  chemical erosion of stone and the dry deposition of nitric acid was
responsible for 2 to 6%  of the erosion (Baedecker et al., 1991).
     Niesel (1979) completed a literature review on the weathering of building stone in
atmospheres containing SOX, which includes references  from 1700 to 1979.  In summary,
he reported that weathering of porous building stone containing lime is generally characterized
by accumulation of calcium sulfate dihydrate in the near-surface region. The effect of
atmospheric pollutants on the rate of weathering is believed to be predominantly controlled by
the stone's permeability and moisture content. Migrating moisture serves primarily as a transport
medium.  Sulfur dioxide is sorbed and thus can be translocated internally while being oxidized
to sulfates. Reacting components of the building stone are
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thus leached, the more soluble compounds inward and the less soluble toward the surface, often
forming a surface crust.
     Sengupta and de Gast (1972) reported that SO2 sorption causes physical changes in stone
involving changes in porosity and water retention.  Removal of CaCO3 changes the physical
nature of the stone surface.  The hard, nonporous layer that forms as a result of alternate freezing
and thawing may blister, exfoliate, and separate from the surface. If the stone contains some
substances that are unaffected by SO2, the surface can deteriorate unevenly.  The conversion of
CaCO3 to calcium sulfate results in a type of efflorescence called "crystallization spalling."
     Baedecker et al. (1992) reported the results of a study on carbonate stone conducted as a
part of National Acid Precipitation Assessment Program. Physical measurements of the
recession of test stones exposed to ambient conditions at an angle of 30°  to horizontal at 5 sites
ranged from 15 to 30 //m/y for marble and from 25 to 45 //m/y for limestone and were
approximately double the recession estimates based on the observed calcium content of run-off
solutions from test slabs.  The difference between the physical and chemical recession
measurements was attributed to the loss of mineral grains from the stone surfaces that were not
measured in the run-off experiments.  The erosion due to grain loss did not appear to be
influenced by rainfall acidity, however, preliminary evidence suggested that grain loss may be
influenced by dry deposition of SO2 between rain events. Chemical analysis of the run-off
solutions and associated rainfall blanks suggested 30% of erosion by dissolution could be
attributed to the wet deposition of hydrogen ion and the  dry deposition of SO2 and nitric acid
between rain events.  The remaining 70% of erosion by dissolution is accounted for by the
solubility  of carbonate stone in rain that is in equilibrium with atmospheric CO2 (clean rain).
These results are for slabs exposed at 30° angles.  The relative contribution of SO2 to chemical
erosion was significantly enhanced for slab having an inclination of 60° to 85°. The dry
deposition of alkaline particles at the two urban sites competed with the stone surface for
reaction with acidic species.
     Sweevers and Van Grieken (1992)  studied the deterioration of sandstone, marble and
granite under ambient atmospheric conditions.  Specially constructed sampling devices, called
"micro catchment units", were installed to sample the run-off water (i.e. the rain that flows over
the stones).  Several analysis techniques were invoked for the analysis of the bulk
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runoff water, as well as electron probe X-ray microanalysis for individual particles in the runoff.
There was a strong calcium to sulfate correlation on sandstone but not on granite after extended
exposures.
     Webb et al. (1992) studied the effects of air pollution on limestone degradation in Great
Britain. There was a significant trend to increased weight loss with increased average SO2
concentration, but a negative trend with total NOX and with NO2.  Rainfall did not significantly
affect limestone degradation. Based on a mass and ion balance model, the natural solubility of
limestone in water was the dominant term in describing the stone loss. The average overall
recession rate was 24 //m/y.  The increase in stone loss due to SO2 was less than 1 //m/year/ppb.
     Butlin et al. (1992b) correlated damage to stone samples exposed at 29 monitoring sites in
Great Britain. Portland limestone, White Mansfield dolomitic sandstone, and Monks Park
limestone tablets (50 x 50 x g //m) were exposed both under sheltered and unsheltered
conditions. Weight change and ionic composition of surface powders were determined  after one
and two years of exposure.
     The results showed the expected increases in acidic species and soluble calcium in the
sheltered tablets. The  stone deterioration data were statistically analyzed with respect to the
environmental variables at the sites.  Significant correlations existed between the mean annual
SO2 concentration, rainfall volume, and hydrogen ion loading and the weight changes.  These
three correlations contain the three components that appear to be responsible for the degradation
of calcareous stone, (1) dry deposition of acid gases and aerosols, (2) dissolution by acid species
in rain water, and (3) the dissolution of stone by unpolluted rain water.
     By analyzing storm runoff from a Vermont marble sample and comparing the results with
the pollution exposure history, Schuster et al.  (1994) have determined the relative contributions
of wet and dry deposition to accelerated damage. Data were compared with runoff from glass
for the same seven selected summer storms. Even though the exposure site had low
concentrations of SO2, it was estimated that between 10 and 50% of calcium washed from the
marble surface during  a storm was from the dissolution of gypsum formed by the reaction of
SO2 during dry periods.
     Yerrapragada et al. (1994) exposed samples of Carrara and Georgia marble for 6,  12, or 20
mo under normal atmospheric conditions.  The samples were exposed outside, but
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protected from the rain, at sites in Jefferson County, KY. These authors also analyzed samples
of Georgia marble of varying ages from cemeteries in the Los Angeles basin. The researchers
reported that SO2 is more reactive with the calcium in marble under higher NO2  conditions.  The
effects were noted even under relatively low SO2 and NO2 concentrations (10 to 20 and 22 to 32
ppb, respectively).  Carrara marble was found to be more reactive with SO2 than Georgia
marble, possibly due to the more compactness of the Georgia marble.
     The effect of dry deposition of SO2, NO2, and NO both with and without O3 on limestones
and dolomitic sandstone was reported by Haneef et al. (1993).  Samples of Portland limestone,
Massamgis Jaune Roche limestone,  and White Mansfield dolomitic sandstone were exposed to
10 ppm of each of the pollutants at a controlled relative humidity of 84% and a temperature of
292 °K. The stone samples were exposed to the controlled environment for 30 days. There was
a small increase in sample weights after the 30 day exposure for all samples. Those samples
exposed to O3 in addition to one of the  other pollutants (SO2, NO2, or NO) showed a significant
increase in weight gain.  All stone samples also showed retained sulfates or nitrates, particularly
in the presence of O3. When viewed by electron/optical techniques, a crust was noted on the
surface and lining the pores of the stones exposed to SO2 but not those exposed to NO2 or NO.
     Wittenburg and Dannecker (1992) measured dry deposition and deposition velocities of
airborne acidic species on different sandstones. During different air-monitoring campaigns
carried out in urban sites in East and West Germany, the dry deposition of particles and gaseous
sulfur and nitrogen containing species on three different sandstones and on an inert substrate
were measured. The measured depositions were related to the ambient air concentrations of the
most important gaseous and paniculate species.  Dry deposition velocities were calculated and
the proportions of particle and gas input depositions on the sandstones were estimated.
     Salt accumulation in building stones was mainly caused by the gaseous components,
especially SO2.  The deposition velocities were strongly dependent upon stone type. The
contribution of sulfate particle deposition on sandstones was around 5 to 10% for vertical
surfaces depending on the atmospheric conditions  (Wittenburg and  Dannecker, 1992).
     Cobourn et al. (1993) used a continuing monitoring technique to measure the deposition
velocity of SO2 on marble and dolomite stone surfaces in a humid atmosphere over a
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2,000 ppm-h exposure period at approximately 10 ppm SO2 and 100% relative humidity. The
measured average deposition velocities of SO2 over the two stones were comparable in
magnitude. For dolomite, the measured deposition velocity varied between 0.02 and 0.10 cm/s,
whereas for the marble, the deposition velocity varied between 0.03 and 0.23 cm/s. The
measured deposition velocity for both types of stone changed as a function of time. The
deposition velocity over dolomite increased gradually with time.  The increase was attributed to
a gradual increase of liquid water on the surface, brought about by the formation of the
deliquescent mineral epsomite. The wide variation appeared to be associated with the absence or
presence of condensed moisture on the marble sample surfaces.  For most of the marble runs, the
deposition velocity generally decreased slightly with time, after an initial period. The decrease
could have been due to the build-up of reactions products on the stone surface.
     Under high wind conditions, particles have been reported to result in slow erosion of
marble surfaces, similar to sandblasting (Yocom and Upham, 1977). Mansfeld (1980), after
performing statistical analysis of damage to marble samples exposed for 30  mo at 9 air quality
monitoring sites in St. Louis, MO, concluded that exposure to TSP and nitrates were correlated
with stone degradation. However, there is some concern over the statistical techniques used.
     Generally, black and white areas can be observed on the exposed  surfaces  of any building.
The black areas, found in zones protected from direct rainfall and from surface runs, are covered
by an irregular, dendrite-like, hard crust composed of crystals of gypsum mixed with dust,
aerosols, and particles of atmospheric origin.  Among these the most abundant are black
carbonaceous particles originating from oil and coal combustion. On the other hand, surfaces
directly exposed to rainfall show a white color, since the deterioration products formed on the
stone surface are continuously washed out.
     The accumulation of gypsum on carbonate stone has been investigated by McGee  and
Mossotti (1992) through exposure of fresh samples of limestone and marble at monitored sites,
examination of alteration crusts from old buildings, and laboratory experiments. McGee and
Mossotti (1992) concluded that several factors contribute to gypsum accumulation on carbonate
stone. Marble or limestone that is sheltered from direct washing by rain in an urban
environment with elevated pollution levels is likely to accumulate a gypsum crust.
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Crust development may be enhanced if the stone is porous or has an irregular surface area.
Gypsum crusts are a superficial alteration feature; gypsum crystals form at the pore opening/air
interface, where evaporation is greatest. Particles of dirt and pollutants are readily trapped by
the bladed network of gypsum crystals that cover the stone surface, but the particles do not
appear to cause the formation of gypsum crusts.  Sabbioni and Zappia (1992) analyzed samples
of damaged layers on marble and limestone monuments and historical buildings from 8 urban
sites in Northern and Central Italy.  Samples of black crust were taken from various locations at
each site to be representative of the entire site. The predominant species in the black crust
matrix was calcium sulphate dihydrate (gypsum). The evaluation of enrichment factors with
respect to the stone and to the soil dust showed the main components of the atmospheric
deposition to be from the combustion of fuels and incineration.  Saiz-Jimenez (1993) also found,
after analyzing the organic compounds extracted for black crusts removed for building surfaces
in polluted areas, that the main components were composed of molecular markers characteristic
of petroleum derivatives. The composition of each crust, however, is governed by the
composition of the particular airborne pollutants in the area.
      Sabbioni et al. (1992) conducted a laboratory study on the interaction between
carbonaceous particles and carbonate building stones.  Three types of building stones with the
common characteristic of a carbonate matrix were used:  (1) Carrar marble, (2) Travertine, and
(3) Trani stone. Samples of the emissions from two oil-combustion sources, representative of a
centralized domestic heating system and an electric generating plant, were characterized by
means of chemical and physical analysis and spread manually on the stone samples. Any  excess
was removed using compressed air. The distribution of the particles on the surface of the
samples was controlled by  optical microscopy.  The stone samples were weighed before and
after the particle deposition. Stones without particles were also exposed as reference samples.
The samples with particles containing the highest carbon content had the lowest reactivity in the
sulfation process.  Particles with high sulphur content enhanced the reactivity of the stone
samples with SO2 (Sabbioni et al., 1992).
     Del Monte et al. (1981) reported evidence of a major role for carbonaceous particles in
marble deterioration, using  scanning electron microscopy. The majority of the carbonaceous
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particles were identified as products of oil fired boiler/combustion.  Particle median diameter
was «10 //m.
     Delopoulou and Sikiotis (1992) compared the corrosive action of nitrates and sulfates on
pentelic marble with that of NOX and SO2. This was achieved by passing the polluted ambient
air through a filter pack before it entered the reactor chamber holding the marble grains. As a
consequence, the air reaching the marble was free of nitrates and sulfates while it contained all
the NOX and SO2. The effects on the marble grains were quantified and compared with those
from a reactor through which unfiltered ambient air was passed simultaneously and under the
same conditions. They reported that the action of the acids was much greater than that of the
oxides, despite the fact that the concentrations of the latter were much greater.

9.1.6    Corrosive Effects of Acid-Forming Aerosols and  Particles on Other
         Materials
     Exposure to ionic dust particles can contribute significantly to the corrosion rate of
electronic devices, ultimately leading to failure of such device. Anthropogenically and naturally
derived particles ranging in size from tens of angstroms to 1 //m cause corrosion of electronics
because many are sufficiently hygroscopic and corrosive at normal  relative humidities to react
directly with non-noble metals and passive oxides, or to form sufficiently conductive moisture
films on insulating surfaces to cause electrical leakage. The effects of particles on electronic
components were first reported by telephone companies, when particles high in nitrates caused
stress corrosion cracking and ultimate failure of the wire spring relays (Hermance, 1966;
McKinney and Hermance, 1967).  More recently, attention has been directed to the effects of
particles on electronic components, primarily in the indoor environment.
     Sinclair (1992) discussed the relevance of particle contamination to corrosion of
electronics.  Data collected during the 1980s show that the indoor mass concentrations of
anthropogenically derived airborne particles and their arrival rates at surfaces are comparable to
the concentrations and arrival rates of corrosive gases for many urban environments.
     Frankenthal et al. (1993) examined the effects of ionic dust particles,  ranging from 0.01 to
1 (j,m in size, on copper coupons under laboratory conditions. The copper coupons,
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after being polished with diamond paste, were inoculated with ammonium sulfate [(NH4)2SO4)]
particles and exposed to air at 100 °C and relative humidities ranging from 65 to 100% for up to
600 h.  The particles were deposited on the metal surface by thermophoretic deposition and
cascade impaction.
     Exposure of the copper coupons to (NH4)2SO4 at 65% relative humidity had little effect on
the corrosion rate.  However, when the relative humidity was increased to 75%, the critical
relative humidity for (NH4)2SO4 at 100 °C, localized areas of corrosion were noted on the metal
surface. The corrosion product, determined to be brochantite, was only found in areas where the
(NH4)2SO4 was deposited on the metal surface. When relative humidity was increased to 100%,
the corrosion became widespread (Frankenthal et al., 1993).
9.2    SOILING AND DISCOLORATION
     A significant detrimental effect of particle pollution is the soiling of manmade surfaces.
Soiling may be defined as a degradation mechanism that can be remedied by cleaning or
washing, and depending on the soiled material, repainting. Faith (1976) described soiling as the
deposition of particles of less than 10 //m on surfaces by impingement. Carey (1959) observed
when particles descended continuously onto paper in a room with dusty air, the paper appeared
to remain clean for a period of time and then suddenly  appeared dirty. Increased frequency of
cleaning, washing, or repainting over soiled surfaces becomes an economic burden and can
reduce the life usefulness of the material soiled. In addition to the aesthetic effect, soiling
produces a change in reflectance from opaque materials and reduces light transmission through
transparent materials (Beloin and Haynie, 1975; National Research Council, 1979).  For dark
surfaces, light colored particles can increase reflectance (Beloin and Haynie, 1975).
     Determining at what accumulated level particle pollution leads to increased cleaning is
difficult. For instance, in the study by Carey (1959), it was found that the appearance of soiling
only occurred when the surface of the paper was covered with dust specks spaced 10 to 20
diameters apart. When the contrast was strong, e.g., black on white, it was possible to
distinguish a clean surface from a surrounding dirty surface when only 0.2% of the areas was
covered with specks, while 0.4% of the surface had to be covered with specks
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with a weaker color contrast.  Still, the effect is subjective and not easy to judge between
coverages.
      Support for the Carey (1959) work was reported by Hancock et al. (1976).  These authors
also found that with maximum contrast, a 0.2% surface coverage (effective area coverage; EAC)
by dust can be perceived against a clean background.  A dust deposition level of 0.7% EAC was
needed before the object was considered unfit for use. The minimum perceivable difference
between varying gradations of shading was a change of about 0.45% EAC. Using the
information on visually perceived dust accumulation and a telephone survey, Hancock et al.
(1976) concluded that a dustfall rate of less than 0.17% EAC/day would be tolerable to the
general public.
      Some materials that are soiled are indoors. In general, particle pollution levels indoors
may be affected by outdoor ambient levels; however, other factors generally have greater effects
on concentration and composition (Yocom, 1982). For that reason, discussion of indoor soiling
will be limited primarily to works of art.

9.2.1    Building Materials
     Dose-response relationships for particle soiling were developed by Beloin and Haynie
(1975) using a comparison of the rates of soiling and TSP concentrations on different building
materials (painted cedar siding, concrete block, brick, limestone, asphalt singles, and window
glass) at 5 different study sites over a 2-y period.  Particle concentrations ranged from 60 to 250
mg/m3 for a rural residential location and an industrial residential location, respectively. The
results were expressed as regression functions of reflectance loss (soiling) directly proportional
to the square root of the dose. With TSP expressed in mg/m3 and time in months, the regression
coefficients ranged from -0.11 for yellow brick to +0.08 for a coated limestone depending on
the substrate color and original reflectance. For dark surfaces, light colored particles can
increase reflectance.  Not all of the coefficients were significantly different from zero.
     A theoretical model of soiling of surfaces by airborne particles has been developed and
reported by Haynie (1986). This  model provides an explanation of how ambient concentrations
of particulate matter are related to the accumulation of particles  on surfaces and ultimately the
effect of soiling by changing reflectance. Soiling is assumed to  be the
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contrast in reflectance of the particles on the substrate to the reflectance of the bare substrate.
Thus, the average reflectance from the substrate (R) equals the reflectance from the substrate not
covered by particles [Ro(l-X)] plus the reflectance from the particles (RpX) where X is the
fraction of surface covered by particles.
     Under constant conditions, the rate of change in fraction of surface covered is directly
proportional to the fraction of surface yet to be covered. Therefore, after integration: X = 1-
exp(-kt) where k is a function of particle size distribution and dynamics and t is time.   Lanting
(1986) evaluated similar models with respect to soiling by paniculate elemental carbon (PEC) in
the Netherlands. He determined that the models were good predictors of soiling of building
materials by fine mode black smoke.  Based on the existing levels of PEC, he concluded that the
cleaning frequency would be doubled.
     An important particle dynamic is deposition velocity which is defined as flux divided by
concentration and is a function of particle diameter, surface orientation, and surface roughness,
as well as other factors such as wind speed, atmospheric stability, and particle density.  Thus,
soiling is expected to vary with the size distribution of particles within an ambient concentration,
whether a surface is facing skyward (horizontal versus vertical), and whether a surface is rough
or smooth.
     Van Aalst (1986) reviewed particle deposition models existing at that time and  pointed out
both their benefits and their faults. The lack of significant experimental verification  was a major
fault. Since then, Hamilton and Mansfield (1991, 1993) have applied the model reported by
Haynie (1986) and Haynie and Lemmons (1990) to soiling experiments with  relatively good
predictive success.
     Terrat and Joumard (1990) found that the simple plate method (a measurement of the
number of particles deposited on a flat inert plate of material),  as well  as the measurement of
reflectance and transmission of the light really showed the amount of soiling  deposit  in a town.
The simple plates are more suitable for high particle polluted areas and the optical methods are
more suitable for low pollution areas. This study also provided evidence that motor vehicles are
mainly responsible for soiling the facades along roads.
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9.2.1.1    Fabrics
     No recent information on the effects of particles on fabrics was located in the published
literature. Earlier studies indicate particles are only damaging to fabrics when they are abrasive.
Yocom and Upham (1977) reported that curtains hanging in an open window often split in
parallel lines along the fold after being weakened by particle exposure. The appearance and life
usefulness also may be lessened from increased frequencies of washing as a result of particle
"soiling". Rees (1958) described the mechanisms (mechanical, thermal, and electrostatic) by
which cloth is soiled.  Tightly woven cloth exposed to moving air containing fine carbon
particles  was found to be the most resistant to soiling. Soiling by thermal precipitation was
related to the surface temperature of the cloth versus that of the air.  When the surface
temperature of the cloth was greater than that  of the air, the cloth resisted soiling. When cloth
samples were exposed to air at both positive and negative pressure, the samples exposed to
positive pressure showed greater soiling than those exposed to equivalent negative pressure.

9.2.1.2    Household and Industrial Paints
     Research suggest that particles can serve as carriers of more corrosive pollutants, allowing
the pollutants to reach the underlying surface or serve as concentration sites for other pollutants
on painted surfaces (Cowling and Roberts, 1954). Paints may also be soiled by liquids and solid
particles  composed of elemental carbon, tarry acids, and various other constituents.
     Haynie and Lemmons (1990) conducted a soiling  study at an air monitoring site in a
relatively rural environment in Research Triangle Park,  NC. The study was designed to
determine how various environmental factors  contribute to the rate of soiling of white painted
surfaces. White painted surfaces are highly sensitive to soiling by dark particles  and represent a
large fraction of all manmade surfaces exposed to the environment.  Hourly rainfall and wind
speed, and weekly data for dichotomous sampler measurements and TSP concentrations were
monitored. Gloss and flat white paints were applied to hardboard house siding surfaces and
exposed vertically and horizontally for  16 weeks, either shielded from or exposed to rainfall.
Particle mass concentration, percentage of surfaces covered by fine and coarse mode fractions,
average wind speed and rainfall amounts, and paint reflectance
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changes were measured at 2, 4, 8, and 16 weeks. The scanning electron microscopy stubs, that
had been flush-mounted on the hardboard house siding prior to painting, were also removed and
replaced with unpainted stubs at these intervals.
     The unsheltered panels were initially more soiled by ambient pollutants than the sheltered
panels; however, washing by rain reduced the effect.  The vertically exposed panels soiled at a
slower rate than the horizontally exposed panels. This was attributed to additional contribution
to particle flux from gravity. The reflectivity was found to decrease faster on glossy paint than
on the flat paint (Haynie and Lemmons, 1990).
     Least squares fits through zero of the amounts on the surfaces with respect to exposure
doses provided the deposition velocities. There was no statistical difference between the
horizontal and vertical surfaces for the fine mode and the combined data given a deposition
velocity of 0.00074 + 0.000048 cm/s (which is lower than some reported values).  The coarse
mode deposition velocity to the horizontal surfaces at 1.55 cm/s is around five times greater than
to vertical surfaces at 0.355  cm/s.  By applying assumptions these deposition velocities can be
used to calculate rates of soiling for sheltered surfaces.  The empirical prediction equation for
gloss paint to a vertical surface based on a theoretical model (Haynie, 1986) is:

         R = R0 exp (-0.0003 [0.0363Cf + 0.29CJt)                                 (9.8)


where R and R0 are reflectance and original reflectance, respectively, Cf and Cc are coarse and
fine mode particle concentrations in //g/m3, respectively, and t is time in weeks of exposure.
     The fine mode (<2.5 //m) did not appear to be washed away by rain, but most of the coarse
mode (>2.5 //m to 10 //m) was either dissolved to form a stain or was washed away.  Therefore,
for the surfaces exposed to rain, the 0.0363 coefficient for the fine mode should remain the same
as it is  for sheltered surfaces but there should be a time-dependent difference in the coefficient
for the coarse mode.
     Based on the results of this study, the authors concluded that:  (1) coarse mode particles
initially contribute more to soiling of both horizontal and vertical surfaces than fine mode
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particles; (2) coarse mode particles, however, are more easily removed by rain than are fine
mode particles; (3) for sheltered surfaces reflectance changes is proportional to surface coverage
by particles, and particle accumulation is consistent with the deposition theory; (4) rain interacts
with particles to contribute to soiling by dissolving or desegregating particles and leaving stains;
and (5) very long-term remedial actions are probably taken because of the accumulation of fine
rather than coarse particles (Haynie and Lemmons, 1990).
     Similar results were also reported by Creighton et al. (1990). They found that horizontal
surfaces, under the test conditions, soiled faster than did the vertical surfaces, and that large
particles were primarily responsible for the soiling of horizontal surfaces not exposed to rainfall.
Soiling was related to the accumulated mass of particles from both the fine and coarse fractions.
Exposed horizontal  panels stain because of dissolved chemical constituents in the deposited
particles.  The size distribution of deposited particles was bimodal, and the area of coverage by
deposited particles was also bimodal with a minimum at approximately 5 //m.  The deposition
velocities for each of the size ranges onto the horizontal, sheltered panel was in general
agreement with both the theoretical settling velocity of density 2.54 g/cm3 spheres and the
reported results of laboratory tests. An exponential model (Haynie, 1986) was applied to the
data set and gave a good fit.
     Spence and Haynie  (1972) reported on the published data on the effects of particles on the
painted exterior surfaces of homes in Steubenville and Uniontown, OH, Suitland and Rockville,
MD, and Fairfax, VA. There was a direct correlation between the ambient concentration of
particulate matter in the city and the number of years between repainting.  The average
repainting time for homes in Steubenville, where parti culate matter concentrations averaged 235
Mg/m3, was approximately one year. In the less polluted city, Fairfax, where the  particulate
matter concentrations only reached 60 //g/m3 (arithmetic means), the time between repainting
was 4 years. Parker (1955) reported the occurrence of black specks on the freshly paint surface
of a building in an industrial area.  The black specks were not only aesthetically unappealing, but
also physically  damaged the painted surface. Depending on the particle concentration, the
building required repainting  every 2 to 3 years.
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9.2.1.3    Soiling of Works of Art
     Ligocki et al. (1993) studied potential soiling of works of art.  The concentrations and
chemical composition of suspended particles were measured in both the fine and coarse size
modes inside and outside five Southern California museums during  summer and winter months.
The seasonally averaged indoor/outdoor ratios for particle mass concentrations ranged from 0.16
to 0.96 for fine particles and from 0.06 to 0.53 for coarse particles, with lower values observed
for buildings with sophisticated ventilation systems that include filters for particle removal.
Museums with deliberate particle filtration systems showed indoor fine particle concentrations
generally averaging less than 10 //g/m3.  One museum with no environmental control system
showed indoor fine particles concentrations averaging nearly 60 //g/m3. Analysis of indoor
versus outdoor concentrations of major chemical species indicated that indoor sources of
organics may exist at all sites, but that none of the other measured species appear to have major
indoor sources at the museums studied.  The authors concluded that a significant fractions of the
dark-colored fine elemental carbon and soil dust particles present in the outdoor environment
had penetrated to the indoor atmosphere of the museums studied and may constitute  a soiling
hazard to displayed works of art.
     Methods for reducing the soiling rate in  museums that included reducing the building
ventilation rate, increasing the effectiveness of particle filtration, reducing the particle deposition
velocity onto surfaces of concern, placing  objects within display cases or glass  frames, managing
a site to achieve lower outdoor aerosol concentrations, and eliminating indoor particle sources
were proposed by Nazaroff and Cass (1991).  According to model results, the soiling rate can be
reduced by at least two orders of magnitude through practical application of these control
measures. Combining improved filtration with either a reduced ventilation  rate for the entire
building or low-air-exchange display cases would likely reduce the soiling hazard in museums.
9.3  ECONOMIC ESTIMATES
     Only limited new information was located in the published literature on the economic cost
of soiling and corrosion by particles. Many of these studies are flawed or represent monetary
cost for materials damage and soiling that are not representative of monetary losses
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today.  A detailed discussion of earlier studies on economic loss from exposure to acid forming
aerosols and other particles can be found in the previous criteria document for paniculate matter
(U.S. Environmental Protection Agency, 1982). The following sections describe methods for
determining economic losses from materials damage and soiling from air pollution and includes
the limited body of new information available since publication of the 1982 particulate matter
criteria document.

9.3.1    Methods for Determining Economic Loss from Pollutant  Exposure
     Several types of economic losses result from materials damage and soiling. Financial or
out-of-pocket losses include the reduction in service life of a material, decreased utility,
substitution of a more expensive material, losses due to an inferior substitute, protection of
susceptible materials, and additional required maintenance, including cleaning.  The major losses
of amenity, as defined by Maler and Wyzga (1976), are associated with enduring and suffering
soiled, damaged, or inferior products and materials because of particle pollution and any
corrosive pollutant that may be absorbed on or adsorbed to particles. In addition, amenity losses
are suffered when pollution damage repair or maintenance procedures result in inconvenience or
other delays in normal operations. Some of these losses, such as effects on monuments and
works of art, are especially difficult to specify (Maler and Wyzga, 1976).
     The compilation and assessment of materials damage and soiling research  reveals a variety
of techniques employed by different disciplines to estimate economic losses associated with
soiling and materials damage. Attempts have been made to address the following questions.
     •  At what concentration or deposition rate is materials damage and soiling perceived?
     •  What is the relationship between the color of the particle and perceived materials
        damage and soiling?
     •  What is the physical or economic life of various materials,  coatings, structures, etc.?
     •  What is the inventory of pollution sensitive materials, coatings, structures, etc.?
     •  What behaviors are  undertaken to avert, mitigate, or repair pollution-related damages?
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     •  What is the economic cost of materials damage and soiling due to exposure to acid
        forming aerosols and other particles?
     The answers to these questions are certainly relevant to the structure of a modeling
framework, the collection of data, and the estimation of effects of materials damage and soiling
on economic values.  The analytical approach selected depends on whether financial losses or
losses of amenity are emphasized, the type of damage being considered, and the availability of
cost information. Economic losses  from pollutant exposure can be estimated using the damage
function approach or using direct economic methods.
     In the damage function approach, physical damage (any undesirable change in the function
of specific materials, including appearance, leading to failure of specific components) is
determined before economic cost is estimated. Physical  damage is estimated from ambient
pollutant concentrations over a specified period of time.  Depending on the material damaged,
both short-term and long-term exposure data may be necessary to determine a more accurate
estimate of damage related to pollution exposure.  The damage function is expressed in terms
appropriate to the interaction of the pollutant and  material. For example, the corrosion of metal
may be expressed in units of thickness lost, while the deterioration of paint from soiling may be
expressed in units of reflectance lost.  A willingness-to-pay value,  mitigation, or replacement
cost is then applied to estimate a monetary value of damages caused by changes in pollutant
concentrations. It is, however, difficult to estimate fully the financial losses because reliable
information is not available on the physical damage of all economically important materials, and
on the spatial and temporal distribution of these materials. Further, current techniques do not
reflect the use of more resistant and reduced-maintenance materials, and loss estimates may
assume that substitute materials cost more than the original materials, and that the cost
differential is attributable solely to pollution.
     Another major problem in developing reliable damage functions is the inability  to separate
pollutant effects from natural weathering processes due to various meteorological parameters
(temperature, relative humidity, wind speed, and surface wetness).  Since weathering  is a natural
phenomenon, proceeding at a finite rate irrespective of anthropogenic pollution, materials
damage estimates must represent only that damage directly produced by
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anthropogenic pollutant exposure. Also, this approach cannot account for irreplaceable items
such as works of art or national monuments.
     In the studies that do not use the physical damage approach to derive monetized economic
damages reflecting the estimates of damages associated with pollution, the loss of amenity or
direct financial losses are estimated econometrically. These approaches have been used to relate
changes in air pollution directly with the economic value of avoidance or mitigation of damages.
A major source of error using these approaches is the requirement that all factors that affect cost
other than air quality have to be accounted for. In general all approaches to estimating costs of
air pollution effects on materials are limited by the difficulty in quantifying the human response
to damage based upon the ability and the incentive to pay additional costs (Yocom and
Grappone, 1976).

9.3.2    Economic Loss Associated with  Materials Damage and Soiling
     Information on the geographic distribution  of various types of exposed materials may
provide an indication of the extent of potential economic costs of damge to materials from air
pollution. Lipfert and Daum (1992) analyzed the efforts made to determine the geographic
distribution of various types of materials. They focused on the identification, evaluation and
interpretation of data describing the distribution of exterior construction materials, primarily in
the United States. Materials distribution surveys for 16 cities in the United States and Canada
and five related data bases from government agencies  and trade organizations were examined.
Data on residential buildings were more available than non-residential buildings; little
geographically resolved information on distributions on materials in infrastructure was found.
     Lipfert and Daum (1992) observed several  important factors relating pollution to
distribution of materials.  In the United States, buildings constitute the largest category of
surface areas potentially at risk to pollution damage. Within this category, residential buildings
are the most important. On average, commercial and industrial buildings tend to be larger than
residential buildings and to use more durable materials. However, because they are more
numerous (and use less durable materials) more surface area for residential buildings is exposed
to potentially damaging pollutants.  For residential buildings in general, painted surfaces are
preferred over masonry in the Northeastern United States (with the
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exception of large inner cities), brick is popular in the South and Midwest) and stucco in the
West.  The use of brick appears to be declining, painted wood increasing, and the use of vinyl
siding is gaining over aluminum. One of the factors underlying the present regional distribution
of materials is their durability under the environmental conditions which exist when they were
installed.  Thus, changing pollution levels have possibly affected materials selection, and is
expected to do so.
     Haynie (1990) examined the potential effects of PM10 nonattainment on the costs of
repainting exterior residential walls due to soiling in 123 counties.  The analysis was based on a
damage function methodology developed for a risk assessment of soiling of painted exterior
residential walls (Haynie, 1989). The data base was updated with 1988 and 1989 AIRS data.
An extreme value statistical model was used to adjust every sixth day monitoring to 365 days for
counting violation days (one violation in 60 does not translate to 6 violations in 360).  The
resulting paint cost due to soiling was subjected to a  sensitivity analysis using various assumed
values.  When the model is restricted to only a national average of 10% of households repainting
because of soiling, the effects of other assumptions become inversely related and tend to cancel
out each other (possibly associated with individual cost minimization choices).
     The top twenty counties were ranked by estimated soiling costs. Fourteen of the counties
with actual violation days in 1989 were in this group. All but three were west of the Mississippi.
A total of 29 counties with measured violations are in the set of 123 counties for which PM10
nonattainment soiling costs were calculated.  When the given set of behavior assumptions was
used, there were no costs calculated for 19 counties that actually measured violations in 1989.
The distribution of a national estimated $1 billion in  painted exterior residential wall soiling
costs is shown in Figure 9-2.
     An experimentally determined soiling function for unsheltered, vertically exposed house
paint was used to determine painting frequency (Haynie and Lemmons, 1990) .  An equation
was set up to express paint life in integer years because the painting of exterior surfaces is
usually controlled by season (weather). Different values for normal paint life without soiling
and levels of unacceptable soiling could be used in the equation. If four was taken as the most
likely average paint life for other than soiling reasons, then painting because of soiling would
likely be done at  1, 2, or 3 year intervals.
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 >100  10-100   1-10  0.1-1   0.01-0.1
 County Paint Soiling Costs - Million  Dollars
Figure 9-2.  Geographic distribution of paint soiling costs.
Source: Haynie (1990).


     Soiling costs by county were calculated and ranked by decreasing amounts and the
logarithm of costs plotted by rank.  The plot consisted of three distinct straight lines with
intersections at ranks 4 and 45. The calculated cost values provide a reasonable ranking of the
soiling problem by county, but do not necessarily reflect actual painting cost associated with
extreme concentrations of particles.  Households exposed to extremes are not expected to
respond with average behavior. The authors concluded that repainting costs could be lowered if:
(1) individuals can learn to live with higher particle pollution, accepting greater reductions in
reflectance before painting; (2) painted surfaces were washed rather than repainted; and (3) if
materials or paint colors that do not tend to show dirt were used.
     Extrapolating the middle distribution of costs to the top four ranked counties reduces their
estimated costs considerably.  For example Maricopa County, AR, was calculated to rank first at
$70.2 million if all households painted each year as predicted, but was calculated to be only
$29.7 million based on the distribution extrapolation.
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     Based on these calculations and error analysis, the national soiling costs associated with
repainting the exterior walls of houses probably were within the range of $400 to $800 million a
year in 1990. This sector represents about 70% of the exterior paint market, so that
extrapolating to all exterior paint surfaces gives a range of from $570 to $1,140 million (Haynie
andLemmons, 1990).
     A number of other studies have attempted to model the economic losses of soiling due to
particulate air pollution. Based on the hypothesis that air pollution affects the budget allocation
decisions of individuals, MathTech (1983) used a household sector model to establish a
statistical relationship between TSP and the demand for laundry and cleaning products and
services using 1972-1973 Bureau of Labor Statistics Consumer Expenditure data. Given
knowledge of the pattern of demand for these goods, standard methods of welfare economics
were used to estimate the benefits (or compensating variation) of changes in TSP concentrations.
The results of this study indicated that the annual benefits of attaining the primary PM10 standard
were approximately $88.3  million to $1.2 billion in 1980 dollars for the period  1989 to 1995.
The applicability of the underlying  relationship to current air quality and economic conditions is
uncertain given that potential changes in consumer tastes and the opportunity set of goods
influencing budget allocation decisions could have changed over the intervening 20 years.
     MathTech (1990) also assessed the effects of acidic deposition on painted wood surfaces
using individual maintenance behavior data. The effects were a function of the repainting
frequency of the houses as well as pollution levels.
     Gilbert (1985) used a household production function framework to design and estimate the
short-run costs of soiling.  The results were comparable to those reported by MathTech (1983).
Smith and Gilbert (1985) also used a hedonic property value model to  analyze the effects of
particles in the long term, examining the possibility of households moving in response to air
pollution.
     McClelland et al. (1991) conducted a field  study valuing eastern visibility using the
contingent valuation method.  Given the problem of embedding between closely associated
attributes, the survey instrument provided for separation of the visibility, soiling, and health
components of the willingness-to-pay estimates.  Households were found to be willing to pay
$2.70 per //g/m3 change in particle  pollution to avoid soiling effects.
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     The findings of the aforementioned studies are consistent with the hypotheses that there are
economic costs associated with elevated pollution levels across multiple sectors and that
households are willing to pay positive amounts to reduce particle concentrations to reduce the
risk of materials damage and soiling. However, these studies have done little to advance our
knowledge of perception thresholds in relationship to concentration, particle size, and chemical
composition. Without such information it is very difficult and highly uncertain to quantify the
relationship between ambient particle concentrations and soiling and associated economic cost.
9.4  SUMMARY
     Available information supports the fact that exposure to acid forming aerosols promotes
the corrosion of metals beyond the corrosion rates expected from exposure to natural
environmental elements (wind, rain, sun, temperature fluctuations, etc.). Many metals form a
protective film that protects against corrosion; however, high concentrations of anthropogenic
pollutants, lessen the effectiveness of the protective film. Acid forming aerosols have also been
found to limit the life expectancy of paints by causing discoloration, loss of gloss, and loss of
thickness of the paint film layer.
     Various building  stones and cement products are damaged from exposure to acid-forming
aerosols. However, the extent of the damage to building stones and cement products produced
by the pollutant species, beyond that expected as part of the natural weathering process is
uncertain. Several investigators have suggested that the damage attributed to acid forming
pollutants is overestimated and that stone damage is predominantly associated with relative
humidity, temperature, and, to a lesser degree, air pollution.
     A significant detrimental effect of particle pollution is the soiling of painted surfaces and
other building materials.  Soiling is defined as a degradation mechanism that can be remedied by
cleaning or washing, and depending on the soiled surface, repainting.  Available data on
pollution exposure indicates that particles can result in increased cleaning frequency of the
exposed surface, and may reduce the life usefulness of the material soiled.  Data on the effects of
particulate matter on other surfaces are not as well understood. Some evidence does, however,
suggest that exposure to particles may  damage fabrics, electronics, and works
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of art composed of one or more materials, but this evidence is largely qualitative and sketchy.
     The damaging and soiling of materials by acid forming aerosols and other particles have an
economic impact, but this impact is difficult to measure. One problem is the lack of sufficient
data to separate costs between various pollutants and to separate cost of pollutant exposure from
that of normal maintenance. Attempts have been made to quantify the pollutants exposure levels
at which materials damage and soiling have been perceived.  However, to date, insufficient data
are available to advance our knowledge regarding perception thresholds with respect to pollutant
concentration, particle size, and chemical composition.
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   10.  DOSIMETRY OF INHALED PARTICLES IN THE
                         RESPIRATORY TRACT
10.1  INTRODUCTION
     Development of an efficient air-breathing respiratory tract was a critical requirement for
mammalian evolution. The combination of airways and airspaces in an internalized and
arborized arrangement that expands with incoming tidal air and contracts with its ebb led to the
vertebrate lung. This very design that led to the close proximity of the alveolar air spaces to the
outside environment for efficient air exchange also makes the lung vulnerable to insult by
inorganic and organic dusts, and by microorganisms. The intense perfusion of these spaces by
essentially the entire cardiac output also makes the lung vulnerable to many blood-borne,
chemical, microbial, and immunologic agents.
     It is a basic tenet of toxicology that the dose delivered to the target site, not the external
exposure, is the proximal cause of a response.  Therefore, there is increased emphasis on
understanding the exposure-dose-response relationship. In the case of PM, exposure is what gets
measured (or estimated) in the typical study and what gets regulated; inhaled dose is the
causative factor.  Even if inhaled dose could be easily defined, it fits within a complex
continuum. For example, as illustrated in Figure 10-1, it is ultimately desirable to have a
comprehensive biologically-based dose-response model that incorporates the mechanistic
determinants of chemical disposition, toxicant-target interactions, and tissue response integrated
into an overall model of pathogenesis. Mathematical dosimetry models that incorporate
mechanistic determinants of disposition (deposition, absorption, distribution, metabolism, and
elimination) of chemicals have been useful in describing relationships along this continuum
(e.g., between exposure concentration and target tissue dose), particularly as applied to
describing these relationships for the exposure-dose-response component of risk assessment.
With each progressive level, incorporation and integration of mechanistic determinants allow
further elucidation of the exposure-dose-response continuum and, depending on the knowledge
of model parameters and fidelity to the biological system, a more accurate characterization of the
pathogenetic process. Thus, once the site and
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 Protective
 Predictive
                  Chemical
                  Exposure
                Concentration
"Dose"
                  Exposure
                                          Default
                  Exposure
                           Mechanisms v
                         Disposition Models
                  Exposure
Toxicological
 Response
                     Response
                                      Qualitative
                     Response
                     Response
                         Disposition Models Toxicant-Target Models
                         Disposition Models Toxicant-Target ModelsTissue Response Models
                                      Quantitative
Figure 10-1.  Schematic characterization of comprehensive exposure-dose-response
              continuum and the evolution of protective to predictive dose-response
              estimates.
Source: Adapted from Conolly (1990) and Andersen et al. (1992).
mechanisms are known, dosimetry may prove useful in linking exposure to internal dose and
effects, and to the extrapolation of variability both within and across species.  For example, a
healthy individual and a person with emphysema will not get identical doses to specific lung
regions even if their external exposure is identical.  Knowledge of how and to what extent
disease factors affect dose can assist in characterizing susceptible subpopulations. If a rat and a
human are identically exposed, they will receive different doses to regions of the respiratory
tract. Insofar as this is quantitatively understood, laboratory animal data can be made more
useful in assessing human health risks.
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     Characterization of the exposure-dose-response continuum for PM requires the elucidation
and understanding of the mechanistic determinants of inhaled particle dose, toxicant-target
interactions, and tissue responses. Only the first level of characterization, i.e., description of the
factors that influence inhaled dose has been accomplished to any degree for PM.  Inhaled
particles are deposited in the respiratory tract by mechanisms of interception, impaction,
sedimentation, diffusion, and electrostatic precipitation. The relative contribution of each
deposition mechanism to the fraction of inhaled particles deposited varies for each region of the
respiratory tract (extrathoracic, ET; tracheobronchial, TB; and alveolar, A). Subsequent
clearance of deposited particles depends on the initial deposition site, physicochemical properties
of the particles (e.g., solubility), translocation mechanisms such as mucociliary transport and
endocytosis by macrophages or epithelial cells, and on the time since initial deposition.
Retained particle burdens and ultimate particle disposition are determined by the dynamic
relationship between deposition and clearance mechanisms.
     The biologically effective dose resulting from inhalation of airborne particles can be
defined as the time integral of total inhaled particle mass, particle number, or particle surface
area per unit of surface area (e.g., surface area of a given region such as the TB) or per unit mass
of the respiratory tract. Choice of the metric to characterize the biologically effective inhaled
dose should be motivated by insight on the mechanisms of action of the compound (or particles)
in question.  Conceptually,  as illustrated in Figure 10-2, the exposure-dose-response continuum
can be represented as events in the progression from exposure to disease. The components
depicted in Figure 10-2 are not necessarily discrete, nor the only events in the continuum, and
represent a conceptual temporal sequence.  The left-most component of the continuum generally
precedes any component to the right, but some impacts may be detectable in parallel.  As our
understanding of the continuum is supplemented by identification of the important intervening
relationships and the components are characterized more precisely or with greater detail, the
health events of concern can be viewed as a series of changes from homeostatic adaption,
through dysfunction, to disease and death.  The critical effect could become that biologic marker
deemed most pathognomonic or of prognostic significance, based on validated hypotheses of the
role of the marker in the development of disease. The  appropriate dose metric would then be
defined by a measure
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                      Exposure
Effect
                                      Susceptibility
Figure 10-2.  Biological marker components in sequential progression between exposure
              and disease.
Source: Schulte (1989).
that characterizes the biologically effective dose for the mechanism of action causing that critical
effect.
     Elucidation of the toxic moiety as well as the mechanism of action for PM have remained
elusive, however. The link to the epidemiological findings discussed in Chapter 12 lies in
understanding the sites of injury and the types of injury. The appropriate dose metric for PM
might accurately be described by particle deposition alone of the particles exert their primary
action on the surface contacted (Dahl et al., 1991).  For longer-term effects, the deposited dose
may not be a decisive metric, since particles clear at varying rates from the different respiratory
tract regions. At this point, when considering the epidemiologic data, dose metrics can only be
separated into two major categories: (1) the pattern and quantity of deposited particle burdens,
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and (2) the pattern and quantity of retained particle burdens.  The deposited dose or initial acute
deposition (e.g., particle mass burden per 24-hours) may be relevant to "acute" effects observed
in the epidemiologic studies such as "acute" mortality, hospital admissions, work loss days, etc.
On the other hand, retained dose may be more appropriate for chronic responses such as
induction of chronic disease, shortening of life-span ("premature mortality"), morbidity, or
diminished quality of life.
     Another aspect of the definition of the dose metric that would benefit from mechanism of
action information include whether mass is the appropriate measure of particle burden and how
to normalize the inhaled particle burdens. To date, most of the epidemiologic studies have relied
upon the particle mass concentration (//g/m3) to characterize particle exposures. Alternative
expressions that may be more relevant to certain mechanisms of injury include numbers of
particles or aggregate particle surface area. For example, the fine fraction contains by far the
largest number of particles and those particles have a large aggregate surface area.  Oberdorster
et al. (1992) have shown ultrafme particles are less effectively phagocytosed by macrophages
than larger particles. Anderson et al. (1990) have shown that the deposition of ultrafme particles
in patients with COPD is greater than in healthy subjects.  The need to consider particle number
is accentuated when the high deposition efficiency of small particle numbers in the lower
respiratory tract, the putative target for both the mortality and morbidity effects of PM
exposures, is taken into account.
     Insight on how PM causes injury would also inform what normalizing factor to use to
define the dose metric. Particle mass or number burdens could be normalized to respiratory tract
surface area, to lung mass, or to other anatomical or functional units critical to determining the
toxicity such as ventilatory units, alveoli, or macrophages.  Clearly, inhaled dose is important,
but the most appropriate dose metric or metrics to quantitatively link with the observed acute or
chronic health outcomes await elucidation of the pertinent mechanisms of injury and  tissue
response.
     For the present document, average daily deposited particle mass burden in each region of
the respiratory tract has been selected as the dose metric to characterize "acute" effects. Average
retained particle mass burden in each region for humans and in the lower respiratory tract for
laboratory animals has been selected as the dose metric  for "chronic" effects.  As discussed  in
Section 10.7.3., these choices were dictated by the selection of the dosimetry models  and the
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availability of anatomical and morphometric information. Both deposited particle mass and
number burdens in each respiratory tract region are estimated for human exposures.  Retained
particle burdens are normalized per gram of lung tissue.
     The chapter first describes important particle characteristics and the basic mechanisms of
particle deposition and clearance in the respiratory tract.  The available mathematical dosimetry
models for humans and laboratory animals are reviewed as a background to the application
presented in Section 10.7.  Dosimetry models are selected for human exposure simulations and
to perform interspecies extrapolation of laboratory animal toxicity studies.  The rationale for
selection of the extrapolation models is provided. An attempt is made to ascertain whether
dosimetry modeling can provide insight into the apparent discrepancies between the
epidemiologic and laboratory animal data, to identify plausible dose metrics of relevance to the
available health endpoints, and to identify modifying factors that may enhance susceptibility to
inhaled particles.  Simulations of variability due to key modifying factors (age, gender, disease
status) are also  attempted.  This information should be useful to the interpretation of health
effects data in Chapters 11 and 12.
     The chapter deals exclusively and genetically with aerosols  (i.e., both airborne droplets
and solid particles, including the hygroscopic, acidic variety). It briefly reviews selected studies
that have been reported in the literature on particle deposition and retention since the publication
of the 1982 Air Quality Criteria Documents on Particulate Matter and Sulfur Oxides and the
1989 Acid Aerosols Issue Paper (U.S. Environmental Protection Agency; 1982, 1989), but the
focus is on newer information.
10.2  CHARACTERISTICS OF INHALED PARTICLES
     Information about particle size distribution aids in the evaluation of the effective inhaled
dose. Because the characteristics of inhaled particles interact with the other major factors
controlling comparative inhaled dose, this section discusses aerosol attributes requiring
characterization and provides general definitions.
     An aerosol is a suspension of finely dispersed solids or liquids in air.  It is intrinsically
unstable, and hence, tends to deposit both continuously and inelastically onto exposed surfaces.
From the perspective of health-related actions of aerosols, interest is limited to particles that can
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at least penetrate into the nose or mouth and that deposit on respiratory tract surfaces.  For
humans, this constraint ordinarily eliminates very coarse particles, viz., greater than about 100
fj.m diameter. Particles between 1 jim and 20 jim diameter are commonly encountered in the
work place and the ambient air. Still smaller, i.e., submicron diameter particles (less than 1 jim
in diameter) are generally the most numerous in the environmental air, with the number
concentration of particles tending to increase markedly for smaller particles. Even particles
down to the nanometer (nm) size domain are found in the  atmosphere and are of interest,
although until recently, these "ultrafine" particles were of  greater interest to atmospheric
scientists than to biomedical scientists. Typically, "ultrafine" aerosols are produced by highly
energetic reactions (e.g., high temperature sublimation and combustion, or by gas phase
                                                               o
reactions involving atmospheric pollutants). Note that 10  nm = 100 Angstroms = 0.01 //m or
IxlO"6 cm diameter.
     Because aerosols can consist of almost any material, descriptions of aerosols in simple
geometric terms can be misleading unless important factors relating to size, shape, and density
are  considered.  Aerosol constituents are usually described in terms of their chemical
composition and geometric or aerodynamic sizes. Additionally,  aerosol particles may be defined
in terms of particle surface area. It is important to note that aerosols present in natural and work
environments all have polydisperse size distributions. This means that the particles comprising
the  aerosols have a range of geometric size, aerodynamic size, and surface area and are more
appropriately described in terms of size distribution parameters.  Aerosol sampling devices can
be used to collect bulk or size fractions of aerosols to allow defining the size distribution
parameters. In  this procedure, the amount of particles in defined size parameter groups (number,
mass, or surface area) is divided by the total number, mass, or surface of all particles collected
and divided also by the size interval for each group.  Data from the sampling device are then
expressed in terms of the fraction of particles per unit size interval.  The next step is to use this
information to define an appropriate particle size distribution.
     The lognormal  distribution has been widely used for describing size distributions of
radioactive aerosols (Hatch and Choate, 1929; Raabe, 1971) and is also generally used as a
function to describe other kinds of aerosols. For many aerosols,  their size distribution may be
described by a lognormal distribution, meaning that the distribution will resemble the bell-
shaped Gaussian error curve, if the frequency distribution  is based on the logarithms of the
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particle size.  The lognormal distribution is a skewed distribution characterized by the fact that
the logarithms of particle diameter are normally distributed.  In linear form, the logarithmic
mean is the median of the distribution.  The standard deviation, a, of this logarithmic normal
distribution is a logarithm, so that addition and subtraction of this logarithm to and from the
logarithmic mean is equivalent to multiplying and dividing the median by the factor og, with In
og = a. The factor og is defined as the geometric standard deviation. When any aerosol
distribution is "normalized", it acquires parameters and properties equivalent to those of the
Gaussian distribution. Accordingly, the only two parameters needed to describe the log normal
distribution are the median diameter and the geometric standard deviation, og, (ratio of the log
84%/log 50% size cut or log 50%/log 16% size cut, where the 50% size cut is the median). For
a distribution formed by counting particles, the median is called the count median diameter
(CMD). While there may be occasions when the number of the particles is of the greatest
interest, the distribution of mass in an aerosol according to particle  size is of interest if particle
mass determines the dose  of interest. Derivation of the particle mass distribution is essentially a
matter of converting a diameter distribution to a diameter-cubed distribution since the volume of
a sphere with diameter d is 7id3/6 and mass is simply the  product of particle volume and
physical density.
     The cumulative distribution of a lognormally distributed size distribution is conveniently
evaluated using log-probability graph paper on which the cumulative distribution forms a
straight line (Figure 10-3). This distribution can be used  for all three lognormally  distributed
particle size parameters discussed above, which are related as indicated in Figure 10-3.  The
characteristic parameters of this distribution are the size and og. The CMD is characterized by
the fact that half of the particles in  the size distribution are larger than the CMD and half of the
particles are smaller. Multiplying and dividing the CMD by og yields the particle size interval
for the distribution that contains about 68% of the particles by number.
     When particles are not spherical, equivalent diameters can be used in place of the physical
diameters of particles. A calculated parameter, the projected area diameter (diameter of a circle
having a cross sectional area equivalent to the particles in the distribution of interest) is often
used as the equivalent diameter.
                                           10-8

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                         103
                          5-
                          1:
                      E
                      ~ 0.5
                      o
                      4-*
                      o
                      E
                      ra
                      Q
                      o
                        0.1:
                       0.05.
                       0.01
                                        MMD
MMD = 2.0 M
SMD = 0.93
CMD = 0.20
cb=2-4
                           2   5  10   20 30   50    70 80  90  95 98
                                   Percent Less Than Indicated Size
Figure 10-3.  Lognormal particle size distribution for a hypothetical polydisperse aerosol.
     The mass median diameter (MMD) and surface median diameter (SMD), also shown in
Figure 10-3, are additional ways to describe size distributions of lognormally distributed
aerosols. In these distributions, half of the mass or surface area of particles is associated with
particles smaller than the MMD or SMD; the other half of the particles is associated with
particles larger than the MMD or SMD, respectively.
     The relationship of the various lognormal distribution parameters based on geometric
diameter of particles is unique, since the CMD, SMD, and MMD are all lognormal with the
same og, but with different means that can be calculated.  The CMD and og can be determined
and extrapolated to MMD, and SMD using the following relationships
                              In(MMD) = In(CMD) + 3(lnoJ2,
                                 (10-1)
and
                                           10-9

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                             In(SMD) = In(CMD) + 2(lnog)2.                        (10-2)

     For most aerosols, it is useful to define a particle's size in terms of its aerodynamic size
whereby particles of differing geometric size, shape and density are compared aerodynamically
with the instability behavior of particles that are unit density (1 gm/cm3) spheres.  The
aerodynamic behavior of unit density spherical particles can be determined, both experimentally
and theoretically, consequently, the aerodynamic diameter constitutes a useful standard by which
all particles can be compared in matters of inertial impaction and gravitational settling. Thus, if
the terminal settling velocity of a unit density sphere of 10 //m diameter is measured in still air,
the velocity induced by gravity would be ~3 x 10"1 cm/s. If the gravitational settling of an
irregularly shaped particle of unknown density was measured and the same terminal velocity was
obtained, the particle would have a 10 //m aerodynamic diameter (dae). Its tendency to deposit
by inertial processes on environmental surfaces or onto the surfaces of the human respiratory
tract will be the same as for the 10 //m unit density sphere.
     A term that is frequently encountered is mass median aerodynamic diameter (MMAD),
which refers to the mass median of the distribution of mass with respect to aerodynamic
diameter. With commonly-encountered aerosols having low to moderate polydispersity, og <2.5,
the Task Group on Lung Dynamics (TGLD) (1966) showed that mass deposition in the human
respiratory tract could be approximated by the deposition behavior of the particle of median
aerodynamic size in the mass distribution, the so-called MMAD.  This is successful because the
particles which dominate the mass distribution are those which deposit mainly by settling and
inertial impaction.
     In many urban environments, the aerosol frequency and mass distributions have been
found to be bimodal or trimodal (Figure 10-4), usually indicating a composite of several log
normal distributions where each aerosol mode was presumably derived from different formation
mechanisms or emission sources (John et al.,  1986). Conversely, in the laboratory,
experimentalists often create aerosol distributions which are lognormal or normal, and very
frequently, they generate monodisperse aerosols consisting of particles of nearly one size. The
use of monodisperse aerosols  of nearly uniform, unit density, spherical particles
                                          10-10

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O)
_0
<
51
   0)
   .a
   E
     1.2

     1.0

   ''o 0.8
   -h.
   0
r  | o.e

     0.4
   o>
   o
   IB
   S 0.2
     o1-
                  o 4
                  O)
                  |3
               0)
               £
               I 1
                                                I   I   |IIH     I  I  I
                                                     Volume
                                                                             11
                           0.01
                                       0.1              1
                                        Particle diameter (urn)
                                                                  10
Figure 10-4.  These normalized plots of number, surface, and volume (mass) distributions
              from Whitby (1975) show a bimodal mass distribution in a smog aerosol.
              Historically, such particle size plots were described as consisting of a coarse
              mode (2.5 to 15 /^m), a fine mode (0.1 to 2.5 ^m), and a nuclei mode (<
              O.OSjum). The nuclei mode would currently fall within the ultrafine particle
              range (0.005 to 0.1
greatly simplifies experimental deposition and retention measurements and also instrument
calibrations. With nearly uniform particles, the mass, surface area and frequency distributions
are nearly identical, another important simplification.
     The terms count median aerodynamic diameter (CMAD) and surface median aerodynamic
diameter (SMAD) might be encountered.  These distributions are useful in that they include
consideration of aerodynamic properties of the particles. If the particle aerodynamic or diffusive
diameter is determined when sizing is done, then the median  of the particle size distribution is
the CMAD, or count median diffusive (or thermodynamic) diameter (CMDD or CMTD),
respectively.  If the mass of particles is of concern, then the median that is derived is the MMAD
or mass median diffusive (or thermodynamic) diameter (MMDD or MMTD). Generally,
MMTDs or MMADs are generally used to evaluate particle deposition patterns in the respiratory
tract because deposition of inhaled aerosol particles, as discussed in detail later in this chapter, is
                                          10-11

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determined primarily by particle diffusive and aerodynamic properties of the particles rather
than simply particle physical size, surface area, volume, or mass. Activity median aerodynamic
diameter (AMAD) is the median of the distribution of radioactivity or toxicological or biological
activity with respect to size. Both MMAD and AMAD are determined using aerosol sampling
devices such as multistage impactors.  When particles become smaller than about 0.1 //m
diameter, their instability as an aerosol depends mainly on their interaction with air molecules.
Like particles in Brownian motion, they are caused to "diffuse".  For these small particles and
especially for ultrafine particles, this interaction is independent of the particle density and varies
only with geometric particle diameter.  Very small particles are not expressed in aerodynamic
equivalency, but instead to a thermodynamic-equivalent size. The thermodynamic particle
diameter (dra) is the diameter of a spherical particle that has the same diffusion coefficient in air
as the particle of interest. The activity median thermodynamic diameter (AMTD) is the diameter
associated with 50 percent of the activity for particles classified thermodynamically.
     The selection of the particle size distribution to  associate with health effects depends on
decisions about the importance of number of particles, mass of particles, or surface area of
particles  in producing the effects. In some situations, numbers of particles or mass of particles
phagocytized by alveolar macrophages may be important; in other cases, especially for particles
that contain toxic constituents, surface area may be the most important parameter that associates
exposures with biological responses or pathology. These particle distributions should all be
considered during the course of evaluating relationships between inhalation exposures to
particles  and effects resulting from the exposures.
     Most of the discussion in the remainder of this chapter will focus on MMAD because it is
the most  commonly used measure of aerosol distributions. If MMAD is not measured directly,
an alternative is to estimate MMAD from one of the particle size distributions that is based on
physical  size of the particles (CMD, MMD, and SMD), which can all be readily converted to
MMAD.  The approximate  conversion of MMD to MMAD is made using the following
relationship (neglecting correction for slip)
                           MMAD = MMD • (particle density)  .                      (10-3)
                                          10-12

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By definition, MMDD = CMTD, because behavior of particles in this size category does not
usually depend on aerodynamic properties.
     Because small particles have a large aggregate surface area, aerosols comprised of such
particles have increased potential for reactivity. For example, tantalum is a very stable,
unreactive metal, whereas aerosols of tantalum particles can be caused to explode by a spark.
The rates of oxidation and solubility are proportional to surface area as are the processes of gas
adsorption and  desorption, and vapor condensation and evaporation. Accordingly, special
concerns arise from gas-particle mixtures and from "coated" particles.  For a general review of
atmospheric aerosols, their characteristics and behavior, the publication Airborne Particles
prepared under the aegis of the National Research Council (1979) is recommended.
10.3  ANATOMY AND PHYSIOLOGY OF THE RESPIRATORY TRACT
     The respiratory systems of humans and various laboratory animals differ in anatomy and
physiology in many quantitative and qualitative ways. These differences affect air flow patterns
in the respiratory tract, and in turn, the deposition of an inhaled aerosol. Particle deposition
connotes the removal  of particles from their airborne state due to their inherent instabilities in air
as well as to addtional instabilities in air induced when additional external forces are applied.
For example, in tranquil air, a 10 jim diameter unit-density particle only undergoes
sedimentation due to the force of gravity.  If a 10 jim particle is transported in a fast moving air
stream, it acquires an  inertial force that can cause it to deposit on a surface projecting into the air
stream without significant regard to gravitational settling. For health-related issues, interest in
particle deposition is limited to that which occurs in the respiratory tract of humans and
laboratory animals during the respiration of dust-laden air.
     Once particles have deposited onto the surfaces of the respiratory tract, some will undergo
transformation, others will not, but subsequently, all will be subjected either to absorptive or
non-absorptive particulate removal processes, e.g., mucociliary transport, or a combination
thereof. This will result in their removal from the respiratory tract surfaces.  Following this,
they will undergo further transport which will remove them, to a greater or less degree, from  the
respiratory tract.  Such particulate matter is said to have undergone clearance. To the extent
                                           10-13

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particulate matter is not cleared, it is retained.  The temporal persistence of uncleared (retained)
particles within the structure of the respiratory tract is termed retention.
     Thus, either the deposited or retained dose of inhaled particles in each region is governed
by the exposure concentration, by the individual species anatomy (e.g., airway size and
branching pattern, cell types) and physiology (e.g., breathing rate, and clearance mechanisms),
and by the physicochemical properties (e.g.,  particle size, distribution, hygroscopicity,
solubility) of the aerosol. The anatomic and physiologic factors are discussed in this section.
The physicochemical properties of particles were discussed in Section 10.2. Deposition and
clearance mechanisms will  be discussed in Section 10.4.
     The  respiratory tract in both humans and various experimental mammals can be divided
into three  regions on the basis of structure, size, and function:  the extrathoracic (ET) region or
upper respiratory tract (URT) that extends from just posterior to the external nares to the larynx,
i.e., just anterior to the trachea; the tracheobronchial region (TB) defined as the trachea to the
terminal bronchioles where proximal mucociliary transport begins;  and the alveolar (A)  or
pulmonary region including the respiratory bronchioles and alveolar sacs. The thoracic  (TH)
region is defined as the TB  and A regions combined. The anatomic structures included in each
of these respiratory tract regions are listed in Table 10-1,  and Figure 10-5 provides a
diagrammatic representation of these regions as described in the International Commision on
Radiological Protection (ICRP) Human Respiratory Tract Model (ICRP66, 1994).
     Figure 10-6 depicts how the architecture of the respiratory tract influences the airflow in
each region and thereby the dominant deposition mechanisms.  The 5 major mechanisms
(gravitational settling, inertial impaction, Brownian diffusion, interception and electrostatic
attraction) responsible for particle deposition are schematically portrayed in Figure 10-6 and will
be discussed in detail in Section 10.4.1.
     In humans, the nasal hairs, anterior nares, turbinates of the nose, and glottic aperture in the
larynx are areas of especially high air velocities, abrupt directional  changes, and turbulence,
hence, the predominant  deposition mechanism in the ET region for large particles is inertial
impaction. In this process,  changes in the inhaled airstream direction or magnitude of air
velocity streamlines or eddy components are not followed by airborne particles because  of their
inertia.  Large particles (>5 //m in humans)  are more efficiently removed from the
                                          10-14

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                   TABLE 10-1. RESPIRATORY TRACT REGIONS
 Region
    Anatomic Structure
      Other Terminology
 Extrathoracic (ET)
 Tracheobronchial (TB)
 Alveolar (A)
Nose
Mouth
Nasopharynx
Oropharynx
Laryngopharynx
Larynx

Trachea
Bronchi
Bronchioles (including
terminal bronchioles)

Respiratory bronchioles
Alveolar ducts
Alveolar sacs
Alveoli
Head airways region
Nasopharynx (NP)
Upper respiratory tract (URT)
Naso-Oro-Pharyngo-Laryngeal
(NOPL)


Lower conducting airways
Gas exchange region
Pulmonary region
Adapted from: Phalenet al. (1988).



airstream in this region. The respiratory surfaces of the nasal turbinates are in very close

proximity to and designed to warm and humidify the incoming air, consequently they can also

function effectively as a diffusion deposition site for very small particles and an effective

absorption site for water-soluble gases. The turbinates and nasal sinuses are lined with cilia

which propel the overlying mucous layer posteriorly via the nasopharynx to the laryngeal region.

Thus, the airways of the human head are major deposition sites for the largest inhalable particles

(>10 jam aerodynamic diameter) as well as the smallest particles (<0.1 micrometers diameter).

For the most part, the ET structures are lined with a squamous, non-ciliated mucous membrane.

Collectively, the movement of upper airway mucus, whether transported by cilia or gravity, is

mainly into the gastrointestinal (GI) tract.

     As air is conducted into the airways of the head and neck during inspiration, it first passes

through either the nasal passages or mouth. Whereas nasal breathing is normal with most people

most of the time, the breathing mode usually depends upon the work load.  Work loads which

tend to treble or quadruple minute ventilation i.e., go from 10 L/m to
                                         10-15

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                     T
               Extrathoracic
                  Region
                            Pharynx"!
    Posterior
    Nasal Pasage
J~Nasal Part
   Oral Part
             Tracheobronchial
                  Region
                                                       Ciliated Bronchi:
                                                       Epithelium
                                                       (Secretory and
                                                       Basal Cells)
                                                                                     Bronchiolar

                                                                                     Alveolar Interstitial
                                                                       Bronchioles
                                                                          Terminal Bronchioles
                                                                      Respiratory Bronchioles
                                                                    Alveolar Duct +
                                                                    Alveoli
                                                         Alveolar Endothelium,
                                                         Epithelium and Interstitium
                                                         (Endothelial Cells, Type II
                                                         Epithelial Cells and Clara Celfe)
Figure 10-5.  Diagrammatic representation of respiratory tract regions in humans.

-------
  Directional
    Change
      Very
     Abrupt
                 Air
             Velocity
Impactiorj
                         lmpactioi|i
      Less
     Abrupt
       M
                               Interceptioji
            Impactioti V,  *r
            	
                                                             0
       Electrostati
       Precipitatio
Figure 10-6.  Schematic representation of five major mechanisms causing particle
           deposition where airflow is signified by the arrows and particle trajectories
           by the dashed line.


Source: Adapted from Casarett (1975); Raabe (1979); Lippmann and Schlesinger (1984).
                                  10-17

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30 to 40 L/m, cause most subjects to change from nasal to oronasal breathing.  In either case, the
inspired air then passes through the pharyngeal region into the larynx.
     From the larynx, inspired air passes into the trachea, a cylindrical muscular- cartilaginous
tube. The trachea measures approximately 1.8 cm diameter x 12 cm long in humans.  The
trachea, like other conducting airways of the lungs, is ciliated and richly endowed with secretory
glands and mucus-producing goblet cells.  The major or main stem bronchi are the first of
approximately 16 generations of branching that occur in the human bronchial "tree".  For
modeling purposes, Weibel (1963; 1980) described bronchial branching as regular and
dichotomous, i.e., where the branching parent tube gives rise, symmetrically, to two smaller (by
              3 r
approximately \/2) tubes of the same diameter. While this pattern provides a  simplification for
modeling, the human bronchial tree actually has irregular dichotomous branching, wherein the
parent bronchi gives rise to two smaller tubes of differing diameter and length. The number of
generations of branching occurring before the inspired air reaches the first alveolated structures
varies from about 8 to 18 (Raabe  et al.,  1976; Weibel, 1980). The junction of conducting and
respiratory airways appears to be  a key anatomic focus. Many inhaled particles of critical size
are deposited in the respiratory bronchioles that lie just distal to this junction, and many of the
changes characteristic of chronic  respiratory disease involve respiratory bronchioles and alveolar
ducts.
     Impaction remains a significant deposition mechanism for particles larger than 2.5 //m
aerodynamic equivalent diameter (dae) in the larger airways of the TB region in humans and
competes with sedimentation, with each mechanism being influenced by mean flow rate and
residence time, respectively.  As the airways successively bifurcate, the total cross-sectional area
increases.  This increases airway  volume in the region, and the air velocity is decreased.  With
decreases in velocity and more gradual changes in air flow direction as the branching continues,
there is more time for gravitational forces  (sedimentation) to deposit the particle.  Sedimentation
occurs because of the influence of the earth's gravity on airborne particles.  Deposition by this
mechanism can occur in all airways except those very few that are vertical.  For particles «4 //m
dae, a transition zone between the  two mechanisms, from impaction to predominantly
sedimentation, has been observed (U.S. Environmental Protection Agency,  1982).  This
transition zone shifts toward smaller particles for nose breathing.
                                          10-18

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     The surface area of the adult human TB region is estimated to be about 200 cm2 and its
volume is about 150 to 180 mL.  At the level of the terminal bronchiole, the most peripheral of
the distal conducting airways, the mean airway diameter is about 0.3 to 0.4 mm and their
number is estimated at about 6* 104. As to the variability of bronchial airways of a given size,
Weibel's model (1963) considered 0.2 cm diameter airways and noted that such airways occur
from the 4th to 14th generations of branching, peaking in frequency around the 8th generation.
An insight into the variabilities in various lung models was provided by Forrest (1993) who
indicated that the number of terminal bronchioles incorporated in Weibel's model was about
66,000, whereas, Findeisen (1935) used 54,000 and Horsfield and Cumming (1968) estimated
only 28,000.  The transitional airways of the human lung, the respiratory bronchioles and
alveolar ducts, undergo an average of another 6 generations of branching according to Weibel
(1980) before they become alveolar sacs.  On this basis, the dichotomous lung model indicates
there should be about 8.4><106 branches (223), serving 3><108 alveoli.  The "typical path" model of
Yeh and Schum (1980), adopted by the National Council on Radiation Protection (NCRP)
(Cuddihy et al., 1988), cites approximately 33,000 terminal bronchioles. The International
Commission on Radiological Protection (ICRP) utilized the dimensions from three sources in its
human respiratory tract model (ICRP66, 1994).
     The parenchymal tissue of the lungs surrounds all of the distal conducting airways except
the trachea  and portions of the mainstem bronchi.  This major branch point area is termed the
mediastinum; it is where the lungs are suspended in the thorax by a band of pleura called the
pulmonary  ligament, the major blood vessels enter and leave the hilus of each lung, and the site
of the mediastinal pleura which envelopes the heart and essentially subdivides the thoracic
cavity.
     Humans lungs are demarcated into 3 right lobes  and 2 left lobes by the pleural lining. The
suspension  of the lungs in an upright  human gives rise to a gradient of compliance increasing
from apex to base and thereby controls the sequential  filling and emptying of the lungs.
Subdivisions of the lobes (segments)  are not symmetrical due to a fusion of 2 (middle left lung)
of the 10 lobar segments of the lung and occasionally  an underdeveloped segment in the lower
left lobe.  Lobar segments can be related to specific segmental bronchi and  are useful anatomical
delineators  for bronchoalveolar lavage.
                                         10-19

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     The lung parenchyma is composed primarily of alveolated structures of the A region and
the associated blood vessels and lymphatics.  The parenchyma is organized into functional units
called acini which consist of the dependent structures of the first order respiratory bronchioles.
The alveoli are polyhedral, thin-walled structures numbering approximately 3*108 in the adult
human lung.  Schreider and Raabe (1981) provided a range of values, viz, 2 x 108 to 5.7 x 108.
The parenchymal lung tissue can be likened to a thin sheet of pneumocytes (0.5 to 1.0 jim
thickness) that envelopes the pulmonary capillary bed and is supported by a lattice of connective
tissue fibers:  these fibers enclose the alveolar ducts (entrance rings), support the alveolar septa,
and anchor the parenchymal structures axially (e.g. from pulmonary veins) and peripherally
(from the pleural surface).
     The alveolar walls or septa are constructed of a network of meandering capillaries
consisting mainly of endothelial cells, an overlying epithelium made of Type I cells or
membranous  pneumocytes (95% of the surface) with Type II cells or metabolically-active
cuboidal pneumocytes (5%  of the surface), and an interstitium or interseptal connective tissue
space that contains interstitial histiocytes and fibroblasts (Stone  et al., 1992). For about one-half
of the alveolar surface, the Type I pneumocytes and the capillary endothelia share a fused
basement membrane. Otherwise, there is an interstitial space within the septa which
communicates along the capillaries to the connective tissue cuffs around the airways and blood
vessels. The  connective tissue spaces or basal lamina of these structures are served by
pulmonary lymphatic vessels whose lymph drainage, mainly perivascular and peribronchial, is
toward the hilar region where it is processed en route by islets of lymphoid tissue and filtered
principally by the TB lymph nodes before being  returned to the circulation via the subclavian
veins. From the subpleural  connective tissue, lymphatic vessels also arise whose drainage is
along the lobar surfaces to the hilar region (Morrow, 1972).
     The epithelial surface of the A region is covered with a complex lipo-proteinaceous liquid
called pulmonary surfactant. This complex liquid contains a number of surface-active materials,
primarily phospholipids, with a predominance of dipalmitoyl  lecithin.  The surfactant materials
exist on the respiratory epithelium non-uniformly as  a thin film (<0.01 |im thick) on a hypophase
approximately 10 times thicker.  This lining layer stabilizes alveoli of differing dimensions from
collapsing spontaneously and helps to prevent the normal capillary effusate from diffusing from
the interstitium into the alveolar spaces. The role of the lining layer as an environmental
                                          10-20

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interface is barely understood, especially in terms of how the layer may modify the
physicochemical state of deposited particles and vice versa.
     The epithelial surface of the A region, which can exceed 100 m2 in humans, maintains a
population of mobile phagocytic cells, the alveolar macrophage (AM), that have many important
functions, e.g. removing cellular debris, eliminating bacteria and elaborating many cytologic
factors. The AM is also considered to play a major role in non-viable particle clearance. The
resident AM population varies, inter alia, according to conditions of particle intake, as does their
state of activation.  An estimate of the normal AM population in the lungs of non-smokers is
about 7x 109 (Crapo et al. 1982) while in the Fischer 344 rat, estimates are about 2.2x 107 to 2.91
x 107 AM (Lehnert et al., 1985; Stone et al., 1992).  According to prevailing views, the
importance of AM-mediated particle clearance via the bronchial airways in the rat and human
lungs may be different (refer to Section 10.4.2.).
     The respiratory tract is a dynamic structure. During respiration, the caliber and length of
the airways changes as do the angles of branching at each bifurcation. The structural changes
that occur during inspiration and expiration differ.  Since respiration, itself,  is a constantly
changing volumetric flow, the combined effect produces a complex pattern  of airflows during
the respiratory cycle within the conducting airways and volumetric variations within the A
region. Even if the conducting airways were rigid structures and a constant airflow was passed
through the diverging bronchial tree, the behavior of air flow within these structures would
differ from that produced by the identical constant flow passed in the reverse or converging
direction. Consequently, important distinctions exist between inspiratory and expiratory
airflows through the airways, especially those associated with the glottic aperture and nasal
turbinates.  Distinctions occurring in particle deposition during inspiration and expiration are not
as marked as those in airflow. This is because the particles with the greatest tendency to deposit,
will deposit during inspiration and will mostly be absent from the expired air.
     At rest, the amount of air that is inspired, the tidal volume (VT), is normally about 500 mL.
If a maximum inspiration is attempted, about 3300 mL of air can be added;  this constitutes the
inspiratory reserve volume (IRV). During breathing at rest, the average expired VT is essentially
unchanged from the average inspired VT. At the end of a normal expiration, there still remains
in the lungs about 2200 mL, the functional residual capacity (FRC). When  a maximum
expiration is made at the end of a normal tidal volume, approximately 1000 mL of additional air
                                          10-21

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will move out of the lung:  this constitutes the expiratory reserve volume (ERV). Remaining in
the lungs after a maximal expiration is the residual volume (RV) of approximately  1200 mL.
These volumes and capacities are illustrated in Figure 10-7. From the perspective of air volumes
within the respiratory tract, estimates are based on both anatomic and physiologic measurements.
The ET airways have a volume in the average adult of about 80 mL, whereas the composite
volume of the transitional airways is about 440 mL.  At rest, the total volume in the lungs at end
exhalation is usually around 2200 mL and is called the functional residual capacity (FRC). Both
the RV and FRC tend to increase with age and in some forms of lung disease (e.g., COPD). The
gas exchange volume of the lungs contacts with between 60 and 100 m2 of alveolar epithelium
depending on the state of lung inflation, viz, Alvsa = 22 (VL)2/3 where the surface area (Alvsa) is
in m2 and the lung volume (VL) in liters (or cubic decimeters). The alveolar volume is
juxtaposed with a pulmonary capillary blood volume (70 to 230 mL) which varies with cardiac
output and contacts an endothelial surface area of comparable size to that of the alveoli.
     The average respiratory frequency of an adult human at rest is about 12 to 18 cycles per
min. This indicates a cycle length of 4 to 5 s: about 40% for inspiration and 60% for expiration.
With a 500 mL VT, this results in a minute ventilation (VE) of about 6 to 7.5 L/min: about 60 to
70% of the VE is considered alveolar ventilation due to the dead space volume constituting about
30 to 40% of the VT.  With the foregoing assumptions, the mean inspiratory  and expiratory air
flows will be about 250 mL/s and 166 mL/s, respectively. During moderate to heavy exercise,
the VE will increase by up to 10-fold or more (35 to 70 L/min or more). This is accomplished
initially and primarily by an increase in VT (VT reaches approximately 2.0 L and frequency
approximately 30 to 35 per min at a ventilation of 60 to 70 L per min).  There is considerable
variation in response.  One impact of such an assumed change in VE is that the duration of the
respiratory phases become shorter and more similar, consequently, the mean inspired and
expired air flows will both likely increase to about >2,000 mL/s. With nose breathing, an
inspiratory airflow of
                                         10-22

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                                  Maximal Inspiratory
                                  Level
                                  Resting Expiratory Level
                                  Maximal Expiratory Level
Figure 10-7.  Lung volumes and capacities. Diagrammatic representation of various lung
             compartments, based on a typical spirogram. TLC, total lung capacity; VC,
             vital capacity; RV, residual volume; FRC, functional residual capacity; 1C,
             inspiratory capacity; VT, tidal volume; IRV, inspiratory reserve volume;
             ERV, expiratory reserve volume. Shaded areas indicate relationships
             between the subdivisions and relative sizes as compared to the TLC.  The
             resting expiratory level should be noted, since it remains more stable than
             other identifiable points during repeated spirograms, hence is used as a
             starting point for FRC determinations, etc.

Source: Ruppel (1979).
800 mL/s would be expected to produce linear velocities in the anterior nares greater than 10

m/s.

     Because of the irregular anatomic architecture of the nasal passages, the incoming air

induces many eddies and turbulence in the ET airways.  This is also true in the upper portions of

the TB region largely due to the turbulence created by the glottic aperture. As the collective

volume and cross sectional area of the bronchial airways increases, the mean airflow rates fall,

but "parabolic airflow", a characteristic of laminar airflow does not develop because of the
                                        10-23

-------
renewed development of secondary flows due to the repetitive airway branching. Conditions of
true laminar flow probably do not occur until the inspired air reaches the transitional airways.
Whether air flow in a straight circular tube is laminar or turbulent is determined by a
dimensionless parameter known as the Reynolds number (Re) which is defined by the ratio
paDaU/ji where pa is the air density, Da is the tube diameter, U is the air velocity, and |i is the
viscosity of air. As a general rule, when Re is below 2000, the flow is expected to be laminar
(Owen, 1969).  See Table 10-2.
     Pattle (1961) was the first investigator to demonstrate that the nasal deposition of particles
was proportional to the product of the aerodynamic diameter (dae) squared and the mean
inspiratory flow rate (Q); where the aerodynamic diameter is the diameter of a unit density
sphere having the same terminal settling velocity (see Section 10.2) as the particle of concern.
Albert et al.  (1967) and Lippmann and Albert (1969) were among the earliest to report
experimentally that the same general relationship governed inertial deposition of different
uniformly-sized particles in the conducting airways of the TB region. Recent papers by
Martonen et al.  (1994a,b,c) have considered the influence of both the cartilaginous rings and the
carinal ridges of the upper TB airways on the dynamics of airflow. As  in the case of the glottic
aperture, these structures appear to contribute to the non-uniformity of particulate deposition
sites within these airways.  Concomitantly, Martonen et al. have pointed to the limitations
incurred by assuming smooth tubes in modeling the aerodynamics of the upper TB airways (see
also  Section 10.5.1.5).
     Smaller particles, i.e. those with an aerodynamic size of between  0.1 and 0.5 jam, are the
particles with the greatest airborne stability.  They are too small to gravitate appreciably and are
too large to diffuse; hence they tend to persist in the inspired air as a gas would, but in teams of
alveolar mixing, they behave as "non-diffusible" gas. The study of these particles has provided
very useful information on the distribution of tidal air under different physiologic conditions
(Heyder et al., 1985). A recent analysis of airflow dynamics in human  airways, conducted by
Chang and Menon (1993), concluded that the measurement of flow dynamics aids in the
understanding of particle transport and the development of enhanced areas of particle deposition.

     Sedimentation becomes insignificant relative to diffusion as the particles become smaller.
Deposition by diffusion results from the random (Brownian) motion of very small

                                         10-24

-------
                    TABLE 10-2. ARCHITECTURE OF THE HUMAN LUNG ACCORDING TO WEIBEL'S (1963)
                                           MODEL A, WITH REGULARIZED DICHOTOMY
to
At flow of 1 L/sec
Region
Trachea0
Main bronchus
Lobar bronchus

Segmental bronchus

Bronchi with
cartilage in wall


Terminal bronchus


Bronchioles with
muscle in wall

Terminal bronchiole
Resp. bronchiole
Resp. bronchiole
Resp. bronchiole
Alveolar duct
Alveolar duct
Alveolar duct
Alveolar sac
Alveoli, 21 per duct
Generation
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23

Number
1
2
4
8
16
32
64
128
256
512
1,020
2,050
4,100
8,190
16,400
32,800
65,500
131 x 103
262 x 103
524 x 103
1.05 x 106
2.10x 106
4.19 x 106
8.39 x 106
300 x 106
Diameter
(mm)
18
12.2
8.3
5.6
4.5
3.5
2.8
2.3
1.86
1.54
1.30
1.09
0.95
0.82
0.74
0.66
0.60
0.54
0.50
0.47
0.45
0.43
0.41
0.41
0.28
Length
(mm)
120.0
47.6
19.0
7.6
12.7
10.7
9.0
7.6
6.4
5.4
4.6
3.9
3.3
2.7
2.3
2.0
1.65
1.41
1.17
0.99
0.83
0.70
0.59
0.50
0.23
Cum."
Length (mm)
120
167
186
194
206
217
226
234
240
246
250
254
257
260
262
264
266
267
269
270
271
271
272
273
273
Area"
(cm2)
2.6
2.3
2.2
2.0
2.6
3.1
4.0
5.1
7.0
9.6
13
19
29
44
70
113
180
300
534
944
1,600
3,200
5,900
12,000

Volume
(mL)
31
11
4
2
3
3
4
4
4
5
6
7
10
12
16
22
30
42
61
93
139
224
350
591
3,200
Cum.b Volume
(mL)
31
42
46
47
51
54
57
61
66
71
77
85
95
106
123
145
175
217
278
370
510
734
1,085
1,675
4,800
Speed
(cm/s)
393
427
462
507
392
325
254
188
144
105
73.6
52.3
34.4
23.1
14.1
8.92
5.40
3.33
1.94
1.10
0.60
0.32
0.18
0.09

Reynolds
Number
4,350
3,210
2,390
1,720
1,110
690
434
277
164
99
60
34
20
11
6.5
3.6
2.0
1.1
0.57
0.31
0.17
0.08
0.04
—

     "Area = total cross sectional area.
     bCum. = cumulative.
     °Dead space, approx. 175 mL + 40 mL for mouth.

     Source: Y.C. Fung (1990).

-------
particles caused by the collision of gas molecules in air.  The terminal settling velocity of a
particle approaches 0.001 cm/s for a unit density sphere with a physical diameter of 0.5 //m,  so
that gravitational forces become negligible at smaller diameters. The main deposition
mechanism is diffusion for a particle having physical (geometric) size <0.5 //m. Impaction and
sedimentation are the main deposition mechanisms for a particle whose size is greater than
0.5 //m. Hence, dae = 0.5 //m is convenient for use as the boundary between the diffusion and
aerodynamic regimes. Although this convention may lead to confusion in the case of very dense
particles, most environmental aerosols have densities below 3 g/cm3  (U.S. Environmental
Protection Agency, 1982). Diffusional deposition is important in the small airways and in the A
region where distances between the particles and airway epithelium are small. Diffusion has
also been shown to be an important deposition mechanism in the ET region for small particles
(Cheng etal., 1988, 1990).
      With mouth-only breathing, the regional deposition pattern changes dramatically when
compared to nasal breathing, with ET deposition being reduced and both TB and A deposition
enhanced. Oronasal breathing (partly via the mouth and partly nasally), however, typically
occurs in healthy adults while undergoing exercise. Therefore, the appropriate activity pattern of
subjects for risk assessment estimation remains an important issue. Miller et  al. (1988)
examined ET and thoracic deposition as a function of particle size for ventilation rates ranging
from normal respiration to heavy exercise.  A family of estimated deposition curves was
generated as a function of breathing pattern (See Section 10.5.1.4.).  Anatomical and functional
differences between adults and children are likely to interact with the major mechanisms
affecting respiratory tract deposition in a complex way which will have important implications
for risk assessment.
     Humidification and warming of the inspired air begins in the nasal passages and continues
into the deep lung. This conditioning of the ambient air does not significantly affect  particle
deposition unless the paniculate material is intrinsically hygroscopic, in which case, it is very
important. For both liquid and solid aerosol particles that are hygroscopic, there are physical
laws that control both particle growth and deposition, and these have been modeled extensively.
In a review of this general subject (Morrow, 1986), many experimental measurements of the
humidity (RH) and temperature of the air within the respiratory tract have been reported, but
because of the technical problems involved, uncertainties remain.  Two major problems prevail:
                                          10-26

-------
(1) the accurate measurement of temperature requires a sensor with a very rapid response time;
and (2) hygrometric measurements of conditions of near saturation (>99% RH) are the most
difficult to make.  The latter technicality is of special significance, because the growth of
hygroscopic aerosols are greatest near saturation. For example, the effect of a difference in
humidity between 99.0% and 99.9% is more important than the difference between 20 and 80%
RH.  A more complete discussion of models and experimental determinations of the deposition
of hygroscopic aerosols is given in Section 10.4.
     The differences in respiratory tract anatomy summarized briefly in this section are the
structural basis for the species differences in particle deposition.  In addition to the structure of
the respiratory tract, the regional thickness and composition of the airway epithelium (a function
of cell types and distributions) are important factors in clearance  (Section 10.4). Characteristic
values and ranges for many respiratory parameters have been published for "Reference Man" by
the International Commission on Radiological Protection (ICRP) (1975) and they  are also
available from many reference sources (Altose,  1980; Collett et al., 1988; Cotes, 1979).  A
typical description of respiratory tract morphology, cytology, histology, structure, and function
is given in Table 10-3. This description of the respiratory tract is used in the human dosimetry
model applied in Section 10.7 (ICRP66, 1994).  For additional information on human respiratory
tract structure, the papers of Weibel (1963; 1980), Hatch and Gross (1964), Proctor (1977),
Forrest (1993), and Gehr (1994) are recommended.

10.4  FACTORS CONTROLLING COMPARATIVE INHALED DOSE
     As discussed in Section 10.1, comprehensive characterization of the
exposure-dose-response continuum is the fundamental objective of any dose-
response assessment. Within human and interspecies differences in anatomical
and physiological characteristics, the physicochemical properties of the
inhaled aerosol, the diversity of cell types that may be  affected, and a myriad
of mechanistic and metabolic differences all  combine to make the
characterization particularly complex for the respiratory tract as the portal of
entry.  This section attempts to discuss these factors within the exposure-dose-
response context in order to present unifying concepts. These concepts are used
to  construct a framework by which to

                                         10-27

-------
                 TABLE 10-3. MORPHOLOGY, CYTOLOGY, HISTOLOGY, FUNCTION, AND STRUCTURE OF THE
                RESPIRATORY TRACT AND REGIONS USED IN THE ICRP66 (1994) HUMAN DOSIMETRY MODEL

Functions
Air Conditioning
Temperature am
Humidity, and
Cleaning; Fast
Particle
Conduction













Air Conduction;
Gas Exchange;
Slow Particle
Clearance





Gas Exchange;
Very Slow
Particle
Clearance





Cytology (Epithelium)
Respiratory Epithelium with Goblet
Cells
Cell Types:
• Ciliated Cells
• Nonclllated Cells:
Goblet Cells
Mucous (Secretory) Cell!
Serous Cells

Basal Cells
Intermediate Cells





Respiratory Epithelium with Clara
Cells (No Goblet Cells)
Cell Types:
• Ciliated Cells
• Nonclllated Cells:
Clara (Secretory) Cells


Respiratory Epithelium Consisting
Mainly
of Clara Cells(Secretory) and Few
Ciliated Cells





Squamous Alveolar Epithelial Cells
(Type 1), Covering 93% of Alveolar


Cuboldal Alveolar Epithelial Cells

Covering 7% of Alveolar Surface Arei
Alveolar Macrophages

Histology (Walls)
Mucous Membrane, Respiratory

Ciliated, Mucous), Glands
Mucous Membrane, Respiratory
or Stratified Epithelium, Glands

Mucous Membrane, Respiratory
Epithelium Cartilage Rings,
Glands

Mucous Membrane, Respiratory
Epithelium, Cartilage plates,
Smooth Muscle Layer, Glands
Mucous Membrane, Respiratory
Epithelium, No Cartilage, No
Glands, Smooth Muscle Layer

Mucous Membrane, Single-Layer
Respiratory Epithelium, Less
Ciliated, Smooth Muscle Layer

Mucous Membrane, Single-Layer
Respiratory Epithelium of
Cuboldal Cells, Smooth Muscle
Layer





Wall Consists of Alveolar
Entrance Rings, Squamous
Epithelial Layer, Surfactant



Interalveolar Septa Covered by
Squamous Epithelium, Containin
Capillaries, Surfactant

Number





0

1


2-8





15



16-18






(c)




(c)



Anatomy
Anterior Nasal Passages

I /Nose
\S Mouth, *

f ^^jT
Trachea 1*

^LPharynx
\ Posterior
^^Esophagus

v
Main Bronchy^'x
Bronchi l^j
Bronchioles 1 1

II
2y




Terminal ^\ *
Bronchloles^X

Respiratory -J ^
Bronchioles S fj
DucS" ^^V "Vvy**1^

-------
evaluate the different available dosimetry models; to appreciate why they are constructed
differently, and to determine which are the most appropriate for extrapolation of the available
toxicity data. The section discusses the major factors controlling the disposition of inhaled
particles. Note that disposition is defined as encompassing the processes of deposition,
absorption, distribution, metabolism, and elimination.
     It must be emphasized that dissection  of the factors that control inhaled dose into discrete
topic discussions is  deceptive and masks the dynamic and interdependent nature of the intact
respiratory system.  For example, although  deposition in a particular respiratory region will be
discussed separately from the clearance mechanisms for that region, retention (the actual amount
of inhaled agent found in the respiratory tract at any time) is determined by the relative rates of
deposition and clearance.  Retention and the toxicologic properties of the inhaled agent are
related to the magnitude of the pharmacologic, physiologic, or pathologic response. Therefore,
although the deposition  mechanisms, clearance mechanisms, and physicochemical characteristics
of particles are described in distinct sections, assessment of the overall dosimetry and toxic
response requires integration of the various  factors.
     Inasmuch as particles which are too massive to be inhaled occur in the environmental air,
the description "inhalability" has been used  to denote the overall spectrum of particle sizes which
are potentially capable of entering the respiratory tract of humans and depositing therein.  Except
under conditions of microgravity (spaceflight) and possibly some other rare circumstances, unit
density particles >100 jim diameter have a low probability of entering the mouth or nose in still
air. Nevertheless, there  is no sharp cutoff to zero probability because air velocities into the nose
or mouth during heavy breathing, or in the presence of a high wind, may be comparable to the
settling velocity of >100-|im particles.  Even though the settling velocity of particles of this size
is >25 cm/s, wind velocities of several m/s can result in them being blown into the nose  or
mouth.  Inhalability can be defined as the ratio of the  number concentration of particles  of a
certain aerodynamic diameter, dae, that are inspired through the nose or mouth to the number
concentration of the same dae present in the  inspired volume of ambient air (ICRP66, 1994).  The
concept of aerodynamic diameter is discussed in Section 10.2. In studies with head and  torso
models, inhalability has  been considered generally under conditions of different wind velocities
and horizontal head orientations.
                                          10-29

-------
     The American Conference of Governmental Industrial Hygienists (ACGIH) (1985)
expressed inhalability in terms of an intake efficiency of a hypothetical sampler. This
expression was replaced in 1989 by international definitions for inspirable (also called
inhalable), thoracic, and respirable fractions of airborne particle (Soderholm, 1989).  Agreement
on these definitions has been achieved between the International Standards Organization (ISO)
and the ACGIH (Vincent, 1995). Health-related sampling should be based on one or more of the
three, progressively very-finer, particle size-selective fractions; inhalable, thoracic, and
respirable.
     Each definition is expressed as a sampling efficiency (S) which is a function of particle
aerodynamic diameter (dae) and specifies the fraction of the ambient concentration of airborne
particles collected by an ideal sampler. For the inspirable fraction,

                SI(dae) = 0.5(1 +  e~°-°6
-------
It should be emphasized that these conventions do not purport to reflect deposition per se, but
are rather intended to be representative of the penetration of particles to a region and hence their
availability for deposition.  The thoracic fraction corresponds to penetration to the TB plus A
regions, and the respirable fraction to the A region. Inhalability for laboratory animals is
discussed in Section 10.5.2.
     Swift (1976) estimated the deposition of particles by impaction in the nose, based on a
nasal entrance velocity of 2.3 m/s and a nasal entrance width of 0.5 cm, and deduced that
particles >61 jim dae have a negligible probability of entering the nasal passages due to the high
impaction efficiency of the external nares. Experiments by Breysse  and Swift (1990) in tranquil
air estimated a practical upper limit for inhalability to be ~ 40 jim dae for individuals breathing at
15 breaths per min at rest. No information on tidal volumes was provided.  Studies reported by
Vincent (1990) of inhalability made use of a mannequin with mouth and nasal orifices that could
be placed in a wind tunnel and rotated 360 degrees horizontally. At low wind speeds, the intake
efficiency approached 0.5 for particle sizes between 20  jam and 100 jim dae.  Vincent derived the
following empirical relationship from these studies

             ri! (sampler) = 0.5 [1 + exp(-0.06 dae) = 1  x 10'5 U2'75 exp (0.055 dj,       (10-9)

where r^ is the intake efficiency of the  sampler, dae is the aerodynamic diameter, and U is the
wind speed. For particles with dae less than about 40 //m, intake efficiency generally tends to
decrease with increasing dae. However, for large particles, the intake efficiency tends to increase
with windspeed. For particles with  dae < 10 //m, the ICRP modified Vincent's expression to
increase the accuracy in representing the data.  Thus,  in the 1994 ICRP66 model (ICRP66,  1994)
the intake efficiency of the head, % i.e., the particle inhalability, is represented by

           rh = 1 - 0.5 (1 - [7.6 x 10 -4 (dj 2'8 + I]'1) + 1 x ID'5 U2'75 exp (0.055 dae),
                                                                                  (10-10)
where dae is in //m and  U is the windspeed in (m s"1) (for 0 < U < 10 ms"7).
     While there is some contention about the practical upper size limit of inhalable particles in
humans,  there is no lower limit to inhalability as long as the particle  exceeds a critical
                                          10-31

-------
(Kelvin) size where the aggregation of atomic or molecular units is stable enough to endow it
with "particulate" properties, in distinction to those of free ions or gas molecules. Inter alia,
particles are considered to experience inelastic collisions with surfaces and with each other. The
lower limit for the existence of aerosol particles is assumed to be around 1 nanometers for some
materials (refer to Section 10.2.).  If the parti culate material has an appreciable vapor pressure,
particles of a certain size may "evaporate" as fast as they are formed. For example, pure water
droplets as large as  1 jim diameter will evaporate in less than 1 second even when they are in
water-saturated air at 20° Celsius (Greene and Lane, 1957).
     Description of a "respirable dust fraction" was first suggested by the British Medical
Research Council and implemented by C.N. Davies (1952) using the experimentally-estimated
alveolar deposition  curve of Brown et al. (1950).  This curve described the respirable dust
fraction as that which would be available to deposit in the alveolated lung structures including
the respiratory bronchioles, thereby making "respirable dusts" applicable to pneumoconiosis-
producing dusts.  The horizontal elutriator was chosen  as a particle size selector, and respirable
dust was defined as that dust passing an ideal horizontal elutriator. The elutriator cutoff was
chosen to result in the best agreement with experimental lung deposition data. The
Johannesburg International Conference on Pneumoconiosis in 1959 adopted the same standard
(Orenstein, 1960). Later, an Atomic Energy Commission working group defined "respirable
dust" by a deposition curve which indicated 0% deposition at 10 jam dae and 100% deposition for
particles <2.0 jim dae.  "Respirable dust" was defined as that portion of the inhaled dust which
penetrates to the nonciliated portions of the lung (Hatch and Gross, 1964). The AEC respirable
size deposition curve was pragmatically adjusted to 100% deposition for <2 jim dae particles so
that the "respirable" curve could be approximated by a two-stage selective sampler and because
comparatively little dust mass was represented by these small particles (Mercer 1973a). This
definition was not intended to be applicable to dusts that are readily soluble in body fluids or are
primarily chemical intoxicants, but rather only for poorly soluble particles that exhibit prolonged
retention in the lung.
     Other groups,  such as the American Conference of Governmental Industrial Hygienists
(ACGIH), incorporated respirable dust sampling concepts in setting acceptable exposure levels
for other toxic dusts. Such applications are more complicated, since laboratory animal
                                          10-32

-------
and human exposure data, rather than predictive calculations, form the data base for standards.
The size-selector characteristic specified in the ACGIH standard for respirable dust (Threshold
Limits Committee, 1968) was almost identical to that of the AEC, differing only at 2 //m dae,
where it allowed for 90% passing the first-stage collector instead of 100 percent.  The difference
between them appeared to be a recognition of the properties of real particle separators, so that,
for practical purposes, the two standards could be considered equivalent (Lippmann, 1978).
     The cutoff characteristics of the precollectors preceding respirable dust samplers are
defined by these criteria.  The two sampler acceptance curves have similar, but not identical,
characteristics, due mainly to the use of different types of collectors.  The BMRC curve was
chosen to give the best fit between the calculated characteristics of an ideal horizontal elutriator
and available lung deposition data; on the other hand, the design for the AEC curve was based
primarily on the upper respiratory tract deposition  data of Brown et al. (1950). The separation
characteristics of cyclone type collectors simulate the AEC curve. Whenever the particle size
distribution has a og > 2, samples collected with instruments meeting either criterion will be
comparable (Lippmann, 1978).  Various comparisons of samples collected on the basis of the
two criteria are available (Knight and Lichti, 1970; Breuer, 1971; Maquire and Barker, 1969;
Lynch, 1970; Coenen, 1971; Moss and Ettinger, 1970).
     The various definitions of respirable dust were somewhat arbitrary, with the BMRC and
AEC definitions being based on the poorly soluble particles that reach the A region. Since part
of the aerosol that penetrates to the alveoli remains suspended in the exhaled air, respirable dust
samples are not intended to be a measure of A deposition but only a measure of aerosol
concentration for those particles that are the primary candidates for A deposition.  Given that the
"respirable" dust standards were intended for "insoluble dusts", most of the samplers developed
to satisfy their criteria have been relatively simple  two-stage instruments. In addition to an
overall size-mass distribution curve, multistage aerosol sampler data can provide  estimates of the
"respirable" fraction and deposition in other functional regions. Field application of these
samplers has been limited because of the increased number and cost of sample analyses and the
lack of suitable instrumentation. Many of the various samplers, along with their limitations and
deficiencies, were reviewed by Lippmann (1978).
                                          10-33

-------
     PM10 dust is based on the PM10 sampler efficiency curve promulgated by the U.S.
Environmental Protection Agency.  This sample is equivalent to the thoracic dust sample defined
by the American Conference of Governmental Industrial Hygienists (Raabe, 1984).
     The medical field also refers to a "respirable fraction". Aerosols are widely used for both
therapy and diagnosis (Swift,  1993). Aerosols are used to deliver bioactive substances to the
respiratory tract to affect a physiological change (e.g., nasal or bronchial medication),
provocation tests in the diagnosis of bronchial asthma, and the administration of contrast
substances for radiological studies. In pharmaceutical applications, the "respirable fraction"
refers to particles with an aerodynamic diameter between 0.5 and 5 //m for most therapeutic
products, although larger size particles (up to 10 //m) are recognized as important in certain
situations (Hallworth, 1993; Lourenco and Cotromanes, 1982). Aerosols produced by
metered-dose-inhaler (MDI) systems are about 2.5 to 2.8 //m in size upon entering the lung (Kim
et al., 1985) and 40 to 50% of these aerosols are expected to deposit during normal tidal
breathing. The lung deposition, however, is usually higher in the abnormal lung, and can be
further increased by changing the mode of breathing.

10.4.1   Deposition Mechanisms
     This section will review briefly the aerosol physics that both explains how and why
particle deposition occurs and provides the theoretician a capability to develop predictive
deposition models. Some of these models will be described in Section 10.5, together with recent
experimental results on particle deposition. The ability of the experimentalist to measure
deposition quantitatively has continued to advance, but theoretical models remain the only
practical way for predicting the impact of aerosol exposures and for delineating the patterns of
intra-regional deposition.
     The motion of an airborne particle between 1 and 100 |im dae is primarily related to its
mass, and the resulting resistive force of air which is proportional to

                                          |ivd,                                    (10-11)

where |i is the viscosity of air, v is the velocity of the particle  relative to the air, and d is the
particle diameter. This is a statement of Stokes law for viscous resistance which is
                                          10-34

-------
appropriate to a sphere moving in air at low particle Reynolds numbers, i.e., less than 1.  The
particle Reynolds number (Rep) is defined as
                                                                                   (10-12)
where pa is the density of air. When the particle velocity relative to air is sufficiently slow that
the airflow pattern around the sphere is symmetrical and only viscous stresses resist the sphere's
motion, Stokes law applies.  As the value of Rep increases, asymmetrical flow about the moving
sphere and a pressure drop across the sphere, both progressively develop. These changes in flow
signify that the condition of inertial resistance prevails and Stokes law does not pertain (Mercer,
1973b).
     For the range of particle sizes just discussed (1 to 100 jim), the motion of airborne particles
is characterized by a rapid attainment of a constant velocity whereby the viscous resistance of air
matches the force(s)  on the sphere responsible for its motion. This constant velocity is termed
the terminal velocity of the particle. For the size region below 1  |im diameter, particle motion is
also based on the viscous resistance of air and described by its terminal velocity.  In this particle
size region, the viscous resistance of air on the particle, using Stokes law, begins to be
overestimated and the particle's terminal velocity, underestimated.  This general phenomenon is
termed "slip";  consequently, Slip Correction Factors have been developed. These slip
corrections become more important as the particle diameter nears, or is less than,  the mean free
path of air molecules (« 0.068 //m at 25 °C and 760 mm Hg air pressure).

10.4.1.1   Gravitational Settling or Sedimentation
     All aerosol particles are continuously influenced by gravity, but for practical purposes,
particles with an dae > 0.5 jim are mainly involved. Within the respiratory tract, an dae of 100 jim
will be considered as an upper cut-off.  A spherical, compact particle within these arbitrary
limits will acquire a terminal settling velocity when a balance is achieved between the
acceleration of gravity, g, acting on the particle of density, p, (g/cm3) and the viscous resistance
of the air according to Stokes law
                                           10-35

-------
                    (7t/6)pdjg = 37tjidvt.                                         (10-13)


The left hand side of Equation 10-13 is the force of gravity on the particle, neglecting the effect
of the density of air. Solving for the terminal velocity, vt, gives
                     t  = da2epg Ks /  18ji.                                         (10-14)
In Equation 10-14 a slip correction factor, Ks, is added to account for the slip effect on particles
with diameters about or below 1 jim.  For particles as small as 0.02 jim, the K,, used by Knudsen
and Weber increases vt six fold (cited by Mercer, 1973c).
     The relationship for the terminal settling velocity, just described, is not restricted to
measurements in tranquil  air. For example, moving air in a horizontal airway will tend to carry
the particle at right angles to gravity at an average velocity, U.  The action of gravity on the
particle will nonetheless result in a terminal settling velocity, vt; consequently the particle will
follow, vectorially, the two velocities; and, provided the airway is sufficiently long or the
settling velocity is relatively high, the particle will sediment in the airway.  For every  orientation
of the airways with respect to gravity, it is possible to calculate the particle's settling behavior
using Stokes law.

10.4.1.2  Inertial Impaction
     Sudden changes in airstream direction and velocity, cause particles to fail to follow the
streamlines of airflow as depicted in Figure 10-5.  As a consequence, the relatively massive
particles impact on the walls or branch points of the conducting airways.  The ET and upper TB
airways have been described as the dominant sites of high air velocities and sharp directional
changes; hence, they dominate as sites of inertial impaction. Because the air (and particle)
velocities are affected by the breathing pattern, it is easy to imagine that even small  particles also
experience some inertial impaction.  Moreover, as nasal breathing shifts to oral breathing during
work or exercise, the particle that would normally be expected to impact in the ET region will
pass into the TB region, greatly increasing TB deposition. That all
                                           10-36

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impaction sites occur lower down in the TB region when such a shift takes place is also
expected.
     The probability that a particle with a diameter, d, moving in an air stream with an average
velocity, U, will impact at a bifurcation is related to a parameter called the Stokes number, Stk;
defined as
                      pd2 U/9ji  Da ,                                           (10-15)
or
                          2
                      pdae2  U/9ji Da.                                           (10-16)


     As far as particulate properties are concerned, the aerodynamic diameter (dae) is again the
significant parameter (see Section 10.2). In Landahl's lung deposition model (1950a) of
impaction in the TB region, impaction efficiency was proportional to

                  pd2lL sin 0, / Dai S,.!,                                       (10-17)


where U; is the air velocity in the airway generation i, 6; is the branching angle between
generations i and i-1, Dai is diameter of the airway of generation i, and S^ is the total cross
sectional area of airway generation i-1.
     Prevailing TB models have simplistically represented the airways as smooth, bifurcating
tubes. Martonen et al. (1993; 1994a,b,c) have predicted that the cartilaginous rings and carinal
ridges perturb the dynamics of airflow and help to explain the non-uniformity of particle
deposition.
     It should be evident that both gravitational  settling and inertial impaction cause the
deposition of many particles within the same size range. These deposition forces are always
acting together in the ET and TB regions, with inertial impaction dominating in the upper
airways and gravitational settling becoming increasingly dominant in the lower conducting
                                          10-37

-------
airways, and especially for the largest of the particles which can penetrate into the transitional
airways and alveolar spaces.
     For sedimenting particles with diameters between 0.1 jim to 1.0 |im, their Slip Correction
Factor will be greater than 1.0, although the magnitude of their respective vt will only range
from about 1 |im/s to 35 |im/s. Concurrently,  0.1 jim diameter particles are affected by diffusion
such that the root mean displacement they experience in one second is about 0.3 jim. The size
region,  1.0 jim down to about 0.1 jim, is frequently described as consisting of particles which are
too small to settle and too large to diffuse.  Indeed, it is this circumstance that makes them the
most persistent and stable particles in aerosols and those which undergo the least deposition in
the respiratory tract.  As any aerosol ages and continuously undergoes deposition without
particle replenishment, the ultimate aerosol will exist largely within this same size range, i.e.,
have a median size of about 0.5 jam diameter.
10.4.1.3  Brownian Diffusion
     Particles <1 jim diameter are  increasingly subjected to diffusive deposition as their size
decreases.  Even particles in the nanometer diameter range are large compared to individual air
molecules, hence, the collisions resulting between air molecules, undergoing random thermal
motion, and the surface of a particle produce numerous very small changes in the particle's
spatial position.  These frequent, minute excursions are each made at a constant or terminal
velocity due to the viscous resistance of air. The root mean square (r.m.s.) displacement that the
particle experiences in a unit of time along a given cartesian coordinate, x, y or z is a measure of
its diffusivity. For instance, a 0.1  jim diameter particle has a r.m.s. displacement of about 37 jim
during one s. This 1  |im displacement in one s does not describe a velocity of particle motion
because the displacement resulted from numerous relatively high velocity excursions.
     The diffusion of particles by Brownian motion is described by the Einstein-Stokes'
equation
                        Ax =    D,                                             (10-18)
                                          10-38

-------
where Ax is the root-mean-square displacement in one second along coordinate x, D is the
diffusion coefficient for the particle expressed in cm2/s, t is time in seconds. The diffusion
coefficient of a particle of diameter, d, is

                     D = KTKs/37i:jid,                                         (10-19)
where K is the Boltzmann constant, and T the absolute temperature, collectively describing the
average kinetic energy of the gas molecules.
     It is apparent that the density of the particle is ordinarily unimportant in determining
particle diffusivity which increases as Ks increases and d decreases. Instead of having an
aerodynamic equivalent size, diffusive particles of different shapes can be related to the
diffusivity of a thermodynamic equivalent size based on spherical particles (Heyder and
Scheuch, 1983). In terms of the architecture of the respiratory tract, diffusive deposition of
particles is favored by proximate surfaces and by relatively long residence times for particles,
both conditions occurring in the alveolated structures of the lungs, the A region. Experimental
studies with diffusive particles (<0.5  jim) in replicate casts of the human nose and theoretical
predictions both indicate a rising deposition efficiency for the nasal airways as d becomes very
small (Cheng et al., 1988).

10.4.1.4  Interception
     The interception potential of any particle depends on its physical size. As a practical
matter, particles that approach sizes > 150  //m or more in one dimension will be too massive to
be inhaled. Airborne fibers (length/diameter > 3), however, frequently exceed 150 jim in length
and appear to be relatively stable in air. This is because their aerodynamic size is determined
predominantly by their diameter, not their  length.  Fibers, therefore, are the chief concern in the
interception process, especially as their length approaches the diameters of peripheral airways
(>150 nm).
     The theoretical model of Asgharian and Yu (1988, 1989) for the deposition of fibrous
particles in the respiratory tract is complex. While the model includes interception as an
important process for long fibers, it also depends on a combination of inertial, gravitational
                                          10-39

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and diffusional forces to explain fiber deposition. The deposition efficiencies of the three
deposition mechanisms cited have been developed for spherical particles, but these can be
extended to fibrous particles by considering orientation effects which are strongly related to the
direction of airflow.  The orientation of fibers depends upon the velocity shear of the airflow and
Brownian motion.
     For their analysis of orientational effects throughout the respiratory tract, Asgharian and
Yu (1988, 1989) defined the equivalent mass diameter, dem, of fibers as
                                                                                 (10-20)
where df is the fiber diameter and P is its aspect ratio (length/diameter). For example, a fiber
100 jim long and 3 jim diameter has a dem of 10 jim diameter.  In Figure 10-8, two sets of TB
deposition predictions for the rat are reproduced from Asgharian and Yu (1989) that clearly
show an example of the relative importance of particle interception.
   0.5n
                                                 0.5n
Figure 10-8.  Estimated tracheobronchial (TB) deposition in the rat lung, via the trachea,
              with no interceptional deposition. Graph A is shown in relation to total TB
              deposition, via the trachea; Graph B for the same fibrous aerosol under
              identical respiratory conditions including interception.
Source: Asgharian and Yu (1989).
                                          10-40

-------
     Several general reviews of particle deposition mechanisms in the human respiratory tract
have been published, e.g, Stuart (1973), Lippmann (1977), and Brain and Blanchard (1993), and
are recommended to the reader, as is the excellent review of particle deposition mechanisms
prepared by Phalen (1984).

10.4.1.5   Electrostatic Precipitation
     The minimum charge an aerosol particle can have is zero, when it is electrically neutral.
This condition is rarely achieved because of the random charging of aerosol particles by the
omnipresent air ions. Every cubic centimeter of air contains about 103 ions in approximately
equal numbers of positive and negative ions.  Aerosol particles that are initially neutral will
acquire charges from these ions by collisions with them due to their random thermal motion.
Aerosols that are initially charged will lose their charge slowly as the charged particles attract
oppositely charged ions.  An equilibrium state of these competing processes is eventually
achieved. The Boltzmann equilibrium represents the charge distribution of an aerosol in charge
equilibrium with bipolar ions.  The minimum amount of charge is very small, with a statistical
probability that some particles will have no charge and others will have one or more charges.
     The electrical charge on some particles may result in an enhanced deposition over what
would be expected from size alone. This is due to image charges induced on the surface of the
airway by these particles or to space-charge effects whereby repulsion of particles containing
like charges results in increased migration toward the airway wall.  The effect of charge is
inversely proportional to particle size and airflow rate. This deposition is probably small
compared to the effects of turbulence and other deposition mechanisms and is generally a minor
contributor to overall particle deposition, but it may be important in some laboratory studies.
This deposition is also negligible for particles below  0.01 //m because so few of these particles
carry any charge at Boltzmann equilibrium.
     Many of freshly generated particles are electrostatically charged. Experimental studies in a
lung cast (Chan et al., 1978) and measurements in rats and humans (Melandri et al., 1977, 1983;
Tarroni et al., 1980; Jones et al., 1988; Scheuch et al., 1990) all showed that particle charge
increased deposition. For low particle number concentration (<105 cm"3), the deposition increase
is due to  the presence of electrostatic image force acting on the
                                          10-41

-------
particle by particle-wall interaction (Yu, 1985). Figure 10-8 shows the experimental data on
human deposition of Melandri et al. (1983) and Tarroni et al. (1980) for three particle sizes and
the modeling results by Yu (1985). The vertical axis in Figure 10-9 is the deposition increment,
defined as
                                AT = (DE-DE0)/(1-DE0),
                                                                   (10-21)
where DE is total deposition at particle charge level, q, and DE0 is the total deposition of
particles at Boltzmann charge equilibrium. As seen for each particle size, deposition increments
increase linearly with q. Figure 10-9 also shows that there exists a threshold charge level above
which the increase in deposition becomes significant.  For 1 jim particles, the threshold charge
was estimated to be about 54 elementary charges (Yu, 1985).
                 16
                 14
                 12
               « 10
               a
o
:•=  e
(0
o
0.
Q  4

   2
                                                                 d = 1.0 |jm
                                                                0.3|jm
                                                                0.6|jm
                         20     40      60      80     100
                                      Particle Charge, q
                                              120
140
Figure 10-9.  Deposition increment data versus particle electronic charge (q) for three
              particle diameters at 0.3, 0.6, and 1.0 /j,m (unit density).  The solid lines
              represent the theoretical predictions.
Source: Yu(1985).
                                          10-42

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10.4.1.6   Additional Factors Modifying Deposition
     The available experimental deposition data in humans are commonly for healthy adult
Caucasian males using stable, monodisperse particles in charge equilibrium.  When these
conditions do not hold, changes in deposition are expected to occur.  In the following, the effects
of different factors on deposition are summarized based upon the information reported from
various studies.

Gender
     The average size of the adult human femal thorax is smaller than the average thorax size in
adult human males.  The diameter of the female trachea is approximately 75% that of the male
(Warwick and Williams, 1973), and the size of the bronchi is proportional to the size of the
trachea (Weibel, 1963). In addition, the minute ventilation and inspiratory flow rate are smaller
for females. It is therefore expected that deposition will be different in females than males.
Using radioactive-labeled polystyrene particles in the 2.5  to 7.5 jim size range, Pritchard et al.
(1986) measured total and regional  deposition in 13 healthy nonsmoking female adults at mouth
breathing through a tube.  Because deposition of particles in this particle size range in the ET
region is controlled by impaction, they reported the data as a function of d^e Q to accommodate
the difference in flow rate between  male and female.  The data of Pritchard et al. (1986) for
females are shown together with data obtained for a group of male nonsmokers using the same
technique in Table 10-4. At a comparative value of d^e Q, females were found to have higher ET
and TB deposition and smaller A deposition.  The ratio of A deposition to total thoracic
deposition in females was also found to be smaller. The differences in depositions were
attributed by Pritchard et al. (1986) to the differences in the airway size between males and
females.

Age
     As a human grows from birth to adulthood, both airway structure and respiratory
conditions vary with  age.  These variations are likely to alter the deposition pattern of inhaled
particles.  Total deposition data for particles of 1 to 3.1 jim size range were reported by
Becquemin et al. (1987, 1991) for a group of 41 children at 5 to 15 years of age and by Schiller-
Scotland et al. (1992) for 29 children at two age groups (6.7 and 10.9 years).

                                          10-43

-------
             TABLE 10-4. DEPOSITION DATA FOR MEN AND WOMEN
Deposition as a Fraction of
Inhaled Material (%) ± Standard Error
Sex
Female
Male
(//m2 Lmin"1)
405 ± 47
430 ±41
Total
75.9 ± 1.7
81. 5± 1.8
ET
21.2 ±2.4
19.9 ±2.5
TB
16.9± 1.5
14.7 ± 1.7
A
37.5 ±2.5
46.9 ±2.7
Although Becquemin et al. (1987, 1991) did not find a clear dependence of total deposition on
age, slightly higher deposition was found by Schiller-Scotland et al. (1992), for each diameter
when children breathed at their normal rates (see Figure 10-10), than was found in adults.
     Mathematical models for children have been developed by many workers (Hofmann, 1982;
Crawford, 1982; Xu and Yu, 1986; Yu and Xu, 1987; Phalen et al., 1988; Hofmann  et al., 1989;
Yu et al., 1992; Martonon and Zhang, 1993). Phalen et al. (1988) reported morphometric data
of twenty TB airway casts of children and young adults from 21 days to 21 years. With the use
of these data, they calculated a higher TB deposition in children during inhalation for particle
diameters between 0.01 and 10 jim. If the entire respiratory tract and a complete breathing cycle
at normal rate are considered in the model, the results show that ET deposition in children is
higher than adults, but that TB and A deposition in children may be either higher or lower than
the adult depending upon the particle size (Xu and Yu, 1986).

Respiratory Tract Disease
     Effect of airway diseases on deposition have been studied extensively.  In 8 healthy
nonsmokers, Svartengren et al. (1986, 1989) found A deposition at different flow rates to be
lower (26% versus 48% of thoracic deposition) in subjects after induced bronchoconstriction.
The degree of bronchoconstriction was quantified by measurements of airway resistance using a
whole-body plethysmograph. An inverse relationship between airway resistance and A
deposition was found.  Data from the same laboratory (Svartengren et al., 1990, 1991) using 2.6
|im dae particles with maximally deep slow inhalations at 0.5 L/min showed no
                                         10-44

-------
      n Q
    o O.o
    Q.
    0
   Q
    « 0.6
    o
      0.4
   I 0.2
         0123
                                      Particle Size (|jm)
                      - adults    A 1:1 urn   * 1: 2 pm   * 1: 2.3
                      ° 1:3 pm   ^ II: 1 pm  • II: 2 pm  * II: 3 pm

Figure 10-10.  Total deposition data in children with or during spontaneous breathing as a
               function of particle diameter (unit density). Group I (10.6 ± 2.0 yrs);
               Group II (5.3 ± 1.5 yrs).  The adult curve represents the mean value of
               deposition from the data of Stahlhofen  et al. (1989).
Source:  Schiller-Scotland et al. (1992).
significant differences in mouth and throat deposition in asthmatics versus healthy subjects, but
thoracic deposition was higher in asthmatics than in healthy subjects (83% versus 73% of total
deposition).  TB deposition was also found to be higher in asthmatics. The results are similar to
those found in subjects with obstructive lung disease (e.g., Dolovich et al., 1976; Itoh et al.,
1981; Anderson et al., 1990).
     Another extensive study of the relationship between deposition and lung abnormality was
made by Kim et al. (1988). One-hundred human subjects with various lung conditions (normal,
asymptomatic smoker, smoker with small airway disease, chronic simple bronchitis and chronic
obstructive bronchitis) breathed 1 jim test particles from a bag at a rate of 30 breaths/min.  The
number of rebreathing breaths needed to produce a 90% loss of aerosol
                                         10-45

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from the bag was determined. From these data, they estimated total deposition and found that
total deposition increased with increasing level of airway obstruction.

Particle Polydispersity
     Aerosol particles are often generated polydisperse and can be approximated by a lognormal
distribution (Section 10.2). The mass deposition of spherical particles in the respiratory tract
depends upon mass median diameter (MMD), geometric standard deviation, og, and physical
density (Diu and Yu, 1983; Rudolf et al., 1988).  For large particles (dae > 1 jam), deposition is
governed by impaction and sedimentation.  The dependence on MMD and mass density can be
combined with the use of mass medium aerodynamic diameter (MMAD), as suggested by TGLD
(1966). However,  this method is not valid for particles in the size range where diffusion
deposition becomes important. Figure 10-11 shows the calculated total and regional mass
deposition results by Yeh et al. (1993) for polydisperse aerosols of unit density with various og
as function of MMD at quiet mouth breathing. The variation of deposition with og depends
strongly on the MMD of the aerosol.  At certain MMD's, variability with og is zero; however,
variations at other MMD's can be very large.  One of the main effects of polydisperse deposition
is the flattening of the deposition curves as a function of particle size, as shown in Figure 10-11.

Particle Hygroscopicity
     Another important particle factor that affects deposition is the hygroscopicity of the
particle. Many  atmospheric particles such as acid particles  are water soluble.  As these particles
travel along the humid respiratory tract, they grow in size and, as a result, the deposition pattern
is altered.  A discussion on deposition of hygroscopic particles follows in  Section 10.4.3.

10.4.1.7   Comparative Aspects of Deposition
     The  various species used in inhalation toxicology studies that serve as the basis for dose-
response assessment do not receive identical doses in a comparable respiratory tract region (ET,
TB, or A) when exposed to the same aerosol or gas (Brain and Mensah, 1983). Such
interspecies differences are important because the adverse toxic effect is likely more
                                          10-46

-------
             1.0 -I
             0.8-
          «  0.6-
          g  0.41
          Q.
             0.2-
             0.0
                        Og= 1

                        Og=2

                        Og=4
               0.001
0.01
 I
0.1
 I
10
100
                                         MMD(|jm)
             1.0 -I
                          0.01
            0.1          1
               MMD(|jm)
                      10
          100
Figure 10-11.  Calculated mass deposition from polydisperse aerosols of unit density with
              various geometric standard deviations (og) as a function of mass median
              diameter (MMD) for quiet breathing (tidal volume = 750 mL, breathing
              frequency = 15 min *).  The upper panel is total deposition and the lower
              panel is regional deposition (NOPL = Naso-oro-pharyngo-laryngeal, TB =
              Tracheobronchial, A = Alveolar). The range of og values demonstrates the
              extremes of monodisperse to extremely polydisperse.

Source: Yeh et al. (1993).
                                        10-47

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related to the quantitative pattern of deposition within the respiratory tract than to the exposure
concentration; this pattern determines not only the initial respiratory tract tissue dose but also the
specific pathways by which the inhaled material is cleared and redistributed (Schlesinger,
1985b). Differences in ventilation rates and in the URT structure and size and branching pattern
of the lower respiratory tract between species result in significantly different patterns of airflow
and particle deposition.  Disposition varies across species and with the respiratory tract region.
For example, interspecies variations in cell morphology, numbers, types, distributions, and
functional capabilities contribute to variations in clearance of initially deposited dose.  Tables
10-5, 10-6, and 10-7 summarize some of these differences for the ET, TB, and A  regions,
respectively. This section only briefly summarizes these considerations. Comprehensive and
detailed reviews of species differences have been published (Phalen and Oldham, 1983; Patra,
1986; Mercer and Crapo, 1987; Gross and Morgan, 1992; Mercer and Crapo, 1992; Parent,
1992).
     The geometry of the upper respiratory tract exhibits major interspecies differences (Gross
and Morgan, 1992).  In general, laboratory animals have much more convoluted nasal turbinate
systems than do humans, and the length of the nasopharynx in relation to the entire length of the
nasal passage also differs between species.  This greater complexity of the nasal passages,
coupled with the obligate nasal breathing of rodents, is generally thought to result in greater
deposition in the upper respiratory tract (or ET region) of rodents than in humans breathing
orally or even nasally (Dahl et al., 1991), although limited comparative data are available.
Species differences in gross anatomy, nasal airway epithelia (e.g., cell types and location) and
the distribution and composition of mucous secretory products have been noted (Harkema, 1991;
Guilmette et al., 1989).  The extent of upper respiratory tract removal affects the amount of
particles or gas available to the distal respiratory tract.
     Airway size (length and diameter) and branching pattern affect the aerodynamics of the
respiratory system in the following ways:
     •  The airway diameter affects the aerodynamics of the air flow and the distance from the
        particle to the airway surface.
     •  The cross-sectional area of the airway determines the airflow velocity for a given
        volumetric flow.
     •  Airway length,  airway diameter, and branching pattern variations affect the mixing
        between tidal and residual air.
                                           10-48

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               TABLE 10-5. INTERSPECIES COMPARISON OF NASAL CAVITY CHARACTERISTICS

Body weight
Nans cross-section
Bend in nans
Length
Greatest vertical diameter
Surface area (both sides of nasal
cavity)
Volume (both sides)

Bend in nasopharynx
Turbinate complexity
Sprague-Dawley Rat
250 g
0.7 mm
40°
23 cm
9.6 mm
10.4 cm2

0.4cm

15°
Complex scroll
Guinea Pig
600 g
2 5 mm2
40°
3.4 cm
12.8mm
27.4 cm2

039 cm3

30°
Complex scroll
Beagle Dog
10kg
16.7 mm2
30°
10cm
23 mm
220.7 cm2

20cm3

30°
Very complex membranous
Rhesus Monkey
7kg
22.9 mm2
30°
5.3 cm
27mm
61.6 cm2

8cm3

80°
Simple scroll
Human3
-70kg
140 mm2

7-8 cm
40-45 mm
181 cm2

16-19 cm3 (does not
include sinuses)
-90°
Simple scroll
aAdult male.
Source: Schreider (1983); Gross and Morgan (1992).

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                 TABLE 10-6.  COMPARATIVE LOWER AIRWAY ANATOMY AS REVEALED ON CASTS
Mammal/
Body Mass
Human/70 kg

Rhesus
monkey/2 kg

Beagle dog/
10kg
i—1 Ferret/
"P 0.61 kg
O Guinea pig/
1kg
Rabbit/
4.5kg
Rat/0.3 kg
Golden
hamster/
0.14kg

Left Lung
Lobes
Upper and
lower

Superior,
middle, and
inferior

Apical,
intermediate,
and basal
NR'
Superior
and
inferior
Superior
and
inferior
One lobe
Superior
and
inferior

Right Lung
Lobes
Upper, middle,
and lower

Superior,
middle, and
inferior,
azygous
Apical,
intermediate,
and basal
NR
Superior,
middle, and
inferior
Cranial,
middle, caudal,
and postcaval
Cranial,
middle, caudal,
and postcaval
Cranial, middle,
caudal, and
postcaval
Gross Structure
Airway
Branching
Relatively
symmetric

Monopodial

Strongly
monopodial
strongly
monopodial
Monopodial
Strongly
monopodial
Strongly
monopodial
Strongly
monopodial

Trachea Major
Length/Diameter Airway
(cm) Bifurcations
12/2 Sharp for about
the first
10 generations,
relatively
blunt thereafter
3/0.3 Mixed blunt
and sharp

17/1.6 Blunt tracheal
bifurcation,
others sharp
10/0.5 Sharp
5.7/0.4 Very sharp
and high
6/0.5 Sharp
2.3/0.26 Very sharp and
very high
throughout lung
2.4/0.26 Very sharp
Typical Structure
(Generation 6)
Average Branch Angles
Airway (Major Daughter/
L/D Minor Daughter)
(ratio) (degrees)
2.2 11/33

2.6 20/62

1.3 8/62
2.0 16/57
1.7 7/76
1.9 15/75
1.5 13/60
1.2 15/63
Typical Number
of Branches
to Terminal Respiratory
Bronchiole Bronchioles
14-17 About 3-5 orders

10-18 About 4 orders

15-22 About 3-5 orders
12-20 About 3-4 orders
12-20 About 1 order
12-20 About 1-2 orders
12-20 Rudimentary
10-18 About 1 order
"NR = Not reported.




Source: Phalen and Oldham (1983); Patra (1986); Mercer and Crapo (1987).

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TABLE 10-7.  ACINAR MORPHOMETRY
Species
Human






Rabbit

Guinea pig

Rat



Number of
Fixation Acini/Lung

27,992
75% TLC 23,000
80,000

TLC 26,000-32,000
FRC 43,000
17,900
55% TLC 18,000
5,100
FRC 4,097
2,500
2,487
FRC 2,020
70% TLC 5,993
V
(mm3)
1.33-30.9

160.8
15.6

187.0
51.0
2.54
3.46
1.25
1.09
1.0
5.06
1.9
1.46
Alveolar
D or L (mm)2 Number Duct
Alveoli/Acinus Generations References
15,000
10,714
7.04 (L) 14,000-20,000

5.1 (L) 7,100
8.8 (L) 10,344
6.0 (D) 8,000

1.95 (L)

1.56(D) 6,890


1.5(D) 5,243
1-5 (L)

6
9
2-5
8-12
9
9

6

9-12


10-12
6
Pump (1964)
Horsfield and Gumming (1968); Parker et
Hansen and Ampay a (1975); Hansen et al
Boy den (1972)
Schreider and Raabe (1981)
Haefeli-Bleuer and Weibel (1988)
Mercer, and Crapo (1992)
Kliment(1973)
Rodriguez et al. (1971)
Kliment(1973)
Mercer and Crapo (1992)
Kliment(1973)
Yehetal. (1979)
Mercer et al., 1987
Rodriguez et al. (1987)

al. (1971)
. (1975)












'Volume of lung at fixation (TLC, total lung capacity;
2Acinar size (D, diameter; L, length).

Source: Mercer and Crapo (1992).
FRC, functional residual capacity).

-------
     The airways show a considerable degree of variability within species (e.g., size and
branching pattern) and this is most likely the primary factor responsible for the deposition
variability seen within single species (Schlesinger, 1985a).
     Larger airway diameter results in greater turbulence for the same relative flow velocity
(e.g., between a particle and air). Therefore, flow may be turbulent in the large airways of
humans, whereas for an identical flow velocity, it would be laminar in the smaller laboratory
animal. Relative to humans, laboratory animals also tend to have tracheas that are much longer
in relation to their diameter. This could result in increased relative deposition in humans
because of the increased likelihood of laryngeal jet flow extending into the bronchi. Human
airways are characterized by a more symmetrical dichotomous branching than that found in most
laboratory mammals, which have highly asymmetrical airway branching (monopodial).  The
more symmetrical dichotomous pattern in humans is susceptible to deposition at the carina
because of its exposure to high air flow velocities toward the center of the air flow profile.
     Alveolar size also differs between species, which may affect deposition efficiency due to
variations on the distance between the airborne particle and alveolar walls (Dahl et al., 1991).
     Addressing species differences in ventilation, which affects the tidal volume and
ventilation to perfusion ratios, is also critical to estimating initial absorbed dose. Due to the
expected variations  in airflows within the respiratory tract, the variability among lungs in the
human or laboratory animal population, and the variations in respiratory performance that
members of the population experience during their normal activities, e.g. sleep and exercise,
must be considered  in order to gain some insight into the variability that might be expected  in
particle deposition, total and regional, of particles in the urban atmosphere.  The experimentalist
must try to keep  respiratory parameters relatively constant to obtain reasonably consistent
deposition data.

10.4.2  Clearance and Translocation Mechanisms
     Particles that deposit upon airway surfaces may be cleared from the respiratory tract
completely, or may  be translocated to other sites within this system, by various regionally
distinct processes.  These clearance mechanisms, which are outlined in Table 10-8, can be
                                          10-52

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   TABLE 10-8.  OVERVIEW OF RESPIRATORY TRACT PARTICLE CLEARANCE
                        AND TRANSLOCATION MECHANISMS
 Extrathoracic region
      Mucociliary transport
      Sneezing
      Nose wiping and blowing
      Dissolution (for "soluble" particles) and absorption into blood
 Tracheobronchial region
      Mucociliary transport
      Endocytosis by macrophages/epithelial cells
      Coughing
      Dissolution (for "soluble" particles) and absorption into blood
 Alveolar region
      Macrophages, epithelial cells
      Interstitial
      Dissolution for "soluble" and "insoluble" particles (intra-and
	extracellular)	

Source: Schlesinger (1995).
categorized as either absorptive (i.e., dissolution) or nonabsorptive (i.e., transport of intact
particles) and may occur simultaneously or with temporal variations.  It should be mentioned
that particle solubility in terms of clearance refers to solubility within the respiratory tract fluids
and cells. Thus, an "insoluble" particle is considered to be one whose rate of clearance by
dissolution is insignificant compared to its rate of clearance as an intact particle.  For the most
part, all deposited particles are subject to clearance by the same mechanisms, with their ultimate
fate a function of deposition site, physicochemical properties (including any toxicity),  and
sometimes deposited mass or number concentration. Clearance routes from the various regions
of the respiratory tract are schematically outlined in Figures 10-12  and 10-13.  Furthermore,
clearance is a continuous process and all mechanisms operate  simultaneously for deposited
particles.

10.4.2.1   Extrathoracic Region
     The clearance of insoluble particles deposited in the nonolfactory portion of nasal passages
occurs via mucociliary transport, and the general flow of mucus is backwards, i.e., towards the
nasopharynx (Figure 10-12).  However, the epithelium of the most anterior portion of the nasal
passages is not ciliated, and mucus flow just distal to this is forward,

                                            10-53

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                               'Nasal Passag
                   !°JL )
                                                   C^V
                                                     Posterior  )
   Extrinsic Clearance	
                                               Pharynx
                              G
                           Tracheobronchial Tre
Figure 10-12.  Major physical clearance pathways from the extrathoracic region and
             tracheobronchial tree.
      Deposited Particle
       Phagocytosis by
    Alveolar Macrophages
             I
            ieni
            larl
                                           Endocytosis by
                                           Type I Alveolar
                                           Epithel al Cells
Movement within
Alveolar Lumen
 Passage Through
Alveolar Epithelium
              ^ ^
      ithelium ^ s I
      -
                                                  Passage through
                                                 Pulmonary Capillary
                                                    Endothelium
    Bronchiolar/ Bronchial
           Lumen
Interstitium
             *
                            Lymphatic Channels
      Mucociliary Blanket              I
                                                   Phagocytosis by
                                                      Interstitial
                                                    Macrophages ^
                                Lymph Nodes
Figure 10-13.  Diagram of known and suspected clearance pathways for poorly soluble
             particles depositing in the alveolar region.


Source: Modified from Schlesinger (1995).
                                     10-54

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clearing deposited particles to a site (vestibular region) where removal is by sneezing (a reflex
response), wiping, or blowing (mechanisms known as extrinsic clearance).
     Soluble material deposited on the nasal epithelium will be accessible to underlying cells if
it can diffuse to them through the mucus prior to removal via mucociliary transport. Dissolved
substances may be subsequently translocated into the bloodstream following movement within
intercellular pathways between epithelial cell tight junctions or by active or passive transcellular
transport mechanisms.  The nasal passages have a rich vasculature, and uptake into the blood
from this region may occur rapidly.
     Clearance of poorly soluble particles deposited in the oral passages is by coughing and
expectoration or by swallowing into the gastrointestinal tract.  Soluble particles are likely to be
rapidly absorbed after deposition (Swift and Proctor, 1988).

10.4.2.2   Tracheobronchial Region
     Poorly soluble particles deposited within the tracheobronchial tree are cleared primarily by
mucociliary transport, with the net movement of fluid towards the oropharynx, followed by
swallowing.  Some poorly soluble particles may traverse the epithelium by endocytotic
processes, entering the peribronchial region (Masse et al., 1974; Sorokin and Brain, 1975).
Clearance may also occur following phagocytosis by airway macrophages, located on or beneath
the mucous lining throughout the bronchial tree.  They then move cephalad on the mucociliary
blanket, or via macrophages which enter the airway lumen from the bronchial or bronchiolar
mucosa (Robertson, 1980).
     As in the nasal passages, soluble particles may be absorbed through the mucous layer of
the tracheobronchial airways and into the blood, via intercellular pathways between epithelial
cell tight junctions or by active or passive transcellular transport mechanisms.
     The bronchial surfaces are not homogeneous; there are openings of daughter bronchi and
islands of non-ciliated cells at bifurcation regions.  In the latter, the usual progress of mucous
movement is interrupted, and bifurcations may be sites of relatively retarded clearance. The
efficiency with which such non-ciliated regions are traversed is dependent upon the traction of
the mucous layer.
     Another method of clearance from the tracheobronchial region, under some circumstances,
is cough, which can be triggered by receptors located in the area from the
                                          10-55

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trachea through the first few bronchial branching levels.  While cough is generally a reaction to
some inhaled stimulus, in some cases, especially respiratory disease, it can also serve to clear the
upper bronchial airways of deposited substances by dislodging mucus from the airway surface.

10.4.2.3  Alveolar Region
     Clearance from the alveolar (A) region occurs via a number of mechanisms and pathways,
but the relative importance of each is not always certain and may vary between species.
     Particle removal by macrophages comprises the main nonabsorptive clearance process in
the A region. Alveolar macrophages reside on the epithelium, where they phagocytize and
transport deposited material.  They come into contact with phagocytized material by random
motion, or more likely via directed migration under the influence of local chemotactic factors
(Warheit et al, 1988). Contact may be facilitated as some deposited particles are translocated,
due to pressure gradients or via capillary action within the alveolar surfactant lining, to sites
where macrophages congregate  (Schurch et al., 1990; Parra et al., 1986).
     Alveolar macrophages normally comprise «3 - 5%  of the total alveolar cells in healthy
(non-smoking) humans and other mammals, and represent the largest subpopulation of
nonvascular macrophages in the respiratory tract (Gehr, 1984; Lehnert, 1992).  However, the
actual cell count may be altered by particle loading.  While a slight increase of deposited
particles may not result in an increase in cell number, macrophage numbers will increase
proportionally to particle number until some peak accumulation is reached (Adamson and
Bowden, 1981; Brain, 1971). Since the magnitude of this increase is related more to the number
of deposited particles than to total deposition by weight, equivalent masses of an identically
deposited substance would not produce the same response if particle sizes differed; thus,
deposition of smaller particles would tend to result in a greater elevation in macrophage number
than would larger particle deposition.
     Particle-laden macrophages may be cleared from the A region along a number of pathways
(Figure  10-13).  One route is cephalad transport via the mucociliary system after the cells reach
the distal terminus of the mucus blanket. However, the manner by which macrophages actually
reach the ciliated airways is not certain.  The possibilities are chance
                                         10-56

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encounter; passive movement along the alveolar surface due to surface tension gradients between
the alveoli and conducting airways; directed locomotion along a gradient produced by
chemotactic factors released by macrophages ingesting deposited material; or passage through
the alveolar epithelium and the interstitium, perhaps through aggregates of lymphoid tissue
known as bronchus associated lymphoid tissue (BALT) located at bronchoalveolar junctions
(Sorokin and Brain,  1975; Kilburn, 1968; Brundelet, 1965; Green, 1973; Cony et al., 1984;
Harmsen et al., 1985).
     Some of the cells which follow interstitial clearance pathways are likely resident interstitial
macrophages that have ingested particles which were transported through the alveolar
epithelium, probably via endocytosis by Type I pneumocytes (Brody et al., 1981; Bowden and
Adamson, 1984).  Particle-laden interstitial macrophages can also migrate across the alveolar
epithelium, becoming part of the alveolar macrophage cell population (Adamson and Bowden,
1978).
     Macrophages that are not cleared via the bronchial tree may actively migrate within the
interstitium to a nearby lymphatic channel or, along with uningested particles, be carried in the
flow of interstitial fluid towards and into the lymphatic system (Harmsen et al., 1985). Passive
entry into lymphatic vessels is fairly easy, since the vessels have loosely connected endothelial
cells with wide intercellular junctions (Lauweryns and Baert, 1974).  Lymphatic endothelium
may also actively engulf particles from the surrounding interstitium (Leak, 1980). Particles
within the lymphatic system may be translocated to tracheobronchial lymph nodes, which often
become reservoirs of retained material. Particles penetrating the nodes and subsequently
reaching the post-nodal lymphatic circulation may enter the blood.
     Uningested particles or macrophages in the interstitium may traverse the alveolar-capillary
endothelium, directly entering the blood (Raabe,  1982; Holt, 1981); endocytosis by endothelial
cells followed by exocytosis into the vessel lumen seems, however, to be restricted to particles
<0.1 //m diameter, and may increase with increasing lung burden (Lee et al., 1989; Oberdorster,
1988).  Once in the systemic circulation, transmigrated macrophages, as well as uningested
particles, can travel to extrapulmonary organs.  Some mammalian species have alveolar
intravascular macrophages, which can remove particles from circulating blood and which may
play some role in the clearance of material deposited in the alveoli (Warner and Brain, 1990).
                                         10-57

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     Uningested particles and macrophages within the interstitium may travel to perivenous,
peribronchiolar or subpleural sites, where they become trapped, increasing particle burden. The
migration and grouping of particles and macrophages within the lungs can lead to the
redistribution of initially diffuse deposits into focal aggregates (Heppleston, 1953).  Some
particles can be found in the pleural space, often within macrophages which have migrated
across the visceral pleura (Sebastien et al., 1977; Hagerstrand and Siefert, 1973).  Resident
pleural macrophages do occur, but their role in clearance, if any, is not certain.
     During clearance, particles can be redistributed within the alveolar macrophage population
(Lehnert, 1992). This can occur following death of a macrophage, and release of free particles
to the epithelium, followed by uptake by other macrophages. Some of these newly freed
particles may, however, translocate to other clearance routes.
     Clearance by the absorptive  mechanism involves dissolution in the alveolar surface fluid,
followed by transport through the epithelium and into the interstitium, and diffusion into the
lymph or blood.  Some soluble particles translocated to and trapped in interstitial sites may be
absorbed there. Although the factors affecting the dissolution of deposited particles are poorly
understood, solubility is influenced by the particle's surface to volume ratio and other surface
properties (Morrow, 1973; Mercer, 1967). Thus, materials generally considered to be relatively
insoluble may still have high dissolution rates and short dissolution half-times if the particle  size
is small.
     Some deposited particles may undergo dissolution in the acidic milieu of the
phagolysosomes after ingestion by macrophages, and such intracellular dissolution may be the
initial step in translocation from the lungs for these particles (Kreyling, 1992; Lundborg et al.,
1985). Following dissolution, the material can be absorbed into the blood. Dissolved materials
may then leave the lungs at rates which are more rapid than would be expected based upon their
normal dissolution rate in  lung fluid. For example, while insoluble (in lung fluid) MnO2
dissolves in the macrophage following ingestion, soluble manganese chloride (MnCy likely
dissolves extracellularly and is not ingested, resulting in manganese clearing at different initial
rates depending upon the form in which it was initially inhaled (Camner et al,  1985).
Differences in rates of clearance may also occur for particles whose rate of dissolution is pH
dependent (Marafante et al., 1987).
                                          10-58

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     Finally, some particles can bind to epithelial cell membranes or macromolecules, or other
cell components, delaying clearance from the lungs.

10.4.2.4   Clearance Kinetics
     Deposited particles may be cleared completely from the respiratory tract.  However, the
actual time frame over which clearance occurs affects the cumulative dose delivered to the
respiratory tract, as well as to extrapulmonary organs. Particle-tissue contact and retained dose
in the extrathoracic region and tracheobronchial tree are often limited by rapid clearance from
these regions.  On the other hand, the retained dose from material deposited in the A region is
more dependent upon the physicochemical characteristics of the particles.
     Various experimental techniques have been used to assess clearance rates in both humans
and laboratory animals (Schlesinger, 1985b). Because of technical differences and the fact that
measured rates are strongly influenced by the specific methodology, comparisons between
studies are often difficult to perform. However, regional clearance rates, i.e., the fraction of the
deposit which is  cleared per unit time, are well defined functional characteristics of an individual
human or laboratory animal when repeated tests are performed under the same conditions; but,
as with deposition, there is a substantial degree  of inter-individual variability.

Extrathoracic Region
     Mucus flow rates in the posterior nasal passages are highly  nonuniform.  Regional
velocities in the healthy adult human may range from < 2 to > 20 mm/min (Proctor, 1980), with
the fastest flow occurring in the midportion of the nasal passages. The median rate in a healthy
adult human is about 5 mm/min, the net result being a mean anterior to posterior transport time
of about  10-20 min for poorly soluble particles deposited within the nasal passages (Stanley et
al., 1985; Rutland and Cole, 1981). However, particles deposited in the anterior portion of the
nasal passages are cleared more slowly, at a rate of 1-2 mm/h (Hilding, 1963).  Since clearance
at this rate may take upwards of 12 h, such deposits are usually more effectively removed by
sneezing, wiping, or nose blowing, in which case clearance may occur in 0.5 h (Morrow, 1977;
Fry and Black, 1973).
                                          10-59

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Tracheobronchial Region
     Mucus transport in the tracheobronchial tree occurs at different rates in different local
regions; the velocity of movement is fastest in the trachea, and it becomes progressively slower
in more distal airways. In healthy non-smoking humans, and using non-invasive procedures and
no anesthesia, average tracheal mucus transport rates have been measured at 4.3 to 5.7 mm/min
(Leikauf et al., 1981, 1984; Yeates et al., 1975, 1981b; Foster et al., 1980), while that in the
main bronchi has been measured at -2.4 mm/min (Foster et al., 1980). While rates of movement
in smaller airways have not been directly determined, estimates for human medium bronchi
range between 0.2-1.3 mm/min, while those in the most distal ciliated airways range down to
0.001 mm/min (Yeates and Aspin, 1978; Morrow et al., 1967b; Cuddihy and Yeh, 1988).
     It is not certain whether the transport rate for deposited poorly soluble particles is
independent of their nature, i.e., shape, size, composition. While particles of different materials
and sizes have been shown to clear at the same rate in the trachea in some studies (Man et al.,
1980; Patrick,  1983; Connolly et al., 1978), other studies (using instillation) have indicated that
the rate of mucociliary clearance may be greater for smaller particles (<2//m) than for larger
ones (Takahashi et al,  1992). Reasons for such particle-size related differences are not known.
There may, however, be more than one phase of clearance within individual tracheobronchial
airways. For example, the rat trachea shows a biphasic clearance pattern, consisting of a rapid
phase within the first 2-4 h after deposition, clearing up to 90% of deposited particles with a half
time of < 0.5 h, followed by a second, slower phase,  clearing most of the remaining particles
with a half-time of 8-19 h (Takahashi et al, 1992).
     The total duration of bronchial clearance, or some other time parameter, is often used as an
index of mucociliary kinetics, yet the temporal clearance pattern is not certain. In healthy adult
non-smoking humans, 90% of poorly soluble particles depositing within the tracheobronchial
tree were found to be cleared from 2.5 to 20 h after deposition, depending upon the individual
subject and the size of the particles (Albert et al., 1973). While particle size does not affect
surface transport, it does affect the depth of particle penetration and deposition and the
subsequent pathway length for clearance.  Due to differences in regional transport rates,
clearance times from different regions of the bronchial tree will differ.
                                          10-60

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While removal of a TB deposit is generally 99% completed by 48 h after exposure (Bailey et al.,
1985a), there is the possibility of longer-term retention under certain circumstances.
      Studies with rodents, rabbits, and humans have indicated that a small fraction («1%) of
insoluble material may be retained for a prolonged period of time within the upper respiratory
tract (nasal passages) or tracheobronchial tree (Patrick and Stirling,  1977; Gore and Patrick,
1982; Watson and Brain, 1979; Radford and Martell,  1977; Svartengren et al.,  1981). The
mechanism(s) underlying this long-term retention is unknown, but may involve endocytosis by
epithelial cells with subsequent translocation into deeper (submucosal) tissue, or merely passive
movement into this tissue. In addition, uptake by the epithelium may  depend upon the nature, or
size, of the deposited particle (Watson and Brain, 1980). The retained particles may eventually
be cleared to regional lymph nodes, but with a long half time that may be > 80 days (Patrick,
1989; Oghiso and Matsuoka,  1979).
      There is some suggestion of a greater extent of long term retention in the bronchial tree.
Stahlhofen et al. (1986), using a specialized inhalation procedure, noted that a significant
fraction, up to 40%, of particles which were likely deposited in the conducting airways were not
cleared up to six days post-deposition. They also noted that the size of the particles influenced
this retention, with smaller ones being retained to a greater extent than were larger ones
(Stahlhofen et al., 1987, 1990).  Although the  reason for this is not certain, the suggested
presence of a surfactant film on the mucous lining of the airways (Gehr et al., 1990) may result
in a reduced surface tension which, in turn, influences the displacement of particles into the gel
layer and, subsequently, into the sol layer towards the epithelial cells.  Particles that reach these
cells may then be phagocytized, increasing retention time  in the lungs. However, the issue of
retention of large fractions of tracheobronchial deposit is not resolved.
      Long-term TB retention patterns are not uniform.  There is an  enhancement at bifurcation
regions (Cohen et al., 1988; Radford and Martell, 1977; Henshaw and Fews, 1984), the likely
result of both greater deposition and less effective mucus clearance within these areas. Thus,
doses calculated based upon uniform  surface retention density may be misleading, especially if
the material is, lexicologically, slow acting. Solubilized material may also undergo long-term
retention in ciliated airways due to binding to  cells or macromolecules.
                                          10-61

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Alveolar Region
     Clearance kinetics in the A region are not definitively understood, although particles
deposited there generally remain longer than do those deposited in airways cleared by
mucociliary transport.  There are limited data on rates in humans, while within any species rates
vary widely due to different properties of the particles used in the various studies. Furthermore,
some of these studies employed high concentrations of poorly soluble particles, which may have
interfered with normal clearance mechanisms, producing rates different from those which would
typically occur at lower exposure levels. Prolonged exposure to high particle concentrations is
associated with what is termed particle "overload." This is discussed in greater detail in Section
10.4.2.7.
     There are numerous pathways of A region clearance, and these may depend upon the
nature of the particles being cleared. Thus, generalizations about clearance kinetics are difficult
to make, especially since the manner in which particle characteristics affect clearance kinetics is
not resolved. Nevertheless,  A region clearance can be described as a multiphasic process, each
phased considered to represent removal by a different mechanism or pathway, and often
characterized by increased retention half-times with time post-exposure.
     Clearance of inert, poorly soluble particles in healthy, nonsmoking humans has been
generally observed to consist of two phases, with the first having a half-time  measured in days,
and the second in hundreds of days. Table 10-9 presents some observed times for the longer,
second phase of clearance as reported in a number of studies.  Differences in technique,
chemistry, and solubility of the particles in Table  10-9 are largely responsbile for the variations.
Although wide variations in retention reflect a dependence upon the nature of the deposited
material (e.g., particle size) once dissolution is accounted for, mechanical removal to the
gastrointestinal tract and/or lymphatic system appears to be independent of size, especially for
particles < 5 //m (Snipes  et al., 1983).  Although not evident from Table 10-9, there is
considerable intersubject variability in the clearance rates of identical particles, which appears to
increase with time post-exposure (Philipson et al., 1985; Bailey et al., 1985a). The large
differences in clearance kinetics among different individuals suggest that equivalent chronic
exposures to poorly soluble  particles may result in large variations in respiratory tract burdens.
                                           10-62

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  TABLE 10-9.  LONG-TERM RETENTION OF POORLY SOLUBLE PARTICLES IN
              THE ALVEOLAR REGION OF NON-SMOKING HUMANS
Particle
Material
Polystyrene latex
Polystyrene latex
Polystyrene latex
Polystyrene latex
Teflon
Aluminosilicate
Aluminosilicate
Iron oxide (Fe2O3)
Iron oxide (Fe2O3)
Iron oxide (Fe3O4)
Size (//m)
5
5
0.5
3.6
4
1.2
3.9
0.8
0.1
2.8
Retention Half-Time3
(days) Reference
150 to 300
144 to 340
33 to 602
296
100 to 2,500
330
420
62
270
70
Booker etal. (1967)
Newton etal. (1978)
Jammettetal. (1978)
Bohningetal. (1982)
Philipson et al. (1985)
Bailey etal. (1982)
Bailey etal. (1982)
Morrow et al. (1967a,b)
Waite and Ramsden (1971)
Cohen etal. (1979)
^Represent the half-time for the slowest clearance phase observed.
     While the kinetics of overall clearance from the A region have been assessed to some
extent, much less is known concerning relative rates along specific pathways, and any available
information is generally from studies with laboratory animals.  The usual initial step in
clearance, i.e., uptake of deposited particles by alveolar macrophages, is very rapid.  Ingestion
by macrophages generally occurs within 24 h of a single inhalation (Naumann and Schlesinger,
1986; Lehnert and Morrow, 1985). But the actual rate of subsequent macrophage clearance is
not certain; perhaps 5% or less of their total number is translocated from the lungs each day in
rodents (Lehnert and Morrow, 1985; Masse et al., 1974).
     The rate and amount of particle uptake by macrophages is likely governed by particle size
and surface properties (Tabata and Ikada, 1988), although these experiments were performed
with peritoneal macrophages and not with alveolar macrophages.  For example, the effect of
particle size was examined by incubating mouse peritoneal macrophages with polymer
microspheres (0.5 to 5 //m). Both the number of particles ingested per cell and the volume of
these particles per cell reached a maximum for particle diameters of 1-2 //m, declining on either
side of this range.  In terms of particle surface, those with hydrophobic surfaces were ingested to
a greater extent than were those with hydrophilic surfaces. Phagocytosis also increased as the
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surface charge density of a particle increased, but for the same charge density there was no
difference in uptake between positively or negatively charged particles.
     The time for clearance of particle-laden alveolar macrophages via the mucociliary system
depends upon the site of uptake relative to the distal terminus of the mucus blanket at the
bronchiolar level. Furthermore, clearance pathways, and subsequent kinetics, may depend to
some extent upon particle size. For example, some smaller ultrafine particles (perhaps < 0.02
//m) may be less effectively phagocytosed than are larger ones (Oberdorster, 1993). But once
ingestion occurs, alveolar macrophage-mediated kinetics are independent of the particle
involved, as long as solubility and cytotoxicity are low.
     In terms of other clearance pathways, uningested particles may penetrate into the
interstitium, largely by Type I cell endocytosis, within a few hours following deposition (Ferin
and Feldstein,  1978; Sorokin and Brain, 1975; Brody et al., 1981). This transepithelial passage
seems to increase as particle loading increases, especially to a level above the saturation point for
increasing macrophage number (Adamson and Bowden, 1981; Ferin,  1977). It may also be
particle size dependent, since insoluble ultrafine  particles (<0.1 //m diameter) of low intrinsic
toxicity show increased access to and greater lymphatic uptake than do larger ones of the same
material (Oberdorster et al., 1992). However, ultrafine particles of different materials may not
enter the interstitium to the same extent.  Similarly, any depression of phagocytic activity or the
deposition of large numbers of smaller ultrafine particles may increase the number of free
particles in the alveoli, enhancing removal by other routes.  In any case, free particles and
alveolar macrophages may reach the lymph nodes, perhaps within a few days after deposition
(Lehnert et al., 1988; Harmsen et al., 1985), although this route is not certain and may be species
dependent.
     The extent of lymphatic uptake of particles may depend upon the effectiveness of other
clearance pathways. For example, lymphatic translocation probably increases when phagocytic
activity of alveolar macrophages is decreased (Greenspan,  et al.,  1988).  This may be a factor in
lung overload, as discussed in Section  10.4.2.7. However, it seems that the deposited mass or
number of particles must reach some threshold below which increases in loading do not affect
translocation rate to the lymph nodes (Ferin and Feldstein, 1978;  LaBelle and Brieger, 1961).
                                          10-64

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     The rate of translocation to the lymphatic system may be somewhat particle size
dependent. Although no human data are available, translocation of latex particles to the lymph
nodes of rats was greater for 0.5 to 2 //m particles than for 5 and 9 //m particles (Takahashi et
al., 1992), and smaller particles within the 3 to 15 //m size range were found to be translocated
at faster rates than were larger sizes (Snipes and Clem, 1981). On the other hand, translocation
to the lymph nodes was similar for both 0.4 //m barium sulfate or 0.02 //m gold colloid particles
(Takahashi et al., 1987). It seems that particles < 2 //m clear to the lymphatic system at a rate
independent of size, and it is particles of this size, rather than those > 5 //m, that would have
significant deposition within the A region following inhalation.
     In any case, and regardless  of any particle size dependence, the normal rate of translocation
to the lymphatic system is quite slow, on the order of 0.02-0.003%/day (Snipes, 1989), and
elimination from the lymph nodes is even slower, with half-times estimated in tens of years
(Roy, 1989).
     Soluble particles depositing in the A region may be rapidly cleared via absorption through
the epithelial surface into the blood, but there are few data on dissolution and transfer rates to
blood in humans. Actual rates depend upon the size of the particle (i.e., solute size), with
smaller ones clearing faster than larger ones. Chemistry also plays a role, since water soluble
compounds generally clear at a slower rate than do lipid soluble materials.
     Absorption may be considered as a two stage process, with the first stage dissociation of
the deposited particles into material that can be absorbed into the circulation (dissolution) and
the second stage the uptake of this material. Each of these stages may be time dependent.  The
rate of dissolution depends upon  a number of factors, including particle surface area and
chemical structure.  Uptake into the circulation is generally considered as instantaneous,
although a portion of the dissolved material may be absorbed more slowly due to binding to
respiratory tract components. Accordingly, there is a very wide range for absorption rates
depending upon the physicochemical properties of the material deposited.  For example, a highly
soluble particle may be absorbed at a rate faster than the particle transport rate and  significant
uptake may occur in the conducting airways. On the other
                                          10-65

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hand, a particle that is less soluble and remains in the lungs for years would have a much lower
rate, perhaps <0.0001%/day.

10.4.2.5   Factors Modifying Clearance
     A number of host and environmental factors may modify normal clearance patterns,
affecting the dose delivered by exposure to inhaled particles. These include aging, gender,
workload, disease and irritant inhalation. However, in many cases, the exact role of these factors
is not resolved.

Age
     The evidence for aging-related effects on mucociliary function in healthy individuals is
equivocal, with studies showing either no changes or some slowing in mucous clearance function
with age after maturity (Goodman et al., 1978; Yeates et al., 1981a; Puchelle et al., 1979).
However, it is  often difficult to determine whether any observed functional decrement was due
to aging alone, or to long-term, low level ambient pollutant exposure (Wanner,  1977). In any
case, the change in mucous velocity between approximately age 20 and 70 in humans is about a
factor of two (Wolff, 1992) and would likely not significantly affect overall kinetics.
     There are few data to allow assessment of aging-related changes in clearance from the A
region. Although functional differences have been found between alveolar macrophages of
mature and senescent mice (Esposito and Pennington, 1983), no age-related decline in
macrophage function has been seen in humans (Gardner et al., 1981).
     There are also insufficient data to assess changes in clearance in the growing lung.  Nasal
mucociliary clearance time in a group of children (average age = 7 yrs) was found to be ~ 10 min
(Passali and Bianchini Ciampoli, 1985); this is within the range for adults. There  is one report
of bronchial clearance in children (12 yrs old), but this was performed in patients hospitalized
for renal disease (Huhnerbein et al., 1984).

Gender
     No gender related differences were found in nasal mucociliary  clearance rates in children
(Passali and Bianchini Ciampoli, 1985) nor in tracheal transport rates in adults
                                          10-66

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(Yeates et al., 1975).  Slower bronchial clearance has been noted in male compared to female
adults, but this was attributed to differences in lung size (and resultant clearance pathway length)
rather than to inherent gender related differences in transport velocities (Gerrard et al., 1986).

Physical Activity
     The effect of increased physical activity upon mucociliary clearance is unresolved, with the
available data indicating either no effect or an increased clearance rate with exercise (Wolff et
al., 1977; Pavia, 1984).  There are no data concerning changes in A region clearance with
increased activity levels, but CO2-stimulated hyperpnea (rapid, deep breathing) was found to
have no effect on early alveolar clearance and redistribution of particles (Valberg et al., 1985).
Breathing with an increased tidal volume was noted to increase the rate of particle clearance
from the A region, and this was suggested to be due to distension related evacuation of
surfactant into proximal airways, resulting in a facilitated movement of particle-laden
macrophages or uningested particles due to the accelerated motion of the alveolar fluid film
(Johnetal., 1994).

Respiratory Tract Disease
     Various respiratory tract diseases are associated with clearance alterations. The
examination of clearance in individuals with lung disease requires careful interpretation of
results, since differences in deposition of tracer particles used to assess clearance function may
occur between normal individuals and those with respiratory disease, and this would directly
impact upon the measured clearance rates, especially in the tracheobronchial tree.  In any case,
nasal mucociliary clearance is prolonged in humans with chronic sinusitis, bronchiectasis, or
rhinitis (Majima et al., 1983; Stanley et al., 1985), and in cystic fibrosis (Rutland and Cole,
1981). Bronchial mucus transport may be impaired in people with bronchial carcinoma
(Matthys et  al., 1983), chronic bronchitis (Vastag et al., 1986), asthma (Pavia et al., 1985), and
in association with various acute infections (Lourenco et al., 1971; Camner et al., 1979; Puchelle
et al., 1980). In certain of these cases, coughing may enhance mucus clearance, but it generally
is effective only if excess  secretions are present.
     Normal mucociliary function is essential to respiratory tract health. Studies of individuals
with a syndrome characterized by impaired clearance, i.e., primary ciliary dyskinesia (PCD),
                                           10-67

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may be used to assess the importance of mucociliary transport and the effect of its dysfunction
upon respiratory disease, and to provide information on the role of clearance in maintaining the
integrity of the lungs.  The lack of mucociliary function in PCD is directly responsible for the
early development of recurrent respiratory tract infections and, eventually, chronic bronchitis
and bronchiectasis (Rossman et al., 1984; Wanner, 1980). It is, however, not certain whether
partial impairment of the mucociliary system will increase the risk of lung disease.
     Rates of A region particle clearance appear to be reduced in humans with chronic
obstructive lung disease (Bohning et al., 1982) and in laboratory animals with viral infections
(Creasia et al., 1973).  The viability and functional activity of macrophages was found to be
impaired in human asthmatics (Godard  et al., 1982).
      Studies with laboratory animals have also found disease related clearance changes.
Hamsters with interstitial fibrosis showed an increased  degree of alveolar clearance (Tryka et al.,
1985). Rats with emphysema showed no clearance difference from control (Damon et al.,
1983), although the co-presence of inflammation resulted in prolonged retention (Hahn and
Hobbs, 1979). On the other hand, inflammation may enhance particle and macrophage
penetration through the alveolar epithelium into the interstitium, by increasing the permeability
of the epithelium and the lymphatic endothelium (Corry et al., 1984). Neutrophils, which are
phagocytic cells present in alveoli during inflammation, may contribute to the clearance of
particles via the mucociliary system (Bice et al., 1990).
     Macrophages have specific functional properties,  namely phagocytic activity and mobility,
which allow them to adequately perform their role in clearance. Alveolar macrophages from
calves with an induced interstitial inflammation (pneumonitis) were found to have enhanced
phagocytic activity compared to normal animals (Slauson et al., 1989).  On the other hand,
depressed phagocytosis was found with virus-induced acute bronchiolitis and alveolitis (Slauson
et al., 1987).  How such alterations affect clearance from the A region is not certain, since the
relationship between macrophage functional characteristics and  overall clearance is not always
straightforward.  While changes in macrophage function do impact upon clearance, the manner
by which they do so may not always be easily
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predictable. In any case, the modification of functional properties of macrophages appear to be
injury specific, in that they reflect the nature and anatomic pattern of disease.

Inhaled Irritants
     Inhaled irritants have been shown to have an effect upon mucociliary clearance function in
both humans and laboratory animals (Schlesinger, 1990; Wolff, 1986).  Single exposures to a
particular material may increase or decrease the overall rate of tracheobronchial clearance, often
depending upon the exposure concentration (Schlesinger, 1986).  Alterations in clearance rate
following single exposures to moderate concentrations of irritants are generally transient, lasting
< 24 h. However, repeated exposures may result in an increase in intra-individual variability of
clearance rate and persistently retarded clearance. The effects of irritant exposure may be
enhanced by exercise, or by coexposure to other materials.
     Acute and chronic exposures to inhaled irritants may also alter A region clearance (Cohen
et al., 1979; Ferin and Leach, 1977; Schlesinger et al., 1986; Phalen et al., 1994), which may be
accelerated or depressed, depending upon the specific material and/or length of exposure.  While
the clearance of poorly soluble particles from conducting airways is due largely to only one
mechanism, i.e., mucociliary transport, clearance from the respiratory region involves a complex
of multiple pathways and processes. Because transit times along these different pathways vary
widely, a toxicant-induced change in clearance rate  could be due to a change in the time for
removal along a particular pathway and/or to a change in the actual route taken.  Thus, it is often
quite difficult to delineate specific mechanisms of action for toxicants which alter overall
clearance from respiratory airways. Alterations in alveolar macrophages likely underlay some of
the observed changes, since numerous irritants have been shown  to impair the numbers and
functional properties of these cells (Gardner, 1984).
     Since a great number of people are exposed to cigarette smoke, it is of interest to
summarize effects of this irritant upon clearance processes. Smoke exposed animals and humans
show increased number of macrophages recoverable by bronchopulmonary lavage (Brody and
Davis, 1982; Warr and Martin, 1978; Matulionis,  1984; Zwicker et al., 1978).  However, the rate
of particle clearance from the A region of the lungs  appears to be reduced in cigarette smokers
(Bohning et al., 1982; Cohen et al., 1979).
                                          10-69

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     While cigarette smoking has been shown to affect tracheobronchial mucociliary clearance
function, the effects range from acceleration to slowing.  Some of the apparent discrepancies in
different studies is related to differences in the effects of short-term versus long-term effects of
cigarette smoke. Long term smokers appear to have mucociliary clearance which is slower than
that in nonsmokers (Lourenco et al., 1971; Albert et al., 1971) and which also show certain
anomalies, such as periods of intermittent clearance stasis. On the other hand, the short term
effects of cigarette smoke range from acceleration to retardation depending upon the number of
cigarettes smoked (Albert et al., 1971; Lippmann et al., 1977; Albert et al., 1974).

10.4.2.6   Comparative Aspects of Clearance
     As with deposition analyses, the inability to study the retention of certain materials in
humans for direct risk assessment requires use of laboratory animals.  Since dosimetry depends
upon clearance rates and routes, adequate toxicologic assessment necessitates that clearance
kinetics in these animals be related to those in humans.  The basic mechanisms and overall
patterns of clearance from the respiratory tract appear to be similar in humans and most other
mammals.  However, regional clearance rates can show substantial variation between species,
even for similar particles  deposited under comparable exposure conditions (Snipes, 1989).
      Dissolution rates and rates of transfer of dissolved substances into the blood may or may
not be species independent, depending upon certain chemical properties of the deposited material
(Griffith et al.,  1983; Bailey et al., 1985b; Roy, 1989). For example, lipophilic compounds of
comparable molecular weight are cleared from the lungs of various species at the same rate
(dependent solely upon solute molecular weight and the lipid/water partition coefficient), but
hydrophilic compounds do show species differences.
     On the other hand, there are distinct interspecies differences in rates of mechanical
transport in the conducting and A airways. While mucous transport rates in the nasal passages
seem to be similar in humans and the limited other species examined (Morgan et al., 1986;
Whaley, 1987), tracheal mucous velocities vary among species as a function of body weight
(Felicetti et al., 1981; Wolff, 1992).
                                          10-70

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     In the A region, macrophage-mediated clearance of poorly soluble particles is species
dependent, with small mammalian species generally exhibiting faster clearance than larger
species, with the exception of the guinea pig which clears slower than laboratory rodents. This
may result from interspecies differences in macrophage-mediated clearance of poorly soluble
particles (Valberg and Blanchard, 1992; Bailey et al., 1985b), transport of particles from the
A region to alveolar lymph nodes (Snipes et al., 1983; Mueller et al., 1990), phagocytic rates and
chemotactic responses of alveolar macrophages (Warheit and Hartsky, 1994), or the prevalence
of BALT (Murray and Driscoll, 1992).  These likely result in species-dependent rate constants
for these clearance pathways, and differences in regional (and perhaps total) clearance rates
between some species are a reflection of these differences in mechanical processes. For
example, the relative proportion of particles cleared from the A region in the short and longer
term phases of clearance differs between laboratory rodents and larger mammals, with a greater
percentage cleared in the faster first phase in laboratory rodents.  The end result of interspecies
differences in deposition and clearance is that the retention of deposited particles can differ
between species, and this may result in differences in response to similar particulate exposure
atmospheres.

10.4.2.7  Lung Overload
     Some experimental studies using laboratory rodents employed high exposure
concentrations of relatively nontoxic, poorly soluble particles, which interfered with normal
clearance mechanisms, producing clearance rates different from those which would occur at
lower exposure levels.  Prolonged exposure to high particle concentrations is associated with
what is termed particle "overload." This is defined as the overwhelming of macrophage-
mediated clearance by the deposition of particles at a rate which exceeds the capacity of that
clearance pathway.  It is a nonspecific effect noted in experimental studies, generally in rats,
using many different kinds of poorly  soluble particles (including TiO2, volcanic ash, diesel
exhaust particles, carbon black, and fly ash) and results in A region clearance slowing or stasis,
with an associated inflammation and aggregation of macrophages in the lungs and increased
translocation of particles into the interstitium (Muhle et al., 1990; Lehnert, 1990; Morrow,
1994).  While some overload induced effects are reversible, the extent of such reversibility
decreases  as the degree of overloading increases (Muhle et al., 1990). Once
                                          10-71

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some critical particle burden is reached, particles of all sizes (those studies ranged from ultrafme
to 4 //m) show increased translocation into the interstitum (Oberdorster et al., 1992). This
phenomenon has been suggested to be due to the inhibition of alveolar macrophage mobility.
     While the exact amount of deposition needed to induce overload is uncertain, it has been
hypothesized that it will begin, in the rat, when deposition approaches 1 mg particles/g lung
tissue (Morrow, 1988). When the concentration reaches 10 mg particles/g lung tissue,
macrophage-mediated clearance of particles would effectively cease.  Overload may be related
more to the volume of particles ingested than to the total mass (Morrow, 1988; Oberdorster
et al., 1992b).  Following overloading, the subsequent retardation of lung  clearance,
accumulation of particles, inflammation, and the interaction of inflammatory mediators with cell
proliferative processes and DNA may lead to the development of tumors and fibrosis in rats
(Mauderly, 1994).
     Alternative hypotheses exist for the events that define the onset  of lung overload. One
hypothesis is that if repeated exposures to poorly soluble particles occurs, some critical lung
burden may be reached. Until the critical lung burden is reached, clearance is normal; above the
critical lung burden, clearance becomes progressively retarded and associated other changes
occur.  The other hypothesis is that overload is a function of the amount of poorly soluble
particles which deposit daily, i.e., deposition rate (Muhle, 1988; Creutzenberg et al., 1989;
Bellmann et al., 1990). Clearance retardation was suggested to occur at exposure levels of 3
mg/m3 or higher.  Thus, some critical deposition rate over a sufficient exposure duration would
result in retardation of clearance (Yu et al., 1989).
     The relevance of lung overload to humans, and even to species other than  laboratory rats
and mice, is not clear. While it likely to be of little relevance for most "real world" ambient
exposures of humans, it is of concern in interpreting some long-term experimental exposure
data. It may, however, be of some concern to humans occupationally  exposed to some particle
types (Mauderly,  1994), since overload may involve all insoluble materials and affect all species
if the particles are deposited at a sufficient rate (Pritchard, 1989), (i.e., if the deposition rate
exceeds the clearance rate). In addition, the relevance to humans is also clouded by the
suggestion that macrophage-mediated clearance is normally slower and
                                          10-72

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perhaps less important in humans than in rats (Morrow, 1994), and that there will be significant
differences in macrophage loading between the two species.

10.4.3   Acidic Aerosols
     An Issue Paper on Acid Aerosols was published by the Environmental Protection Agency
in 1989.  Section 3 of that document was devoted to the deposition and fate of acid aerosols.
Moreover, that Section provided an update of particle deposition data from both human and
laboratory animal studies, described hygroscopic aerosol studies reported between 1977 and
1987, and presented a thorough discussion of the neutralization of acid aerosols by airway
secretions and absorbed ammonia.
     This section consists of two subsections: the first concerns the phenomenon of
hygroscopicity; and the second presents current information on acidic aerosol neutralization.

10.4.3.1  Hygroscopicity of Acidic Aerosols
     Hygroscopicity can be defined as the propensity of a material for taking up and retaining
moisture under certain conditions of humidity and temperature.  It is well known that action of
ocean waves continuously disperses tons of hygroscopic saline particles into the atmosphere and
these contribute to worldwide meteorologic phenomena. As industrialization has expanded, the
evolution of gaseous pollutants, especially the oxides of sulfur and nitrogen, has caused a greatly
increased atmospheric burden of aerosols mainly derived from gas-phase reactions.  These
aerosols are predominantly both acidic and hygroscopic, consisting of mixtures  of partially
neutralized nitric, sulfuric and hydrochloric acids:  i.e., inorganic salts, such as nitrites,
bisulfates, sulfates and chlorides.  In addition, small amounts of organic acid salts, e.g., formate
and acetate, are present as are a variety of trace elements, e.g., cadmium, carbon, vanadium,
chromium and phosphorus, whose oxides and other chemical forms tend also to be acid forming
(Aerosols, 1986).
     Experimental studies on deposition of acid aerosols are limited. There have been two
studies in laboratory animals using H2SO4 aerosols. Dahl and Griffith (1983) measured regional
deposition of these aerosols in the size range from 0.4 to 1.2 jim MMAD generated at 20% and
80% relative humidities. Their data showed greater total and regional deposition of H2SO4
aerosols in rats compared to nonhygroscopic aerosols having the same MMAD's
                                          10-73

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(Figure 10-14). Deposition of H2SO4 aerosols generated at 20% RH was also higher than those
generated at 80% RH, indicating that the increase in deposition was caused by the growth of the
particles in the highly humid environment of the respiratory tract.
     However, a similar study by Dahl et al. (1983) found that deposition of H2SO4 aerosols in
beagle dogs at these two relative humidities was similar to that of nonhygroscopic aerosols
having the same size although deposition at 20% RH was again higher than that at 80% RH.
The inconsistent results were explained by Dahl et al. (1985) to be caused by the large
intersubject variability of deposition in dogs.
     Two reviews (Morrow, 1986; Hiller, 1991) have been published on hygroscopic aerosols
which consider the implications of hygroscopic particle growth on deposition in the human
respiratory tract. Much of the treatment of hygroscopic particle growth is based on theoretical
models (e.g., Xu and Yu, 1985; Perron et al., 1988; Martonen and Zhang, 1993). Suffice it to
say, particulate sodium chloride has been commonly  utilized in these models and to a lesser
extent, sulfuric  acid droplets, and ammonium sulfate  and ammonium bisulfate particles.  There
are no major distinctions in the growth of these hygroscopic materials except that sulfuric acid
does not manifest a deliquescent point (when the particle becomes an aqueous droplet). It can be
seen in Figure 10-15 that the growth rate of hygroscopic particles is  controlled by the relative
humidity (RH): the closer to saturation (100% RH), the faster the growth rate.
     In humans, deposition of acid aerosols in the respiratory tract has only been estimated by
model studies.  Martonen and Zhang (1993) estimated deposition of H2SO4 aerosols in the
human lung for various ages and three different activity levels. The H2SO4 aerosol was
considered to be in equilibrium with atmospheric conditions outside the lung prior to being
inhaled. The results of their calculation for rest breathing without considering extrathoracic
deposition are shown in Figure 10-16.  Comparing to nonhygroscopic aerosols such as Fe2SO3,
deposition of H2SO4 aerosols in different regions of the lung may be higher or lower depending
upon the initial particle size. There is a critical initial size of H2SO4 in the 0.2 to 0.4 jim range.
For larger particles the influence of hygroscopicity of H2SO4 aerosols is to increase total lung
deposition,  whereas for smaller particles the opposite occurs.
     Hygroscopic particles or droplets of different initial size will experience  different growth
rates: the smallest particles being the fastest to reach an equilibrium size.  For
                                          10-74

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era

 re
     100
    (A
    o
    a
    0 10
    a>
    o.
 100
(A
O
a.
a>

Q10
4-1
C
0)
o

0)
a.
                                              1
         0.2      0.5    1.0     2.0  3.0

            Droplet Size MMAD (|jm)

                       (a)
 100
c
o
4^
"w
o
a
0)

Q10
4-1
C
0)
u
l_
0)
a.
                                           1
     0.2      0.5    1.0     2.0  3.0

        Droplet Size MMAD (|jm)

                   (b)
     0.2      0.5    1.0     2.0  3.

        Droplet Size MMAD (|jm)

                   (C)
Figure 10-14.  Regional deposition data in rats versus particle size for sulfuric acid mists and dry particles. Panel (a) = upper

              airway deposition; (b) = lower airway deposition; and (c) = total deposition.  Circles are 20% relative humidity;

              squares are 80% relative humidity; triangles are dry nonhygroscopic particles. Solid curves represent the mean

              of the data for sulfuric acid mists. Error bars and broken curves represent 95% confidence limits.
Source: Dahl and Griffith (1983).

-------
           4.0
        O)
        c
        (0
        £
        U
        0)
        _N
        5)
        U
        r
        ra
        Q.
3.0
2.0
           1.0
                    10
                20
30
40
50
60
70
80
90    100
                                       % Relative Humidity
Figure 10-15.  Theoretical growth curves for sodium chloride, sulfuric acid, ammonium
               bisulfate, and ammonium sulfate aerosols in terms of the initial (d0) and
               final (d) size of the particle.  Note that the H2SO4 curve, unlike those for the
               three salts, has no deliquescence point.
Source: Tang and Munkelwitz (1977).
example, a 0.5 jam diameter particle will require approximately 1 s, whereas a 2.0 jam particle
will require close to 10 s. It is immediately evident that many inhaled hygroscopic particles will
not reach their equilibrium size (maximum growth) during the duration of a single respiratory
cycle (ca 4 s).  Conversely, the growth of ultrafine particles does not resemble that for particles
>0.1 jim and thereby represents a special case. Moreover, the hygroscopic growth characteristics
of aqueous droplets, containing one or more solutes, depend not only on their initial size, but
their initial composition.  The study of Cocks and Fernando (1982), using the condensation
model of Fukuta and Walter (1970), with ammonium sulfate droplets illustrate both of these last
points (Figure 10-17).
     The direct measurement of the RH of alveolar air and the temperature of air at the alveolar
surface have been attempted, but because of technical limitations, the direct
                                          10-76

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                   .2  1-0-r
                      0.8-
        F6203 Age h^ SO4
        —•— Adult —•-
        —D— 98 mo — D-
        —O— 48 mo — O-
        —ft— 22 mo — A-
        —•— 7 mo — •"
(A
O
a

Q

Is
!c
u
c
o


u
o

-------
        4r
        3 -
2 -
                                                                           X0= 40%
                                                                           X0= 40%
                                                                           X0= 20%
                                                                           X0= 20%
         10
           -3
                10
                   -2
 1C'1
Time (s)
10
Figure 10-17.  Distinctions in growth (r/r0) of aqueous ammonium sulfate [(NH4)2SO4]
              droplets of 0.1 and 1.0 /j,m initial size are depicted as a function of their
              initial solute concentrations (X0).
Source: Cocks and Fernando (1982).
successful.  For deep-lung temperature, Edwards et al. (1963) used solubility of a helium-argon
mixture in arterial blood. By this approach they found the mean pulmonary capillary
temperature in five normal subjects to be 37.52 °C. Because of individual variability, they also
provided an equation for estimating the deep lung temperature in an individual from a
measurement of rectal temperature.
     Perron and co-workers (1983, 1985) made the logical assumption that the RH of the
alveolar air was determined by an equilibrium with the vapor pressure of blood serum at the
capillary level. The  osmolarity of serum at 37 °C (287 ± 4 mmol/kg) provided these
investigators a sound basis for selecting 99.5% RH as the value to use in all of the modeling
estimations. In Figure 10-18 (from Xu and Yu, 1985) the calculated equilibrium diameters
                                         10-78

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                                                                            H = 0.995
            I
  I
I
I
I
  0.01    0.02
0.05    0.1
       0.2       0.5
          d0 (Mm)
                                             10
Figure 10-18.  The initial diameter of dry sodium chloride particles (d0) and equilibrium
               diameter achieved (d) are shown for three relative humidity assumptions.
Source: Xu and Yu (1985).
for sodium chloride particles on the basis of their initial size (d0) is depicted. The equilibrium
diameters (d00) that can be achieved theoretically for each particle size is shown as a function of
three different RH values. For an RH of 99.5%, the growth of salt particles with  an initial size
greater than 0.5 jim, yields about a 6-fold increase in diameter.
     Perron et al. (1988) calculated the RH in the human airways by employing a transport
theory for heat and water vapor using cylindrical coordinates.  Several parameters of the theory
were chosen to best fit the available experimental data.  These authors also used the transport
theory to model the growth and deposition of three salts, viz., NaCl, CoCl2-6H2O,
                                         10-79

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and ZnSO4 7H2O, which were selected because these differentially hydrated particles have large,
moderate and small hygroscopic growth potentials, respectively. Figure 10-19 depicts the
growth of these three salts when their initial dry particle size is 1.0 jim diameter, the average
inspired airflow is 250 cc/s, and the inhalation is by mouth. In this depiction, the particle growth
is expressed as the ratio of the achieved aerodynamic diameter to the initial aerodynamic size.
     ae,s
          4.0-
          3.0-
          2.0-
           1.0-
          0.0
             0.01
                    Q = 250 cm3 Is

                    mouth
                    inhalation
                                                           NaCI
                                                   CoCI4 •
                                  •'
                               *    f
                             ; /I
                                                                  (c)
0.1
    1
Time (s)
10
100
Figure 10-19.  The initial dry diameter (daes) of three different salts is assumed to be 1.0
              //m. Their subsequent growth to an equilibrium diameter at 99.5%RH is
              shown by the ratio (dae/dae s). The highly hydrated salts of cobalt chloride
              and zinc sulfate exhibit a reduced growth potential compared to sodium
              chloride.

Source: Perron et al. (1988).
                                        10-80

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     A recent experimental study by Anselm et al. (1990) used an indirect method, similar to
that employed earlier by Tu and Knudsen (1984), to validate the 99.5% RH assumption for
alveolar air. In this instance, monodisperse NaCl particles between 0.2 and 0.5 jim were
made by vibrating orifice generator and administered, by mouth, as boli during a constant
inspiratory airflow. During expiration, the particles suspended in the same volume element were
size classified. To determine equilibrium particle sizes, 600 mL of aerosol was inspired
followed by 400 mL of clean air. Expiration was initiated after different periods of breath
holding and the behavior of NaCl particles (loss and settling velocities) was compared to that of
a stable (nonhygroscopic) aerosol. Through this approach, the investigators found that the
diameters  of the NaCl particles initially 0.2 jim and 0.25 jim, increased 5.55 and 5.79-fold,
respectively. These values were found to be consistent with a 99.5% RH.
     To make the transport theory model estimations more pragmatic, Perron and coworkers
(1992,  1993) made estimations for heterodisperse aerosols of salts with the range of growth
potentials  used in their 1988 study.  Also, deposition estimates for H2SO4 aerosols,
incorporating variabilities in age-related airway morphometry and in physical activity levels,
have been reported by Martonen and Zhang (1993) using some innovative modeling
assumptions.
     In his excellent review of hygroscopic particle growth and deposition and their
implications to human health, Hiller (1991) concluded that despite the  importance of models,
there remains insufficient experimental  data on total and regional deposition of hygroscopic
aerosols in humans to confirm these models  adequately.

10.4.3.2   Neutralization and Buffering of Acidic Particles
     The  toxicity of acidic particles may be modulated following their inhalation.  This may
occur within the inhaled air, by neutralization reaction with endogenous respiratory tract
ammonia,  or following deposition, due to buffering within the fluid lining of the airways.

Reaction of Acidic Particles with Respiratory Tract Ammonia
     Ammonia (NH3) is present in the air within the respiratory tract.  Measurements taken in
exhaled air have found that the NH3 concentration varies, depending upon the site of
measurement, with levels obtained via oral breathing greater than those measured in the nose
                                          10-81

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or trachea (Larson et al., 1977; Vollmuth and Schlesinger, 1984).  Because of these
concentration differences between the oral and nasal passages, the route of acidic particle
inhalation likely plays a significant role in determining the hydrogen ion (IT) available for
deposition in the lower respiratory tract.  Thus, for the same mass concentration of acidic
particles, inhalation via the mouth will result in more neutralization compared to inhalation via
the nose, and less FT available for deposition in the lungs (Larson et al., 1982).  The toxicity of
acidic particles is likely due to the H+, as discussed in Chapter 11.
     The possibility that endogenous ammonia could chemically neutralize inhaled acidic
particles to their ammonium salts prior to deposition on airway surfaces, thereby reducing
toxicity, was originally proposed by Larson et al. (1977) in relation to acidic sulfate aerosols.
Since, stoichiometrically, 1 //g of NH3 can convert 5.8 //g of H2SO4 to ammonium bisulfate
(NH4HSO4), or 2.9 //g of H2SO4 to ammonium sulfate [(NH4)2SO4], they determined, based upon
the range of NH3 levels measured in the exhaled air of humans, that up to 1,500 //g/m3 of inhaled
H2SO4 could be converted to (NH4)2SO4.  For a given sulfate content in an exposure atmosphere,
both ammonium bisulfate and ammonium sulfate are less potent irritants than is sulfuric acid.
     Complete neutralization of inhaled sulfuric acid or ammonium bisulfate would produce
ammonium sulfate.  However, partial neutralization of sulfuric acid would reduce to varying
extents the amount of FT" available for deposition, thereby modulating toxicity.  The extent of
neutralization has been shown to play a role in measured toxicity from inhaled sulfuric acid.
Utell et  al. (1989) exposed asthmatic subjects to sulfuric acid under conditions of high or low
levels of expired ammonia. The response to inhaled acid exposure was greater when exposure
was  conducted under conditions of low oral ammonia levels.
     The extent of reaction of ammonia with acid sulfates depends upon a number of factors.
These include  residence time within the airway, which is a function of ventilation rate, and
inhaled  particle size. In terms of the latter, for a given amount of ammonia, the extent of
neutralization is inversely proportional to particle size, at least within the diameter range of
0.1-10 //m (Larson et al., 1993).  In addition, for any given ammonia concentration, the extent of
neutralization of sulfuric acid increases as mass concentration of the acid aerosol decreases
(Schlesinger and Chen, 1994).
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     Cocks and McElroy (1984) presented a model analysis for neutralization of sulfuric acid
particles in human airways. Particle acidity was a function of both dilution by particle growth
and neutralization by ammonia. As an example of their results, neutralization would be
complete in 3 sec for H2SO4 (3M) having a particle size of 0.5 //m and a mass concentration of
100 //g/m3, with the ammonia level at 500 //g/m3.  If the NH3 level is reduced to 50 //g/m3,
neutralization would take longer.
     Larson (1989) presented another model for neutralization of inhaled acidic sulfate aerosols
in humans.  It was concluded that significant deposition of acid in the lower respiratory tract
would occur in the presence of typical respiratory tract NH3 levels, for both oral or nasal
inhalation of H2SO4 particles at 0.3//m.  However, particles at 0.03//m should be completely
neutralized in the upper respiratory tract.  While this latter seems  to contradict findings of
significant biological responses in guinea pigs following exposure to ultrafine acid particles
(Chapter 11), this could reflect differences in residence times and ammonia levels between
different species.  Furthermore, it is likely that under most circumstances, only partial
neutralization of inhaled sulfuric acid occurs prior to deposition (Larson et al., 1977).  In any
case, these conclusions support toxicological findings of biological effects following inhalation
of sulfuric acid concentrations that should, based solely upon stoichiometric considerations, be
completely neutralized, and highlights the complexity of neutralization processes in the
respiratory tract.
     Larson et al. (1993) examined the role of ammonia and ventilation rate on response to
inhaled (oral) sulfuric acid by estimating, using the model of Larson (1989), the acid
concentrations to which the lungs would be exposed during oral inhalation. They concluded that
combinations of high ammonia and low ventilation rate or low ammonia and high ventilation
rate produce smaller or larger amounts of acid deposition, respectively, even if the acid
concentration at the point of inhalation remained constant. The former condition resulted in
greater neutralization than did the latter.

Buffering by Airway Surface Fluid (Mucus)
     Mucus lining the conducting airways has the ability to buffer acid particles which deposit
within it.  The pH of mammalian tracheobronchial mucus has been reported to be within a range
of about 6.5 to 8.2 (Boat et al., 1994; Gatto, 1981; Holma et al., 1977).
                                          10-83

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     This variability may be due to differences in the methods used and species examined, as
well as the likelihood that the acid-base equilibrium differs at different levels of the
tracheobronchial tree, but may also reflect variations in secretion rate and the occurrence of
inflammation. The influence on pH of various other endogenous factors, such as secretion of
hydrogen or bicarbonate ions, and the role of specific mucus constituents, such as secreted acidic
glycoproteins and basic macromolecules, have not been extensively examined.
     The buffering capacity of human sputum, a mixture of saliva and mucus, was examined by
Holma (1985), by titrating sputum equilibrated with 5% carbon dioxide at 37 °C and 100%
relative humidity (RH) with sulfuric acid. While the buffering capacity was variable, depending
upon the sputum sample examined, depression of pH from 7.25 to 6.5 required the addition of
approximately 6 //mol of hydrogen ion (H+) per milliliter of sputum. Assuming a
tracheobronchial mucus volume of 2.1 mL, between 8 and 16 //mol of H+, if evenly distributed
through the airways, would be required to depress mucus pH from 7.4 to 6.5. Since 1 //g H+ is
obtained from 49 //g  of sulfuric acid, between 390 and 780 //g of sulfuric acid would be required
to cause this change in pH.  With an inhalation exposure duration of 0.5 h, ventilation at 20
L/min and 50% deposition (in the total respiratory tract) of 100 //g/m3 sulfuric acid (at 1M), 0.6
//mol of H+ would be deposited in the lungs. However, the distribution of submicrometer acid
particles in the respiratory tract is not uniform and, therefore, greater changes in pH may be
anticipated on a regional basis in those areas having higher than average deposition.  If, for
example, 30 //g of acid deposited in 0.2 mL of mucus, a greater change in pH would likely
occur.
     The above example may apply to healthy individuals. However, the buffering capacity of
mucus may be altered in individuals with compromised lungs. For example, sputum from
asthmatics had a lower pH than that from healthy subjects, and a reduced buffering capacity
(Holma, 1985). This group may, therefore, represent a portion of the population which is
especially sensitive to inhaled acidic particles.  The potential sensitivity of asthmatics to acid
particles is discussed in greater detail  in Chapter 11.
     While biological responses following the inhalation of acidic aerosols are likely due to the
H+ component of these particles, it has been suggested that pH may not be the sole determinant
of response to acid particles, but that response may actually depend upon total available
hydrogen ion, or titratable acidity, depositing upon airway surfaces. Fine et al.
                                          10-84

-------
(1987) hypothesized that buffered acid aerosols (with a greater H+ pool) would cause a greater
biological response than would unbuffered acid aerosols having the same pH.  Since airway
surface fluids have a considerable capacity to buffer acid, it was suggested that the buffered acid
would cause a more persistent decrease in airway surface fluid pH. Thus, it appears that the
specific metric of acidity used, i.e., pH or titratable acid, would, therefore, be reflected in the
relationship between amount of deposited acidity and resultant biological response.
10.5  DEPOSITION DATA AND MODELS
     The background information in Sections 10.4 demonstrates that a knowledge of where
particles of different sizes deposit in the respiratory tract and the amount of their deposition is
necessary for understanding and interpreting the health effects associated with exposure to
particles. As was seen, the respiratory tract can be divided into the ET, TB and A regions on the
basis of structure, size and function. Particles deposited in the various regions have large
differences in clearance pathways and, consequently, retention times. This section discusses the
available data on particle deposition in humans and laboratory animals. Different approaches for
modeling these data are also discussed.  Theoretical models must assume average values and
simplifying conditions of respiratory performance in  order to make reasonable estimates.  This
latter approach was initiated by the meteorologist Findeisen (1935) over fifty years ago, when he
developed a simplified anatomic model of the respiratory tract and assumed steady inspiratory
and expiratory air flows in order to estimate the interactions between the anatomy of the
respiratory tract and particle deposition based on physical laws.  Despite much progress in
respiratory modeling, there are not major distinctions in total particle deposition predictions
among models and experimental verifications have been generally satisfactory.

10.5.1  Humans
     The deposition of particles within the human respiratory tract have been assessed using a
number of techniques  (Valberg, 1985). Unfortunately, the use of different experimental
methods and assumptions results in considerable variations in reported values. This section
                                          10-85

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discusses the available particle deposition data in humans for either the total respiratory tract or
in terms of regional deposition.

10.5.1.1   Total Deposition
     If the quantity of aerosol particles deposited in the entire respiratory tract is divided by that
inhaled, the result is called total deposition fraction or total deposition.  Thus, total deposition
can be measured by comparing particle concentrations of the inhaled and exhaled, but the
regional involvement cannot be distinguished.  By the use of test aerosol particles with
radiolabels, investigators have been able to separate deposition by region,  beginning from the ET
region with either nasal and nasopharyngeal deposition for nose breathing or oral and pharyngeal
deposition for mouth breathing. The measurement of clearance of the radiolabeled particles
from the thorax can be used to separate fast clearance, usually assumed to be an indicator of TB
deposition, from the more slowly cleared A deposition (see below for more discussion).
     Total human deposition data, as a function of particle size with nose and mouth breathing
compiled by Schlesinger (1988) are depicted in Figure 10-20.  These data were obtained by
various investigators using different sizes of test spherical particles  in healthy male adults under
different ventilation conditions. Deposition with nose breathing is generally higher than that
with mouth breathing because mouth breathing bypasses the filtration capabilities of the nasal
passages.  For large particles with aerodynamic diameters dae greater than  1 jim, deposition  is
governed by impaction and sedimentation and it increases with increasing dae. When  dae >  10
|im, almost all inhaled particles are deposited.  As the particle size decreases from 0.1  jim,
diffusional deposition becomes dominant and total deposition depends more upon the  physical
diameter d of the particle. Decreasing particle  diameter leads to an  increase in total deposition in
this particle size range. Total deposition shows a minimum for particle  diameters in the range  of
0.1 fj.m to 0.5 jim where neither sedimentation  nor diffusion deposition are effective.  The
particle diameter at which the minimum deposition occurs is different for nose breathing and
mouth breathing and it depends upon flow rate and airway dimensions.  For all particle sizes,
mixing of the tidal air and functional residual air can  enhance particle deposition by providing a
mechanism for keeping the inhaled particles in the lung for a longer time and
                                          10-86

-------
         100
           80
      -   60
      c
      o
      (A
      O
      I   40
           20
               v.    O
      I
O Human (Oral)
• Human (Nasal)
                   0.01
    0.1                1.0
 Particle Diameter (urn)
10
Figure 10-20.  Total deposition data (percentage deposition of amount inhaled) in humans
              as a function of particle size. All values are means with standard deviations
              when available. Particle diameters are aerodynamic (MMAD) for those >
              0.5
Source:  Schlesinger (1988).


thereby increasing the probability of the particles to deposit. This factor is more significant for
particle sizes for which deposition is low.  Good deposition experiments therefore should
account for mixing into the residual volume by requiring subjects to fully exhale.
     Although various studies in Figure 10-20 all appear to show the same trend, there is a
significant amount of scatter in the data. Much of this scatter can be explained by the use of
different test particles and methods in the experimental studies, as well as different breathing
modes  and ventilation conditions employed by the subjects. However, a good portion of the
scatter  is caused by the differences in  airway morphology and breathing pattern among
                                        10-87

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subjects (Heyder et al., 1982, 1988; Yu et al., 1979; Yu and Diu, 1982a,b; Bennett and
Smaldone, 1987; Bennett, 1988). In addressing the health-related issues of inhaled particles, this
intersubject variability is an important factor which must be taken into consideration.
     Indeed, for well controlled experiments and controlled breathing patterns (constant
inspiratory flow in half a cycle and constant expiratory flow in another half cycle and no pause),
total deposition data do not have the amount of scatter shown in Figure 10-20. Figure 10-21
shows the data by Heyder et al. (1986) and Schiller et al. (1986, 1988) reported by Stahlhofen et
al. (1989) at controlled mouth breathing for particle size ranging from 0.005 jam to 15 jam and
three different ventilation conditions. Total deposition was found higher for larger tidal volume
while the minimum deposition occurred at about 0.4 jim for all three ventilation conditions.
                0.2-
                0.0
                    Total Deposition
                    (unit density spheres)
                    mouth breathing
                    Symbols: Experimental data
                    Curves  : Model calculations
          Tidal volume
    AA    »0   BD
cm3  500   1,000  2,000
          Volumetric flow rate cm g-1 250
          Breathing frequency min1  15
          250
          7.5
250
3.75
                        0.01
      0.1               1
Diameter of unit density spheres (urn)
              10
Figure 10-21.  Total deposition as a function of the diameter of unit density spheres in
               humans for variable tidal volume and breathing frequency. Experimental
               data are by Heyder et al. (1986) and Schiller et al. (1988). The curves
               represent empirical fitting.
Source: Stahlhofen et al. (1988).
                                           10-88

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10.5.1.2  Extrathoracic Deposition
     The fraction of inhaled particles depositing in the ET region can be quite variable,
depending on particle size, flow rate, breathing frequency and whether the breathing is through
the nose or through the mouth. During exertion, the flow resistance of the nasal passages cause
a shift to mouth breathing in almost all individuals, thereby bypassing much of the filtration
capabilities of the head and leading to increased deposition in the lung (TB and A regions).  For
nose breathing, the usual technique for measuring inspiratory deposition is to draw the aerosol
through the nose and out of the mouth while the subject holds his mouth open (Pattle, 1961;
Lippmann, 1970; Hounam et al., 1969, 1971).  The aerosol concentration is measured before it
enters the nose and after it leaves the mouth. Neglecting mouth deposition during expiration,
inspiratory nasal deposition can be calculated from the concentration difference.  Another
method to measure the nasal deposition is to use the lung as a part of the experimental system
(Giacomelli-Maltoni et al., 1972; Martens and Jacobi, 1973; Rudolf, 1975).  The deposition of
particles in the nose is calculated from total deposition of particles in the entire respiratory tract
for mouth, nose, mouth-nose and nose-mouth breathing.  Because mouth deposition is not
significant under the experimental conditions, this method  allows the determination of nasal
deposition for both inspiration and expiration.
     Deposition in the mouth for expiration is normally  assumed to be negligible. For
inspiration, the deposition in mouth has been measured using radioactive aerosol particles
(Rudolf,  1975; Lippmann,  1977; Foord et al., 1978;  Stahlhofen et al., 1980; Chan and
Lippmann, 1980; Stahlhofen et al., 1981, 1983).  The amount of deposition is obtained from the
difference of activity measurements, one immediately after exposure and the other after the
deposited particles are removed with mouthwash or other means.  Because the subjects in these
experiments breathe through a large bore tube, the deposition via the mouth occurs
predominantly in the larynx. Rudolf et al. (1984, 1986) have suggested to name this laryngeal
deposition. Mouth deposition by natural mouth breathing without using a mouthpiece was
measured in an earlier study by Dennis (1961) and recently by Bowes and Swift (1989) during
natural oronasal breathing at moderate and heavy exercise conditions. The data showed a much
greater deposition than breathing through a mouth-piece.
                                          10-89

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     For dae > 0.2 |im, ET deposition is usually expressed as a function of dae2Q,
where Q is the flow rate.  This is the appropriate parameter for normalizing
impaction-dominated deposition when the actual flow rates in the experimental
studies are not identical. Even with this normalization, deposition data in the
extrathoracic region by various workers exhibit a very large amount of scatter as
shown in Figures 10-22 and 10-23, respectively, for inspiratory nasal and mouth
deposition. Besides uncertainty in measurement techniques, one major source of
this scatter, similar to the case of total deposition, comes from intersubject
and intrasubject variabilities. The intersubject variability may arise from the
difference in anatomical structure and dimensions, number of nasal hairs,
breathing pattern, etc., while the intrasubject variability may be caused by the
degree of mouth opening and by the nasal resistance cycle in which airflow may be
redistributed from one side to the other side, by as much as 20 to 80%.
     Mathematical model studies on the deposition in the nose and mouth are very
limited.  There have been only two attempts to determine nasal deposition during
inspiration (Landahl,  1950b; Scott et al.,  1978). At present, formulas useful
for predicting ET deposition are  derived empirically from experimental data
(Pattle,  1961; Yu et al., 1981; Rudolf et al., 1983, 1984, 1986; Miller et al.,
1988; Zhang and Yu, 1993).  The formulas by Rudolf et al. (1983, 1984, 1986) given
below, with some modification, have been adopted by the International Commission
on Radiological Protection (ICRP, 1994) in their dosimetry model. Deposition
efficiency via the nose (r|N) or mouth (r|M) is expressed in terms of an impaction
parameter (dae2Q), as

              % = 1 - [3.0x10 -'(d^Q) + I]-1 ,                                   (10-22)

or

          TIM =  1 - [1.1x10 4(d O^VT0'2)1-4 + I]"1 •                               (10-23)
where dae is in the unit of |im, Q in cm3/s, and VT is the tidal volume in cm3.
Equation 10-22 applies to both inspiration and expiration since the data by
Heyder and Rudolf (1977) do not show a systematic difference between the two
efficiencies. The
                                         10-90

-------
  I
       1.0
0.8 -
       0.6  -
D  Landahl&Tracewell 1949
V  Rattle               1961
•  Lippmann           1970
A  Hounam et al.        1971
O  Giacomelli-Maltoni et a I! 972
A  Martens & Jacobi     1973
        O Rudolf
                                     1975
       0.4  -
Figure 10-22.Inspiratory deposition of the human nose as a function of particle
               aerodynamic diameter and flow rate (dae2Q). The curve represents
               Equation 10-22.

Source:  Stahlhofen et al. (1988).

inclusion of VT in Equation 10-23 is caused by the fact that the size of the ET
region during mouth breathing increases with increasing flow rate and with
increasing tidal volume.
     For ultrafine particles (d < 0.1  |im), deposition in the ET region is
controlled by the mechanism of diffusion which depends only on the particle
geometric diameter, d.  At this time, ET deposition for this particle size range
has not been studied extensively in humans. George and Breslin (1969) measured
nasal deposition of radon progeny in three subjects but the diffusion
coefficient of the progeny was uncertain. Schiller et al. (1986, 1988) later
obtained inspiratory nasal deposition from total deposition measurements using
a nose in -
                                         10-91

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       1.0
      0.8-
      0.6-
Q, cm?s'1  V, cnf
A ~500  ~1,000  Lippmann
+  500   1,000
        -1,000
         1,000
          250
          500
         1,000
         1,500
• -500
D 333
O 250
   250
   250
              A
              O
              D
                1977
Foord et al.       1978
Chan & Lippmann 1980
Emmett et al.     1982
 Stahlhofen etal.
   750
      0.4-
                                            ^dae2(f3V\WcrTr/4 s2'3)

Figure 10-23. Inspiratory extrathoracic deposition data in humans during mouth
              breathing as a function of particle aerodynamic diameter, flow
              rate, and tidal volume (dae2Q2/3VT"1/4). The curve represents
              Equation 10-23.
Source:  Stahlhofen et al. (1988).

mouth  out and mouth in-nose out maneuver. However, their data cannot be
considered reliable because mouth deposition is not negligible compared to nose
deposition.
     The only data available to date for ET deposition of ultrafine particles are
from cast measurements (Cheng et al., 1988, 1990, 1993; Yamada et al., 1988;
Gradon and Yu, 1989; Swift et al., 1992). Figure 10-24 shows these data on
inspiratory nasal deposition from several laboratories reported by Swift et al.
(1992) as a function of the diffusion parameter,  D1/2Q"1/8, where D is the particle
diffusion coefficient in cm2/sec and Q is the flow rate in  L/min.  Swift et al.
(1992) also proposed an equation to fit the data in the form
                                         10-92

-------
                                                Cast A, Harwell
                                              • Cast G, Harwell
                                              O Cast C, ITRI
                                              • Cast B, ITRI
                                              A Cast A, Clarkson
                                              V Cast B, Clarkson
                                              A Cast G, Clarkson
                         0.05
   0.1
                               0.15
0.2
0.25
0.3
D1/2Q-1/8  (Lmiri  )
                                                 1  1/8  (erf  s1  j/2
Figure 10-24. Inspiratory deposition efficiency data and fitted curve for human
              nasal casts plotted versus Q1/8D1/2 (LminJ)1/8(cm2s~lf\ The solid
              curve represents Equation 10-24 and the dotted lines are 95%
              confidence limits on the mean.
Source:  Swift et al. (1992).
IN
                     -exp[-12.65£>1/2Q
                                              (10-24)
which was adopted by ICRP66 in the 1994 model. Expiratory nasal deposition for
particles between 0.005 jim to 0.2 jim was found to have the same trend as Figure 10-
24 but was approximately 10% higher than the inspiratory nasal deposition
(Yamada et al., 1988). Cheng et al. (1993) derived the following empirical
equations to fit the data for expiratory nasal deposition
                                         10-93

-------
              TIN  =  1 - exp[ - 15.0Z)1/2Q -1/8].                                   (10-25)


Diffusional deposition in human oral casts was found to be smaller than that in
nasal casts (Cheng et al., 1990). Based upon these data, Cheng et al. (1993)
derived the following equation for oral deposition

              TIM = 1 - exp (- 10.3Z)1/2Q -1/8) ,                                   (10-26)


on inspiration, and

              TIM = l-exp(-8.51Z)1/2Q 1/8) ,                                   (10-27)
for deposition on expiration. Contrary to nasal deposition, deposition in the
mouth is slightly higher for inspiration than for expiration. Figure 10-25 shows
the inspiratory oral deposition data and Equation 10-26.
     ICRP66 (1994) took a more conservative view of the experimental data on
deposition of small particles in the oral passageway.  Oropharyngeal deposition
for mouth breathing was assumed to be only half the value for nose breathing so
that

                              r|m = 1 - exp  (-6.33 D1/2 Q '1/8).                        (10-28)

10.5.1.3  Tracheobronchial Deposition

     Particles escaping from deposition in the ET region enter the lung, but
their regional deposition in the lung cannot be precisely measured.  All the
available regional deposition data have been obtained from experiments with
radioactive labeled poorly soluble particles above 0.1 jim in diameter.  The
amount of activity retained in the lung as a function of time normally exhibits a
fast and slow decay component that have been identified as mucociliary and
macrophage clearance. Since the tracheobronchial airways are ciliated, the
rapidly
                                         10-94

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1.0-
0.8-
o
0
'o
it 0.6-
UJ
c
o
'35
£ 0.4-
0)
0
0.2-









^^^H ^^^^B ^^^
                                                            O NaCI (Cheng et al., 1990)
                                                            • 212Pb (Cheng etal., 1993)
0.0001
                     0.0010
0.0100
0.1000
1.0000
10.0000
                           D1'2 Q-1/8  (cm2 /sec)72  (L/minf8
Figure 10-25.  Inspiratory deposition efficiency data in human oral casts plotted
               versus flow rate and particle diffusion coefficient [Q~1/8D1/2
               (Lmin"1)"1'8 (cmV1)172].  The solid curve represents Equation 10-26
               and the dotted lines are the 95% confidence limits.
Source:  Cheng et al. (1993).
cleared fraction of initial activity can be considered as a measure of the amount
of material deposited in the TB region, whereas the slowly cleared fraction
corresponds to the material deposited in the A region. However, there is
experimental evidence that a significant fraction of material deposited in the
TB region is retained much longer than 24 h (Stahlhofen et al., 1986a,b; Scheuch
and Stahlhofen, 1988; Smaldone et al., 1988).  This may be caused by the fact that
the TB airway surface is lined with ciliated epithelium, but not all of the
ciliated epithelium is covered with mucus all the time (Stahlhofen et al., 1989).
Other mechanisms for prolonged TB clearance include phagocytosis by airway
macrophages and
                                         10-95

-------
deposition of particles further down into the A region due to mixing of flow
during inspiration. Thus, TB and A deposition measured based upon the clearance
of radioactive labeled particles have been suggested as the "fast-cleared" and
"slow-cleared" thoracic deposition (Stahlhofen et al., 1989).
     Figure 10-26 shows the data from various investigators (Lippmann, 1977;
Foord et al., 1978; Chan and Lippmann, 1980; Emmett et al., 1982; and Stahlhofen
et al., 1980, 1981,  1983) on TB deposition or fast-cleared thoracic deposition
for mouth breathing as a function of dae reported by Stahlhofen et al. (1989).
Again, the data are quite scattered due to differences in experimental technique
and intersubject and intrasubject variabilities that have been cited
previously.  Another cause for the scatter is from the difference in the flow rate
employed by various studies.  For dae  > 0.5 jim, deposition in the TB region is
caused by both impaction and sedimentation. Whereas the impaction deposition is
governed by the parameter dae2Q, sedimentation deposition is controlled by the
parameter dae2/Q.  It is therefore not possible to have a single relationship
between deposition and dae for different flow rates.
     Data in Figure 10-26 show that  TB deposition does not increase monotonically
with dae. A higher dae leads to a greater ET deposition and consequently a lower TB
deposition.  For the range of flow rates employed in various studies, the maximum
TB deposition occurs at about 4 jim dae. It is also seen that the data by Stahlhofen
et al. (1980, 1981,  1983) in Figure  10-26  are considerably lower than those from
other investigators. Chan and  Lippmann (1980) cited two possible reasons for
this difference.  One was that Stahlhofen and coworkers used constant
respiratory  flow rates in their studies as opposed to the variable flow rates
used by others.  The second reason  was that different methods of separating the
initial thoracic burden into TB and A  regions were used.  Stahlhofen et al. (1980)
extrapolated the thoracic retention values during the week after the end of fast
clearance back to the time of inhalation; they considered A deposition to be the
intercept at that time, with the remainder of the thoracic burden considered as
TB deposition.  This approach yields  results similar to, but not identical with,
those obtained by treating TB deposition as equivalent to the particles cleared
within 24 h.
                                          10-96

-------
 DE
    TB
        1.0
        0.8-
        0.6-
        0.4-
        0.2-
Q. cm3 s'1  V. cm3
              Lippmann        1977
              Foordetal.       1978
              Chan & Lippmanri980
              Emmett et al.     1982
                               Stahlhofen etal.
                              1980
                              1981
                             J983
           0.1
                                                10
                                                                          dae (Mm)
Figure 10-26.  Tracheobronchial deposition data in humans at mouth breathing as a
              function of particle aerodynamic diameter (dae). The solid curve
              represents the approximate mean of all the experimental data; the
              broken curve represents the mean excluding the data of Stahlhofen
              etal.
Source:  Stahlhofen et al. (1988).
10.5.1.4 Alveolar Deposition


     The A deposition data as a function of dae for mouth breathing are shown in
Figure 10-27. These data are from the same studies that reported TB  deposition in
Figure 10-25 but there is a better agreement between different studies than with
the TB data. Alveolar deposition is favored by slow and deep breathing.  The data
of Stahlhofen et al. (1980, 1981, 1983) at 1000 cm3 tidal volume and 250  cm3/sec
flow rate thus are higher than other data. Figure 10-27 also shows (1) that A
deposition reaches the maximum at about
                                        10-97

-------
 DE,
  t
        1.0
0.8 -
        0.6 -
        0.4-
        0.2 -
         Q. ctrPs'1 V. cnf
         A-500 -1,000  Lippmann        1977
         +  500  1,000  Foordetal.      1978
•-500 -1,000
n  333  1,000
Chan & Lippmanr1980
Emmett et al.     1982
                                                                 10
                                                                           dae (Mm)
Figure 10-27. Alveolar deposition data in humans as a function of particle
              aerodynamic diameter (dae). The solid curve represents the mean of
              all the data; the broken curve is an estimate of deposition for nose
              breathing by Lippmann (1977).
Source:  Stahlhofen et al. (1988).
3.5 |im dae and (2) that for dae between 0.2 jim and 1.0 jim, A deposition does not show
significant change although a minimum deposition may occur near 0.5 jim.
     By switching from mouth breathing to nose breathing, alveolar deposition
will decrease.  Lippmann (1977) made an estimate by analysis of the difference in
the ET deposition for nose and mouth breathing.  The nose breathing (dashed line)
result is also shown in Figure 10-26.  For dae greater than 7 jim, practically no
particles deposit in the A region in this breathing mode.
                                         10-98

-------
     During exercise, most subjects switch from nose breathing to breathing
partly through the mouth (Niinimaa et al., 1981).  The amount of inhaled material
that deposits in the lungs is affected because the mouth and nose have different
filtration efficiencies.  Niinimaa et al. (1981) found that in thirty subjects,
twenty switched to oro-nasal breathing (normal augmenters), typically at a
ventilation rate of about 35 L/min, five continued to breathe through the nose,
and the rest who were habitual mouth breathers breathed oro-nasally at all levels
of exercise.  These data were reviewed by Miller et al. (1988) and used to
estimate thoracic deposition (TB and A deposition) at different ventilation
rates. At higher ventilation rates, Miller et al. (1988) predicted little
difference in thoracic deposition between normal augmenters and mouth
breathers, but for ventilation rates less than 35 L/min they predicted
substantially lower deposition in normal argumenters compared to mouth
breathers. Based upon this finding, ICRP (1994) recommended a different
breathing pattern for normal augmenters and mouth breathers that typifies the
breathing habits of adult males as a function of ventilation rate.  The split in
airflow for the recommended breathing patterns by ICRP (1994) is shown in
Figure 10-28.  Table 10-10 provides the same information on the percentages of
total ventilatory airflow passing through the nose versus mouth at reference
levels of physical exertion for a normal augmenter and a mouth breather adult
male. These are the same levels of exercise and values for fraction of nasal
ventilatory airflow used to construct the activity patterns in Section 10.7.  In
the absence of specific data, it must be assumed that a similar breathing pattern
applies to young healthy subjects at equivalent levels of exercise.  Alveolar
deposition at different ventilation rates can be estimated from Figure 10-28 or
Table 10-10. For example, a mouth breather doing light exercise (VE =1.5 m3/h)
has about 40% ventilatory air-flow passing through the nasal route. At a
particle size of 2 //m dae Figure 10-28 gives, respectively,  0.24 and 0.36 A
deposition for mouth and nose breathing.  Thus, the resultant A deposition at
this ventilation rate is 0.4 x 0.36 + 0.6 x 0.24 = 0.288.

10.5.1.5  Nonuniform  Distribution of Deposition and Local Deposition Hot Spots

     The deposition data in different regions of the respiratory tract do not
provide information on deposition nonuniformity in each region and local
deposition intensity at a specific site.  Such information may be of great
importance from a toxicology perspective.
                                          10-99

-------
   100
     80
60
 ra
 4-1
 O
 I-
 M-
 o
 0)
 O)
 ra
 a  40
 o
 
          O
          4-1
          (0
          0)
          OL


         \
   a
   .52
+-  "o ^
•£, <5 «T
5* x *:
_i  m —'
                                            a
       0           1             2            3^4             5

                               Ventilation Rate (VE)(m3- h'1)

Figure 10-28.  Percentage of total ventilatory airflow passing through the nasal
              route in human "normal augmenter" (solid curve) and in habitual
              "mouth breather" (broken curve).
Source: International Commission on Radiological Protection (ICRP66, 1994).
                10-10.  FRACTION OF VENTILATORY AIRFLOW PASSING
        THROUGH THE NOSE IN HUMAN "NORMAL AUGMENTER" AND
                              "MOUTH BREATHER"3
Level of Excertion
Sleep
Rest
Light exercise
Heavy exercise
F.
Nasal Augmenter
1.0
1.0
1.0
0.5

Mouth Breather
0.7
0.7
0.4
0.3
"(ICRP66, 1994) as derived from Miller et al. (1988).
                                      10-100

-------
Because airway structure and its associated air flow patterns are exceedingly
complex (Chang and Menon, 1993), and ventilation distribution of air in
different parts of the lung is uneven (Milic-Emili et al., 1966), it is expected
that particle deposition patterns in ET, TB, and A regions are highly nonuniform.
Fry and Black (1973) measured regional deposition in the human  nose using
radiolabelled particles and found that most of deposition occurred in the
anterior region of the nose.  Schlesinger and Lippmann (1978) found nonuniform
deposition in the trachea to be caused by the airflow disturbance of the larynx.
In a single airway bifurcation model, measurements show that deposition occurs
principally around the carinal ridge (e.g., Bell and Friedlander, 1973; Lee and
Wang, 1977); Martonen and Lowe, 1983; Kim and Iglesias, 1989 a,b).  A similar
result was observed in the alveolar duct bifurcations in rats and mice (Brody and
Roe, 1983). Figure 10-29 shows the data on local deposition pattern obtained by
Kim and Iglesias (1989) and Kim et al. (1989) in a bifurcating tube for both
inspiration and expiration.  The peak deposition occurs in the daughter tube
during inspiration and the parent tube during expiration, but always near the
carinal ridge. In addition, airways are not smooth tubes. More recently,
Martonen et al. (1994 a,b,c) have called attention to the existence of
cartilaginous rings on the wall of airways in the tracheobronchial  region. Using
a numerical analysis, they showed that such surface structure can  lead to a
considerable alteration of the flow pattern and enhancement of deposition.
     Deposition measurements in small laboratory rodents (Raabe et al., 1977)
also showed differences in lobar distribution with up to 60 percent higher
deposition than the average  in the right apical lobe (corresponding to the human
upper lobe). The difference was greater for large particles than for small
particles. Raabe et al. (1977) further showed that these differences in relative
lobar deposition  were related to geometric mean number of airway bifurcations
between trachea  and terminal bronchioles in each lobe for rats and hamsters.
Since similar morphologic differences occur in the human lungs,  nonuniform lobar
distribution should also occur.

10.5.1.6 Approaches to Deposition Modeling

     Mathematical models of lung deposition have been developed in recent years
to help interpret  experimental  data and to make predictions of deposition for
cases where data are not available. A review of various mathematical models was
given by Morrow and Yu
                                         10-101

-------
                c
                o
                o
                a
                CD
                O
                "a
                +*
                o
                   100-,
                    80-
      60-
                    40-
                    20-
                                  IB )c
 Stk
00.05
• 0.09 - 0.27
                            I
                           A
                        I          I           I
                        BCD
                        Branch Sections
                                            I
                                            E
                c
                o
                   100-1
      80-
                (0
                o
                u   60
                    40-
                    20-
   O 0 = 30
   A 0 = 45
Figure 10-29.
             A          B         C          D         E
                        Branch Sections

Local deposition pattern in a bifurcating tube for inhalation (top
panel) and exhalation (bottom panel).  Deposition in each section
is expressed as a percent of total deposition for the entire model.
Symbols and error bars in the top panel represent means and
standard deviations of the 0 = 30° and 45°. Symbols and error bars
in the bottom panel represent means and standard  deviations of the
entire data obtained in the Stokes number range from 0.05 to 0.28.
Source: Kim and Iglesias (1989); Kim et al. (1989).
                                       10-102

-------
(1993).  There are three major elements involved in mathematical modeling.
First, a model of airways simulating the real structure must be specified.
Secondly, deposition efficiency in each airway due to various mechanisms must be
derived.  Finally, a computational procedure must be developed to account for the
transport and deposition of the particles in the airways.
     Three different approaches have been used in the mathematical modeling.  The
first approach is a compartmental model first formulated by Findeisen (1935).
Starting with the trachea, Findeisen divided the airways into nine compartments
based upon the anatomical structure.  Particles which did not deposit in one
compartment remained airborne and transported to the next compartment for
deposition.  Findeisen's  lung model and analysis were later modified by Landahl
(1950a,  1963) and Beeckmans (1965). Detailed calculations of regional
deposition with additional consideration of nasal deposition based upon the
Findeisen-Landahl-Beeckmans theory were later published in a report by the Task
Group on Lung Dynamics (TGLD) in 1966.
     Because of advancement in measuring techniques, refined airway models have
become available (as discussed in Section 10.2). Several new models based upon
the compartmental analysis have been proposed (e.g., Gerrity et al., 1979; Yeh
and Schum,  1980; Martonen and Graham, 1987). The expressions used for deposition
efficiency of each compartment differed somewhat in these models.  In the absence
of any careful comparison with the experimental data, it is difficult to assess
the applicability of these models to deposition prediction. However, one
difficulty often encountered in the compartmental model is the  derivation of
deposition efficiency in  each airway for combined mechanisms of impaction,
sedimentation and diffusion. A commonly used assumption is that each deposition
mechanism is independent, thus the joint efficiency can be written in the form
                                                                               (10-29)
where % r|s, and r|D are, respectively, deposition efficiency in an airway or
compartment by the individual mechanisms of impaction, sedimentation and
diffusion, and r| is the joint efficiency. Yu et al. (1977) have shown, in a
detailed mathematical analysis of a combined sedimentation and diffusion
problem, that the above equation is an inaccurate expression for deposition when
r|s and r|D are not small and have about the same magnitude.  Another
                                        10-103

-------
difficulty in the compartmental model is that the air-mixing effect (i.e.,
mixing of tidal air and lung air) on deposition cannot be easily accounted for.
Such an effect is important for transient exposure. However, the compartmental
model is easy to formulate and to understand conceptually.
     The second approach to deposition modeling was put forward by Yu and
coworkers (Taulbee and Yu, 1975; Yu, 1978; Yu and Diu, 1983) and later by Egan and
Nixon (1985, 1989).  In this approach, the many generations of airways are viewed
as a chamber shaped like a trumpet. The cross-sectional area of the chamber
varies with airway depth measured from the beginning of the trachea, according to
anatomical data. The concentration of inhaled particles in the chamber as a
function of airway depth and time during breathing is described by a convective
diffusion equation with a loss-term accounting for airway deposition. This
equation can be solved either exactly (without longitudinal diffusion) or
numerically with appropriate initial and boundary conditions. Deposition at
different sites in the airways is then calculated once the concentration is
known.
     The deposition model formulated in this manner has some advantages over the
compartmental model. The use of differential airway length in the model allows
the joint deposition efficiency per unit airway length to be the superposition of
efficiencies by each individual mechanism.  Variation of airway dimensions
during breathing is accounted for in the model. The model is time-dependent and
can thus be applied to any breathing pattern and transient exposure condition.
Air-mixing and uneven airway path lengths can be accounted for with the use of an
equivalent longitudinal diffusion term in the convective-diffusion equation.
Finally, in the case of no longitudinal diffusion, the exact solution of the
convective-diffusion is obtainable, thus reducing the time required for
calculating deposition.
     The airway geometry of the human lung is not identical within a population.
In a given lung, the dimension of the airways in a specified generation is also
not uniform and the bifurcation is not symmetric (Weibel, 1963). The above two
modeling approaches have been extended to account for the randomness of airway
geometry (Yu et al., 1979; Yu and Diu, 1982a,b; Koblinger and Hofmann, 1990;
Hofmann and Koblinger, 1990). Yu and Diu (1982b) compared their modeling results
with total and regional deposition data of Stahlhofen et al. (1981) and Heyder et
al. (1982) for controlled breathing and suggested that differences
                                        10-104

-------
in lung morphology were probably the principal cause for intersubject
variability in deposition.
     Another approach to deposition modeling is an empirical one proposed by
Rudolf et al. (1983, 1984, 1986, 1990) similar to that developed for ET
deposition. This model considers the lung as a series of two filters
representing the TB and A regions of the lung. The model requires no assumptions
about airway geometry, airflow pattern and distribution, or particle deposition
efficiency in each airway. However, the construction of the model relies heavily
on experimental data of regional deposition for a wide range of particle sizes
(monodisperse) and breathing conditions.  These data are not always available.
An additional difficulty in empirical modeling is the development of deposition
equations in each region for combined deposition mechanisms.  As discussed
earlier, impaction, sedimentation and diffusion deposition depend,
respectively, on the parameters dae2Q, Dae2/Q and D/Q, where D is a function of
particle geometric diameter.  It is a very difficult task to come up with an
equation for deposition in terms of these parameters which can match all
experimental data.  Furthermore, because only a few compartments are used in the
empirical model, more detailed deposition information such as deposition at a
specific airway generation cannot be predicted.  However, as mentioned, with an
empirical model the geometry and relative importance of mechanisms and airflow
splits are all "correct" in the subjects tested and are reflected in the measured
deposition. This may be an advantage over theoretical models that must rely on
extremely limited information on geometry. As described in Appendix 10A, the
ICRP based their 1994 model of respiratory tract deposition on a theoretical
calculation of the type introduced by Taulbee  and Yu (1975), which was found to be
consistent with the experimental data taken as a whole.  However, for
mathematical simplicity in applying the results of these complex calculations,
which included the effects of airway dimension scaling for subject gender and
age, the ICRP developed a set of algebraic expressions to represent regional lung
deposition in terms of the controlling parameters, i.e., particle diameter,
density, shape factor, breathing mode (nose or mouth), tidal volume, respiratory
frequency, functional residual capacity, gender, and subject height.
                                        10-105

-------
10.5.2  Laboratory Animals

     Since much information concerning inhalation toxicology is collected from
laboratory animals, the comparative regional deposition in these laboratory
animals must be considered to help interpret, from a dosimetric viewpoint, the
possible implications of animal toxicological results for humans.  In evaluating
deposition studies in terms of interspecies extrapolation, it is not adequate to
express  the amount of deposition merely as a percentage of the total inhaled. For
some particle sizes, regional deposition in humans and laboratory animals may be
quite similar and appears to be species independent (McMahon et al.,  1977; Brain
and Mensah,  1983). However, different species exposed to identical particles at
the same exposure concentration will not receive the same particle mass per unit
exposure time because of their differences in tidal volume and breathing rate.
In addition, because of differences in the lung weight and airway surface area,
the amount of deposition normalized to these quantities is also very different
between species.
     It is difficult to systematically compare interspecies deposition patterns
obtained from various reported studies, because of variations in experimental
protocols, measurement techniques, definitions of specific respiratory tract
regions, and so on. For example, tests with humans are generally conducted under
protocols that standardize the  breathing pattern, whereas those using
laboratory animals involve a wider variation in respiratory exposure conditions
(for example, spontaneous breathing versus ventilated breathing as well as
various  degrees of sedation).  Much of the variability in the reported data for
individual species may be due to the lack of normalization for specific
respiratory parameters during exposure. In addition, the various studies have
used different exposure techniques, such as nasal mask, oral mask, oral tube, or
tracheal intubation.  Regional  deposition may be affected by the exposure route
and delivery technique employed.
     Figure 10-30 shows the regional deposition data versus particle diameter in
commonly used laboratory animals obtained by various investigators and compiled
by Schlesinger (1988). Although there is much variability in the data, it is
possible to make some generalizations concerning comparative deposition
patterns. The relationship between total respiratory tract deposition and
particle  size is approximately  the same in humans and most of these animals;
deposition increases on both sides of a minimum, which occurs for particles of
0.2 to 0.9 jim. Interspecies differences in regional deposition occur due to
anatomical and
                                         10-106

-------
1UU


80
60

40

20
r\
1 1 1
O Rat
E Hamster
A Mouse
~ O Guinea Pig
_
ET
A

- I
" i v % JfErtSfc
0.01 0.1 1.0
60
1 40
+j
0
Q.
Q 20
1 1
ORat
- P Hamster
A Mouse
VGuinea Pig
Voog
-

-
lll&w



T __

1 D
^3/1
w -
f •
10
I
TB



                       0.01
0.1
1.0
10
                   60
                   40
                   20
' O Rat
D Hamster
A Mouse
^Guinea Pig
VDog
I
1
V

i
V
V
V
1 1





<
r
i





>
i

k
^
ij
^

0.5 //m and geometric (or diffusion equivalent) for those < 0.5 Source: Schlesinger (1988). 10-107


-------
physiological factors.  In most laboratory animal species, deposition in the ET
region is near 100 percent for dae greater than 5 jim (Raabe et al., 1988),
indicating greater efficiency than that seen in humans. In the TB region, there
is a relatively constant, but lower, deposition fraction for dae greater than 1 jim
in all species compared to humans.  Finally, in the A region, deposition fraction
peaks at a lower particle size (dae about 1  |im) in laboratory animals, than in
humans.
     Mathematical deposition models for rats, hamsters, and guinea pigs have
been developed by several investigators (e.g., Schum and Yeh, 1980; Xu and Yu,
1987; Martonen et al., 1992) in a similar manner as the human models without
including diffusion deposition in the ET region. Although the modeling results
are generally in agreement with experimental data, there is a considerable
uncertainty in the respiratory and anatomical parameters of the laboratory
animals used in the modeling studies.  In addition, the airway branching patterns
in the animals are commonly monopodial as compared to the dichotomous branching
in the human lung.  The deposition efficiency of an airway (the amount of
deposition in an airway divided by the amount entered) developed in the human
model may not be applicable to laboratory animal species. Despite some of these
difficulties, modeling studies in laboratory animals remain a useful step in
extrapolating exposure-dose-response relationships from laboratory animals to
the human (Yu  et al., 1991).
     Asgharian et al. (1995) developed an empirical model of particle deposition
in the A region based on the published data reviewed by Schlesinger (1985a).
Although restricted to the A region, the approach could be applied to  other
regions. A deposition function (FA) was described using a polynomial regression
of the form

                 N
            FA  = £  ^(log^d)1 for d
-------
reason, Equation 10-31 was added to be consistent with the deposition data and
dcut.off was determined by setting Equation 10-30 to zero. Newton's method was
employed to find dcut.off for different cases. Particle deposition was then
integrated with particle distributions differing in median particle diameter
and og to calculate deposition mass fraction for specific polydisperse size
distributions.
     Menache et al. (1996) developed an empirical model to estimate fractional
regional deposition efficiency.  This model represents a revised version of
previously published models used for dosimetric interspecies extrapolation
(Jarabek et al., 1989, 1990; Miller et al.,  1988) that have been useful to develop
inhalation reference concentration (RfC) estimates for dose-response
assessment of air toxics (U.S. Environmental Protection Agency, 1994).  For
example, rather than linear interpolation between the published (Raabe et al.,
1988) means for deposition measured at discrete particle diameters, as
previously done for the rat deposition modeling, equations have now been fit to
the individual animal data  for each of the discrete, monodisperse particle
exposures (U.S. Environmental Protection Agency, 1994; Menache et al., 1996).
     A description of the complete study including details of the exposure may be
found elsewhere (Raabe et al., 1988). Briefly, the animals were exposed to
radiolabelled ytterbium (169Yb) fused aluminosilicate spheres in a nose-only
exposure apparatus. Twenty unanesthetized rodents or eight rabbits were exposed
to particles of aerodynamic diameters (dae) approximately 1, 3, 5, or 10 //m. Half
the animals were sacrificed immediately  post exposure; the remaining half were
held 20 h post exposure. One-half of the animals at each time point were female.
The animals were dissected into 15 tissue compartments, and radioactivity was
counted in each compartment.  The compartments included the head,  larynx, GI
tract, trachea, and the five  lung lobes.  This information was used directly in
the calculation of the deposition fractions. Radioactivity was also measured in
other tissues including heart, liver, kidneys, and carcass; and additionally in
the urine and feces of a group of animals held 20 h.  Data for the animals
sacrificed immediately  post exposure were used to ensure that there was no
contamination of other tissue, whereas the data from the animals held 20 h were
used in the calculation of a fraction used to partition bronchial deposition
between the  TB and A regions. Radioactivity was measured in the pelt, paws,  tail,
and headskin as a control on the exposure.
                                         10-109

-------
     Although there are some other studies of particle deposition in laboratory
animals (see review by Schlesinger, 1985a), no other data have the level of
detail or the experimental design (i.e., freely breathing, unanesthetized,
nose-only exposure to monodisperse particle size distributions) required to
provide deposition equations representative of the animal exposures used in many
inhalation toxicology studies. However, many inhalation toxicology studies are
not nose-only exposures.  While nose-only exposures are necessary to determine
fractional particle deposition, adjustments can be made to estimate deposition
fractions under whole-body exposure conditions. Similarly, deposition of
polydisperse size distributions can be estimated by integrating the size
distribution and monodisperse fractional deposition.
     The advantages of using the data of Raabe et al. (1988) to develop the
deposition efficiency equations include:

     •     the detailed measurements were made in all tissues in the animal,
           providing mass balance information and indicating that there was no
           contamination of nonrespiratory tract tissue with radioactivity
           immediately post exposure,

     •     the use of unanesthetized, freely breathing animals, and

     •     the use of monodisperse or near monodisperse particle size
           distributions in the exposures
     Regional fractional deposition, Fr, was calculated as activity counted in a
region normalized by total inhaled activity (Table 10-11). The proportionality
factor, fL, in Equations 10-33 and 10-34 was used to partition thoracic
deposition between the TB and A regions.  It was calculated using the 0 and 20-h
data and is described in detail by Raabe and co-workers (1977).
     These regional  deposition fractions, Fr,  however, are affected not only by
the minute volume (VE), MMAD and og, but also by deposition in regions through
which the particles have already passed.  Deposition efficiency, r|r, on the other
hand, is affected only by MMAD, og and VE. The relationships between deposition
fraction and efficiency are calculated as provided below and are described in
more detail elsewhere (Menache et al., 1995). In the aerodynamic domain, that is
for particles with diameters >0.5 //m, efficiencies increase monotonically and
are bounded below by 0 and above by 1. The
                                         10-110

-------
               TABLE 10-11.  REGIONAL FRACTIONAL DEPOSITION
                            P    Activity Counted in a Region
	[	Total Inhaled Activity	
                             [head  + GI  tract  + larynxL h
   Extrathoracic (ET): FET = 	—                          (10-32)
                                Total Inhaled  Activity
                                                5
                               trachea,  + fT  x Y^  lobe. n,,
                                    "0 h     L   Z-^      1,0  h                        /-JQ ^g^
 Tracheobronchial (TB): F^ =  	—	                        v   "  ;
                                  Total Inhaled Activity
                                        5
                             (1 - fT) x Y)  lobCio„
         Alveolar (A):  FA = 	^	                                (1°"34)
                             Total Inhaled Activity
Source: U.S. Environmental Protection Agency (1994).


logistic function has mathematical properties that are consistent with the shape
of the efficiency function (Miller et al., 1988)
where E(r|r) is the expected value of deposition efficiency (r|r) for region r, and
x is expressed as an impaction parameter, dae2Q, for extrathoracic deposition
efficiency and as aerodynamic particle size, dae,  for TB and A deposition
efficiencies. The flow rate, Q (mL/s), in the impaction parameter may be
approximated by (2VE/60). The parameters a and P are estimated using nonlinear
regression techniques.
      To fit this model, efficiencies must be derived from the deposition
fractions that were calculated as described in Table 10-11. Efficiency may be
defined as activity  counted in a region divided by activity entering that region.
Then, considering the region as a sequence of filters in steady state,
efficiencies may be calculated as follows

                         r|ET = FET                                               (10-36)
                                         10-111

-------
                                                                                  (10-37)
                     5
   trachea^, h + fL x J^  lobCj 0 h

            v~-
                 5
      (1  ~~ tT ) X /   i\ju\si n L
            L/   ^      '                                         (10-38)
IA
                       (1  - IET) (1  - T!TB)
     Using these calculated regional efficiencies in the individual animals, the
logistic function was fit for the ET, TB, and A regions for the five animal
species and humans. Figure 10-3 1 shows the deposition efficiency in the rat ET
region versus the impaction parameter, dae2Q.  The logistic curve was fit to the
experimental data assuming negligible deposition on exhalation. The open
circles represent the data for animals having extreme studentized residuals
(>1.96) compared to the data for other animals (closed circles) in the ET region.
Deposition efficiency curves were fit for the TB and A regions also.  In all three
regions, the curve fits provided good descriptions of the data with asymptotic R2
of 0.98 or greater (Menache et al., 1996). The root MSE, an estimate of the
average error in the regression model in the data units, ranged between 0.08  and
0.10.  These differences are well within the limits of biological variability
seen in this study and other studies (Schlesinger, 1988). The parameter
estimates from these fits are listed in Table 10-12.
     The fitted equations are then used to generate predicted efficiencies (fj) as
a function of impaction in the ET  region and of dae in the TB and A regions.
Finally, the predicted efficiencies  are multiplied together and adjusted for
inhalability, I, as shown in Equations 10-39 through  10-41 to produce predicted
deposition fractions (Fr) for monodisperse and near monodisperse (og < 1 .3)
particles

                      FET = I x flET                                              (10-39)

                Fra = I x (1  - fjET) x fjra                                       (10-40)

           FA = I x (1 -  f^) x (1  -  f^ x  V                                  (10-41)
                                         10-112

-------
Figure 10-31.
                    1.0-1
                    0.8-
                  o  0.6-1
                  o
                  ui
                  ui  0.4-
                    0.2-
                    0.0-
                         A.  Negligible Deposition
                            on Exhalation
                      10              100
                         Impaction [(|jm3  ml/s]
                                                                      1,000
Regional deposition efficiency in the rat extrathoracic (ET)
region versus an impaction parameter (dae2Q) as predicted by model
of Menache etal. (1996).
Source: Menache et al. (1996).
     Inhalability, I, is an adjustment for the particles in an ambient exposure
concentration that are not inhaled at all. For humans, an equation has been fit
applying the logistic function (Menache et al., 1995) to the experimental data of
Breysse and Swift (1990)
               I =  1
                                 1
                         1  + e
                              10.32-7.17
                                                                                   (10-42)
The logistic function was also fit to the data of Raabe et al. (1988) for
laboratory animals (Menache et al., 1995)
                I  = 1
                                 1
                         1 + e
                               2.57-2.81
                                                                                   (10-43)
     Figure 10-32 illustrates the relationship between the predicted
efficiencies and predicted depositions using this model for the rats. The
particles were assumed to be monodisperse.
                                          10-113

-------
               TABLE 10-12. DEPOSITION EFFICIENCY EQUATION ESTIMATED PARAMETERS
                            AND 95% ASYMPTOTIC CONFIDENCE INTERVALS
Species
Human
Rat

a
7.129
6.348(5.14,
7.56)
ET (Nasal)

-1.957"
-5.269 (-6.
4.35)

P
19,-


o
J
2,
o
J

a
.298a
.822 (2.54,
.11)
TB

-4.588a
-4.576 (-5
4.10)

P
.06,-


0,
2.
2.

a
.523*
,241 (1.72,
,77)
A

-1.3893
-10.463
8.19)

P
(-12.74, -
"Source: Miller et al. (1988).

-------
A default body weight (BW) for the rats of 0.38 kg was used to calculate a default
VE using allometric scaling (U.S. Environmental Protection Agency, 1994).
Regional deposition efficiencies and fractions were calculated for particles
with dae ranging from 1.0 to 10 //m. These calculated points were connected to
produce the smooth curves shown in Figure 10-30. The three panels on the left of
Figure 10-32 are plots of the predicted regional deposition efficiencies; the
three panels on the right show the predicted regional deposition fractions
derived from the estimated efficiencies and adjusted for inhalability. The
vertical axis for the predicted deposition efficiency panels range from 0 to 1.
Although the deposition fraction is also bounded by 0 and 1, the vertical axes in
the figure are less than 1 in the TB and A regions. The top two panels of Figure
10-32 are the predicted deposition efficiency and fraction, respectively, for
the ET region. These two curves  are plotted as a function of the impaction
parameter described for Equation 10-35.  The middle two and lower two panels show
the predicted deposition efficiencies and fractions for the TB and A regions,
respectively. These four curves are plotted as a function of dae.
     When a particle is from a monodisperse size distribution, the dae and the
MMAD are the same. If, however, the particle is from a polydisperse size
distribution, the particle cannot be described by a single dae; the average value
of the distribution, the MMAD,  must be used. In the aerodynamic particle size
range, the deposition efficiency  curves all increase monotonically as a function
of the independent variable (i.e., either the impaction parameter or dae) and
have both lower and upper asymptotes.  The curves describing the deposition
fractions, however, have different shapes that are dependent on the respiratory
tract region. Deposition fractions in all three regions are nonmonotonic—
initially increasing as a function of particle size but decreasing as particle
sizes become larger.  This is because particles that have been deposited in
proximal regions are no longer available for deposition in distal regions. As an
extreme example, if all particles are deposited in the ET region,  no particles
are available for deposition in either the TB or A regions. In the ET region, the
nonmonotonic shape for fractional deposition is due to the fact that not all
particles in an ambient concentration are inhalable.
     As discussed in Section 10.2, particles in an experimental or ambient
exposure are rarely all a single size but rather have some distribution in  size
around an average value.
                                         10-115

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          Predicted Regional Deposition Efficiency    Predicted Regional Deposition Fraction
        1.0-1                   ^_	1.00000
      > 0.8
      o
      c
      0)
      O 0.6
      UJ
        0.4
        0.2
        0.0
                                                0.80000
                                                0.60000
                                                0.40000
                                                0.20000
                                                0.00000
                      10         100        1000
                  Impaction [((Jm)2 ml/sec]
                                      1         10        100
                                         Impaction [((Jm)2 ml/sec]
                                                                                   1000
        0.0
                                                                                   10
                Aerodynamic diameter (|jm)
                                       Aerodynamic diameter (|jm)
        1.0
        0.0
          0.1                1
               Aerodynamic diameter (|jm)
                                   0.1               1
                                      Aerodynamic diameter (|jm)
                                                                                   10
Figure 10-32.
Comparison of regional deposition efficiencies and fractions for
the rat.  A default body weight of 0.38 kg (U.S. Environmental
Protection Agency, 1994) was used in these calculations. The
fractional deposition (solid line) and inhalability (dashed line)
are shown in the upper right panel.
                                          10-116

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As this distribution becomes greater, the particle is said to be polydisperse.
The empirical model of Menache et al. (1996) was developed from exposures using
essentially monodisperse particles (which are treated as though they are exactly
monodisperse). It is therefore possible to multiply the particle size
distribution function (which is customarily considered to be the lognormal
distribution) by the predicted depositions (calculated as described in
Equations 10-39 through 10-41) and integrate over the entire particle size
range. Mathematically, this calculation is performed as described by
Equation 10-44
                                  x exp
-1/2
                                             Gog cl   - log MMAD)2
                                                    Gog  of
dd,.
where log refers to the natural logarithm, [^r]p is the predicted polydisperse
fractional deposition for a given MMAD and og, and [^r]m is the predicted
monodisperse fractional deposition for particles of size dae.  The limits of
integration are defined from 0 to °° but actually include only four standard
deviations (99.95% of the complete distribution).  For each particle size in the
integration, [Fr]m is  calculated and then multiplied by the probability of
observing a particle of that size in a particle size distribution with that MMAD
and og.  Rudolf and colleagues (1988) have also investigated the effect of
polydisperse particle size distributions on predicted regional uptake of
aerosols in humans  and present a more detailed discussion of these and related
issues.
     As discussed by Schlesinger (1985a), there are many sources of variability
that could explain differences in predicted deposition using the model of
Menache et al. (1996) and the observed deposition data in the studies reported by
Schlesinger (1985a). However, results from the model of Asgharian et al. (1995),
based on the data reported in Schlesinger (1985a), are similar to estimates
derived using the model of Menache et al. (1996).
     Data from inhalation studies, particularly chronic inhalation exposures,
are often difficult to interpret in terms of respiratory tract deposition
efficiency, because  the amounts of material retained in the respiratory tract
and other body organs are often determined by complex relationships between
initial lung deposition, lung retention, subsequent organ uptake and retention,
and body uptake by ingestion of material contaminating the body surface. As an
example, review of the literature indicates that data from most inhalation
                                                                                   (10-44)
                                          10-117

-------
deposition studies are not appropriate for direct comparison or model validation
with the estimates from the Menache et al. (1996) model because the data are
normalized to the deposition in or on the animal rather than to what was inhaled
(Newton and Pfledderer, 1986; Dahlback et al., 1989), used anesthetized animals
(McMahon et al., 1977; Johnson and Ziemer, 1971; Raabe et al.,  1977), or used
cannulated animals (Shiotsuka et al., 1987). Berteau and Biermann (1977)
exposed female Sprague Dawley rats to an aerosol with a mass median diameter
(MMD) of 2.1 //m and a og of 2.0 for 20 minutes.  These authors calculated total
deposition in 8 animals to be 28 ± 9.3%. The model of Menache et al. (1996) would
predict approximately 60% deposition, assuming the MMD = MMAD. Berteau and
Biermann (1977) noted substantially lower deposition in rats than in mice for
this same study  and proposed a decrease in VE as a possible reason. Some
adjustment of VE would bring the model prediction into closer agreement with the
data. Differences in exposure  such as whole-body and group housing versus nose-
only could also  contribute to some of the variability.  Although there is
substantial disagreement between the model prediction and the experimental
measurement for this polydisperse aerosol, it seems likely that the experimental
data are unusually low.
     Dahlback  and Eirefelt (1994) exposed male Sprague Dawley rats to
monodisperse fluorescent polystyrene latex microspheres ranging in size from
0.63 to 5.7 //m count median diameter.  Deposition was reported  as the sum of nose,
esophagus, stomach, and lung  normalized to the amount deposited in the sum of
these four compartments. Menache et al. (1996) compared their model predictions
with the experimental data for all particles >  1 //m. Because the experimental
data were expressed as regional deposition normalized to total respiratory tract
deposition, the model predictions were also normalized to total predicted
respiratory tract deposition.  To distinguish this presentation from
presentation of deposition fractions elsewhere in this chapter, upper
respiratory tract (URT)  deposition is defined  as the sum of the nose, esophagus,
and stomach deposition divided by those three compartments plus the lung for the
data of Dahlback and Eirefelt (1994); and as deposition in the ET region divided
by deposition in the sum of the ET, TB, and A regions for the predictions using the
Menache et al. (1996).  Lower respiratory tract (LRT) deposition may then be
defined as

                         LRT deposition = 1 - URT deposition.                    (10-45)
                                        10-118

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The experimental and model-predicted deposition fractions are shown in Figure
10-33 for the data of Dahlback and Eirefelt (1994), as well as for the data of
Raabe et al. (1988) that were used to develop the model.  The solid line is the
line of identity and represents the situation in which the predicted and observed
deposition match exactly.  As can be seen in Figure 10-33, there is considerable
scatter in the  data, particularly in the range associated generally with
particles of about 2 to 3 //m MMAD.  Under the conditions for which the model would
predict 50 to  60 percent deposition, the observed deposition for both the URT and
LRT ranges from 10 to 80 percent. As noted earlier (Figure 10-31) deposition in
rats increases very rapidly from low to high values in this range.  Similarly, in
humans, regional deposition associated with particles of 2 to 3 //m ranges from 10
to 20 percent to 60 to 80 percent (Figure 10-22, 10-26, and 10-27).
10.6  CLEARANCE DATA AND MODELS

     As discussed in previous sections, the biologic effects of inhaled
particles are a function of their disposition.  This, in turn, depends on their
patterns of both deposition (i.e., the sites within which they initially come
into contact with airway epithelial surfaces and the amount removed from the
inhaled air at these sites) and clearance (i.e., the rates and  routes by which
deposited materials are removed from the respiratory tract).  Removal of
deposited materials involves the competing processes of macrophage - mediated
clearance  and dissolution - absorption. Deposition and clearance mechanisms
were discussed in Sections 10.5 and 10.6, respectively.
     Respiratory-tract clearance begins immediately upon deposition of inhaled
particles.  Given sufficient time, the deposited particles may be completely
removed by these clearance processes. However, single inhalation exposures may
be the exception rather than the rule.  It is generally accepted that repeated or
chronic exposures are common for environmental aerosols.  As a result of such
exposures, accumulations of the particles may occur. Chronic exposures produce
respiratory tract burdens of inhaled particles that continue to increase with
time until the rate of deposition is balanced by the rate of clearance. This is
defined as the "equilibrium respiratory tract burden". The accumulation
patterns are unique to each
                                         10-119

-------
             1-1
         £  0.8'
         o
         (B
         O

         ^  0.6'
         o
         Q.
         4)
         Q
         T3
         4)

         £
         4)
            0.4-
            0.2-
                    •  Data if Raabe et al., 1988

                    O  Data of Dahlback & Eirefelt, 1994
                       model underpredic
                                                   URT = URT/(URT + LRT)
                                                  O  O
                                                   ^    model overpredicts
                                                                           (a)
                           0.2           0.4           0.6           0.8

                                  Predicted URT Deposition Fraction
         5  0.8-
         o
         (B
                                                   LRT = LRT/(URT + LRT)
                    •  Data if Raabe et al., 1988

                    O  Data of Dahlback & Eirefelt, 1994
                 model underpredict
                                                         model overpredicts
                                        0.4           0.6

                                  Predicted LRT Deposition Fraction
0.8
Figure 10-33.  Experimental deposition fraction data and predicted estimates

               using model of Menache et al. (1996). The solid line is the line of

               identity and represents the situation in which the predicted and

               observed deposition match exactly.
               Source: Menache et al. (1996).
                                         10-120

-------
laboratory animal species, and possibly unique to the inhaled material,
especially if the inhaled material alters deposition and/or clearance patterns.
     It is important to evaluate these accumulation patterns, especially when
assessing ambient chronic exposures, because they dictate what the equilibrium
respiratory tract burdens of inhaled particles will be for a specified exposure
atmosphere. Equivalent concentrations can be defined as "species-dependent
concentrations of airborne particles which, when chronically inhaled, produce
equal lung deposits of inhaled particles per gram of lung during a specified
exposure period". This section presents available data and approaches to
evaluating exposure atmospheres that produce similar respiratory tract burdens
in laboratory animals and humans.

10.6.1  Humans

     Models for deposition, clearance, and dosimetry of the respiratory tract of
humans have been available for the past four decades and continue to evolve. The
International Commission on Radiological Protection  (ICRP) has recommended
three different mathematical models during this time period (ICRP 1959, 1979,
1994).  The models changed substantially in structure, expanding from two
compartments in the 1959 model (ICRP, 1959) to five compartments in the 1994
model (ICRP,  1994).  These models have been an important aspect of radiation
protection programs for inhaled radioactive materials. However, they make it
possible to calculate the mass deposition and retention by different parts of the
respiratory tract and provide, if needed, mathematical  descriptions of the
translocation of portions of the deposited material to other organs and tissues
beyond the respiratory tract.  The structure and complexity of the ICRP models
increased with each version.  These increases  in complexity reflect both the
expanded knowledge of the behavior and dosimetry of inhaled  materials in the
respiratory tract that has become available and an increased need for models that
can be applied to a broader range of uses.
     The 1959 model (ICRP, 1959) had a very simple structure in which the
respiratory tract was divided into an upper respiratory tract (URT), and a lower
respiratory tract (LRT). No information was given on the anatomical division
between the URT and the LRT. In the 1959 model, 50% of inhaled particles
deposited in the URT, 25% deposited in the LRT, and the remaining 25% was exhaled.
No information on the effects of the sites or magnitude of
                                        10-121

-------
particle deposition was given, and relationships between particle size,
deposition, and clearance were not incorporated into the 1959 model.  The URT was
considered an air passage from which all deposited particles cleared quickly by
mucociliary activity and swallowed.  Particles deposited in the LRT were
classified as soluble or insoluble. For soluble particles, chemical
constituents of all 25% of the inhaled particles that reach the LRT were assumed
to be rapidly absorbed into the systemic circulation. For poorly soluble
particles, 12.5% were assumed to clear by mucociliary activity and be swallowed
during the first 24 h following deposition.  The remaining 12.5% was assumed to be
retained with a biological half-time of 120 d. No clearance of particles to the
regional lymph nodes was included in the 1959 model.
     The  1979 model (ICRP, 1979) was based on the Task Group Lung Model (TGLM)
report (Morrow et al.,  1966) and was divided into three compartments
(nasopharyngeal, NP; tracheobronchial, TB; and pulmonary, PU). The NP region
included anatomical structures from the tip of the nose to the larynx. The TB
region extended from the trachea to the end of the terminal bronchioles.  The PU
region (equivalent to the A regional as described in Table 10-1) was the
remaining, non-ciliated pulmonary parenchyma. Deposition probabilities were
given for the NP, TB, and PU regions for activity median aerodynamic diameters
(AMAD) of inhaled particles that covered about two orders of magnitude (0.2 -  10
|im). This incorporation of particle size considerations and the AMAD concept
were major improvements in the health protection aspects of modeling related to
inhaled radioactive particles. The 1979 ICRP model also incorporated
consideration for clearance rates using three classes (D, W, Y).  Class D
particles cleared rapidly  (T1/2 = 0.5 d), class W particles cleared at an
intermediate rate (T1/2 = 50 d), and class Y particles cleared slowly (T1/2 = 500 d).
It was also recognized that the competing processes of dissolution-absorption
and physical clearance operated on the deposited particles, but inadequate
information was available to differentiate between the two mechanisms.  This
model  also included a clearance pathway to the tracheobronchial lymph nodes. The
long-term clearance of particles by either physical transport processes or by
dissolution-absorption processes are described by the same clearance half-time.
     A substantial increase in knowledge about the effects of particle size on
the deposition of inhaled particles occurred since the publication of the TGLM
report (Morrow et al.,
                                         10-122

-------
1966). This new information is reflected in the latest ICRP66 model (IRCP66,
1994). This new ICRP66 model considers the respiratory tract as four anatomical
regions. The extrathoracic (ET) region is divided into two sub-regions: the
anterior nasal airways, which clear only by extrinsic processes such as nose
blowing, defined as ETl5 and the posterior nasal passages, pharynx, mouth and
larynx defined as ET2, which clears to the gastrointestinal tract via a
combination of mucociliary action and fluid flow. The airways within the lungs
are comprised of the bronchial  (BB) and bronchiolar (bb) regions, which combined
are equivalent to the Tracheobronchial (TB) region described in Table 10-3. The
division of the TB region into two parts (bronchi and bronchi olar) by the ICRP
enables mass deposition in the  small airways to be evaluated separately, and
possible related to such effects  as small airways constriction. The
gas-exchange tissues are defined as the alveolar-interstitial (AI) region,
which is exactly comparable to the pulmonary region or A region (see Tables  10-1
and 10-3). There are two lymph node regions; LNET drains the extrathoracic region
and LNra drains the BB, bb, and AI regions.
     Deposition in the four anatomical regions (ET, BB, bb, and AI) is given  as a
function of particle size covering five orders of magnitude, and two different
types of particle size parameters are used. The activity median thermodynamic
diameter (AMTD) is used to describe the deposition of particles ranging in size
from 0.0005 to 1.0 micrometer; the AMAD is used to describe deposition for the
size range of 0.1 to 100 micrometer. The model applies to hygroscopic particles
by estimating particle growth in each region during inhalation.  Reference
values of regional deposition are provided, and guidance is given for
extrapolating to specific individuals and populations under different levels of
activity.  Deposition is expressed as a fraction of the number or activity of
particles of a given size that is  present in a volume of ambient air before
inspiration, and activity is assumed to be log-normally distributed as a
function of particle size for a typical particle density of 3 g/cm3 and dynamic
shape factor of 1.5, although particle density and shape factor are included as
variables in the deposition calculations. As discussed in Section 10.5, the 1994
ICRP66 model also includes consideration of particle inhalability, which is a
measure of the degree to which particles can enter the respiratory tract and be
available for deposition.
     After deposition occurs in a given region, two different clearance
processes act competitively on  the deposited particles, except in the ETX region
where the only clearance
                                         10-123

-------
process is extrinsic. These processes are particle transport, which includes
mucociliary clearance from the respiratory tract and physical clearance of
particles to the regional lymph nodes, and absorption, which includes movement
of material to blood including both dissolution-absorption and transport of
ultra fine particles. Rates of particle clearance which were derived from
studies with human subjects are assumed to be the same for all types of particles.
Particle clearance from the BB and bb regions includes two slow phases: (1) to
account for observations of slow mucociliary clearance in humans and (2) to
account for observations of long term retention of small fractions of deposited
material in the tracheobronchial tissues of both laboratory animals and humans.
The structure for the ICRP66 1994 model is shown in Figure 10-34. A summary of the
development of the ICRP66 1994  model is provided in Appendix 10A. This includes
comparison of model predictions against the available depostion data discussed
in Section 10.5.
     A considerable amount of information has accumulated relevant to the
biokinetics of inhaled  radioactive materials. The radiation associated with
these materials allows relative ease of analysis to determine temporal patterns
for retention, distribution, and excretion of inhaled radioactive particles and
their constituents.  Non-radioactive particles are difficult to study because
the particles and their  chemical constituents are generally difficult to detect
in biological systems,  tissues, and excreta.  Some studies have shown that the
physicochemical forms and sites of deposition of chemical toxicants influence
clearance rates. Also, adsorption of chemicals onto particles can influence
deposition patterns and alter rates  of dissolution-absorption of the particles
and their constituents. For example, vapors that would not normally reach the A
region will do so if they are adsorbed onto particles.  Also, adsorption onto
particles might slow the rates at which chemicals can be absorbed into lung
tissue or the circulatory system. Amounts of inhaled material may markedly
influence clearance as a consequence of particle overload. The  cytotoxicity and
shapes of particles (i.e., fibers) also influence clearance.  Additionally,
metabolic products of the inhaled materials may cause pathology and disease
states that may result in nonpredictable retention and clearance patterns.
     Absorption into blood is material specific, acts in all regions except ETl5
and is assumed to occur at the same rates for all regions.  Absorption into blood
is a two stage process. The first step (dissolution) involves dissociation of
the particles into a form that can
                                         10-124

-------
                             The ICRP 1994 Human Respiratory Tract Model
o
*—k
to
Anterior
Nasal
(ET,)
Naso-
Oropharynx/
Larynx
(ET2)
Bronchi
(BB)
Bronchioles
(bb)
Alveolar
Interstitium
(Al)
Extrathoracic
^^^_^^^i
Surface

/
1



,
Lymp
Node
" 4 	 Pnitholium


oequesiereu /
in Tissue /

(Airway Wall) /
* / »S
L
y
m
P
h
N
o
d
e
s
* — EpitheliurrJ Slow
/ ^/
* — ^EpitheliurrJ Slow



Thoracic

JFast ^
a
Cleared
by Mucus
i
Fast
£

/

t___^_^.
/
1
Fast
T/T /T,
/
=
-------
be absorbed into blood; the second step involves absorption of the subunits of
the particles. Because these processes act independently on the regionally
deposited particles, each can be specified separately and allowed to compete
against the other processes involved in the model.  This approach makes it
possible to use time-dependent functions to describe processes such as
dissolution-absorption.  However, for ease of calculation it is assumed that
time dependent dissolution can be approximated by dividing the material into two
fractions with different  dissolution rates: material in an initial state
dissolves at a constant rate, simultaneously changing to a transformed state in
which it dissolves at another rate. Uptake into blood is treated as
instantaneous for the material immediately absorbed after dissolution. Another
fraction of dissolved material may be absorbed more slowly as a result of binding
with tissue components. The model can use observed rates of absorption for
compounds for which there are reliable human or laboratory animal data. The
absorption of other compounds are specified as fast, moderate or slow.  In the
absence of specific information,  compounds are classified as fast, moderate or
slow according to their  former classification as D, W or Y, respectively, under
the previous ICRP model. Greater attention to the transfer of particles to
regional lymph nodes is given in this model than in the 1979 model by
incorporating these clearance processes at each level in the respiratory tract,
not just in the A or pulmonary region as in the 1979 model. Additionally, while
the new ICRP66 model (ICRP66, 1994) was developed primarily for use with airborne
radioactive particles and gases, its use for describing the  dosimetry of inhaled
mass of non-radioactive substances is also appropriate.
     An alternative new respiratory tract dosimetry model that developed
concurrently with the new ICRP model is being proposed by the National Council on
Radiation Protection (NCRP). This model was described in outline by Phalen et
al. (1991) and at the time of writing, a full report of the model is undergoing
final approval by the NCRP.  As with the 1994 ICRP66 model (ICRP66, 1994), the
proposed NCRP model  addresses (1) inhalability of particles, (2) new sub-regions
of the respiratory tract,  (3) dissolution-absorption as an important aspect of
the model, and (4) body size (and age).  The proposed NCRP model defines the
respiratory tract in terms of a naso-oro-pharyngo-laryngeal (NOPL) region, a
tracheobronchial (TB) region, a pulmonary (P) region, and the lung-associated
lymph nodes (LN). As  with the  1994 ICRP66 model, inhalability of aerosol
particles is considered,  and
                                        10-126

-------
deposition in the various regions of the respiratory tract is modeled using
methods that relate to mechanisms of inertial impaction, sedimentation, and
diffusion.  The rates of dissolution-absorption of particles and their
constituents are derived from clearance data from humans and laboratory animals.
The effect of body growth on particle deposition is also considered in the model,
but particle clearance rates are assumed to be independent of age.  The NCRP model
does not consider the fate of inhaled materials after they leave the respiratory
tract.  Although the proposed NCRP model describes respiratory tract deposition,
clearance, and dosimetry for radioactive substances inhaled by humans, the model
can also be used for evaluating inhalation exposures to all types of particles.
     Both the NCRP and ICRP had the benefit of contributions from respected
investigators in respiratory tract toxicology and biomedical  aerosol research.
Similar mathematical assessments were arrived at by both commissions, although
detailed calculations for specific radionuclides can be  different. Comparison
of regional deposition fraction predictions between the two  models are shown in
Figures 10-35 through 10-37.  As noted above, the various compartments of the two
models are equivalent. That is, the ET region as described in Table 10-3 is
equivalent to the ETX plus ET2 compartments of the ICRP66 1944  model and the NOPL
compartment of the proposed NCRP model.  The TB region of Table 10-3 is equivalent
to the BB plus bb compartments of the ICRP66 1994 model and to the TB compartment
of the proposed NCRP model. The A region of Table 10-3  is equivalent to the AI
compartment of the ICRP66 1994 model and to the P compartment of the proposed NCRP
model. These differences in nomenclature are retained in these figures to aid
distinguishing the predictions from each.  Figures 10-35 and 10-36 show
predictions for an adult male during mild  exercise and at rest. Figure 10-37
shows predictions for a 5-year old child.  These comparisons show that the
behavior of the models are quite comparable, that is, the predicted  deposition
fraction for a given particle size is similar if the models use the same
ventilation parameters as input. In fact, in order to insure a uniform course of
action that provides a coherent and consistent international approach, the NCRP
recommends adoption of the ICRP66 1994 model for calculating exposures for
radiation workers and the public (e.g., for computing annual reference levels of
intake and derived reference air concentrations).
                                        10-127

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                   0.001       0.01        0.1          1
                                       Particle Diameter (\tn)
                                              10
100
                   0.001
              0.01        0.1         1         10
                       Particle Diameter (urn)
100
                           — NCRP Draft Model
                                    ICRP66 (1994) Model
Figure 10-35.
Comparison of regional deposition fractions predicted by the proposed
National Council on Radiation Protection (NCRP) model with those of
the International Commission on Radiological Protection (ICRP)
Publication 66 (1994) model.  Predictions are for unit density,
spherical particles inhaled through the nose by an adult male with a
tidal volume of 1250 mL, respiratory frequency of 20 min"1,  and
functional residual capacity (FRC) of 3300 mL. See text for an
explanation of abbreviations for respiratory tract compartments.
                                      10-128

-------
            0.001
        0.01         0.1           1
                Particle Diameter (im)
10
100
           0.001
        0.01         0.1
                Particle Diameter
10
100
                         NCRP Draft Model   	ICRP66 (1994) Model
Figure 10-36.
Comparison of regional deposition fractions predicted by the proposed
National Council on Radiation Protection (NCRP) model with those of
the International Commission on Radiological Protection (ICRP)
Publication 66 (1994) model.  Predictions are for unit density,
spherical particles inhaled through the nose by an adult male with a
tidal volume of 750 mL, respiratory frequency of 12 min"1, and
functional residual capacity (FRC) of 3300  mL.  See text for an
explanation of abbreviations for respiratory tract compartments.
                                      10-129

-------
0.001       0.01        0.1          1
                     Particle Diameter dm)
                                                           10
                                                     100
           0.001
       0.01        0.1          1
                Particle Diameter (urn)
                                                10
100
                    	NCRP Draft Model  	ICRP66 (1994) Model
Figure 10-37.
Comparison of regional deposition fractions predicted by the proposed
National Council on Radiation Protection (NCRP) model with those of
the International Commission on Radiological Protection (ICRP)
Publication 66 (1994) model.  Predictions are for unit density,
spherical particles inhaled through the nose by a 5-year-old child with
a tidal volume of 244 mL, respiratory frequency of 39 min"1, and
functional residual capacity (FRC) of 767 mL. See text for an
explanation of abbreviations for respiratory tract compartments.
                                      10-130

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10.6.2 Laboratory Animals


     Several laboratory animal models have been developed to help interpret
results from specific studies that involved chronic inhalation exposures to non-
radioactive particles (Wolff et al., 1987; Strom et al., 1988; Stober et al.,
1994). These models were adapted to data from studies involving high level
chronic inhalation exposures in which massive lung burdens of low toxicity,
poorly soluble particles were accumulated and the models have not been adapted to
chronic exposures to low concentrations of aerosols in which particle overload
does not occur.
     Snipes et al. (1983) adapted a materials balance simulation model to
evaluate repeated or chronic inhalation exposures. The simulation model
language for a single inhalation exposure was described by Pritsker (1974) and
uses a Fortran-based numerical  integration of differential equations. The
integration method is a fourth order, variable step-size Runge-Kutta-England
routine for integrating systems of first order ordinary differential equations
with initial values. The model was used to describe the retention and clearance
of poorly soluble aerosol inhaled by mice, rats, and dogs (Snipes et al., 1983)
and guinea pigs (Snipes et al., 1984). A distinct advantage of this kind of model
is the requirement that dissolution-absorption rates for particles retained in
the respiratory tract are approximated as part of the modeling process.  The
model  output includes an estimate of the pulmonary burden of dust for each day of
interest following an inhalation exposure.
     Compartments and pathways of the model used in this chapter were kept as
simple as necessary and were limited to those associated with the alveolar region
of the respiratory tract. Figure 10-38 depicts the model, where
     D(t) =    alveolar deposit of aerosol particles at time t (|ig/g lung);

     MP(t) =  mechanical transfer rate (fraction/day) for particles from the
               alveolar region to the mucociliary escalator for clearance to the
               gastrointestinal tract;

     ML(t) =  mechanical transfer rate (fraction/day) for particles from the
               alveolar region to the thoracic lymph nodes;

     S(t) =     dissolution-absorption rate (fraction/day) for particles in the
               alveolar region or thoracic lymph nodes.
                                         10-131

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                             Airborne Particles
MP(t)
-^

Alveolar Region
S(t)
•»-

                                            ML(t)
                              Thoracic Lymph
                                     Nodes
                                                          S(t)
Figure 10-38.
Compartments of the simulation model used to predict alveolar
burdens of particles acutely inhaled by mice, hamsters, rats,
guinea pigs, monkeys, and dogs. Definitions for parameters are
provided in the text.
     The retention of particles in the alveolar region as a function of time after
a single inhalation exposure is described by
         dD(t)/dt = -D(t)-[MP(t) + ML(t)
                                                              (10-46)
with appropriate initial conditions for a single inhalation exposure. The
solution of differential equations in the GASP IV simulation language is based
upon numerical analysis techniques which adapt to produce solutions to a
prespecified accuracy on either an absolute or relative scale. To maintain the
specified accuracy the algorithm adjusts the size of the time step, making the
step smaller or larger depending upon the estimated error. If the algorithm
detects that the error is growing too large, it goes back to an earlier time and
proceeds with smaller steps.
     The simulation models for acute exposures were adapted to chronic exposures
for the selected species using the assumption that each individual exposure
during a chronic exposure
                                      10-132

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is the same with regard to deposition and clearance kinetics. Chronic exposures
were simulated by defining the exposure duration in days and summing the amounts
of dust retained in the lung from each daily inhalation exposure throughout the
defined chronic exposure period. The model for chronic inhalation exposures
therefore simply integrated the results of the individual exposures to predict
the burdens of dust in the alveolar region during the course of the chronic
exposures.
     This model adequately accounted for the observed lung burdens of diesel
exhaust particles (DEP) achieved in rats over the course of a 2-year chronic
inhalation exposure to 0.35 mg DEP/m3 (Snipes, 1989). The specific lung burdens
of DEP achieved in the rats during the 2-year study were about 0.4 mg DEP/g lung,
which is less that the amount that is generally predicted to cause particle
overload.  This model, and alternatives that are easily adapted to inhalation
exposure scenarios, appears to be useful for predicting alveolar clearance
patterns for a variety of inhaled materials as long as exposure concentrations
are reasonably low and particle overload has not occurred.

10.6.3 Species Similarities and Differences

     Rates for particle translocation from the A region to thoracic lymph nodes
(TLNs) appear to vary considerably among species. Rats and mice have particle
translocation rates from the A region to TLNs that are quite different from those
of guinea pigs, dogs, and possibly humans (Snipes et al., 1983; 1984).
Translocation from the A region to TLNs begins soon after an acute inhalation
exposure.  However, after a few days following the acute exposure, the transport
of particles from the A region to TLNs appears to be negligible in mice and rats
(Snipes et al., 1983), but continues at a constant rate in guinea pigs and dogs
(Snipes et al., 1983; 1984). No experimental information is available about the
rates of translocation of particles from the A region to TLNs in humans. However,
data for amounts of particles accumulated in the lungs of humans exposed
repeatedly to dusty environments (Stober et al., 1967; Carlberg et al., 1971;
Mclnroy et al., 1976; Cottier et al., 1987) suggest that poorly soluble particles
accumulate in TLNs of humans at rates that may be comparable to those observed for
guinea pigs, dogs, and monkeys. However, based on human autopsy data for
particles found in thoracic lymph nodes and lung tissue, the ICRP (1994)
determined a transport rate for particle from lung to lymph nodes that would
result in
                                        10-133

-------
a lymph node/lung particle concentration ratio of 20 at 10,000 days after
inhalation.  The transport rate was 2 x 10"5/day, i.e., lower than the rate for
dogs and monkey by approximately a factor often.
     Physical movement of particles from the A region to the TLNs affords the
opportunity to transport particles out of the lung, but the result is to
sequester, or trap the particles in what is generally perceived to be a dead-end
compartment. Because the TLNs represent traps for particles cleared from the
lung, particles can accumulate to high concentrations in the  TLNs. Thomas (1968,
1972) discussed the implications of particle translocation from the A region to
TLNs when the particles contain specific radionuclides, but  he presented
information that is relevant to all types of particles. Translocation of
particles from the A region to the TLNs results in concentrations of particles in
the lymph nodes that can be more than 2 orders of magnitude higher than
concentrations in the lung.  The implications of this consequence of inhalation
exposures have not been fully evaluated but may have important implications for
immunological responses in humans exposed to specific kinds of aerosols.
     Many measurements of alveolar retention and clearance have been conducted
on humans  and a variety of laboratory animal species. In some cases, at least two
laboratory animal species were exposed to the same aerosolized material, so
direct comparisons among species are possible. Few human inhalation exposure
studies have been performed using the same materials as used for the laboratory
animal studies.  Therefore, only a limited number of direct comparisons are
possible between laboratory animals and humans.
     Table 10-13 contains a summary of selected results for alveolar retention of
inhaled materials after single inhalation exposures to small masses of poorly
soluble particles.  Studies of less than about 3 mo duration were not included.
The variability in these results was caused by several factors.  In many  cases,
the reported results did not allow division of the alveolar burden between short-
and long-term clearance. Also, for most studies, dissolution-absorption of the
exposure materials were not known or were not reported. The broad range  of
particle sizes would have influenced deposition patterns, and
dissolution-absorption rates, but probably not physical clearance of particles
from the A region. The alveolar burden as a function of time in days after acute
inhalation is given by
                                         10-134

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TABLE 10-13. COMPARATIVE ALVEOLAR RETENTION PARAMETERS FOR POORLY SOLUBLE
           PARTICLES INHALED BY LABORATORY ANIMALS AND HUMANS
Species
Mouse




Hamster
Rat















Guinea pig


Aerosol
Matrix
FAP
FAP
FAP
Ru oxide
Pu oxide
FAP
Diesel soot
FAP
FAP
FAP
FAP
FAP
FAP
Asbestos
fibers
Latex
Pu oxide
Pu oxide
U02
U308

Co304
FAP
Diesel soot
Latex
Particle Size3
(jm
0.7
1.5
2.8
0.38
0.2
1.2
0.12
1.25
0.7
1.5
2.8
1.2
1.4
1.2-2.3

3.0
<1.0
2.5
2.7-3.2
-1-2

2.69
2.0
0.12
3.0
Measure
AMAD
AMAD
AMAD
CMD
CMD
CMD
MMAD
CMD
AMAD
AMAD
AMAD
AMAD
AMAD
AMAD

CMD
CMD
AMAD
AMAD
CMD

MMAD
AMAD
MMAD
CMD
P
d 0.93
0.93
0.93
0.88
0.86
0.73
0.37
0.62
0.91
0.91
0.91
0.83
0.76


0.39
0.20
0.75

0.67

0.70
0.22


Alveolar Burdenb
T,(d)
34
35
36
28
20
50
6
20
34
35
36
33
26


18
20
30

20

19
29


P,
0.07
0.07
0.07
e 0.12
0.14
0.27
0.63
0.38
0.09
0.09
0.09
0.17
0.24
1.00

0.61
0.80
0.25
1.00
0.33

0.30
0.78
1.00
1.00
T,(d)
146
171
201
230
460
220
80
180
173
210
258
310
210
46-76

63
180
250
247
500

125
385
>2,000
83
Study
Duration
(days)
850
850
850
490
525
463
33fO
492
850
850
850
365
180
101-171

190
350
800
720
768

180
1100
432
190
References
Snipes etal. (1983)
Snipes et al. (1983)
Snipes etal. (1983)
Bair (1961)
Bair (1961)
Bailey etal. (1985a)
Lee etal. (1983)
Bailey etal. (1985b)
Snipes etal. (1983)
Snipes etal. (1983)
Snipes etal. (1983)
Finch etal. (1994)
Finch etal. (1995)
Morgan etal. (1977)

Snipes etal. (1988)
Langham(1956)
Sanders etal. (1976)
Moms etal. (1990)
Galibin and Parfenov
(1971)
Kreyling et al. (1993)
Snipes etal. (1984)
Lee etal. (1983)
Snipes etal. (1988)

-------
TABLE 10-13 (cont'd). COMPARATIVE ALVEOLAR RETENTION PARAMETERS FOR POORLY SOLUBLE
               PARTICLES INHALED BY LABORATORY ANIMALS AND HUMANS
Species
Dog, (cont'd)




















Monkey

Human

Aerosol
Matrix
Coal dust
Coal dust
Ce oxide
FAP

FAP
FAP
FAP
FAP
Nb oxide
Pu oxide
Pu oxide
Pu oxide
Pu oxide
Pu oxide
Pu oxide
Pu oxide
Pu oxide
Tantalum
U3o8
Zr oxide
Pu oxide
Pu oxide
FAP
FAP
Particle
(jm
2.4
1.9
0.09-1.4
2.1-2.3

0.7
1.5
2.8
2.01
1.6-2.5
1-5
4.3
1.1-4.9
0.1-0.65
0.72
1.4
2.8
4.3
4.0
0.3
2.0
2.06
1.6
1
4
Size
Measure
MMAD
MMAD
MMD
AMAD

AMAD
AMAD
AMAD
AMAD
AMAD
CMD
MMD
MMAD
CMD
AMAD
AMAD
AMAD
MMD
AMAD
CMD
AMAD
CMAD
AMAD
CMD
CMD
Alveolar Burden
P



0.09

0.15
0.15
0.15
0.05




0.10
0.10
0.32
0.22
0.50
0.40
0.47



0.14
0.27
T,(d)



13

20
21
21




~1
200
3.9
87
32
20
1.9
4.5



40
50
P,
1.00
1.00
1.00
0.91

0.85
0.85
0.85
0.95
1.00
1.00
1.00

0.90
0.90
0.68
0.78
0.50
0.60
0.53
1.0
1.0
1.0
0.86
0.73
T,(d)
1,000
«700
8 >570
440

257
341
485
910
>300
1,500
300
400
1,000
680
1,400
1,800
1,600
860
120
340
500-900
770-1,100
350
670
b Study
Duration
(days)
160
301-392
140
181

850
850
850
1,000
128
280
300
468
~ 4,000
730
730
730
270
155
127
128
200
990
372-533
372-533
References
Gibbet al. (1975)
Morrow and Yuile (1982)
Stuart etal. (1964)
Boecker and McClellan,
(1968)
Snipes etal. (1983)
Snipes etal. (1983)
Snipes etal. (1983)
Kreylmg et al. (1988)
Cuddihy (1978)
Bair (1961)
Bairetal. (1962)
Morrow etal. (1967)
Park etal. (1972)
Guilmette et al. (1984)
Guilmette et al. (1984)
Guilmette et al. (1984)
Bair and McClanahan (1961)
Bianco etal. (1974)
Fish (1961)
Waligora(1971)
Nolibeetal. (1977)
LaBauveetal. (1980)
Bailey etal. (1985a)
Bailey etal. (1985a)

-------
       TABLE 10-13 (cont'd).  COMPARATIVE ALVEOLAR RETENTION PARAMETERS FOR POORLY SOLUBLE
                              PARTICLES INHALED BY LABORATORY ANIMALS AND HUMANS
Species
Human,
(cont'd)








Aerosol
Matrix
Latex
Latex
Pu oxide

Graphite and
Pu02
Pu oxide
Th oxide
Teflon
Zr oxide
Particle
(jm
3.6
5
0.3

6
<4-5
<4-5
4.1
2.0
Size
Measure
CMD
CMD
MMD

AMAD
CMD
CMD
CMD
AMAD
Alveolar Burden
P T,(d) P9
0.2 30 0.73
7
0.4 0.5 0.58
2
1.00

1.00
1.00
1.00
0.3 4.5-45 0.70
0
1.00

T2(d)
296
150-300
240

240-290
1,000
300-400
200-2,500
224
b Study
Duration
(days)
^480
160
300

566
427
427
300
261
References
Bohning et al.
(1982)
Booker et al. (1967)
Johnson et al.
(1972)
Ramsden et al.
(1970)
Newton (1968)
Newton (1968)
Philipson et al.
(1985)
Waligora(1971)
aSome aerosols were monodisperse, but most were poly disperse, with geometric standard deviations in the range of 1.5 to 4.
bAlveolar burden = P1-e"(ln2:"/Ti + P2-e"(ln2:"/T2, where Pj and P2 are fractions constrained to total 1.00, Tj and T2 equal retention half-times in (d),
and
t equals days after exposure. Retention half-times are approximations and are the net result of dissolution-absorption and physical
clearance
processes. In some examples, the original data were subjected to a computer curve-fit procedure to derive the values for Pj and Tj presented
in this table.
TAP = fused aluminosilicate particles.
dAMAD = activity median aerodynamic diameter.
eCMD = count median diameter.
fMMAD = mass median aerodynamic diameter.
8MMD  = mass median diameter.

-------
                           .  -(ln2)t/T +P  ' 6-(ln2)t/T2,
                          l  c         2
(10-47)
where Px and P2 are fractions constrained to total 1.0, Tj and T2 equal retention
half-times in days, and t equals days after acute exposure.
      The information shown in Table 10-13 was used to approximate biological
clearance rates for particles inhaled by the species listed in Table 10-14. In
addition, approximations are included for the fractions of alveolar burdens
initially deposited in the A region that were subjected to short- or long-term
clearance. These trends clearly will not apply to all types of inhaled
particles. For example, in some cases, deposition and clearance may be
influenced by the physicochemical and/or biological characteristics of the
inhaled material.  Further, the generalizations that led to Table 10-14 allow
comparisons for the consequences of chronic inhalation exposures among these
animal species and humans that might not otherwise be possible.
         TABLE 10-14. AVERAGE ALVEOLAR RETENTION PARAMETERS
           FOR POORLY SOLUBLE PARTICLES INHALED BY SELECTED
                  LABORATORY ANIMAL SPECIES AND HUMANS
Alveolar Retention Parameters"
Species
Mouse
Rat, Syrian hamster
Guinea pig
Monkey, dog, human
P,
0.9
0.9
0.2
0.3
T,
30
25
29
30
P,
0.1
0.1
0.8
0.7
T2
240
210
570
700
^Alveolar burden (fraction of initial deposition) =
                         (-ln2)t/T
  where:
     Pj and P2   = fractions of alveolar burden in fast and slow-clearing components;
     Tj and T2   = retention half-times (days) for Pj and P2; and
             t = time in days after an acute inhalation exposure.
                                         10-138

-------
     The mathematical expressions for fitting curves to data are dependent on the
study duration.  The values for percent initial alveolar burden (% IAB) versus
time in the following table were obtained by simulating alveolar retention of
poorly soluble particles in the rat using the physical clearance rates from
Table 10-14.  Two-component exponential curves were next fit for % IAB versus
time using the model results for days 1 to 150, 1 to 300, and 1 to 730. As
indicated in Table 10-15, the curve fitting parameters for the data for days 1 to
150 agree well with results typically seen in relatively short-term alveolar
clearance studies with rats.
                   TABLE 10-15. PHYSICAL CLEARANCE RATES
Days
1
7
14
28
35
42
49
56
63
70
100
150
200
250
300
400
500
600
730
%IAB P, T, P2 T2
96.96
81.21
66.89
47.00
40.03
34.43
29.87
26.14
23.06
20.49
13.26
7.80 71.6 18.4 29.4 78.3
5.39
4.10
3.30 84.4 22.0 15.6 131
2.36
1.78
1.37
0.99 91.0 25.6 9.0 221
     Physical clearance patterns for alveolar burdens of particles are similar
for guinea pigs, monkeys, dogs, and humans. For these species, about 20 to 30% of
the initial burden of particles clears with a half-time on the order of 1  mo, the
balance clears with a half-time of several hundred days. Mice, Syrian hamsters,
and rats clear about 90% of the deposited
                                         10-139

-------
particles with a half-time of about 1 month and 10% with a half-time greater than
100 days.  The relative division of the alveolar burden between short-term and
long-term clearance represents a significant difference between most rodents
and larger mammals and has considerable impact on long-term patterns for
retention of material acutely inhaled, as well as for accumulation patterns for
materials inhaled in repeated exposures.

10.6.4 Models To Estimate  Retained Dose

     Models have routinely been used to express retained dose in terms of
temporal patterns for alveolar retention of acutely inhaled materials.
Available information for a variety of mammalian species and humans can be  used
to predict deposition patterns in the respiratory tract for inhalable aerosols
with reasonable degrees of accuracy.  Additionally, as indicated above,  alveolar
clearance data for mammalian species commonly used in inhalation studies are
available from numerous experiments that involved small amounts of inhaled
radioactive particles. The amounts of particles inhaled in those studies were
small and can be presumed to result in clearance patterns characteristic of the
species unless radiation damage was a confounding factor, which was probably not
the case except where acute effects were an experimental objective.
     A very important factor in using models to predict retention patterns in
laboratory animals or humans is the dissolution-absorption rate of the inhaled
material. Factors that affect the dissolution of materials or the leaching of
their constituents in physiological  fluids, and the subsequent absorption of
these constituents, are not fully understood. Solubility is known to be
influenced by the surface-to-volume ratio and other surface properties of
particles (Mercer, 1967; Morrow,  1973). The rates at which dissolution and
absorption processes occur are influenced by factors that include chemical
composition of the material. Temperature history of materials is an important
consideration for some metal oxides.  For example, in controlled laboratory
environments, the solubility of oxides usually decreases when the oxides are
produced at high temperatures, which generally results in compact particles
having small surface-to-volume ratios.  It is sometimes possible to accurately
predict dissolution-absorption characteristics of materials based on
physical/chemical considerations.  However, predictions for in vivo
dissolution-absorption rates for most materials, especially if they contain
multivalent cations or anions, should be confirmed experimentally.
                                         10-140

-------
     Phagocytic cells, primarily macrophages, clearly play a role in
dissolution-absorption of particles retained in the respiratory tract
(Kreyling, 1992). Some particles dissolve within the phagosomes due to the
acidic milieu in those organelles (Lundborg et al., 1984, 1985), but the
dissolved material may remain associated with the phagosomes or other organelles
in the macrophage rather than diffuse out of the macrophage to be absorbed and
transported elsewhere (Cuddihy, 1984). Examples of delayed absorption of
presumably soluble inorganic materials are beryllium (Reeves and Vorwald, 1967)
and americium (Mewhinney and Griffith, 1983). This same phenomenon has been
reported for organic materials. For example, covalent binding of benzo(a)pyrene
or metabolites to cellular macromolecules resulted in an increased alveolar
retention time for that compound after inhalation exposures of rats (Medinsky
and Kampcik, 1985). Certain chemical dyes are also retained in the lung
(Medinsky et al., 1986), where they may dissolve and become associated with
lipids or react with other constituents of lung tissue. Understanding these
phenomena and recognizing species similarities and differences are important
for evaluating alveolar retention and clearance processes and interpreting
results of inhalation studies.
     In one study related to the issue of species differences in dissolution-
absorption, Oberdorster et al. (1987) evaluated clearance of 109Cd from the lungs
of rats and monkeys after inhalation of 109Cd-labeled aerosols of CdCl2 and CdO.
The inhaled Cd was cleared 10 times faster from lungs of the rats than from the
lungs of monkeys.  Cadmium in the lungs of mammalian species is  probably bound to
metallothionein, and these differences in rates of Cd clearance appear to be the
result of species differences in metallothionein metabolism. Bailey et al.
(1989) conducted a study that included an interspecies comparison of the
translocation of 57Co from the A region to blood after inhalation of "COjC^. The
results of this multi-species study suggest that mammalian species demonstrate
considerable variability with regard to rates of dissolution of particles
retained in lung tissue, degree of binding of solubilized materials with
constituents of lung tissue, and rates of absorption into the circulatory
system.
     Dissolution-absorption of materials in the respiratory tract is clearly
dependent on the chemical and physical attributes of the material. While it is
possible to predict rates of dissolution-absorption, it is prudent to
experimentally determine this important clearance parameter to understand the
importance of this clearance process for the lung, TLNs,
                                         10-141

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and other body organs that might receive particles or fibers, or their
constituents which enter the circulatory system from the lung.

10.6.4.1  Extrathoracic and Conducting Airways

     Insufficient data are available to adequately model long-term retention of
particles deposited in the conducting airways of any mammalian species.  It is
probable that some particles that deposit in the airways of the head and TB region
during an inhalation exposure are retained for long times and may represent
significant dosimetry concerns.  Additionally, some of the particles that are
cleared from the A region via the mucociliary transport pathway may become
trapped in the TB epithelium during their transit through the airways.
Additional research must be done to provide the information needed to properly
evaluate  retention of particles in conducting airways.
     Based on the results of longitudinal studies of dogs who inhaled promethium
oxide particles, Stuart (1966) concluded that some particles were retained for
relatively long times in the heads.  A  study by Snipes et al. (1983) included
mice, rats, and dogs exposed by inhalation to monodisperse or polydisperse
134Cs-labeled  fused aluminosilicate particles. In all three species, 0.001 to 1%
of the initial internally deposited burden of particles was retained in the head
airways and was removed only by dissolution-absorption. Tissue autoradiography
revealed that  retained particles were in close proximity to the basement
membrane of nasal airway epithelium.  In another study by Snipes  et al. (1988),
3-, 9-, and 15-|im latex microspheres  were inhaled by rats and guinea pigs.  About
1 and 0.1% of all three sizes of microspheres were retained in the head airways of
the rats and guinea pigs, respectively. For rats, the 9- and 15-|im microspheres
cleared with half-times of 23 days; for guinea pigs, microspheres of this size
cleared with half-times of about 9 days. The 3-|im microspheres were cleared from
the head  airways of the rats and guinea pigs with biological half-times of 173 and
346 days, respectively. The smaller particles are apparently more likely to
penetrate the  epithelium and reach long-term retention sites.
     Whaley et al. (1986) studied retention and clearance of radiolabeled, 3-|im
polystyrene latex particles instilled onto the epithelium of the maxillary and
ethmoid turbinates of Beagle dogs. Retention of the particles at both sites
after 30 days  was about 0.1% of the amount
                                         10-142

-------
initially deposited. Autoradiographs of turbinate tissue indicated that the
particles were retained in the epithelial submucosa of both regions.
     It is also generally concluded that most inhaled particles that deposit in
the TB region clear within hours or days. However, results from a number of
studies in recent years challenge this supposition. These studies have
demonstrated that small portions of the particles that deposit in, or are cleared
through, the TB region are retained with half-times on the order of weeks or
months. Patrick and Stirling (1977) noted that about 1% of barium sulfate
particles instilled intratracheally into rats remained in the bronchial tissue
for at least 30 days. In a followup study, Stirling and Patrick (1980) used
autoradiography to demonstrate the temporal retention patterns for some of the
retained 133BaSO4 particles in TB airways.  The particles were retained within
macrophages in the tracheal wall for at least 7 days after intratracheal
instillation of 133BaSO4.  By two h after instillation, some of the particles were
buried in the tracheal wall.  After 24 h, when most of the initial deposition of
particles had cleared, 74% of 133BaSO4 particles located by autoradiography were
in macrophages proximate to the basement membrane. After 7 days, practically all
of the remaining particles were incorporated into the walls of the airways. The
authors did not  determine the mechanisms by which the particles were moved into
the airway epithelium.  It is possible that the particles were phagocytized by
macrophages and transported into the airway epithelium. Another possibility is
direct uptake by epithelial cells of the airways. It is also probable that
intratracheal instillation procedures perturb airway epithelium and influence
the results of these kinds of studies.
     Gore and  Thorne (1977) exposed rats by inhalation to polydisperse aerosols
of UO2. At 2, 4, 7, and 35 days after inhalation of the UOj, autoradiography was
used to determine the locations of particles retained in the TB and A regions.
The authors did not report seeing particles of UO2 retained in the airways, but
did note two phases of clearance. The first phase was associated with a clearance
half-time of 1.4 days, the second phase with a clearance half-time of about  16
days. The faster clearance was presumably associated with particles deposited
on the conducting airways during the inhalation exposure; the longer-term
clearance was associated with clearance of UO2 particles from the A region. In a
separate study,  Gore and Patrick (1978) evaluated the distribution of UO2
particles in the trachea and bronchi of rats for up to 14 days after inhalation of
aerosols similar to those used by Gore
                                         10-143

-------
and Thorne (1977).  Retention of UO2 at airway bifurcations was noted, as was
retention of particles in the trachea.
     In another study, Gore and Patrick (1982) also compared the retention sites
of inhaled UO2 particles and intratracheally instilled barium sulphate
particles. Both types of particles were found in macrophages at sites near the
basement membrane of the airways of the TB region. The macrophages appeared to
have engulfed the particles in the airways, then passed through the airway
epithelium and remained in the vicinity of the basement membrane. About 4% of the
UO2 in lungs of rats was associated with intrapulmonary airways (Gore, 1983;
Patrick, 1983). Watson and Brain  (1979) observed similar results with aerosols
of gold colloid and iron oxide.  Both types of particles were found in bronchial
epithelium, but more of the iron oxide was observed, suggesting a possible
particle size effect, or a relationship between the process of material uptake
and chemical composition of the material. Both types of particles were found in
bronchial epithelial cells, but neither gold nor iron oxide particles were seen
in interstitial macrophages.
     In another inhalation study, Briant and Sanders (1987) exposed rats to 0.7
fj-m AMAD chain-aggregate aerosols of U-Pu. These authors observed retained
particles of U-Pu in the larynx, trachea, carina, and bronchial airways
throughout the course of their 84-day study. The amounts retained varied, but
were at any time approximately 1% of the concurrent alveolar burden.  The
alveolar burden of U-Pu cleared with a biological half-time of 100 days, and the
relative amounts of U-Pu in the airways suggested comparable particle clearance
rates from the airways.  Particles of U-Pu retained in the airways were located in
epithelial cells.
     Stahlhofen et al. (1981, 1986) conducted inhalation studies with humans to
directly assess deposition and retention of poorly soluble particles that
deposit in the TB region by inhalation.  Human subjects inhaled small volumes of
aerosols using procedures that theoretically allowed deposition to occur at
specific depths in the TB region, but not in the A region. Results of those
studies suggested that as much  as 50% of the particles that deposited in the TB
region clear slowly, presumably because they become incorporated into the airway
epithelium.  Smaldone et al. (1988) reported the results from gamma camera
imaging analyses of aerosol retention in normal and diseased human subjects, and
also suggested that particles deposited on central airways of the human lung do
not completely
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clear within 24 h. There have also been a few reports indicating that poorly
soluble particles associated with cigarette smoke are retained in the epithelium
of the tracheobronchial tree of humans (Little et al., 1965; Radford and Martell,
1977; Cohen et al., 1988). The cumulative results of these studies strongly
suggest that a portion of particles that deposit on the conducting airways can be
retained for long periods of time, or indefinitely.
     Long-term retention and clearance patterns for radioactive particles that
deposit in the head airways and TB region must be thoroughly evaluated because of
the implications of this information for respiratory tract dosimetry and risk
assessment (James et al.,  1991; Johnson and Milencoff, 1989; Roy, 1989; ICRP,
1994). Similar concerns exist for non-radioactive particles that might be
cytotoxic or elicit inflammatory, allergic, or immune responses at or near
retention sites in conducting airways.

10.6.4.2  Alveolar Region

     Model projections are possible for the A region using the cumulative
information in the scientific literature relevant to deposition, retention, and
clearance of inhaled particles. Table 10-16 summarizes reasonable
approximations for physical alveolar clearance parameters for six laboratory
animal species. Alveolar clearance curves produced using the parameters in
Table 10-16 agree with curves produced using the parameters in Table 10-14. An
advantage to using the parameters in Table 10-16 is that they separate physical
clearance from the A region into its two components, physical clearance via the
mucociliary clearance pathway to the GI tract and clearance  to TLNs.  To model the
biokinetics of a specific type of particle in the A regions of these laboratory
animal species, the physical clearance parameters in Table 10-16 were used in
conjunction with a dissolution-absorption parameter to derive rates for
effective clearance from the A region.  As explained below, biokinetic modeling
for particles deposited in the A region of humans was done using the new ICRP66
respiratory tract model (ICRP66, 1994).  To model the alveolar biokinetics of a
specific type of particle, the physical clearance parameters in Table 10-16 are
used in conjunction with a dissolution-absorption parameter  to derive rates for
effective clearance from the A region.
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         TABLE 10-16. PHYSICAL CLEARANCE RATES3 FOR MODELING
              ALVEOLAR CLEARANCE OF PARTICLES INHALED BY
                         SELECTED MAMMALIAN SPECIES

                                 Clearance via Mucociliary       Clearance to Thoracic
 Species	Transport Pathway	Lymph Nodes
 Mouseb                           0.023 exp'0'0081 + 0.0013              0.0007 exp'0'51
 Ratb, Syrian hamster0               0.028 exp'0'0" + 0.0018              0.0007 exp'0'51
 Guinea pigb                       0.007 exp'0'031 + 0.0004              0.00004
 Monkeyd, dogb                    0.008 exp'a°22t + 0.0001              0.0002

Traction of existing alveolar burden physically cleared per day.
bAdapted from Snipes (1989)
°Clearance rates assumed to be the same as for rats.
dClearance rates assumed to be the same as for dogs.
10.7  APPLICATION OF DOSIMETRY MODELS TO DOSE-RESPONSE
      ASSESSMENT

     For the purposes of this document an attempt was made to ascertain whether
dosimetry modeling can provide insight into the apparent discrepancies between
the epidemiologic and laboratory animal data, to identify plausible dose metrics
of relevance to the available health
endpoints, and to identify modifying factors that may enhance susceptibility to
inhaled particles.  In order to accomplish these objectives, this section
presents an application of dosimetry modeling to data typically available from
the epidemiologic and laboratory animal studies.  Choice of a dosimetry model for
humans and laboratory animals, respectively, is discussed and these models are
used to simulate deposition and retained doses of various exposures. Different
dose metrics and their relevance to observed health endpoints are also
discussed.
     Application of the chosen dosimetry models to calculate these estimates are
intended to illustrate the potential influence dosimetry may have on estimation
of dose to provide a linkage between the exposure and the available epidemiologic
and toxicologic data.  At present, respiratory tract dosimetry must rely on many
simplifications and empiricisms, but even a somewhat rudimentary effort will
assist in linking dose to effects and in species extrapolations. As more
information on mechanistic determinants of dose, target tissues, and target dose
and tissue interaction relationships become available, the more  complex and
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 realistic the dosimetry construct will become. It is foreseen that choice of
dose metrics will go beyond dependence on average mass or number concentration in
the future as physiologically-based models become available. The human and
laboratory animal models chosen for the simulations represent semi-empirical
and empirical approaches to characterizing the available deposition and
retention data. Default values for key parameters such as ventilation rate  and
body weight have been used in these simulation exercises. Disagreement with the
limited published deposition and retention data is considered to be within the
known variability among these parameters as well as biological detectability of
the current state of measurement. As with any data-driven process, when
additional data become available, the model structures can be reviewed and
revised as appropriate. Additional experimental measurements would provide
more information to strengthen the predictions and provide better description of
intersubject and interspecies variability.

10.7.1  General Considerations for Extrapolation Modeling

     Major factors that affect the disposition (deposition, uptake,
distribution, metabolism, and elimination) of inhaled particles include the
physicochemical properties of the particles (e.g., particle diameter,
distribution, hygroscopicity) and anatomic (e.g., upper respiratory tract
architecture, regional surface areas, airway diameters, airway lengths,
branching patterns) and physiologic (e.g., ventilation rates, clearance
mechanisms) parameters of individual mammalian species. The relative
contribution of each of these factors is a dynamic relationship. Further, the
relative contribution of these determinants is also influenced by exposure
conditions such as concentration and duration. A comprehensive  description of
the exposure-dose-response continuum is desired for accurate extrapolation.
Therefore, a dosimetry model should incorporate all of the various deterministic
factors into a computational structure. Clearly, many advances in the
understanding and quantification of the  mechanistic determinants of particle
disposition, toxicant-target interactions, and tissue responses (including
species sensitivity) are required before an overall model of pathogenesis can be
developed for a specific aerosol. Such data exist to varying degrees, however,
and may be incorporated into less comprehensive models that nevertheless are
useful in describing delivered doses or in some cases, target tissue
interactions.
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10.7.1.1  Model Structure and Parameterization

     Data on the mechanistic determinants of particle disposition, toxicant-
target interactions, and tissue responses to incorporate into a model vary in
degree of availability for chemicals and animal  species.  An ideal theoretical
mathematical model to describe particle deposition would require detailed
information on all of the influential parameters  (e.g., respiratory rates, exact
airflow patterns, complete measurement of the branching structure of the
respiratory tract, alveolar region mechanics) across different humans or across
various laboratory species of interest. An empirical model (i.e., a system of
equations fit to experimental data) is an alternative approach. A third
approach, the hybrid approach adopted in ICRP66, is to fit a system of empirical
equations to the results of theoretical modeling. Depending on the relative
importance of these various mechanistic determinants, models with less detail
may be used to adequately describe differences in respiratory dosimetry for the
purposes of extrapolation.
     An understanding of the bases for model structures also allows development
of a framework for the evaluation of whether one available model structure may be
considered optimal relative to another.  A model structure might be considered
more appropriate than another for extrapolation when default assumptions or
parameters are replaced by more detailed, biologically-motivated descriptions
or actual data, respectively. For example, a model could be preferred if it
incorporates more chemical or species-specific information or if it accounts for
more mechanistic determinants.  Empirical models may differ in the quality or
appropriateness of the data used to fit the descriptive equations. These
considerations are summarized in Table 10-17.
     The sensitivity of the model to differences in structure may be gauged by
their relative importance in describing the response function for a given
chemical. For example,  a model that incorporates many parameters may not be any
better at describing ("fitting") limited response data than a simpler model.

10.7.1.2  Intraspecies Variability

     There are essentially three areas of concern in assessing the quality of
epidemiologic or toxicity data. These involve the design and methodological
approaches for (1) exposure
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            TABLE 10-17. HIERARCHY OF MODEL STRUCTURES FOR
                        DOSIMETRY AND EXTRAPOLATION
Optimal model structure
       Structure describes all significant mechanistic determinants of
       particle disposition, toxicant-target interaction, and tissue response
       Uses chemical-specific and species-specific parameters
       Dose metric described at level of detail commensurate with the
       epidemiologic or toxicity data
Default model structure
       Limited or default description of mechanistic determinants of particle
       disposition, toxicant-target interaction, and tissue response
       Uses categorical or default values for chemical and species parameters
	Dose metric at generic level of detail	

Source:  Adapted from U.S. Environmental Protection Agency (1994); Jarabek (1995).
measures, (2) effect measures, and (3) the control of covariables and
confounding variables. Although these topics are discussed in detail in other
chapters, it is also important to consider these concerns when evaluating
potential dosimetry models for extrapolation of epidemiologic or toxicity data.
For example, although the epidemiologic investigations attempt to relate an
exposure to a given health effect, the way the exposure is characterized may
influence the choice of an appropriate dosimetry model.  Characterization of a
particular health effect in a human population may include pre-existing
pathologic conditions (e.g., lung disease) that may alter inhalation dosimetry
and have implications for model choice.  The broad genetic variation of the human
population in processes related to chemical disposition and tissue response
(e.g., age, gender, disease status) may cause individual differences in
sensitivity to inhaled aerosols. Sensitivity analyses could be used to
determine ranges of dosimetry model outputs for specific ranges of input for
various parameters (e.g., range in ventilation rate due to gender).

10.7.1.3  Extrapolation of Laboratory Animal Data to Humans

     Toxicological data in laboratory animals typically can aid the
interpretation of human clinical and epidemiological data because they provide
concentration- and duration-response information on a fuller array of effects
and exposures than can be evaluated in humans.
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However, historically, use of laboratory animal toxicological data has been
limited because of difficulties in quantitative extrapolation to humans. The
various species used in inhalation toxicology studies do not receive identical
doses in comparable respiratory tract regions (ET, TB, A) when exposed to the
same aerosol (same composition, //g/m3, MMAD, og).  Such interspecies differences
are important because the adverse toxic effect is likely more related to the
quantitative pattern of deposition within the respiratory tract than to the
exposure; this pattern determines not only the initial respiratory tract tissue
dose but also the specific pathways by which the inhaled particles are cleared
and redistributed.
     Both qualitative and  quantitative extrapolation of laboratory animal data
to humans are of interest.  Qualitative extrapolation refers to the "class" of
the effects. For example, if the function of rabbit alveolar macrophages is
depressed by sulfuric acid, will it also be depressed in humans, albeit at an
unknown exposure? This type of extrapolation is limited to known homologous
effects. For example, given the similarities in human and laboratory animal
alveolar macrophages, and likely toxicity mechanisms, the qualitative
extrapolation is reasonable. However, in some  cases, the homology is not
understood adequately. For example, what is the laboratory animal model
homology to the mortality effects observed in the epidemiological studies?
Would PM exposures of aged animals or animal models of respiratory or cardiac
disease states more closely mimic the mortality observed among the elderly or
those with pre-existing cardiopulmonary disease?  Several hypotheses exist, but
at present there is inadequate evidence for concensus.
     Once a qualitative extrapolation has been justified, a quantitative
extrapolation can be initiated.  In order for the laboratory animal data to be
useful to the risk assessment of PM, interspecies extrapolation should account
for differences in  particle dosimetry and species sensitivity.  Dosimetry, here,
is used broadly to represent the effective dose to target site which may be some
complex combination of regional delivered or retained particle burdens.  Given
the identical exposure, these particle burdens may be different in different
species. Even if there is a comprehensive understanding of dose, there still
needs to be an understanding of species differences in sensitivity to that dose.
For example, perhaps one species has more efficient repair or chemical defense
mechanisms than  another, making that one species less sensitive to a given dose.
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10.7.2  Dosimetry  Model Selection

     Available deposition models for humans and laboratory animals were
presented in Section 10.5.1 and 10.5.2, respectively. Clearance models,
required to calculate retained doses, were discussed in Section 10.6. This
section focuses on modeling efforts intended to present informative and
comparative data relevant to lung burdens that result in humans and laboratory
animals as a consequence of acute and chronic inhalation exposures.  The
information and predictions are intended to illustrate examples of approaches to
lung dosimetry, metrics of deposited and retained particle burdens, and species
similarities and differences that influence exposure and dose metrics.

10.7.2.1  Human Model

     The theoretically-based, semi-empirical lung deposition model of the
International Commission on Radiological Protection (ICRP66, 1994) was chosen
and used to model the dosimetry of inhaled particles in humans (Sections 10.7.4
and 10.7.5 below).  A distinct advantage of this model is that it incorporates
both deposition and clearance mechansisms so that both deposited and retained
particles burdens can be calculated. LUDEP® software version 1.1 was used to run
the ICRP66 1994 model simulations (National Radiological Protection Board,
1994).
     Although the highly-detailed theoretical models described in  Section 10.5
might allow prediction to more localized regions of the respiratory tract,
information about the dimensions of the numerous gross and microscopic
structures of the respiratory tract are extremely limited.  Human experimental
data are still available only for gross regional deposition, for the adult
Caucasian male, and for a limited range of particle size (dae from about 1 //m to  10
Aim), making validation of the most detailed theoretical models impossible at the
present time.  For these reasons, the analysis of respiratory tract deposition by
gross anatomical region adopted by the ICRP was viewed as advantageous. The
parametric analysis of regional lung desposition,  developed by Rudolf et al.
(1986, 1990) and described in Section 10.5, was used to represent the results of
complex theoretical modeling by relatively  simple algebraic approximations. A
theoretical model of gas transport and particle deposition (Egan et al., 1989)
was applied to apportion particle deposition among the lower respiratory tract
regions (BB, bb, Al —  see Section 10.6), and to quantify the effects of lung
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size and breathing rate. The structure of the respiratory tract is represented
explicitly by a morphometric anatomical model as described in Table 10-3 and
Figure 10-4. The 1994 ICRP model reasonably describes the experimental data
relating total thoracic deposition to particle size and breathing behavior.  The
model also succeeds in simulating the variation of regional deposition with
particle size and breathing pattern that was inferred by Stahlhofen et al.
(1980,1983) from their measurements of thoracic depostion and retention. In
common with earlier theoretical models of Yeh and Schum (1980) and Yu and Diu
(1982b), the 1994 ICRP model predicts less thoracic deposition for particles in
the range of dae from 1 //m to 5 //m than the median values reported by Lippmann
(1977) and Chan and Lippmann (1980). These data are crucial since they represent
the largest group of experimental subjects  studied to date. However, as
described in Appendix 10A, according to the analysis in ICRP66 (1994), there is
direct experimental evidence (Gebhart et al., 1988) that particulate material
used in the New York University (NYU) studies exhibits a degree of hygroscopic
growth in the respiratory tract.  When allowance is made in the deposition
calculation for these supplementary data, the key set of experimental
measurements from NYU is also found to  support the 1994 ICRP66 deposition model.
The problem of time-dependent functions to describe clearance from the various
regions in the respiratory tract was overcome by using a combination of
compartments with constant rates of clearance. Clearance from each region by
three routes (absorption into blood, transport to GI tract, and transport to
lymphatics) is accomplished by pathways with assigned rate constants.
     Mathematical models such as the ICRP66 model do not provide site-specific
dosimetry at the level of individual lung lobes, but the objective of this
exercise is to provide useful insights about dose metrics such as average
concentrations and average numbers of particles per unit area of respiratory
regions. The ICRP model provides average concentration or average number values
on a regional basis, i.e., mass or number deposited or retained in the ET, TB, or A
regions. An important aspect of modeling and dosimetry is to relate the modeling
effort to the level or accuracy of measurements. Neither the available
deposition and clearance data nor the response data such as the mortality effects
provide a level of detail that support more  physiologically-based parameters and
compartments.
     The available deposition data were from radioactive tracer studies, in
which accurate measurements were obtained at very low particulate mass burdens.
As such, the particle
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 mass deposited in the respiratory tract was negligible, and did not introduce
the possibility of experimental artifact due to particle overload phenomena.
Biphasic or multiphasic clearance processes do not necessarily imply specific
physiologic associations.  The ICRP model makes use of convenient mathematical
approaches to vary the rates of specific processes involved in clearance. The
time dependence of clearance processes (both physical and dissolution-
absorption) may well be determined by a decrease in the availability of the
particles, e.g., because of (1) burial of the particles in the interstitial
tissue, (2) sequestering in macrophages in areas that have low probability of
physical clearance, or (3)  altered dissolution-absorption rates related to
physical or chemical  changes in the particle with time.
     Both the NCRP and ICRP had the benefit of contributions from respected
investigators in respiratory tract toxicology and biomedical aerosol research.
Similar mathematical assessments were arrived at by both commissions, although
detailed calculations for specific radionuclides can be different. Comparisons
between the models presented earlier and in Appendix 10A show that the behavior
of the models are quite comparable, that is, the predicted deposition fraction
for a given particle size is similar if the models use the same ventilation
parameters as input.   In fact, in order to ensure a uniform course of action that
provides a coherent and consistent international approach, the NCRP recommends
adoption of the ICRP 1994 model for modeling the effects of exposure for
radiation workers and the public (e.g., for computing reference levels of annual
intake and derived reference air concentrations corresponding to recommended
dose limits).
      Some of the human  parameter values used in the ICRP66 model (ICRP66, 1994)
and the LUDEP® software are provided in Appendix 10B. Surface area values were
derived by the ICRP based on the morphometry provided previously in Table 10-3.
LUDEP® allows simulations of either normal augmenter or mouth breather adult
male humans. The proportion of nasal airflow for these two types of breathing at
different levels of activity previously provided in Figure 10-27 and Table 10-11
in Section 10.5. The levels of activity to apportion nasal airflow are the same
as those used to construct the three different activity patterns (general
population; worker, light work; and worker, heavy work) shown in Table 10B-1.
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10.7.2.2  Laboratory Animal Model

     The particle dosimetry model of Menache et al. (1996) descirbed in
Section 10.5.2 was chosen to calculate deposited dose estimates for rats as an
illustration of dosimetric adjustment for laboratory animal species.
Attributes of the model that were viewed as especially advantageous for this
exercise included the detailed measurements made in all tissues that served as
the source of deposition data (Raabe et al.,  1988); that the deposition data were
available for unanesthetized, freely breathing animals; and that inhalability
was accounted for and used to adjust the logistic function to describe deposition
efficiency.  This model represents a revised version of previous models (Miller
et al., 1988;  Jarabek et al., 1989,  1990) that have been useful to develop
inhalation reference concentration (RfC) estimates for dose-response
assessment of air toxics (U.S. EPA, 1994).  The same approach will be used to
calculate deposited doses as discussed below in greater detail (Section 10.7.4).
The range for application of the Menache et al. (1996) model to interspecies
extrapolation was restricted to 1 to 4 //m MMAD because this is the range that had
the most  deposition data for model development and it is also the range most
likely of use for evaluating the available inhalation toxicology
investigations.
     For calculation of retained doses, the  simulation model based on Pritsker
(1974) and described in Section 10.6 was used. This clearance model was applied
to output of the Menache et al. (1996) deposition model in order to calculate
retained dose as discussed below in Section 10.7.5.
     The broad spectrum of mammals used in inhalation toxicology research have
body weights ranging upwards from a few grams to tens of kg; these mammals also
exhibit a  broad range of respiratory parameters.  Table 10B-2 in Appendix  10B
lists body weights, lung weights, respiratory minute ventilation and
respiratory tract region surface areas for six laboratory animal species. Lung
weights and ventilation parameters are important variables for inhalation
toxicology because these parameters dictate the amounts of inhaled materials
potentially deposited in the lung, as well as the specific alveolar burdens (mass
of particles/g lung) that will result from inhalation exposures.  The inverse
relationship between body size and metabolic rate is demonstrated by the values
for respiratory minute ventilation and body weight or lung tissue volume. For
example, liters of air inhaled per minute per gram of lung is about 20 times
higher for resting mice than for resting humans, which is an important
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factor to consider relative to potential amounts of aerosol deposited in the
respiratory tract per unit time during inhalation exposures.

10.7.3 Choice of Dose Metrics

     As discussed in the preceding sections, inhaled dose, especially to
different regions or locations within the respiratory tract, is not necessarily
related linearly to the exposure concentration.  For this reason, an internal
dose to characterize the dose-response relationship of PM is desired. In
general, the objective is to provide a metric that is mechanistically-motivated
by the observed response. Unfortunately, at this  point in time, the crucial
definition and determination of the relevant dose has not been accomplished for
PM. Mechanistic determinants of the observed health effects have not been
adequately elucidated.  The health effects data discussed later (Chapter 11, 12,
and 13) include effects that could be characterized as either "acute" (e.g.,
effects associated with mortality) or "chronic" (e.g., morbidity or laboratory
animal pathology after two-year bioassays). Dose may be accurately described by
particle deposition alone  if the particles exert their primary action on the
surface contacted (Dahl et al.,  1991), i.e., deposited dose may be an appropriate
metric for acute effects. For longer-term effects, the initially deposited dose
may not be as decisive a metric since particles clear at varying rates from
different lung compartments. To characterize these effects, a retained dose
that accounts for differences between deposition  and clearance is more
appropriate.
     Conventionally and conveniently, doses usually are expressed in  terms of
particle mass (gravimetric dose).  However, when different types of particles
are compared, doses may be more appropriately expressed as particle volume,
particle surface area, or numbers of particles,  depending on the effect in
question (Oberdorster et al., 1994). For example, the retardation of alveolar
macrophage-mediated clearance  due to particle overload appears to be  better
correlated with phagocytized particle volume rather than mass (Morrow, 1988).
As shown in Figures 10-2 and 10-3, the smaller size fractions  of aerosols are
associated with greater amounts of particles when characterized by surface area
or by number rather than by mass. That is, concentrations in this size fraction
are very small by mass but extremely high by number. The need to consider this is
accentuated when the high rate of deposition of small particles in the lower
respiratory tract (TB and A regions), the putative target for the
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mortality and morbidity effects of PM exposures, is also taken into account.
Anderson et al. (1990) have shown that the deposition of ultrafine particles in
patients with COPD is greater than in healthy subjects.
     Miller et al. (1995) recently investigated considerations for both
intraspecies and interspecies dosimetry. Using a multipath dosimetric model,
simulations for different particle sizes (0.1, 1, and 5 //m) were performed and
different dose metrics calculated for the rat and both normal and compromised
human lung status. A summary table of this exercise is provided as Table 10-18.
These simulations support the conclusion that particle number per various
anatomical normalizing factors indicate a need to examine the role of fine
particles in eliciting acute morbidity and mortality, particularly in patients
with compromised lung status (Miller et al., 1995).
     For the present document, average deposited particle mass burden in each
region of the respiratory tract has been selected as the dose metric for "acute"
effects in both humans and laboratory animals. Average retained particle mass
burden in  each region for humans and in the lower respiratory tract for
laboratory animals has been selected as the dose metric for "chronic" effects.
These choices were dictated by the selection of the dosimetry models and the
availability of anatomical and morphometric information.
     Because mass may not be the appropriate metric, especially to characterize
effects of the fine fraction, average particle number burdens and the number of
particles deposited per day were calculated in addition for humans. An attempt
to address the variability due to differences in the population was made by
calculating deposited particle mass burdens in each  region for eight different
demographic groups that included a range of ages and one selected for
cardiopulmonary symptoms.

10.7.3.1 Interspecies Extrapolation

     In order to gain insight on species similarities  and differences that may
account for the apparent discrepancies between epidemiologic and laboratory
animal data, interspecies adjustments  to the observed exposure levels must be
made for the dose metrics selected for "acute"  and "chronic"  effects. This
section discusses an approach to calculate human equivalent concentration (HEC)
estimates based on the observed laboratory animal toxicological data.
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TABLE 10-18.  SPECIES COMPARISONS BY MILLER ET AL. (1995) OF VARIOUS DOSE METRICS AS A
            FUNCTION OF PARTICLE SIZE FOR 24-HOUR EXPOSURES TO 150 ,ug/m3
Particle Dose Metric
Size
Mass/unit area
0.1 (j,m No. deposited
No./unit surface
area
No./ventilatory
unit
No./alveolusc

No./macrophagec
o
^ 1 (j,m Mass/unit area
~° No. deposited
No./unit surface
area
No./ventilatory
unit
No./alveolusc
No./macrophagec
5 (j,m Mass/unit area
No. deposited
No./unit surface
area
No./ventilatory
unit
No./alveolusc
Rat
3.74.3.76 x 10
1.2 x IO10
7.1 x io6

4.9 x IO6

303-598

262-399
1.1-1.2 x 10
3.5 x 10
2,130

1,470

0.12-0.18
0.08-0.12
2.8-4.4 x 10
7.1 x 10
4

3

0.0002
Human
a Normal
5.0 x -ft)'4
5.9 x IO11
9.5 x IO5

1.8 x IO7

1,190-
1,930
100-61
2.8 x 1Q-4
3.3" x IO6
532

9,910

0.7-1.1
0.06-0.09
9.1 x io4
8.5 x IO6
14

260

0.02-0.03
Lung Status
Compromised
NCd
4.3 x IO11
2.8 x IO6

5.3 x IO7

3,570-5,790

298-482
NCd -3
2.4 x IO8
1,590

29,700

2.0-3.3
0.2-0.3
NCd -4
6.4 x IO6
42

780

0.05-0.09
Ratio:
Normal
0.13
49
0.1

4

2-5

0.3-0.6
0.23-0.25
92
0.3

7

4-9
0.5-1.2
2.09-3.23
1,195
3.2

88

49-120
Human/Rat
Compromised
NC
37
0.4

11

6-15

0.8-1.8
NC
69
0.8

20

11-28
1.4-3.5
NC
897
9.7

263

145-359

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     A HEC would be calculated by


                       HEC (//g/m3) = NOAEL[ADJ] (//g/m3) x DAFr,                 (10-48)
where the NOAEL[ADJ] is the no-observed-adverse-effect level (or other effect
level) of the laboratory animal study (this level, if from an intermittent
exposure regimen, is often adjusted for the number of hours per day and days per
week (#/24 x #/7) in order to model a continuous exposure) and DAFr is a
dosimetric adjustment factor for a specific respiratory tract region, r (ET, TB,
A). The DAFr is either the regional deposited dose ratio (RDDRr) for "acute"
effects of deposited particles or the regional gas dose ratio (RGDRj.) for
"chronic" effects of retained particles.  The DAFr is a multiplicative factor
that represents the laboratory animal to human ratio of a specific inhaled
particle burden. The HEC is expected to be associated with the same delivered
particle burden to the observed target tissue as in the laboratory animal
species. A DAFr above the value of 1.0 indicates that the human receives a
relatively smaller deposited or retained particle burden than the particular
laboratory animal species.  Values of the DAFr below 1.0 indicate that the human
receives a relatively larger deposited or retained particle burden than the
laboratory animal species, and application of the DAFr would adjust the
resultant HEC lower than the laboratory animal exposure level.
     For deposited particle burdens, regional deposited dose (RDDr) can be
calculated as


               RDDr = 10 3 x q  x VE x  Fr,                                     (10-49)

where:
    RDDr =  dose deposited in region r (//g/min),
    Q     =  concentration (//g/m3),
    VE    =  minute ventilation (L/min), and
    Fr     =  fractional deposition in region r.

     If the RDD in  laboratory animals is expressed relative to humans, the
resultant regional deposited dose ratio  (RDDR,.) can be used as the DAFr in
Equation 10-48 to adjust an inhalation particulate exposure in a laboratory
species to a predicted HEC that would be
                                         10-158

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expected to be associated with the same particle burden delivered to the rth
region of the respiratory tract. The RDDR,. can be calculated as a series of
ratios
DDR, =             x                       x       x                             no.50)
        (10 3 x q)H   (Normalizing Factor)A   (y^   (Fr)H
where the normalizing factor can be selected based on consideration of the
mechanism of action. Because poorly soluble particles deposit along the surface
of the respiratory tract, the surface area of an affected respiratory tract
region (e.g., TB or A region) could be used as the normalizing factor.  For the
purposes of calculating the RDDR,., the exposure concentration for the laboratory
animal (A) and human (H) are assumed to be the same because it is assumed that the
observed effect in the laboratory animal is relevant to human health risk.  The
RDDR,. is used as a factor to adjust for interspecies differences in delivered
dose under the same exposure scenario. The first term in Equation 10-50,
therefore, equals one and will not be discussed further.  The last term, the ratio
of deposition fractions in a given respiratory region, (Fr), is calculated using
the respective human and laboratory animal dosimetry models.
     Because the ICRP66 model utilizes an activity pattern, Equation 10-50 must
be modified to account for the fraction of time spent at each different
ventilation rate, corresponding to each different activity levels, as


RDDRr    = - - -
       [ACT1
              tmxVF   xF   +tr91xVF   xFr  +...+tnlxVp
              W   *%[!]   rH[l]  L4   UH&]   rH[2]      LnJ    ^HM
where t[;] is the fractional time spent breathing minute volume [i],
                '[i]  +t[2] +-+tw =1-  ^d                                       (10-52)
              (Normalizing Factor)H
              ^	e	^ x VDF x FT  ,                                 ,,ne^
              (Normalizing Factor).       EA    IA                                  (10-53)
                                         10-159

-------
where VDg^ js a ^a[\y average ventilation rate (L/min x 1440 min/day).  It should
be noted that the human denominator is the fractional deposition value output
from the ICRP model simulations using the LUDEP® software using an activity
pattern.
     Although clearance is dependent on the site of initial deposition,
calculation of retained dose is probably more appropriate for assessing chronic
heatlh effects. Different normalizing factors such as retained mass per region,
retained mass  per surface area, or retained mass per other available
morphometric information may be worthwhile to explore.  The regional retained
dose ratio (RRDRj.) for interspecies dosimetric adjustment is calculated as a
series of five ratios

                   (lo3xCi)A    (Normalizing Factor)H    (VE)A     (Fr)A     (AIt)A
                   	 x 	  x 	  x 	 x 	
                   (10 3xCi)H    (Normalizing Factor)A    (VE)R    (Fr)H)    (AIt)H


                                                                                   (10-54)
where:

RRDR,. = relative //g of particles retained in region (r),
Ci = exposure atmosphere concentration (//g/m3),
Normalizing Factor = lung weight (g),
VE = minute ventilation (L/min),
Fr = fractional aerosol deposition in region r, and
(AL) = relative accumulated alveolar interstitial  burden of particles as a
function of time from the start of a chronic exposure.
     Again, since the ICRP66 model allows simulation of an activity pattern,
Equation 10-54 must be adjusted to account for  the fraction of time spent at each
different ventilation rate corresponding to different activity levels so that


          RRDR
                LI
                [ACI1    tm x VF   x Fr   x (AL)    x tr91xVF   x Fr    x (AL)
                        L1J     EHPJ     rH[1]    v   * Hl     L4   HHTO     rH[2]       l
       H[l]      l H[l]    LZJ   ^2]    rH[2]      l H[2]


+ ... + trnl  x Vp   x (AL)
        W     Ejj[n]    v   t'H[n]

                                                   (10-55)
                                          10-160

-------
where t [;] is the fractional time spent breathing at minute ventilation [i],

                                                                                   (10-56)
        (NormalizingFactorr)

   a =  ™	r •   P  t  ^  x (V°E)A x (Fr)A x  (AIt)A '
        (NonnalizingFactorr)
                           A
and (VDE^ js a ^aiiy average ventilation rate (L/min x 1440 min/day).
     The relative accumulated alveolar interstitial burden of particles as a
function of time from the start of a chronic exposure must be calculated for
specific exposure scenarios to account for species differences in clearance,  as
well as the dissolution-absorption characteristics of the inhaled particles.
This ratio is not a constant and must be calculated for the chronic exposure time
of interest.  Physical clearance functions and dissolution-absorption rates for
particles deposited in the A region are used to integrate daily deposition and
clearance over the chronic exposure time period of interest. The equations for
laboratory animals are derived using the information in Table 10-16. Physical
clearance parameters for humans are in the ICRP model  (ICRP66, 1994) and the
calculation of A burden for humans can be made using LUDEP®.
     Calculating these ratios (either deposited or retained) depends on particle
diameter (MMAD) and distribution (og) but not on aerosol concentration, i.e., it
assumes no altered deposition or clearance due to exposure concentration or
chemical-specific toxicity.
     The calculation of the DAFr currently uses point estimates for all the terms
used to construct the ratios, that is, a default VE for each species, a default
regional surface area or lung weight for the normalizing factor, and an estimate
of fractional deposition or retained particle burden.  These  single values are
assumed to be representative of the average value of that term for a member of the
laboratory animal species or human population. As discussed in the previous
sections of this chapter,  there are many sources of intraspecies variability
that contribute to the range of responses observed to a given external exposure
to an inhaled toxicant.  Host factors may affect both the delivered dose of the
toxicant to the target tissue as well as the sensitivity of that tissue to
interaction with the toxicant. The procedures described in  this interspecies
extrapolation section could provide some limited capability to
                                          10-161

-------
examine the effects of population variability on the DAFr by changing the default
VE and surface areas or lung weights in an iterative fashion. However, because
of correlations between VE, surface area, and lung weight, such changes should
be made with caution. Confidence intervals were provided on the parameters for
the deposition efficiency equations. Iterative computational procedures could
be used to generate evelopes of regional fractional deposition that could be used
with distributions of VE, surface areas, and lung weights to provide ranges of
DAFr estimates.  Actual implementation of this procedure is not straightforward
due to the complex nature of the correlation structures.  Future versions of the
deposition and clearance models used to calculate the laboratory animal species
values could estimate distributions that reflect the range of available data for
key parameters.

10.7.4  Choice of Exposure Metrics

10.7.4.1  Human Exposure Data

     Ambient exposure data provided elsewhere in Chapter 3 of this document were
selected to represent typical human exposures.  Three different aerosols were
selected as presented in Appendix IOC.  As discussed in Chapter 3, it is not known
at this time whether the intermodal mode for the trimodal aerosols is real or
whether it is an artifact  of sampling procedures.
     The first is the trimodal aerosol shown in Figure 10C-1.  Table 10C-1  shows
the upper size cut (in //m) for various particle size intervals based on the
distribution of particle count, surface area, mass, or aerodynamic diameter
(dae).  Recall from Section 10.2 that the 50% size cut for each of these diameters
would be the respective median diameter of the distribution, i.e., the 50% size-
cut diameter of the dae is the MMAD.  Table 10C-2a,b,c shows the particle number,
surface, area, and mass  distribution, respectively, for the aerosol from Figure
10C-1.  The distribution of particle mass in Table 10C-2c was used as input to the
human dosimetry (ICRP66, 1994) model to estimate total particle mass deposition.
     The two trimodal  aerosols depicted in Figure 10C-2, panel (a) and (b) for
Philadelphia and Phoenix respectively, were also chosen and treated similarly.
Table 10C-3 shows the  upper size cut (in //m) for various particle size intervals
from the Philadelphia aerosol (Panel a), based on the distribution of particle
count, surface area, mass, or aerodynamic diameter (dae).  Table 10C-4a,b,c  shows
the particle number, surface area, and mass
                                         10-162

-------
distribution, respectively, from Figure 10C-2(a).  The distribution of particle
mass in Table 10C-4c was used as input to the human dosimetry model (ICRP, 1994)
to estimate total particle mass deposition. Tables 10C-5 and 10-C6a,b,c are
analogous to Tables 10-C3 and 10C-4a,b,c but show the data for Phoenix (Figure
10C-2b).

10.7.4.2 Laboratory Animal Data

     As noted previously, the range of application for the Menache et al. (1996)
model was limited to that typically used in laboratory animal studies that are
the basis of the toxicity data in Chapter 11.  For calculation of deposited doses,
fractional deposition was  estimated for a range of particle diameters (dae) and
two distributions (og), one representing a relatively monodisperse  (og = 1.3) and
the other a polydisperse (og = 2.4) aerosol. Deposited doses for two different
particle diameters and distributions were then used in clearance models to
calculate retained doses (see  Section 10.7.5).

10.7.5 Deposited Dose Estimations

     The respective models discussed in Section 10.7.1 were used to estimate
deposition  in each of the respiratory tract regions. Note that the ICRP66 human
model divides the ET region  into compartments, ETX and ET2. The ICRP66 model also
divides the TB region into two compartments, the bronchi (BB) and bronchiole
(bb). The alveolar interstitial (AI)  compartment is equivalent to the A region.
When compared to the laboratory animal data, deposition fractions for ETl and ET2
were summed to calculate ET deposition. Likewise, the BB and bb deposition
fractions were summed to calculate the TB fraction.

10.7.5.1  Human Estimates

     Tables 10-19 through 10-24 present the regional deposition fractions (% deposition) and

regional deposited particle mass (//g) for each of the three ambient human exposure aerosols

depicted in Figures 10C-1, 10C-2a (Philadelphia), and 10C-2b (Phoenix). Data are shown for

normal augmenters (Tables 10-19, 10-21, and 10-23) versus mouth breathers (Tables  10-20,

10-22, and  10-24) for three different activity patterns.
                                         10-163

-------
TABIi;iO-19.DAILYM4SSDEPOSmONOFPARll
-------
o
ON
TABI^lOmDAILYMASSDEPOSmONOFPARTKXESraOMAEROSOLDEF^
"MOUTH BREATHER" ADULT MALE HUMANS EXPOSED
TO A PARTICLE MASS CONCENTRATION OF 50 jig/m3
Contribution to Total Deposited Particle Mass from Each Aerosol Modea
Activity Pattern
General
population0




Workers, light
workd




Workers, heavy
work6




Region of
Respiratory Tract
ETj
ET2
BB
bb
AI
Total
ET2
BB
bb
AI
Total
ET,
ET2
BB
bb
AI
Total
Nuclei
Percent
Deposited11
0.5
1.1
0.4
2.4
7.2
11.6
0.5
1.1
0.4
2.3
7.4
11.6
0.5
1.0
0.3
2.2
7.5
11.6
Mode
Mass of
Particles (|ig)
5
11
4
24
71
116
6
12
4
26
84
133
6
14
4
29
101
155
Accumulation Mode
Percent
Deposition
0.3
0.5
0.2
1.1
4.2
6.3
0.3
0.5
0.2
1.0
4.1
6.1
0.3
0.5
0.2
0.9
4.1
5.9
Mass of
Particles (|ig)
3
5
2
11
42
63
3
6
2
11
47
70
4
7
2
12
54
79
Coarse
Percent
Deposition
7.3
16.2
4.2
2.1
6.2
36.0
6.8
16.8
4.8
2.1
5.8
36.3
6.4
17.2
5.4
2.0
5.4
36.5
Mode
Mass of
Particles (|ig)
72
162
42
21
62
358
78
192
55
24
66
415
86
230
72
27
73
488
     TSTuclei mode MMAD = 0.0169 (jm, og = 1.6, density = 1.4 g/cm3, 15.6% of the aerosol mass; accumulation mode MMAD = 0.180 (jm, og = 1.8,
      density = 1.2 g/cm3, 38.7% of the aerosol mass; coarse mode MMAD = 5.95 (jm, og = 1.87, density = 2.2 g/cm3, 45.7% of the aerosol mass
      (see Tables 10C-1 and  10C-2c).
     ''Expressed as a percentage of the total mass of particles in the volume of ambient air inhaled.
     'Average for 24 h, as derived from ICRP-66 (1994): for 33.3%  sleep, 33.3% sitting, and 33.3% light exercise.  (See Table 10B-1).
     dAverage for 24 h, as derived from ICRP-66 (1994): for 33.3%  sleep, 27.1% sitting, and 35.4% light exercise, 4.2% heavy exercise. (See Table
     10B-1).
     'Average for 24 h, as derived from ICRP-66 (1994): for 33.3%  sleep, 16.7% sitting, and 41.7% light exercise, 8.3% heavy exercise. (See Table
     10B-1).

-------
      TABLE 10-21.  DAILY MASS DEPOSITION OF PARTICLES FROM PHILADELPHIA AEROSOL DEFINED IN
       FIGURE 10C-2(a) IN THE RESPIRATORY TRACT OF "NORMAL AUGMENTER" ADULT MALE HUMANS
                             EXPOSED TO A PARTICLE MASS CONCENTRATION OF 50
Contribution to Total Deposited Particle Mass from Each Aerosol Mode3
Accumulation Mode
Activity Pattern
General
population0




Workers, light
work4
o
Oi

Workers, heavy
work6




Region of
Respiratory Tract
ETj
ET2
BB
bb
AI
Total
ETj
ET2
BB
bb
AI
Total
ETj
ET2
BB
bb
AI
Total
Percent
Deposited11
2.0
1.9
0.2
0.7
3.7
8.5
1.9
1.9
0.2
0.6
3.6
8.3
1.9
2.0
0.2
0.6
3.6
8.3
Mass of
Particles (|ig)
19
19
2
7
37
84
22
22
2
7
42
95
26
26
3
8
48
111
Intermodal
Percent
Deposition
1.9
2.6
0.2
0.2
1.1
6.0
1.8
2.6
0.2
0.2
1.1
5.9
1.8
2.6
0.3
0.2
1.1
6.0
Mode
Mass of
Particles (|ig)
19
26
2
2
11
60
21
30
3
2
13
68
24
35
4
2
14
80
Coarse
Percent
Deposition
13.0
13.4
0.2
0.1
0.1
26.8
12.2
14.2
0.3
0.1
0.1
26.8
11.6
14.7
0.3
0.1
0.1
26.8
Mode
Mass of
Particles (|ig)
130
134
2
1
1
267
139
162
3
1
1
307
156
197
5
1
1
359
Accumulation mode MMAD = 0.436 (jm, og = 1.51, density = 1.3 g/cm3, 48.2% of the aerosol mass; intermodal mode MMAD = 2.20 (jm, og = 1.16,
density =1.3 g/cm3, 7.4% of the aerosol mass; coarse mode MMAD = 28.8 (jm, og = 2.16, density = 1.3 g/cm3, 44.4% of the aerosol mass
(see Tables 10C-3 and 10C-4c).
''Expressed as a percentage of the total mass of particles in the volume of ambient air inhaled.
°Average for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 33.3% sitting, and 33.3% light exercise. (See Table 10B-1).
dAverage for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 27.1% sitting, and 35.4% light exercise, 4.2% heavy exercise.  (See Table
10B-1).
"Average for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 16.7% sitting, and 41.7% light exercise, 8.3% heavy exercise.  (See Table
10B-1)

-------
      TABLE 10-22.  DAILY MASS DEPOSITION OF PARTICLES FROM PHILADELPHIA AEROSOL DEFINED IN
          FIGURE 10C-2(a) IN THE RESPIRATORY TRACT OF "MOUTH BREATHER" ADULT MALE HUMAN
                             EXPOSED TO A PARTICLE MASS CONCENTRATION OF 50
Contribution to Total Deposited Particle Mass from Each Aerosol Modea
Accumulation Mode
Activity Pattern
General
population0




Workers, light
workd




Workers, heavy
work6




Region of
Respiratory
Tract
ETj
ET2
BB
bb
AI
Total
ETj
ET2
BB
bb
AI
Total
ETj
ET2
BB
bb
AI
Total
Percent
Deposited1"
0.5
0.6
0.2
0.7
3.9
5.9
0.5
0.6
0.2
0.7
3.8
5.8
0.5
0.6
0.2
0.6
3.7
5.7
Mass of
Particles
(re)
5
6
2
7
39
59
6
7
2
8
43
66
7
8
3
8
50
76
Intermodal Mode
Percent
Deposition
0.7
1.0
0.3
0.3
1.9
4.2
0.6
1.1
0.4
0.3
1.8
4.2
0.6
1.1
0.5
0.3
1.8
4.3
Mass of
Particles (|ig)
7
10
3
3
19
42
7
12
5
3
21
48
8
15
6
4
24
57
Coarse Mode
Percent
Deposition
6.6
18.3
1.1
0.2
0.4
26.6
6.1
18.8
1.1
0.2
0.3
26.7
5.7
19.3
1.2
0.2
0.3
26.7
Mass of
Particles (|ig)
66
182
11
2
4
265
70
215
13
3
4
305
76
259
16
o
J
4
357
^Accumulation mode MMAD = 0.436 (jm, og = 1.51, density = 1.3 g/cm3, 48.2% of the aerosol mass; intermodal mode MMAD = 2.20 (jm, og = 1.16,
density =1.3 g/cm3, 7.4% of the aerosol mass; coarse mode MMAD = 28.8 (jm, og = 2.16, density = 1.3 g/cm3, 44.4% of the aerosol mass
(see Tables 10C-3 and 10C-4c).
''Expressed as a percentage of the total mass of particles in the volume of ambient air inhaled.
'Average for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 33.3% sitting, and 33.3% light exercise. (See Table 10B-1).
dAverage for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 27.1% sitting, and 35.4% light exercise, 4.2% heavy exercise. (See Table
10B-1).
eAverage for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 16.7% sitting, and 41.7% light exercise, 8.3% heavy exercise. (See Table

-------
oo
               TABLE 10-23. DAILY MASS DEPOSITION OF PARTICLES FROM PHOENIX AEROSOL DEFINED IN
             FIGURE 10C-2(b) IN THE RESPIRATORY TRACT OF "NORMAL AUGMENTER" ADULT MALE HUMAN
                                  EXPOSED TO A PARTICLE MASS CONCENTRATION OF 50
Contribution to Total Deposited Particle Mass from Each Aerosol Modea
Accumulation Mode
Activity Pattern
General
population0




Workers, light
workd




Workers, heavy
work6




Region of
Respiratory
Tract
ETj
ET2
BB
bb
AI
Total
ETj
ET2
BB
bb
AI
Total
ETj
ET2
BB
bb
AI
Total
Percent
Deposited1"
0.4
0.4
0.1
0.7
2.7
4.2
0.4
0.4
0.1
0.6
2.6
4.1
0.4
0.4
0.1
0.6
2.6
4.0
Mass of
Particles
4
4
1
7
26
42
4
4
1
7
30
47
5
5
1
8
34
53
Intermodal Mode
Percent
Deposition
2.9
3.8
0.2
0.3
1.7
8.9
2.8
3.8
0.3
0.3
1.7
8.9
2.8
3.8
0.4
0.3
1.6
8.9
Mass of
Particles (|ig)
29
38
2
3
17
89
32
43
4
3
19
101
37
51
6
4
22
119
Coarse Mode
Percent
Deposition
20.3
21.9
0.6
0.4
1.2
44.4
19.1
22.8
1.0
0.4
1.2
44.3
18.3
23.4
1.3
0.4
1.1
44.4
Mass of
Particles (|ig)
202
218
6
4
12
441
218
260
11
4
13
507
244
313
17
5
14
594
     aAccumulation mode MMAD = 0.188 (jm, og = 1.54, density = 1.7 g/cm3, 22.4% of the aerosol mass; intermodal mode MMAD = 1.70 ^im, og = 1.9,
     density = 1.7 g/cm3, 13.8% of the aerosol mass; coarse mode MMAD = 16.4 (jm, og = 2.79, density = 1.7 g/cm3, 63.9% of the aerosol mass
     (see Tables 10C-5 and 10C-6c).
     Expressed as a percentage of the total mass of particles in the ambient air inhaled.
     °Average for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 33.3% sitting, and 33.3% light exercise. (See Table 10B-1).
     dAverage for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 27.1% sitting, and 35.4% light exercise, 4.2% heavy exercise. (See Table
     10B-1).
     eAverage for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 16.7% sitting, and 41.7% light exercise, 8.3% heavy exercise. (See Table
     10B-1).

-------
          TABLE 10-24. DAILY MASS DEPOSITION OF PARTICLES FROM PHOENIX AEROSOL DEFINED IN
         FIGURE 10C-2(b) IN THE RESPIRATORY TRACT OF "MOUTH BREATHER" ADULT MALE HUMANS
                             EXPOSED TO A PARTICLE MASS CONCENTRATION OF 50
Contribution to Total Deposited Particle Mass from Each Aerosol Mode3
Accumulation Mode
Activity Pattern
General
population0




Workers, light
work4




Workers, heavy
work6




Region of
Respiratory Tract
ETj
ET2
BB
bb
AI
Total
ETj
ET2
BB
bb
AI
Total
ET,
ET2
BB
bb
AI
Total
Percent
Deposited1"
0.2
0.3
0.1
0.7
2.7
4.0
0.2
0.3
0.1
0.6
2.6
3.9
0.2
0.3
0.1
0.6
2.6
3.8
Mass of
Particles (ng)
2
3
1
7
27
40
2
4
1
7
30
44
2
4
1
8
35
50
Intermodal Mode
Percent
Deposition
1.0
1.7
0.5
0.5
2.7
6.4
1.0
1.7
0.6
0.5
2.6
6.4
1.0
1.8
0.8
0.4
2.5
6.5
Mass of
Particles (ng)
10
17
5
5
27
63
11
20
7
5
30
73
13
24
10
6
34
86
Coarse Mode
Percent
Deposition
9.8
25.5
3.1
1.2
3.0
42.7
9.2
26.3
3.4
1.1
2.8
42.8
8.5
27.0
3.7
1.1
2.6
42.9
Mass of
Particles (|ig)
98
254
31
12
30
425
105
301
39
13
31
490
114
362
50
14
34
574
Accumulation mode MMAD = 0.188 (jm, og = 1.54, density = 1.7 g/cm3, 22.4% of the aerosol mass; intermodal mode MMAD = 1.70 (jm, og = 1.9,
density = 1.7 g/cm3, 13.8% of the aerosol mass; coarse mode MMAD = 16.4 (jm, og = 2.79, density = 1.7 g/cm3, 63.9% of the aerosol mass
(see Tables 10C-5 and 10C-6c).
Expressed as a percentage of the total mass of particles in the volume of ambient air inhaled.
°Average for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 33.3% sitting, and 33.3% light exercise. (See Table 10B-1).
dAverage for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 27.1% sitting, and 35.4% light exercise, 4.2% heavy exercise.  (See Table
10B-1).
"Average for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 16.7% sitting, and 41.7% light exercise, 8.3% heavy exercise.  (See Table
10B-1).

-------
     Recall from Section 10.4 that deposition of a particular aerosol (MMAD and og) in the
respiratory tract is a function of inhalability and deposition efficiency.  This is illustrated
schematically in Figure 10-39. The inhalability function (Figure 10-39b) for a specific respiratory
tract region (or for the total respiratory tract as depicted in the figure) is integrated with the
deposition efficiency function (Figure 10-39c). These are integrated with an aerosol characterized
by its particle diameter and mass distribution data (Figure 10-39a) to estimate the mass deposition
fraction (Figure 10-39d) in that region.
     As expected from experimental studies, these simulations predict different deposition
fractions for mouth breathing versus nasal breathing.  This is most noticeable  for deposition of the
intermodal and coarse modes of the Philadelphia and Phoenix aerosols (depicted in Figures IOC-
la and 10C-2b), which showed significant increases in BB and AI deposition  fractions. The
MMAD for the intermodal and coarse modes were 2.20 and 28.8, respectively, for the
Philadelphia aerosol; and 1.70 and 16.4, respectively, for the Phoenix aerosol. Deposition in these
regions of the accumulation mode was less effected by mouth breathing as would be anticipated
for these smaller MMADs.
     Activity pattern influenced the deposition fractions greatly.  ET deposition of all three
modes increased with the ventiliation rates associated with work activity patterns. A noticeable
increase in both BB and A deposition occurred with percent changes of increased deposition
ranging up to 60%. Differences were also apparent in the nuclei and accumulation modes. For
the aerosol depicted in Figure 10C-1, the nuclei mode (MMAD = 0.0169 //m), deposition
fractions decreased in the bb and AI regions with the heavy work activity pattern compared to
that for the general population. For the Philadelphia aerosol, deposition of the accumulation
mode (MMAD = 0.436 //m) stayed the same in the BB region but decreased slightly in the bb and
A regions with the heavy work activity pattern. For the Phoenix aerosol, deposition of the
accumulation mode (MMAD = 0.188) increased in the bb and A compartments with the heavy
work activity pattern. Figures 10-40 and 10-41 show the daily mass deposition (//g/d) predicted
for normal augmenters versus mouth breathers and these different minute volume activity patterns
for the Philadelphia and Phoenix aerosols, respectively.
     Differences among the aerosols were also apparent and reflected the differences in the
MMAD values and percent mass of each mode.  Table 10-25 presents summary data for each
                                          10-170

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      0.025
                  0.1         1         10
                    Aerodynamic Diameter, urn
                                                              (B)
                      0.01
                               0.1        1        10
                                  Aerodynamic Diameter, urn
                                                           100
\Aerodynam


  aiC
                                        _Respiratory Tract Deposition
                                        ^Efficiency Curve
                                                                             (C)
                                     0.01

                                        \
             0.1         1         10
              Aerodynamic Diameter, urn
                                                                          100
                 0.02
                                                o 0.015
                      Particle Mass Deposited in Total Respiratory Tract
                                                              0.1        1        10
                                                                Aerodynamic Diameter, urn
                                                                                          100
Figure 10-39.   Schematic showing integration of inhalability (b) with deposition efficiency
                 (c) functions.  These functions are integrated with particle diameter and
                 distribution data (a) to estimate deposition fractions of particle mass in each
                 region of the respiratory tract (d). The particle mass fraction deposited in
                 the total respiratory tract is illustrated.
                                              10-171

-------
                            0.1
    1
MMAD
10
100
                            0.1
    1
MMAD
10
100
              ~~ General Population (Normal)
              — Heavy Worker (Normal)
              1=1 Light Worker (Mouth)
     — Light Worker (Normal)
      •  General Population (Mouth)
      A  Heavy Worker (Mouth)
Figure 10-40.  Daily mass deposition (/^g/day) in tracheobronchial and alveolar regions for
              normal augmenter versus mouth breather adult males using International
              Commission on Radiological Protection Publication 66 (ICRP66) (1994)
              minute volume activity patterns (general population; worker-light activity;
              worker-heavy activity). The 1994 ICRP66 model simulated an exposure at
              50 Mg/m3 to the Philadelphia aerosol described in Appendix IOC.
of the three chosen ambient aerosols.  To better understand the deposition differences for each
mode, however, the previous Tables 10-19 through 10-24 should also be consulted.
                                       10-172

-------
                              0.1
     1
MMAD
10
100
                                        MMAD
               — General Population (Normal)
               — Heavy Worker (Normal)
                n  Light Worker (Mouth)
         Light Worker (Normal)
         General Population (Mouth)
         Heavy Worker (Mouth)
Figure 10-41.   Daily mass deposition (/^g/day) in tracheobronchial and alveolar regions for
               normal augmenter versus mouth breather adult males using International
               Commission on Radiological Protection Publication 66 (ICRP66) (1994)
               minute volume activity patterns (general population; worker-light activity;
               worker-heavy activity).  The 1994 ICRP66 model simulated an exposure at
               50 Mg/m3 to the Phoenix aerosol described in Appendix IOC.
Intraspecies Variability

     The different deposition predictions for normal augmenter versus mouth breathing humans

illustrates the variability that differences in ventilation rate introduces to deposition estimates. As

discussed in Section 10.4.1.6., age, gender, and disease status can influence
                                        10-173

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                        TABLE 10-25. DAILY MASS DEPOSITION OF AEROSOL PARTICLES IN
               THE RESPIRATORY TRACTS OF "NORMAL AUGMENTER" AND "MOUTH BREATHER"
                               ADULT MALE HUMANS EXPOSED TO 50 //g PARTICLES/m3
Aerosol Figure
Region of Respiratory
Activity Pattern Tract
10C-1
Normal
Augmenter

Mouth
Breather
10C-2(a)
Normal
Augmenter
(Philadelphia)
Mouth
Breather
10C-2(b)
Normal
Augmenter
(Phoenix)
Mouth
Breather
Mass of Particle Cwg)
General population* ETl
ET2
BB
bb
AI
Total
Workers, light workb ET;
ET2
BB
bb
AI
Total
Workers, heavy work0 ETl
ET2
BB
bb
AI
Total
179
207
15
42
136
577
194
240
24
46
157
661
137
290
86
57
188
760
80
178
48
56
175
537
87
210
61
61
197
618
96
251
78
68
228
722
168
179
6
10
49
411
182
214
8
10
56
470
206
258
12
11
63
550
78
198
16
12
62
366
83
234
20
14
68
419
91
282
25
15
78
490
235
260
9
14
55
572
254
307
16
14
62
655
286
369
24
17
70
766
110
274
37
24
84
528
118
325
47
25
91
607
129
390
61
28
103
710
"Average for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 33.3% sitting, and 33.3% light exercise. (See Table 10B-1).
bAverage for 24 h, as derived from ICRP-66 (1974): for 33.3% sleep, 27.1% sitting, 35.4% light exercise, 4.2% heavy exercise. (See Table 10B-1).
cAverage for 24 h, as derived from ICRP-66 (1994): for 33.3% sleep, 16.7% sitting, 41.7% light exercise, 8.3% heavy exercise. (See Table 10B-1).

-------
deposition in the respiratory tract.  Because the simulations in the preceding section were
performed with parameters for adult males using an activity pattern for the general population, an
effort to develop activity patterns for different demographic groups was undertaken.
     Previous efforts on establishing and revising the NAAQS for ozone and carbon monoxide
have attempted to simulate the movement of people through zones of varying air quality so as to
approximate the actual exposure patterns of people living within a defined area (Johnson et al.,
1989; 1990; 1995a,b).  The approach has been implemented through an evolving methodology
referred to as the NAAQS exposure model (NEM). The NEM includes data on ventilation rates
for various cohort populations.
     These cohort data were analyzed to create daily ventilation breathing pattern data for eight
demographic groups as follows:
      1.  Adult Male (18 to 44 years)
     2.  Adult Female (18 to 44 years)
     3.  Elderly Male (over 65 years)
     4.  Elderly Female (over 65 years)
     5.  Children (0 to 5 years)
     6.  Children (6 to 13 years)
     7.  Children (14 to 18 years)
     8.  Compromised
     The compromised demographic group was limited to adults > 19 years of age. The
objective of identifying this cohort was to construct an activity pattern for subjects with symptoms
consistent with cardiopulmonary disease. Those who met this age criterion were included if they
answered "yes - it limits my activity" to one of the following questions from a study of the activity
patterns affecting exposure to air pollution (Johnson,  1989):
      1.   Has a doctor ever determined that you have asthma?
     2.   Has a doctor ever determined that you have a heart  condition?
     3.   Has a doctor ever determined that you have angina?
     4.   Have you had a stroke?
     5.   Have you ever had a heart attack?
                                         10-175

-------
     6.  Has a doctor ever determined that you have hypertension (high blood pressure)?
     7.  Has a doctor ever determined that you have chronic bronchitis?
     8.  Do you have any other diagnosed respiratory or heart ailment which limits your activity?
Respondents were also included if they answered "yes - it does not limit my activity" to question
numbers 1, 2, 3, 4, 5, or 7.
     Figures 10B-1 through 10B-3 in Appendix 10B show the daily minute volume patterns for
each of these demographic groups.  The average minute volume for each of 4 time periods: (1)
24:00 to 06:00; (2) 06:00 to  12:00; (3) 12:00 to 21:00; and (4) 21:00 to 24:00 was used as input
to the 1994 ICRP model in order to create a total 24-h daily breathing pattern for each
demographic group.
     Figure 10-42 shows the fractional deposition in each of the three respiratory tract regions
for these demographic groups.  Figure 10-43 shows the daily  deposition rate (//g/day) of an
exposure to 50 //g/m3.  Some variation between the cohorts exists in the mass deposition fraction
for particles in the aerodynamic size range of the ET region; the cohorts of children, especially the
0 to 5 year age group, show an increased deposition. In the A region, the cohort of children 14 to
18 years showed an enhanced deposition rate (/ug/d) for submicron-sized of particles in all three
regions of the respiratory tract, whereas the cohort of children 0 to 5 years showed a decreased
deposition rate relative to male and female adults. For larger  particles (micron-sized and above),
the 14 to 18 year cohort showed no enhanced deposition rate  in the tracheo bronchichial or
alveolar regions compared to adults, and younger children cohorts showed a progressive decrease
with decreasing age.  When evaluated on the basis of daily mass deposition rate (//g/d), the cohort
of children ages 14 to 18 years showed an increase in deposition for all three regions of the
respiratory tract (Figure 10-43) compared to other cohorts, whereas the cohort of children 0 to 5
years showed a decrease. This is due primarily to differences in respiratory frequency.
     Although constructed for differences in age, gender, and health status, the cohorts as
constructed represent differences for these factors only characterized in terms of differences in
hourly minute volume patterns.  Other effects on dosimetry such as altered respiratory  tract
architecture leading to altered flow pattern or differences in susceptibility of the target
                                          10-176

-------
                c
                o
                o
                (0
                o
                0.
                CD
               O
                    0.001       0.01       0.1          1
                                      Particle Diameter (|jm)
10
                   0.001       0.01       0.1          1
                                      Particle Diameter (|jm)
10
                    0.001       0.01       0.1         1
                                      Particle Diameter (|jm)
10
100
100
100
                          Male Worker  ~~ Male over 65yr   	Compromised
                          Female Worker °  Female over 65yr  *  Child 14-1 Syr
                          Child 6-1 Syr    *  Child 0-5yr
Figure 10-42.  Deposition fraction in each respiratory tract region as predicted by the
               International Commission on Radiological Protection Publication 66
               (ICRP66) (1994) model.  Simulations used daily minute volume activity
               patterns for different demographic groups as provided in Appendix 10B.
                                          10-177

-------
              as
              Q
 0.001
                  500
0.01        0.1         1

        Particle Diameter (|jm)
10
100
              —   400
              in
              o
              CL.
              to
              Q

              
-------
tissue are not addressed in these simulations. As discussed earlier, Anderson et al. (1990) have
shown enhanced deposition in patients with COPD compared to healthy subjects. Miller et al.
(1995) used a more detailed theoretical multipath model and estimated enhanced deposition in a
compromised lung status model defined by decreased ventilation to respiratory tract region
adjustment.  The simulations performed herein were limited to average mass particle burdens per
region of the respiratory tract.  Nevertheless, these simulations do suggest differences for these
cohorts.  For example, the cohort for children 14 to 18 years showed an enhanced deposition rate
(ug/d) in all three respiratory tract regions whereas children 0 to 5 years showed a decrease.

Relevance to PM10 Versus PM25 Sampling
      The dosimetry of particles of different sizes in the human respiratory tract formed one of the
primary bases for selecting the PM10 size fraction in the 1987 review.  Particles in this size range
pose the greatest risk to human health because they penetrate to the putative target regions in the
lower respiratory tract associated with mortality and morbidity, i.e., the TB and A regions.
      Ambient aerosols have been established as bimodal distributions of particles. Fine and
coarse particles generally have different sources, formation mechanisms, physical properties,
chemical composition and properties, atmospheric lifetimes, and outdoor to indoor infiltration
ratios. The fine fraction has been suggested to provide a better exposure surrogate for the
epidemiological data (See Chapters 12 and 13).  In addition, some of the properties of fine
particles may play a role in possible mechanisms of toxicity. For example, the fine mode accounts
for most of the particle number and much of the surface area.  Also, several chemical classes of
concern such as acids  and sulfates are found predominantly in the fine fraction. If particle number
and not mass alone is  an important determinant of response, then a refined characterization of this
mode may enhance the ability to discern effects in the exposed populations.
      Simulations were performed using the 1994 ICRP66 dosimetry model to illustrate the
relationship between deposition efficiency of the respiratory tract, mass burden of particles in the
thoracic portion of the respiratory tract, and the mass distribution of aerosols collected by a PM10
or PM2 5 sampler.
     Figure 10-44 shows the predicted regional deposition fraction in the respiratory tract,
relative to unit mass concentration in ambient air, as a function of the  aerosol size (represented by
the mass median aerodynamic diameter, MMAD, in //m).  The top graph is for aerosols with a

                                          10-179

-------
geometric standard deviation (og) of 1.8 and the other with a og of 2.4. Deposition fraction based
on model simulations are shown for the thoracic region (i.e., tracheobronchial plus alveolar
deposition, TB + A), as well as for the total respiratory tract deposition fraction. The difference
between total respiratory tract and total thoracic fractions represents the extrathoracic or upper
airway deposition fraction.  In addition these figures show curves representing the fraction
collected by a PM10 sampler.  This illustrates that the PM10 sample accounts for almost all of the
thoracic deposition, but does not account for many of the larger particles which would be
deposited in the ET region. Two curves for the PM10 collection fraction are shown illustrating
different wind speed characteristics (i.e., for 2 km/h or 8 km/h). It is seen that wind speed is not a
major factor. These curves represent the deposition fractions for healthy people who breathe
oronasally during exercise (normal augmenters) and healthy people who breathe predominantly
through their mouth (mouth breather).  As before, it is clear that mouth breathers have a greater
deposition of particles >1 jim than do oronasal breathers.
     Figures 10-45 and 10-46 expand on the information presented in 10-44 by illustrating
deposition fraction in each of the two thoracic regions, the alveolar and the TB region, again for
normal augmenters and for mouth breathers. In addition, the collection fraction for a PM2 5
sampler is illustrated.  Whereas PM10 accounts  for all particles in the thoracic size deposition
mode, the PM2 5  sample does not include some larger particles that would  be deposited in the TB
and A regions of mouth breathers, under the simulated conditions (general population activity
pattern 8 h sleep, 8 h sitting, 8 h light activity [see Appendix  10B, Table 10B-l(b)]. Mouth
breathers do not represent a large percentage of the population, but are cited here to illustrate the
effect of breathing habit.  Figure 10-46 provides the same information as Figure 10-45 but
expands the scale for micron-sized particles by excluding particles smaller than 0.1 jim.
     These simulations (Figures 10-44 through 10-46) represent single mode aerosols of various
MMAD and two different og. However, the real world ambient aerosols are
                                          10-180

-------
             c
             g

             "o
             to
             c
             o

             "o
             _OJ

             ~o
             o
             c
             o
             *J
             'w
             o
             Q.
             03
             Q

             M
             M
             to
                0.001
           0.01       0.1         1

               MMAD (|jm) with og = 1.8
10
100
 0

0.001
                           0.01       0.1         1

                               MMAD (|jm) with og = 2.4
         100
               Total Respiratory Tract  — PM10 (2 km/h)   — PM10 (8 km/h)

               Thoracic (Normal)       °  Thoracic (Mouth)
Figure 10-44. Respiratory tract deposition fractions and PM10 sampler collection versus

             mass median aerodynamic diameter (MMAD) with two different geometric

             standard deviations (og = 1.8 or og = 2.4). Thoracic deposition fraction

             predicted for normal augmenter versus mouth breather adult male using a

             general population (ICRP66) minute volume activity pattern and the 1994

             ICRP66 model. Total respiratory tract deposition fraction also shown for

             normal augmenter.  PM10 sampler collection shown at two different wind

             speeds (8 km/h or 2 km/h).
                                       10-181

-------
                                                          Total Respiratory
                                                          Tract
        0.01
             0.1               1              10
                    MMAD (jjm)with og = 1.8
100
        0.01
                                                         Total Respiratory
                                                         Tract
             0.1               1              10
                    MMAD (|jm) with og = 2.4
100
                                   TB (Normal)   D  Total Thoracic (Normal)

                                   TB (Mouth)    D  Total Thoracic (Mouth)
0  Alveolar (Normal)

0  Alveolar (Mouth)
Figure 10-45. Respiratory tract deposition fractions and PM10 or PM2 5 sampler collection
             versus mass median aerodynamic diameter (MMAD) with two different
             geometric standard deviations (og = 1.8 or og = 2.4). Alveolar,
             tracheobronchial, or total thoracic deposition fractions predicted for normal
             augmenter versus mouth breather adult male using a general population
             (ICRP66) minute volume activity pattern and the 1994 ICRP66 model.
                                       10-182

-------
                                                         Total Respiratory
                                                         Tract
                               1                   10
                              MMAD (pm) with og = 1.8
100
                                                         Total Respiratory
                                                         Tract
                               1                   10
                               MMAD (pm) with og = 2.4
100
0 Alveolar (Normal)
0 Alveolar (Mouth)
A TB (Normal)
* TB (Mouth)
D Total Thoracic (Normal)
° Total Thoracic (Mouth)
Figure 10-46.  Respiratory tract deposition fractions and PM10 or PM2 5 sampler collection
              fractions versus mass median aerodynamic diameter (MMAD) with two
              different geometric standard deviations (og = 1.8 or og = 2.4). Alveolar,
              tracheobronchial, or total thoracic deposition fractions predicted for normal
              augmenter versus mouth breather adult male using a general population
              (ICRP66) minute volume activity pattern and the 1994 ICRP66 model.
                                       10-183

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multi-modal, having a broad distribution of particle sizes and composition.  Figure 10-47
illustrates graphically the process of taking the mass distribution for an ambient aerosol and the
deposition efficiency curve for a "typical" (general population adult male) human and deriving the
distribution of particle mass deposited in the lung. This is shown in the sequence of graphs in
Figure 10-47. The mass distribution of the ambient aerosol (Figure 10-47a) is combined with the
deposition efficiency curve (Figure 10-47b; similar to Figure 10-39) to obtain the thoracic mass
deposition for the ambient aerosol (Figure 10-47c).  The corresponding process for collection
with a PM10 sampler is also shown. Figure 10-47a (ambient mass distribution) is combined with
the sampler efficiency curve (Figure 10-47d), resulting in Figure  10-47e,  which shows the
collected mass distribution for the ambient aerosol. If Figure  10-47c is superimposed on Figure
10-47e, figures such as 10-48  and 10-49 will be generated.
     Figures 10-48 and 10-49 illustrate the fractional mass deposition seen with representative
ambient aerosols for the cities of Phoenix  and Philadelphia. These trimodal aerosols were
described in Chapter 3, and their parameters are provided in Appendix IOC. From these graphs it
is shown that the PM25 sampler distribution accounts for the particle mass in the fine (<1.0 |im)
mode and the transition mode (MMAD -2.5 jim) but does not account for the smaller mass of
coarse mode particles that would be deposited in the thorax (mainly affecting tracheobronchial
deposition in mouth breathers).  Failure of the PM2 5 sampler to account for coarse mode particle
thoracic deposition is more evident for the Phoenix aerosol than for the Philadelphia aerosol.
     Because mass deposition is not the only dose metric that is of interest, a similar modeling
exercise was conducted for particle number, using the Philadelphia and Phoenix aerosols.
Simulations were again performed with parameters for adult males and a general population
activity pattern. Figure 10-50 shows the predicted fraction of total number of particles inhaled
that is deposited in each region of the respiratory tract (ET, TB, A) for the Philadelphia aerosol.
Figure 10-51 shows the number of particles deposited each day in each respiratory tract region for
the Philadelphia aerosol assuming an exposure to a total paniculate mass concentration of 50
//g/m3. These figures show that a large fraction of the number of deposited particles is
contributed, as anticipated, by the fine fraction mode, and that this can represent a very large
number of particles deposited per day (on the order of
                                          10-184

-------
                             0.025
                           «  0.02
                                                   (A)
                                   Aerosol Mass vs. Particle Size Distribution
                                  	I	I	L
                                0.01
                                          0.1         1         10
                                            Aerodynamic Diameter (urn)
                                                                       100
           (B)
                                                                           (D)
        0.8
            Characteristic Deposition Curve for Mouth Breather
                                                        0.8
                                                      o 0.6
                                                      T3
                                                      o 0.4
                                                        0.2
                                           Characteristic Collection
                                           Curve for PM10 Sampler
         0.01
                   0.1         1         10
                     Aerodynamic Diameter (urn)
                                                100
                                                         O-l—
                                                         0.01
                                                  0.1        1         10
                                                    Aerodynamic Diameter (urn)
                                                                                               100
           (C)
                                                                           (E)

0
S 0.015
Q
Fractional Mass
g p
Particle Mass Deposited In the Lungs (TB + A Regions











,-\ ,





/^





•^
        0.01       0.1        1        10
                     Aerodynamic Diameter (urn)
                                              100
c
o
•£ 0.015
o
U
i 0.01
"5
0
| 0.005
£
0
0.0
Particle Mas





:
s Collected by
* •
- -
* "
m m
•
V
1 0.1 1
PM10 Sample


S*.
/ '
/

•





•
10 10
                                                    Aerodynamic Diameter (urn)
Figure 10-47.
Schematic illustration of how ambient aerosol distribution data were
integrated with respiratory tract deposition efficiency (using 1994 ICRP66
model) or sampler efficiency to calculate deposition in respiratory tract
regions or mass collected by sampler.
                                               10-185

-------
              0.04
                                    1                 10
                                  Aerodynamic Diameter (urn)
                       100
              0.04
                                  Aerodynamic Diameter
                             Alveolar

                             Total Thoracic
TB

Total Respiratory Tract
Figure 10-48.  Mass deposition fraction in normal augmenter versus mouth breather
              adult male with a general population minute volume activity pattern
              predicted by the International Commission on Radiological Protection
              Publication 66 (1994) model and the mass collected by PM10 or PM2 5
              samplers for Philadelphia aerosol (described in Appendix IOC).
                                       10-186

-------
              0.02
          I  0.015
          o
          CO
          CO
              0.01
             0.005
              0.02
                                     1                  10
                                  Aerodynamic Diameter (\im)
                        100
                                     1                  10
                                  Aerodynamic Diameter (urn)
                        100
                            Alveolar

                            Total Thoracic
TB

Total Respiratory Tract
Figure 10-49.  Mass deposition fraction in normal augmenter versus mouth breather
              adult male with a general population minute volume activity pattern
              predicted by the International Commission on Radiological Protection
              Publication 66 (1994) model and the mass collected by PMia or PM2 5
              samplers for Phoenix aerosol (described in Appendix IOC).
                                       10-187

-------
           1E-02
           1E-09
                0.01
           1E-02
           1E-09
                0.01
0.1             1            10
   Aerodynamic Diameter (pm)
              100
0.1             1            10
   Aerodynamic Diameter (pm)
              100
                   Extrathoracic
       Tracheobronchial
Alveolar
Figure 10-50.  Fractional number deposition in each respiratory tract region for normal
              augmenter versus mouth breather adult male with a general population
              activity pattern as predicted by the International Commission on
              Radiological Protection Publication 66 (1994) model for an exposure to the
              Philadelphia aerosol (described in Appendix IOC).
                                       10-188

-------
       (0
       Q
       L
       O>
       Q.

       •c
       0>
       +*

       0)
       o
       Q.
       0>
       Q
       o

       t
       (0
       Q.
       M-
       o
       ^
       4)


       E
       n
       Q

       0)
       Q.

       •a
       «

       'w
       o
       Q.
       4)
       Q

       in

       "o

       r
       (0
       Q.
       >4-
       o
       ^
       o>


       E
                          Normal Augmenter
                 .01
                 .01
0.1             1            10

   Aerodynamic Diameter (pm)
              100
0.1             1            10

   Aerodynamic Diameter  (pm)
              100
                   Extrathoracic
       Tracheobronchial
Alveolar
Figure 10-51.  Number of particles deposited per day in each respiratory tract region for

              normal augmenter versus mouth breather adult male with a general

              population activity pattern as predicted by the International Commission

              on Radiological Protection Publication 66 (1994) model for an exposure to

              the Philadelphia aerosol (described in Appendix IOC) at a concentration of

              50
                                       10-189

-------
100,000,000) in the alveolar region.  Figure 10-52 shows the predicted fraction of total number
of particles inhaled that is deposited in each respiratory tract region for the Phoenix aerosol, and
Figure 10-53 shows the number of particles deposited each day in each respiratory tract region for
this aerosol assuming an exposure to a total particulate  mass concentration of 50 //g/m3.  The
more disperse intermodal fraction of the Phoenix aerosol (see Figure 10C-2 in Appendix IOC)
contributes more particles to the fine mode size-range than that of the Philadelphia aerosol.

Hygroscopic Aerosols
     The ICRP66 (1994) deposition model as so far described relates to the distribution of
activity or mass of aerosol particles with respect to their size on entering the respiratory tract.
However, in the case of a hygroscopic material, it is necessary to take account of the increase in
particle size that occurs when such materials are exposed to the near-saturated air in the
respiratory tract. The ICRP66 model can be applied for hygroscopic materials by replacing the
values of particle aerodynamic diameter, dae, and diffusion coefficient, D, in ambient air with the
values dae(j) and Dj attained in each region, j, of the respiratory tract.
     Annexe D of ICRP66 describes how the growth of a hygroscopic particle can be
approximated in general terms as a function of its residence time in saturated air at body
temperature.  For a residence time, tj, in region, j, measured from inspiration of the particle (i.e.,
entry to the nose or mouth), the particle aerodynamic diameter and diffusion coefficient attained
by hygroscopic growth are approximately related to dae(0) and D(0), the respective values in
ambient air (i.e., the external environment), and the values at equilibrium, dae(oo) and D(oo) are
                         - dae(0)]
exp
                                        -{iotr}0'55
                                          dae(0)
                                                     0.6
, and
                                                (10-58)
              = D(0) -
                              - dae(0)
    [D(0)-D(oo)J
                           (10-59)
                                          10-190

-------
            1E-02
          u
          £  1E-08
            1E-09
                0.01
0.1             1            10
    Aerodynamic Diameter (|jm)
               100
            1E-02
         •o
         i  1E-03
          «  1E-04
          .a
          E
            1E-05
          m
          o
            1E-06
          o  1E-07
          U
            1E-08
            1E-09
                0.01
0.1             1            10
    Aerodynamic Diameter (|jm)
              100
                   Extrathoracic
       Tracheobronchial
Alveolar
Figure 10-52.  Fractional number deposition in normal augmenter versus mouth breather
              adult male with a general population activity pattern predicted by the
              International Commission on Radiological Protection Publication 66 (1994)
              model for an exposure to the Phoenix aerosol (described in Appendix IOC).
                                       10-191

-------
             1E+09
          n
          Q
          Q.

          •o
          4)
          +-
          '«
          o
          Q.
          «
          O
          in
          £
          o

          '•E
          eg
          a.
          E
          a
             1E+00
                 0.01
1E+09
             1E+08
             1E+02
             1E+01
             1E+00
                 0.01
                   0.1            1            10

                     Aerodynamic Diameter (|jm)
         100
                  0.1            1            10

                     Aerodynamic Diameter (|jm)
         100
                    Extrathoracic
                         Tracheobronchial
Alveolar
Figure 10-53.  Number of particles deposited per day in each respiratory tract region for

              normal augmenter versus mouth breather adult male with a general

              population activity pattern predicted by the International Commission on

              Radiological Protection Publication 66 (1994) model for an exposure to the

              Phoenix aerosol (described in Appendix IOC) at a concentration of

              50 M/m3-
                                       10-192

-------
     To solve the model for a specific material, it is necessary to specify the degree of particle
size growth at equilibrium.  This generally lies in the range of two- to fourfold growth, depending
on the amount of hygroscopic material associated with the particle.  However, ICRP66 suggests
that it is likely to be adequate to assume by default a threefold growth factor at equilibrium, for
substitution in these equations. Note that the initial aerodynamic diameter, dae(0), is increased by
particle growth, whereas the initial diffusion coefficient, D(0), is decreased.
     The effect of hygroscopic particle growth is generally to decrease total lung deposition for
submicron-sized particles, and to increase it for larger particles. As discussed in some detail in
Annexe D of ICRP66, the particle size in ambient air corresponding to minimum lung deposition
is reduced from about 0.4 jim for non-hygroscopic particles to about 0.1 jim for hygroscopic
particles (Tu and Knutson, 1984; Blanchard and Willeke,  1984).

Intrahuman Variability in Regional Deposition
     The experimental data on regional deposition of particles in the human respiratory tract
indicate substantial intersubject variability, even if the particles are inhaled under identical
exposure conditions. In ICRP66, the upper and lower 95% confidence bounds of the data are
represented by a variable coefficient, a, which is incorporated into each algebraic expression for
deposition efficiency (see ICRP66, Chapter 5, Tables 12 and 13, pp.  45 and 46). In each case, the
coefficient is taken to be log-normally distributed, (i.e., a^ = amedian x  Og2, and alower = amedian -
og2) where og is the fitted geometric standard deviation. Other confidence bounds on the
predicted regional deposition efficiency are given by substituting an appropriate value of the
coefficient, a, that is sampled from the defined log-normal distribution.
     Representing the median (or expectation) value of the coefficient, a, for each region, j, by a,j,
then it is convenient to use a dimensionless scaling constant, Cj, as a multiplier or divisor of the
median value.  In Table  14 of ICRP66 (Chapter 5, p. 49), the ICRP gives values of this scaling
constant that are estimated to describe the spread in the experimental data for regional respiratory
tract deposition. The scaling factors defining the upper and lower 95% confidence bounds of
regional deposition range from x or + by 1.4 in the expression for "thermodynamic" deposition
efficiency of the extrathoracic (ET) region, to x or + by 3.3 for the "aerodynamic" deposition
efficiency of the ET region.  To evaluate the uncertainty distribution of the predicted deposition
                                          10-193

-------
fractions in all five regions of the respiratory tract (i.e., ETl3 ET2, BB, bb, and AI) it is necessary
to select the respective values of Cj at random from their assumed log-normal distributions.

10.7.5.2  Laboratory Animal Estimates
     Tables 10-26 through 10-31  provide the deposition fractions of various particle sizes
(MMAD) for either a relatively monodisperse (og = 1.3) versus a more polydisperse (og = 2.4)
distribution in humans or rats.  Deposition fractions of these aerosols for an adult male human
normal augmenter and mouth breather with a general population activity pattern were calculated
using the ICRP66 model (ICRP66, 1994). The deposition fraction for each respiratory tract
region is presented: ET in Tables  10-26 and 10-27; TB in Tables 10-28 and 10-29; and A in
Tables 10-30 and 10-31.  These regional deposition fractions are shown plotted in Figure 10-54.
The left side in each panel represents the deposition fractions for the relatively monodisperse
aerosol  (og = 1.3) and the right side in each panel represents the more polydisperse aerosol (og =
2.4). Note that the y-axis scale changes from one panel to the other and from panel to panel.
As discussed in Section  10.5, polydispersity in the aerodynamic particle size range tends to smear
the  regional  deposition across the range of particles.  The interspecies differences in fractional
deposition are readily apparent from these figures.
     In the  TB region, Figure 10-54 illustrates that at the smaller particle diameters (MMAD < 2
//m for og =  1.3) the rats have higher deposition fractions than normal augmenter (nasal breathing)
humans. At larger particle diameters (MMAD > 2.5 //m for og = 1.3), rats have very little
deposition in the TB or A regions due to the low inhalability of these particles.  This may help
explain  why inhalation exposures of rodents to high concentrations of larger particles have
exhibited little effect in some bioassays.
     The information in Tables 10-26 through 10-31 and depicted in the panels of Figure 10-54
can be used  to calculate the deposition fraction term in Equations 10-50 and 10-54.  The average
ventilation rates and parameters such as surface area which could be used for normalizing factors
for laboratory animals are found in Appendix 10B, Table 10B-2.
                                          10-194

-------
TABLE 10-26. EXTRATHORACIC DEPOSITION FRACTIONS OF INHALED
      MONODISPERSE AEROSOLS (og=1.3) IN RATS AND HUMAN
        "NORMAL AUGMENTER" AND "MOUTH BREATHER"
MMAD
1
1.5
2
2.5
3
3.5
4
Normal Augmenter Mouth Breather
0.273 0.074
0.443 0.141
0.566 0.209
0.651 0.270
0.711 0.326
0.754 0.375
0.785 0.420
Rat
0.18
0.55
0.74
0.77
0.76
0.73
0.70
TABLE 10-27. EXTRATHORACIC DEPOSITION FRACTIONS OF INHALED
POLYDISPERSE AEROSOLS (og=2.4) IN RATS AND HUMAN
"NORMAL AUGMENTER" AND "MOUTH BREATHER"
MMAD
1
1.5
2
2.5
3
3.5
4
TABLE
MMAD
1
1.5
2
2.5
3
3.5
4
Normal Augmenter Mouth Breather
0.326 0.126
0.442 0.193
0.524 0.250
0.582 0.299
0.624 0.340
0.655 0.374
0.678 0.404
Rat
0.30
0.42
0.49
0.53
0.55
0.56
0.56
10-28. TRACHEOBRONCHIAL DEPOSITION FRACTIONS OF INHALED
MONODISPERSE AEROSOLS (og=1.3) IN RATS AND HUMAN
"NORMAL AUGMENTER" AND "MOUTH BREATHER"
Normal Augmenter Mouth Breather
0.022 0.026
0.033 0.048
0.042 0.074
0.048 0.101
0.050 0.125
0.050 0.144
0.049 0.159
Rat
0.10
0.06
0.03
0.01
0.005
0.002
0.001
                             10-195

-------
TABLE 10-29. TRACHEOBRONCHIAL DEPOSITION FRACTIONS OF INHALED
        POLYDISPERSE AEROSOLS (og=2.4) IN RATS AND HUMAN
          "NORMAL AUGMENTER" AND "MOUTH BREATHER"
MMAD
1
1.5
2
2.5
3
3.5
4

Normal Augmenter Mouth Breather
0.028 0.049
0.032 0.068
0.035 0.084
0.036 0.096
0.036 0.104
0.036 0.110
0.035 0.114
TABLE 10-30. ALVEOLAR DEPOSITION FRACTIONS OF
Rat
0.06
0.05
0.04
0.031
0.025
0.021
0.017
INHALED
MONODISPERSE AEROSOLS (og=1.3) IN RATS AND HUMAN
"NORMAL AUGMENTER" AND "MOUTH BREATHER"
MMAD
1
1.5
2
2.5
3
3.5
4

Normal Augmenter Mouth Breather
0.119 0.140
0.146 0.120
0.150 0.237
0.142 0.256
0.126 0.258
0.109 0.248
0.092 0.230
TABLE 10-31. ALVEOLAR DEPOSITION FRACTIONS OF
Rat
0.06
0.10
0.06
0.02
0.011
0.005
0.002
INHALED
POLYDISPERSE AEROSOLS (og=2.4) IN RATS AND HUMAN
"NORMAL AUGMENTER" AND "MOUTH BREATHER"
MMAD
1
1.5
2
2.5
O
3.5
4
Normal Augmenter Mouth Breather
0.111 0.151
0.112 0.171
0.109 0.180
0.103 0.179
0.096 0.175
0.089 0.169
0.082 0.161
Rat
0.04
0.04
0.035
0.031
0.027
0.023
0.020
                               10-196

-------
      (a)
        .2  0.8
           0.6
           0.4
           0.2
      (b)
           0.2
        •2 0.15
        o
        s
        I  0.1
        w
        o
        Q.
        a
        a
        M0.05
                        2       3
                        MMAD (|jm)
                 1234
                        MMAD (Mm)
                                                0.8
                                              5 0.6
| 0.4
in
o
a.
o
0
                                                0.2
                                                                          og = 2.4
        1       2       3
                MMAD (|jm)
U.1Z
= 0-1
o
S 0.08
u.
c
I 0.06
o
S 0.04
m
0.02
n

- 	 Nose - — """"
	 Mouth ^f ""^
	 Rat /
/
./
S''--.
-
""""""" "••-..
Og = 2.4
                234
                 MMAD (Mm)
      .  .   u.o ,	
      (c)      .p^
        o
        Q.
0.25
0.2
0.15
0.1
0.05


-
-


	 Nose
	 Mouth
	 Rat
>
/
/
/
t ^~

1
x"" ^"^
X
r
---.._ Og = 1-3
234
MMAD (Mm)
0.25
A Deposition Fractl
o o
i= P ^ P
Ol -* Ol IO

0
- 	 Nose
	 Mouth
	 Rat
	 og - 2.4

1234
MMAD (Mm)
Figure 10-54.  Predicted extrathoracic deposition fractions versus mass median
              aerodynamic diameter (MMAD) of inhaled monodisperse (og = 1.3) aerosols
              shown in left-side panels or polydisperse (og = 2.4) aerosols shown in right-
              side panels for humans (nose versus mouth breathing) and rats (obligatory
              nose breathers), for (a) the extrathoracic region, (b) tracheobronchial
              region, and (c) alveolar region.
                                        10-197

-------
Respiratory tract region surface areas for humans are found in Table 10B-1. The human male
adult general population activity pattern in Table 10B-1 corresponds to a daily ventilation
volume of 19.9 m3/day.  This is the average ventilation rate that was used to run the LUDEP®
simulations and would be used in the denominator of Equations 10-51 or 10-55. The normal
augmenter or mouth breather deposition fractions found in Tables 10-26 through 10-31
represents the sum of the FrH factors in the denominator of the expression found in Equations
10-51 and 10-55.  Likewise, the deposition fractions for the rat represent the FrA factor in
Equations 10-53 and 10-57.
     Because particles initially deposit along the surface of the respiratory tract, regional surface
area is chosen as the normalizing factor for calculation of the regional deposited dose ratio
(RDDR), as described in Equation 10-50, in order to characterize "acute" effects.  Assuming an
exposure to an aerosol with a MMAD of 1.0 //m and og = 1.3, Equation 10-51 can be used to
calculate RDDRA[ACT] estimates using the deposition fractions provided in Tables 10-26 through
10-31 and surface area and ventilation rate parameters provided in Tables 10B-1 and 10B-2 in
Appendix 10B. A RDDRA[ACT] value of 1.54 is calculated for rats using the alveolar surface area
as a normalizing factor.  The RDDRA[ACT] value for each species would be applied to an
experimental exposure concentration from a laboratory toxicology study using rats to calculate a
human equivalent concentration.
     Interspecies extrapolation to HEC values allows for comparison among species.  For
example, if a rat exhibited an effect in the alveolar region when exposed to an aerosol with a
MMAD =1.0 //m and og = 1.3 at an exposure concentration of 100//g/m3, the resultant FIEC
value calculated for the rat would be 154 //g/m3. This HEC would result in a similar alveolar
deposited dose and thereby a similar effect in humans, assuming species sensitivity to a given
dose is equal. Although laboratory species may be exposed to the same aerosol at the same
concentration, each would have a different fractional deposition, which when normalized to
regional surface area, could result in different HEC estimates. Thus, taking into account species
differences in dosimetry is necessary before  comparing effective concentrations when
interpreting toxicity data.
     For tracheobronchial effects, the RDDR^^,^ would be used to adjust exposure
concentrations for interspecies differences in dosimetry. For an aerosol with an MMAD =1.0
//m and o = 1.3, the RODR^,  value is 9.95 for rats. For an aerosol with an MMAD = 2.5
                                         10-198

-------
and og = 2.4, the RDDR^^^ value is 1.89.  The decrease in the value is due to the decreased
inhalability of the larger particle diameter and the effect of polydispersity. Similarly, the
RDDRA[ACT] value for an aerosol with an MMAD = 2.5 //m and og = 2.4is0.88 for rats, whereas
it was 1.54 for the more monodisperse aerosol.

10.7.6   Retained Dose Estimates
     An important issue in inhalation toxicology is the relationship between repeated or chronic
inhalation exposures and the resulting alveolar burdens of exposure material achieved in the
human lung versus the lungs of laboratory animal species.  It is generally assumed that the
magnitude of the alveolar burden of particles produced during an inhalation exposure is an
important determinant of biological responses to the inhaled particles. Therefore, understanding
the basis for differences among species in alveolar burdens that will result from well-defined
inhalation exposures will provide investigators with a better understanding of alveolar burdens
that would result from exposures of various mammalian species to the same aerosol.
Alternatively, the exposure conditions could be tailored for each species to produce desired
alveolar burdens of particles.
     Predictable deposition, retention, and clearance patterns are possible for acute inhalation
exposures of laboratory animal species and humans. Repeated exposures also occur for humans
and are used routinely in laboratory animals  to study the inhalation toxicology of a broad
spectrum of potentially hazardous particulates. The predicted biokinetics of particles acutely
inhaled can be readily extrapolated to repeated exposures. However, the predictions become
increasingly questionable as exposure conditions deviate from those used for acute inhalation
exposures. The following predictions for repeated inhalation exposures  are therefore intended
to be relative, rather than absolute, and were made using the assumption that physical clearance
parameters for the A region are the same for acute and repeated inhalation exposures.

10.7.6.1   Human Estimates
     The LUDEP® software version 1.1 for the 1994 ICRP66 model was also used to simulate
chronic exposures of adult male "normal augmenters" to the trimodal aerosols described in
Appendix IOC for Philadelphia (Figure 10C-2a, and Tables 10C-3 and 10C-4)  and Phoenix
(Figure 10C-2b, and Tables 10C-5 and 10C-6).  The simulations were of a continuous 24 h/d and
                                         10-199

-------
7 d/week exposure at an air concentration of 50 //g/m3.  For both aerosols, the particles in the
accumulation, intermediate, and coarse modes were assumed to have dissolution/absorption half
times of 10, 100, and 1000 days, respectively.
     Predicted particle mass (//g) lung burdens as a function of exposure days are presented in
Figure 10-55a for the Philadelphia trimodal aerosol and in Figure 10-55b for the Phoenix
trimodal aerosol.  The assumed dissolution/absorption rates and default values for clearance
parameters in the ICRP66 1994 model yielded predicted particle mass lung burdens from the
accumulation, intermediate, and coarse modes that reached equilibrium between deposition and
clearance after about 100, 700, and 7,000 days, respectively. Table 10-32 presents the predicted
ratios of particle mass in the lungs for each of the three modes and for the total amount of
particles. Individuals breathing the Phoenix aerosol would have about 0.7 the amount of the
accumulation mode particles in the their lungs as would individuals breathing the Philadelphia
aerosol, and about 1.5 times as much of the intermediate and 11 times as much of the coarse
modes.  Overall, individuals exposed for long periods to the Phoenix aerosol would have almost
4 times as much total mass of particles in their lungs as would individuals exposed to the
Philadelphia aerosol. Interestingly, the biggest difference is in the predicted amounts of particles
from the coarse mode.
     Another way to present these model simulation results is to express them in terms of
specific lung burden (//g dust / g lung) versus time. This is presented in Figure 10-56a for the
Philadelphia aerosol and in Figure 10-56b for the Phoenix aerosol. Note that the time of
exposure was converted to age in years. Assuming that humans of all ages and gender deposit
and clear about the same amounts of particles from these aerosols per day per gram of lung, this
presentation of data approximates the specific lung burdens of particle mass as a function of age
for young and old alike. For both aerosols, equilibrium amounts of dust are achieved after  about
16-18 years. Assuming that clearance rates are not altered with age or these levels of particle
burden, this suggests that an individual who has lived in these  environments for longer than
about 18 years has accumulated a specific lung burden of these particles and that the burdens
will remain relatively constant as long as exposure conditions and health status are not
appreciably changed. Note again that the data in Table 10-33 predict different relative amounts
of accumulated particles from the three modes.
                                         10-200

-------
             10,000
              1,000-

            8
            <8
r
(0
Q.
               100-
                in-
                     (a) Philadelphia
                      x
                        x

            	  Total
            	Coarse Mode
                 Intermediate Mode
                 Accumulation Mode
 1
10
      100
Days of Exposure
                                             1,000
                                                                     10,000
             10,000
              1,000
            W
            w
            ffl
            
-------
TABLE 10-32. PREDICTED RELATIVE PARTICLE MASS (^g) IN
LUNGS OF ADULT MALE "NORMAL AUGMENTER" EXPOSED
CHRONICALLY TO PHOENIX TRIMODAL AEROSOL VERSUS
          PHILADELPHIA TRIMODAL AEROSOL
Day
1
2
4
6
8
10
12
14
16
18
20
25
30
40
60
80
100
150
200
250
300
400
500
600
700
800
900
1000
1200
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
7000
8000
9000
10,000
Particle Mass (jj,g)
Accum.
0.71
0.71
0.71
0.71
0.71
0.71
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
0.72
Versus Mode:
Intermed.
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.52
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
1.53
Ratio of Phoenix to Philadelphia
Coarse
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
10.8
Aerosols
Total
1.14
1.14
1.16
1.18
1.20
1.23
1.25
1.27
1.29
1.31
1.32
1.37
1.42
1.50
1.64
1.75
1.84
2.01
2.15
2.26
2.36
2.55
2.70
2.83
2.94
3.04
3.12
3.19
3.28
3.41
3.51
3.57
3.60
3.62
3.63
3.64
3.64
3.64
3.64
3.65
3.65
3.65
3.65
                       10-202

-------
           D)
           o
           E
           IB
           O
           4)
           Q.
           *ra
           w
           w
           IB
           ra
           Q.

10

1
0.1-
0.01-
.ooin
o.c
i i i i
(a) Philadelphia
	 . 	
^' ,.-''
x'' .-•'
// -•' x
/ , X/X — • Total
X 	 Coarse Mode
X 	 Accumulation Modi
x
X
I I I I
101 0.01 0.1 1 10 10
                                     Age in Years

0)
C
3
4-
o
E
i_
O
i_
41
Q.

"5
^
M
(A
(0
E
"o
r
ra
0.

10


1-






0.1-




0.01-



i i i i

(b) Phoenix
^•''' ..•••""
xX ^^
x / • '
X / .•'"
x X -•''
/' s^"?^
/' j^^-''
/' Jx5*^***

/' // •'
/ .// .•'
X xxx 	 Total
//- ..••'' 	 Intermediate Mode
	 Coarse Mode
	 Accumulation Modi



.ooin i i i i
0.001 0.01 0.1 1 10 10
                                     Age in Years


Figure 10-56.  Specific lung burden (/zg particles/g lung) versus time (age in years)
              predicted by the International Commission on Radiological Protection
              Publication 66 (1994) model, assuming dissolution-absorption half-times of
              10,100, and 1,000 days for the accumulation, intermodal, and coarse
              modes, respectively, of continuous exposures to Philadelphia and Phoenix
              aerosols (described in Appendix IOC) at 50 /zg/m3. Predictions shown for a
              normal augmenter adult male with a general population activity level.
                                       10-203

-------
10.7.6.2   Laboratory Animal Estimates
     Deposition data for two different aerosols, one with an MMAD of 1.0 and og of 1.3, the
other with an MMAD of 2.55 and a og = 2.4 were chosen to calculate total  alveolar retention
(Table 10-33). The aerosol with an MMAD of 1.0 //m and og of 1.3 was chosen as the smallest
particle diameter for which the laboratory animal dosimetry model calculates fractional
deposition and to represent a relatively monodisperse distribution. The aerosol with an MMAD
of 2.55 //m and a og of 2.4 was chosen to approximate a hypothetical PM10 aerosol in which the
PM25 to PM10 sample size cut ratio is 0.6 Dockery and Pope (1994).
          TABLE 10-33. FRACTION OF INHALED PARTICLES DEPOSITED
            IN THE ALVEOLAR REGION OF THE RESPIRATORY TRACT
                       FOR RATS AND ADULT MALE HUMANS
                             	Fraction of Aerosol Deposited in Alveolar Region
 Aerosol Parameters	Rata	Humanb	
 1.0//mMMAD, og= 1.3                 0.063                         0.119
 2.55 //m MMAD, oa = 2.4                0.031                         0.102

"From Tables 10-30 and 10-31.
bFrom (ICRP 66, 1994) average for general population activity pattern (8 h sleeping, 8 h sitting, and 8 h light
 activity) for adult male "normal augmenter" (See Table 10-18).
     Table 10-34 provides fractional deposition data in the alveolar region for three different
aerosols as predicted for the various demograhic groups.  Table 10-35 provides the particle
deposition rates (//g/d) in the alveolar regional for a 24-h exposure to an airborne mass
concentration of 50 //g/m3. Although model simulations of retained particle burdens were not
performed for these various cohorts, differences in retained particle burdens can be expected
because the clearance modeling output is proportional to the deposition fractions used as input.
Note the greater deposition efficiency for the larger diameter aerosols in elderly males and in
those with respiratory disease.
     Table 10-36 summarizes the common and specific parameters used for predicting alveolar
burdens for exposures of humans and rats of the two different aerosols at a concentration of 50
jig particles/m3. Exposures were assumed to take place 24 h/day at the
                                         10-204

-------
                      TABLE 10-34.  FRACTION OF INHALED PARTICLES DEPOSITED IN THE ALVEOLAR
                      REGION OF THE RESPIRATORY TRACT FOR DIFFERENT DEMOGRAPHIC GROUPS
Fraction of Aerosol Deposited in Alveolar Regiona
Aerosol Parameters
0.5 //mMMAD, og = 1
1.0//mMMAD, og = 1
2.55//mMMAD, oe =

3
3
2.4
Male
Worker
(18-44)b
0.085
0.135
0.118
Female Worker (18-44)
or Elderly Female
(over 65)c
0.079
0.125
0.108
Elderly
Male
over 65d
0.085
0.138
0.123
Male
Respiratory
Compromised6
0.086
0.139
0.126
Child
(14-18)f
0.079
0.120
0.091
Child
(6-13)8
0.067
0.098
0.073
Child
(0-5)h
0.069
0.094
0.062
to
o
^Calculated using ICRP Publication 66 lung deposition model with EPA's hourly lung ventilation rates for each demographic group.
bTotal daily volume of air breathed by a male worker is 19.4 m3.
Total daily volume of air breathed by a female worker is 16.5 m3, and 16.1 m3 for a female over age 65.
dTotal daily volume of air breathed by a male over 65 years old is 18.1 m3.
Total daily volume of air breathed by a an adult male with compromised respiratory system is 17.4 m3.
Total daily volume of air breathed by a a child of age 14-18 years is 25.5 m3.
Total daily volume of air breathed by a a child of age 6-13 years is 18.2 m3.
Total daily volume of air breathed by a a child of age 0-5 years is 11.6 m3.
                 TABLE 10-35. PARTICLE DEPOSITION RATES (//g/d) IN THE ALVEOLAR REGION (FOR 24-H
                               EXPOSURE TO AN AIRBORNE MASS CONCENTRATION OF 50
Daily Mass Deposition in Alveolar Region

Aerosol Parameters
0.5 //mMMAD, og
l.OjumMMAD, og
2.55 //m MMAD, a


= 1.3
= 1.3
, = 2.4

Male Worker
(18-44)
82.5
131.3
114.5

Female Worker
(18-44)
65.2
102.8
89.1

Male
over 65
76.9
124.7
111.3
Male
Respiratory
Compromised
74.8
121.2
109.6

Child
(14-18)
100.7
153.0
116.0

Child
(6-13)
61.0
88.7
66.4

Child
(0-5)
40.0
54.6
36.0

-------
       TABLE 10-36.  SUMMARY OF COMMON AND SPECIFIC INHALATION
    EXPOSURE PARAMETERS USED FOR PREDICTING ALVEOLAR BURDENS
                 OF PARTICLES INHALED BY RATS AND HUMANS
A. Common Parameters:
     Exposure atmosphere                             50 (ig/m3
     Particle MMAD, og                               1.0//m, 1.3; or 2.55//m, 2.4
     Particle dissolution-absorption half-time        10, 100, or 1,000 days
     Chronic inhalation exposure pattern                  24 h/day; 7 days/week
     Duration of continuous exposure                    2 years
B. Specific Parameters:  Particle deposition rates in the alveolar region; data calculated using information in Tables
                    10-33 and Appendix 10B, Tables 10B-1 and 10B-2
Species

Rat
Human3
Daily Deposition
of 1.0 //m MMAD, op = 1.3
Mg Mg/g lung
1.14 0.26
118 0.11
of 2.
Mg
0.56
101
Daily Deposition
55 ,um MMAD, op = 2.4
//g/g lung
0.13
0.092
TBased on human deposition parameters from ICRP66 (ICRP, 1994) for an average general population activity
pattern (8 h sleeping, 8 h sitting, and 8 h light activity) for adult male
"normal augmenter" (See Table 10B-1 in Appendix 10B).
average minute respiratory ventilation and deposition fractions presented in Tables 10B-1, 10B-
2, and 10-34.  Daily alveolar deposition was expressed in units of//g particles/g lung to
normalize deposition rates between the two species.  Particle dissolution-absorption rates were
varied; half-times of 10, 100, and 1000 days were used to simulate particles that are relatively
soluble, moderately soluble, and poorly soluble. The A clearance parameters in Table 10-16
derived from the results of acute inhalation exposures of laboratory animals, were used to predict
the consequences of repeated exposures of these animals. For human modeling of acute or
repeated inhalation exposures, the clearance parameters as recommended by the ICRP (ICRP66,
1994) were used in the human model LUDEP® version 1.1 software.
      Table 10-37 shows the calculated alveolar particle burdens of the 1.0 //m MMAD (og =
1.3) aerosol in rats and an adult human normal augmenter for a general population activity
pattern, assuming a particle dissolution-absorption half-time of 10, 100, and 1,000 days,
respectively.  Table 10-38 shows the analogous calculated alveolar particle
                                          10-206

-------
to
o
                      TABLE 10-37. ALVEOLAR PARTICLE BURDENS (//g) OF EXPOSURE TO
                 50 Mg/m3 OF 1.0 ^m MASS MEDIAN AERODYNAMIC DIAMETER (MMAD) AEROSOL,
             ASSUMING PARTICLE DISSOLUTION-ABSORPTION HALF-TIME OF 10,100, OR 1,000 DAYS
Exposure Days
1
7
14
21
28
35
50
75
91
100
150
200
300
400
500
600
700
730

Rat
1.04
5.52
8.31
9.74
10.5
10.9
11.2
11.3
11.3
11.3
11.3
11.3
11.3
11.3
11.3
11.3
11.3
11.3
10 Days
Human
114
642
1020
1250
1380
1460
1540
1570
1580
1580
1580
1580
1580
1580
1580
1580
1580
1580

Rat
1.11
6.96
12.4
16.8
20.2
23.1
27.5
32.1
33.9
34.7
37.4
38.6
39.7
40.1
40.2
40.3
40.3
40.3
100 Days
Human
117
790
1510
2170
2780
3340
4400
5840
6600
6980
8610
9690
10900
11500
11700
11800
11900
11900

Rat
1.11
7.13
13.0
17.8
21.9
25.3
31.2
37.9
40.9
42.4
48.1
51.8
56.6
59.8
62.1
63.9
65.3
65.7
1000 Days
Human
117
808
1580
2310
3020
3700
5090
7210
8460
9160
12700
15900
21600
26400
30500
34100
37100
38000

-------
        TABLE 10-38. ALVEOLAR PARTICLE BURDENS (//g) OF EXPOSURE TO
   50 ^g/rn3 OF 2.55 ^m MASS MEDIAN AERODYNAMIC DIAMETER (MMAD) AEROSOL,
ASSUMING PARTICLE DISSOLUTION-ABSORPTION HALF-TIME OF 10,100, OR 1,000 DAYS







o
to
o
oo









Exposure Days
1
7
14
21
28
35
50
75
91
100
150
200
300
400
500
600
700
730

Rat
0.51
2.70
4.06
4.76
5.12
5.31
5.47
5.53
5.53
5.53
5.53
5.53
5.53
5.53
5.53
5.53
5.53
5.53
10 Days
Human
96.0
542
861
1050
1160
1230
1300
1320
1330
1330
1330
1330
1330
1330
1330
1330
1330
1330

Rat
0.54
3.40
6.07
8.19
9.89
11.3
13.5
15.7
16.6
17.0
18.3
18.9
19.4
19.6
19.6
19.7
19.7
19.7
100 Days
Human
99.1
666
1280
1830
2340
2820
3710
4930
5570
5890
7260
8170
9200
9660
9890
9980
10000
10000

Rat
0.54
3.49
6.34
8.71
10.7
12.4
15.2
18.5
20.0
20.7
23.5
25.3
27.7
29.2
30.4
31.2
31.9
32.1
1000 Days
Human
99.3
681
1330
1950
2540
3120
4290
6080
7140
7730
10700
13400
18200
22200
25800
28700
31300
32000

-------
burdens for the 2.55 //m MMAD (og = 2.4) aerosol. Note the different patterns for
accumulations of A burdens of particles for these species. These simulations suggest that
significant A burdens of particles can be reached with exposures to relatively low aerosol
concentrations of 50  |ig/m3. Particle burdens increase with time until an equilibrium burden is
achieved.  This burden is achieved more rapidly for less soluble particles. The maximal
equilibrium particle burden is much higher for poorly soluble particles and also slightly higher
for the smaller diameter (1 //m) particles.
     The  exposure concentration is representative of environmental ambient aerosols that have
been recorded for numerous American and European cities. An important point to make is that
the composition of the ambient aerosols vary from one place to another and constituents of the
aerosols undoubtedly cover a broad range of solubilization  and absorption characteristics.
Therefore, the composition of the retained particles would be expected to change with time and
the accumulated A burdens would consist of the more persistent types of particles or constituents
of particles present in ambient aerosols. The more soluble, and perhaps more toxic, constituents
of the aerosols will be rapidly absorbed into the circulatory system, metabolized, excreted, or
redeposited in body organs.
     Data in Tables  10-37 and 10-38 were used together with the data in Table 10B-2 to
calculate the //g of particles per gram of lung tissue for each aerosol at each of the assumed
particle dissolution-absorption half-life times. Panels a, b,  and c in Figure 10-57 show the
alveolar particle burdens normalized to lung tissue weight (//g particles per g lung tissue) for the
1.0 //m MMAD (og = 1.3) aerosol assuming particle dissolution-absorption half-times of 10,
100, and 1,000  days,  respectively. Panels a, b,  and c in Figure 10-58 show the alveolar particle
burdens normalized to lung tissue weight (//g particles per g lung tissue) for the 2.55 //m
MMAD (og = 2.4)  aerosol assuming particle dissolution-absorption half-times of 10, 100, and
1,000 days, respectively. The rat alveolar burden is predicted to be greater than that of humans
if a dissolution-absorption half-time of 10 days is assumed  but remains at lower alveolar particle
burdens than the humans if 100  or 1,000 days is assumed for the dissolution-absorption half-
time.
     Figure 10-58 shows the rat and human alveolar particle burdens for the larger diameter and
more polydisperse  aerosol (2.55 //m MMAD, og = 2.4).  At short dissolution-absorption half-
times, the  rat and human are predicted to have very similar alveolar particle burdens,
                                         10-209

-------
                     10-3
                    01
                    c
                    3
                        (a)
                   T!
                   3
                   m  1-
                   a
                   a
                   a

                     0.1-
                   JOO-q
                     0.1
                                 200
                                            400

                                        Days of Exposure
                                                      600
                                                                 800
                                                               • Human
                                                               Rat
                                 200
                                            400

                                        Days of Exposure
                                                       600
                                                                 800
                                 200
                                            400

                                        Days of Exposure
                                                      600
                                                                 800
Figure 10-57.  Predicted retained alveolar dose 0/g/g lung) in a normal augmenter human

               or in a rat for exposure at 50 Mg/m3 to 1.0 //m mass median aerodynamic
               diameter (MMAD) monodisperse (og = 1.3) aerosol, assuming a dissolution-

               absorption half-time of (a) 10 days, (b) 100 days, or (c) 1,000 days.
                                         10-210

-------
                    101
                                                             Rat
                                                             Human
                                                               800
                                                               800
                                200
                                          400
                                       Days of Exposure
                                                     600
                                                               800
Figure 10-58.  Predicted retained alveolar dose 0/g/g lung) in a normal augmenter human
              or in a rat for exposure at 50 Mg/m3 to 2.55 /j,m mass median aerodynamic
              diameter (MMAD) polydisperse aerosol (og = 2.4), assuming a dissolution-
              absorption half-time (a) of 10 days, (b) 100 days, or (c) 1,000 days.
                                        10-211

-------
with the rat having a slightly greater burden at an assumed dissolution-absorpton half-time of
10-days.  At an assumed dissolution-absorption half-time of 100 days, rat alveolar particle
burden less than that of humans. By  1000 days, the rat burden is considerably lower.
     Panels (a) through (c) in Figure 10-59 show the rat to human alveolar retained dose ratios
(//g/d lung) for both aerosols and assuming particle dissolution-absorption half-times of 10, 100,
and 1,000 days, respectively.  Because retention involves clearance processes that can translocate
particle mass, the particle mass burden was normalized to lung tissue weight (//g particles per g
lung tissue). These ratios could be calculated using Equation 10-54 and could be used for
interspecies extrapolation of "chronic" effects. Tables 10-38 and 10-39 provide the (AI^ term.
Tables 10-27 through 10-32 provide the (Frj term  Normaiizing factor data and ventilation
rates for laboratory humans and laboratory animals are provided in Tables 10B-1 and 10B-2,
respectively.  These figures present the RRDRA[ACT] values that would be applied to a given
concentration to calculate an FIEC for the rat for these simulated continuous exposures.  It is
apparent that a substantial range of exposure concentrations would be required to produce the
same specific A burdens in these mammalian species, and the exposure concentrations depend
on the exposure protocol, or study duration.  These results demonstrate the importance of
understanding respiratory, deposition, and physical clearance parameters of humans and
laboratory animals, as well as the dissolution-absorption characteristics of the inhaled particles.
This combination of factors results in significant species differences in A accumulation patterns
of inhaled particles during the course of repeated or chronic exposures which must be considered
in experiments designed to achieve equivalent alveolar burdens, or in evaluating the results of
inhalation exposures of different mammalian  species to the same aerosolized test materials.
     These retained dose ratios are different than those predicted for deposited dose, reflecting
both a difference in normalizing factor as well as differences in clearance rates and the
dissolution-absorption characteristics of the inhaled particles.

10.7.7   Summary
     Major factors that affect the disposition (deposition, uptake, distribution, metabolism, and
elimination) of inhaled particles in the respiratory tract include physicochemical characteristics
of the inhaled aerosol (e.g., particle size, distribution, solubility,
                                          10-212

-------
         (0
         E
         £
         o
         "-5
         tt
             2-
             2
                                                   = 1.0|jmMMAD,og=1.3
                                                   = 2.55 |jm MM AD, og= 2.4
                                                                   (a)
                                                                   (b)
                           200          400         600
                                 Days of Exposure
800
Figure 10-59.  Predicted alveolar region retained dose ratios in rats versus humans for
             chronically inhaled exposure at 50 //g/m3 to 1.0 //m mass median
             aerodynamic diameter (MMAD) monodisperse (og = 1.3) and 2.55 /j,m
             MMAD polydisperse (og = 2.4) aerosols, assuming a dissolution- absorption
             half-time of (a) 10 days, (b) 100 days, or (c) 1,000 days.
                                     10-213

-------
hygroscopicity) and anatomic (e.g., architecture and size of upper and lower airways, airway
diameters, airway lengths, branching patterns) and physiological (e.g., ventilation rates,
clearance mechanisms) parameters of individual mammalian species.
     Differences in susceptibility can be due to either differences in dosimetry (i.e., differences
in deposited and retained particle mass or number) or tissue sensitivity.  The simulations
performed herein were limited to an exploration of differences in dosimetry.  At present,
respiratory tract dosimetry must rely on many simplifications and empiricisms, but even a
somewhat rudimentary effort assists in linking exposure to potential effects, provides insight on
intrahuman variability, and aids interspecies extrapolations.
     The objective of this exercise was to provide useful insights about dose metrics such as
average mass concentrations and average numbers of particles per unit area of respiratory
regions.  Construction of more detailed theoretical or PBPK model structures to explore site-
specific dosimetry at the level of individual lung lobes awaits the availability of data with which
to estimate parameters.
     Dose may be accurately described by particle deposition alone if the particles exert their
primary action on the surface contacted (Dahl et al.,  1991), i.e., deposited dose may be an
appropriate metric for acute effects.  For longer-term effects, the initially deposited dose may not
be as decisive a metric since particles clear at varying rates from different lung regions.  To
characterize these effects, a retained dose that includes the effects of both deposition and
clearance is more appropriate.  For the present document, average deposited particle mass
burden in each region of the respiratory tract was selected as the dose metric for "acute" effects
in both humans and laboratory animals.  Average retained particle mass burden in each region
for humans and in the lower respiratory tract for laboratory animals was selected as the dose
metric for "chronic" effects. These choices were dictated by the availability of the dosimetry
models and the input of anatomical and morphometric information.
     Ventilatory activity pattern and breathing mode (nose or mouth) were confirmed as major
factors affecting inhaled particle deposition.  Variations in mass deposition fraction were  shown
for adult males with a general population activity pattern versus adult male workers with light or
heavy activity patterns. Eight demographic groups were constructed that differed in ventilation
pattern by age, gender, and cardiopulmonary health status. In the alveolar (A) region, the cohort
of children 14 to 18 years showed slightly higher deposition of particles less than approximately
                                          10-214

-------
0.1 (j,m when compared to the other cohorts, whereas the cohort of children 0 to 5 years showed
a decrease. When evaluated on the basis of daily mass deposition (//g/d), the cohort of children
ages 14 to 18 years showed an increase in deposition for all three regions of the respiratory tract
compared to other cohorts, whereas the cohort of children 0 to 5 years showed a decrease. This
is due primarily to differences in minute volume relative to lung size.
     Other differences in dosimetry such as altered respiratory tract architecture with altered
flow pattern or differences in susceptibility of the target tissue are not addressed in these
simulations. As discussed earlier, Anderson et al. (1990) have shown enhanced deposition of
ultrafine particles in patients with COPD compared to healthy subjects.  Miller et al. (1995) used
a more detailed theoretical multipath model and estimated enhanced deposition in a model of
compromised lung status defined by decreased ventilation to some parts of the respiratory tract.
The simulations performed herein were limited to average particle mass burdens in each region
of the respiratory  tract. Nevertheless, these simulations do suggest differences for these cohorts.
For example, the cohort of children 14 to  18 years showed an enhanced deposition rate (ug/d)
for submicron-sized particles in all three respiratory  tract regions whereas children 0 to 5  years
showed a decrease deposition rate relative to male and female adults. For larger particles
(micron-sized and above), the 14 to 18-year cohort showed no enhanced deposition rate in the
tracheobronchial or alveolar regions compared to adults, and younger children cohorts showed a
progressive decrease with decreasing age.
     A number of simulations were performed in order to illustrate the relationship between
deposition efficiency of the respiratory tract, mass burden of particles in the thoracic portion of
the respiratory tract, and the mass distribution of aerosols collected by a PM10 or PM25 sampler.
Simulations were performed for single mode aerosols of different particle diameters. It is clear
that mouth (habitually oronasal) breathers have a greater deposition of particles >1 jim than do
normal augmenter (habitually nasal) breathers. Whereas PM10 accounts for all particles in the
thoracic size deposition mode, the PM2 5 sample does not include some larger particles that
would be deposited in the TB and A regions of mouth breathers, under  the simulated conditions
(general population activity pattern  8 h sleep, 8 h sitting, 8 h light activity). Habitual oronasal
(mouth) breathers do not represent a large percentage of the population, but are cited here to
illustrate the difference effect of breathing habit.
                                          10-215

-------
     Because the real world situation is more complex and ambient aerosols are multi-modal
having a broad distribution of particle size and composition, similar simulations were performed
using ambient aerosols, as characterized for either Philadelphia or Phoenix. These simulations
of ambient aerosols showed that the PM25 sampler distribution accounts for the particle mass in
the fine (<1.0 |im) mode and the transition mode (MMAD -2.5  jim) but does not account for the
smaller mass of coarse mode particles that would be deposited in the thorax (mainly affecting
tracheobronchial deposition in mouth breathers). Failure of PM25 to account for coarse mode
particle thoracic deposition is more severe for the Phoenix aerosol than for the Philadelphia
aerosol.
     Doses  are conventionally expressed in terms of particle mass (gravimetric dose).
However, when different types of particles are compared, doses may be more appropriately
expressed as particle volume, particle surface area, or numbers of particles, depending on the
effect in question (Oberdorster et al., 1994). For example, the retardation of alveolar
macrophage-mediated clearance due to particle overload appears to be better correlated with
phagocytized particle volume rather than mass (Morrow,  1988).  The smaller size fractions of
aerosols are  associated with the bulk of surface area and particle number.  That is, concentrations
in this size fraction are very small by mass but extremely high by number. The need to consider
alternative dose metrics such as number is accentuated when the high rate of deposition of small
particles in the lower respiratory tract (TB and A regions), the putative target for the mortality
and morbidity effects of PM exposures, is also taken into account. Simulations of particle
number deposition fraction for ambient aerosols characterized for Philadelphia and Phoenix
confirm that the fine mode contributes the highest deposition fraction in each region of the
respiratory tract. Particle numbers deposited per day were shown to be on the order of
100,000,000 and 1,000,000,000 for the fine mode of Philadelphia and Phoenix, respectively, for
hypothethical exposure to a total aerosol mass concentration of 50 //g/m3.
     Inhalability is a major factor influencing interspecies variability. At the larger particle
diameters (MMAD > 2.5 //m for g = 1.3), the laboratory animal  species have very little lower
respiratory tract deposition due to the low inhalability of these particles. This may help explain
why inhalation exposures of laboratory animals to high concentrations of larger diameter
particles have exhibited little effect in some bioassays.
                                         10-216

-------
     Simulations of retained particle burdens confirmed solubility as a major factor influencing
clearance. Assumptions with respect to dissolution-halftimes (10, 100, or 1,000 days) were
shown to dramatically influence the predicted particle mass burdens.  Data on in vivo solubility
are needed to enhance modeling of clearance in all species. Retained particle burden
accumulates more rapidly and reaches a higher equilibrium burden when the particles are poorly
                                         10-217

-------
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                                                   10-251

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                                                   10-252

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                APPENDIX 10A


    PREDICTION OF REGIONAL DEPOSITION IN
  THE HUMAN RESPIRATORY TRACT USING THE
INTERNATIONAL COMMISSION ON RADIOLOGICAL
PROTECTION PUBLICATION 66 MODEL
                     10A-1

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10A.1     INTRODUCTION
     This Appendix gives an overview of how the regional deposition values that are calculated
using the ICRP's newly recommended model of the human respiratory tract (ICRP66, 1994)
compare with the available body of experimental data.  A more complete description and
discussion of these data is given in Annexe D (James et al., 1994) of the ICRP66 report.  That
Annexe also discusses both the theoretical model (Egan et al., 1989) of gas and aerosol particle
transport in the human respiratory tract, which underlies ICRP66's analysis of the experimental
data, and ICRP66's methodology in developing the recommended algebraic expressions to
predict regional deposition for various subjects.
     The deposition of particles in the respiratory tract, and the underlying physical mechanisms
that determine regional deposition, have been intensively  studied. However, in the main,
experimental data are available only for the adult Caucasian male, and for a limited range of
particle size (from about l-|im to 10-|im aerodynamic diameter), whereas the application of this
human respiratory tract model is required to be much broader.  Because of the need to
extrapolate the available data to aerosol particles and vapors from atomic dimensions up to very
coarse wind-borne particles, and also to subjects of different body size and level of physical
exertion, the ICRP66 report applied both theoretical and/or empirical modeling methods, as
appropriate, to develop the recommended predictive deposition model.
     Since the publication of ICRP's previous deposition model (TGLD, 1966; ICRP, 1979),
substantial progress has been made in theoretical modeling of aerosol  transport and deposition
within the lungs (Taulbee and Yu, 1975; Pack et al., 1977; Yu, 1978; Nixon and Egan, 1987).
The development of this theoretical modeling approach was reviewed by  Heyder and Rudolf
(1984).  As a working hypothesis, the ICRP66 report utilized the particular formulation
described by Egan and Nixon (1985), and later improved  by Egan et al. (1989), as the basis for
modeling regional aerosol deposition in the lungs of different subjects as  a function of their
respiratory characteristics.
     In parallel with this more fundamental approach to modeling in purely physical terms,
substantial developments have occurred in the analysis  of measured particle deposition in the
respiratory tract in terms of empirically defined parameters (TGLD, 1966; Davies, 1972; Rudolf
et al., 1986, 1990). As a working hypothesis, the ICRP66 report utilized  the parametric analysis
of regional lung deposition developed by Rudolf et al. (1990) to represent the results of complex
                                         10A-2

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theoretical modeling by relatively simple algebraic approximations. The algebraic formulae so
developed and described in the Annexe to ICRP66 constitute ICRP's recommended respiratory
tract deposition model.
     In ICRP66, and in this annex, the term "deposition" denotes the mean probability of an
inspired particle being deposited. The fraction of the number of inhaled particles deposited in
the whole respiratory tract is referred to as "total" deposition. The fraction of the number of
inhaled particles deposited in a single region of the respiratory tract is referred to as "regional"
deposition. The total deposition is therefore the sum of the regional deposition values. The term
"deposition efficiency" denotes the fraction of the number of particles that enter a single region
of the respiratory tract that is deposited in that region.

10A.2    EXTRATHORACIC DEPOSITION
     The processes that govern deposition of particles in the extrathoracic region of the
respiratory tract, i.e., the nose, naso-oropharyngeal passages, and larynx, depend strongly on
particle size (as they do within the thoracic airways). In broad terms, particles with an
aerodynamic diameter larger than about 0.5 jim are deposited primarily by the so-called
"aerodynamic" transport processes of inertial motion, referred to as "impaction," and
gravitational settling, referred to as "sedimentation." For very large particles and fibers,
interception with surfaces in the extrathoracic airways also contributes to their deposition.
Particles with an equivalent physical diameter less than a few tenths of a micrometer are
deposited primarily by the "thermodynamic" transport process of Brownian "diffusion."

10A.2.1  Nasal Deposition
     The aerodynamic filtration efficiency of the nose is much better documented than that of
any other part of the respiratory tract. A large number of studies have been reported for aerosols
with aerodynamic particle diameters above 0.2 jim.  These studies have been reviewed by
Mercer (1975), Lippmann (1977), Yu et al. (1981), Schlesinger (1985a), and Stahlhofen  et al.
(1989). As discussed in Annexe D of ICRP66, different experimental techniques and evaluation
procedures were used in the various studies, and the  published data are not all directly
comparable. The artificial technique of measuring nasal deposition when aerosol particles were
drawn in continuously through the nose and exhausted through  a filter at the mouth gave

                                         10A-3

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generally lower values than other techniques which utilized normal breathing.  Accordingly,
ICRP66 fitted the recommended empirical model of nasal deposition efficiency to the
experimental data obtained with normal breathing.
     Figure 10A-1 shows the experimental data on the aerodynamic deposition efficiency of the
nose during normal inspiration, plotted as a function of the inertial impaction parameter, d^e V,
where dae is the aerodynamic particle diameter (in jim), and V is the volumetric flow rate (in cm3
s"1). Each of the studies by Lippmann (1970), Giacomelli-Maltoni et al. (1972), and Rudolf
(1975) exhibit a large degree of variability in nasal deposition measured in different subjects.
     ICRP66 adopted the empirical analysis reported by Rudolf et al. (1986) and Stahlhofen et
al. (1989) to represent the trend of the mean of these data for aerodynamic deposition efficiency
of the nose on inhalation in terms of the impaction parameter, dae V. The recommended function
is shown in Figure 10A-l(a), together with the estimated 95% confidence bounds based on the
variability of the data.  The fitted function accounts for the observed slow increase in deposition
efficiency for low values of dae V, and also predicts an asymptotic approach to unity for high
values of this impaction parameter.  As shown in the figure, for intermediate values of dae V, the
predicted deposition efficiency is similar to that given by Pattle's (1961) log-linear
approximation,  which was adopted by the Task Group on Lung Dynamics (TGLD, 1966).
     Nasal deposition for submicron-sized particles has not been studied intensively in human
subjects. Accordingly, to define the "thermodynamic" deposition efficiency of the nose, ICRP66
relied on the experimental measurements made in hollow, anatomical casts of the nasal airways
(Swift et al., 1992).  (See ICRP66 Annexe D for discussion of these data, and their empirical
representation).

10A.2.2    Oropharyngeal Deposition
     Most experimental studies of oropharyngeal deposition have been performed with mouth
breathing through a tube, since this is a convenient method for aerosol administration. The oral
deposition was measured by repeated mouth-washings directly after inhalation. The remainder
of the extrathoracic deposition, i.e., that in the oropharynx and larynx, was measured by external
gamma counting. Emmett and Aitken (1982)  showed that, for particles
                                         10A-4

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                     4- Giacomelli-Maltom etal. (1972)
                     CD Martens and Jacob! (1973)
                     • Lippmann (1970)
                     X Rudolf (1975)
                    	ICRP Publication 66 (1994)

                    --•TGLD(1966)
                                 •       , ,

                                  *
                                             1000
                                       Impaction Parameter,
                                                                          100,000
                              Stahlhofen etal. (1980,1981 a, 1983)
                              Lippmann (1977)
                            o Chan and Lippmann (1980)
                            	 ICRP Publication 66 (1994)
                                       100            1000
                                         Impaction Parameter, X
                                                                  10,000
Figure 10A-1.  Nasal deposition efficiency measured in adult Caucasian males during
                normal breathing (A) and data on extrathoracic deposition when particles
                are inhaled and exhaled through a mouthpiece (B). The solid curves show
                the empirical model used in ICRP Publication 66 (1994).  The outer curves
                on either side represent the estimated 95% confidence bounds in predicted
                extrathoracic deposition based on the variability of the data. The heavy
                dashed line in (A) shows the expression for nasal deposition efficiency used
                in the ICRP Publication 30 (1979) lung model (TGLD, 1966). The
impaction parameter, x, is described in the text as dae2 V° 6 VT ° 2
                                                                                     cm
                                                                                        1 2
                s"'6).
Source: ICRP Publication 66 (1994).
                                          10A-5

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less than about 10-|im aerodynamic diameter, the bulk of the extrathoracic deposition during
mouth breathing occurs in the larynx.
     Figure 10A-l(b) compares the experimental data on extrathoracic deposition during mouth
breathing through tube mouthpieces obtained by Lippmann (1977), Chan and Lippmann (1980),
and Stahlhofen et al. (1980, 198la, 1983).  Again, the measured variability in extrathoracic
deposition is high. The curves shown in the figure represent the empirical model adopted in
ICRP66 to describe the underlying trend of deposition efficiency as a function of an impaction
parameter, (see also Figure 10-22 of Chapter 10), together with the upper and lower 95%
confidence bounds of this estimate.

10A.2.3   Scaling for Body  Size
     Extrathoracic deposition has not been studied systematically in children, nor has the degree
to which the intersubject variability measured in adult subjects is related to variation in
anatomical dimensions. In the absence of data, ICRP66 utilized the dimensional scaling
procedure proposed by Swift (1989) to predict the effect of a subject's body size on nasal and
oropharyngeal deposition of particles in the aerodynamic size-range, and by Cheng et al. (1988)
to predict body-size effects on thermodynamic deposition efficiency, in relation to values
modeled for a reference adult male.
10A.3     REGIONAL LUNG DEPOSITION
     Although the experimental data obtained for the adult human male are sufficient to model
empirically and accurately the deposition efficiency of the lungs as a whole, as a function of
breathing behavior and particle size (Rudolf et al., 1983, 1986), they are not complete enough
nor mutually consistent enough to define precisely the regional deposition in a reference adult
male, nor the effects of different airway size in other subjects.  ICRP66 therefore used the
theoretical model developed by Egan and Nixon (1985), and Nixon and Egan (1987), as updated
by Egan et al. (1989),  to predict the effects of breathing behavior and airway size on the
deposition of particles in discrete anatomical regions of the lungs, i.e.,  in the bronchial (BB),
bronchi olar (bb), and alveolar-interstitial (Al) airways, of various subjects. These theoretical
predictions formed the basis for the simplified algebraic model of regional deposition in the

                                         10A-6

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lungs of various subjects that is recommended in ICRP66, and is applied in Chapter 10. The
model evaluates the combined effects of convective and diffusive gas transport, and aerosol loss
processes, within the airways of the lungs, on the basis of the mathematical formalisms
introduced by Taulbee and Yu (1975) and Pack et al. (1977).

10A.3.1   Comparison with Data from GSF Frankfurt Laboratory
      Stahlhofen et al. (1980, 1981a,b, 1983) measured the fractional deposition of insoluble
monodisperse aerosols of iron oxide particles labeled with 198Au, in a total of nine different
subjects under closely controlled breathing conditions. In these tests, the subjects inhaled and
exhaled particles of various sizes through a mouthpiece, at a constant flow rate of either 250 cm3
s"1 or 750 cm3 s"1.  Four different tidal volumes were studied: 250 cm3, 500 cm3, 1000 cm3 at the
flow rate of 250 cm3 s"1, and 1500 cm3 at the flow rate of 750 cm3 s"1.  The fraction of inhaled
gamma activity deposited initially in the thorax was measured using a calibrated and
well-characterized array of collimated NaI(Tl)-detectors. The retention of the deposited iron
oxide particles in the lungs (obtained by correcting the thorax measurements for the activity of
particles cleared to the stomach) was followed in each subject for several days. In general, two
distinct phases of particle retention were observed: an initial rapid phase, succeeded by
continued slow clearance with a fitted half-time of several tens of days. The exponential
clearance curve fitted to the "slow-cleared" fraction was extrapolated back to the time of
exposure to define the complementary "fast-cleared" fraction of the initial lung deposit. The
"slow-" and "fast-cleared" fractions of the thoracic deposit are conventionally assumed to
represent particles deposited in the A  region and tracheobronchiolar airways (BB and bb
regions), respectively.
      To simulate these experimental data, ICRP66 utilized the theoretical deposition model of
Egan et al. (1989) to calculate the expected fractional deposition summed for all airways in the
A region and the combined BB and bb regions.  Figures 10A-2 and 10A-3 compare the
theoretical predictions of tracheobronchiolar and alveolar-interstitial deposition, respectively,
with the "fast-" and "slow-cleared" fractions of thoracic deposition measured at the GSF
Frankfurt Laboratory.
      It is seen from these figures that both measured fractions of the thoracic deposition exhibit
substantial variability under otherwise identical experimental conditions (as does the
                                         10A-7

-------
  c
  o
  u
  ra
  •o
  0)
  ra
  4)
  ui
  (9
      1.0
      0.8
      0.6
      0.4
     : 0.2
   l/=250mLs'1;VT =1000mL
 * Stahlhofen et al. (1980)
 A Stahlhofen et al. (1981 a)
 v Stahlhofen etal. (1981b)
— Deposition Theory
~ ~ Including Slow Mucus
             v   •*.
                                                      V= 750 mL s"1; VT = 1500
                                                     Stahlhofen etal. (1980)
      0.8
      0.6
      0.4
      0.2
                        -1.
   l/=250mLs
  1 Stahlhofen et al. (1983)
 l/=250ml_s ,' l/T  =250 ml
• Stahlhofen etal. (1983)
                                10           15 0           5
                                Particle Aerodynamic Diameter (|jm)
                                                            10
                                                                        15
Figure 10A-2.  Comparisons of the "fast-cleared" fraction of lung deposition measured at
               the GSF Frankfurt Laboratory with the tracheobronchiolar deposition
               predicted by the theoretical model (shown by the solid curves) of Egan et al.
               (1989). The dashed curves show the effect on the predicted "fast-cleared"
               fraction of allowing for slow clearance of a fraction of the number of
               particles deposited in the tracheobronchiolar airways. This "slow-cleared"
               fraction is assumed to tend to zero for large particles.

Source: ICRP Publication 66 (1994).
total thoracic deposition). It is also seen that, overall, the calculated deposition curves provide
an accurate prediction of the trends in measured values with particle aerodynamic diameter.
                                          10A-8

-------
      1.0
            1/=250mLs-; VT  =1000 ml
                         A Stahlhofen etal. (1980)
                           Stahlhofen era/. (1981 a)
                           Stahlhofen ef a/. (1981 b)
                         — Deposition Theory
                         - - Including Slow Mucus
            V= 250 mL s'1; V-^ = 500 ml
             Stahlhofen era/. (1983)
  = 750 mL s'1; Vr = 1500 mL
   Stahlhofen etal. (1980)
                                               0.3
                                               0.2
                                               0.1
l/=250mLs'1;VT =250mL
A Stahlhofen ef al. (1983)
                             10          15       0          5
                               Particle Aerodynamic Diameter (u.m)
                 10
                             15
Figure 10A-3. Comparisons of the "slow-cleared" fraction of lung deposition measured
               at the GSF Frankfurt Laboratory with the alveolar deposition predicted
               by the theoretical model (shown by the solid curves) of Egan et al. (1989).
               The dashed curves show the effect on the predicted "slow-cleared"
               fraction of allowing for additional slow clearance of a fraction of the
               number of particles deposited in the tracheobronchiolar airways.

Source:  ICRP Publication 66 (1994).
     In Figure 10A-2, except for the experiments carried out at a flow rate of 250 cm3 s"1

and a low tidal volume of 250 cm3 (Figure 10A-2(d)), it is seen that the predicted curves
match the measured "fast-cleared" fractions.  The closest match is obtained for the

experiments carried out at a flow rate of 750 cm3 s"1 and tidal volume of 1500 cm3
                                          10A-9

-------
approximates the breathing rate of ICRP66's "reference worker." The apparently poor match to
the data at low flow rate and low tidal volume arises principally from the two measurements for
12-|im-aerodynamic-diameter particles. Bronchial deposition efficiency for these particles
should clearly be substantially higher than for the next smallest particles (of 7.5-|im aerodynamic
diameter).  The fact that the measured efficiency is lower suggests an experimental artifact in
correcting for extrathoracic particle losses.
     On the whole, the predicted deposition fractions are seen to match the data with increased
accuracy as the particle aerodynamic diameter is increased. For several of the smallest particle
sizes studied, there is a general tendency for the predicted tracheobronchial deposition to be
higher than the measured "fast-cleared" fraction. However, for these particles (with
aerodynamic diameter less than about 5 jim), the fit of the predicted curves to the measured
values is significantly improved by allowing for the incomplete "rapid" clearance of particles
deposited in the human tracheobronchial tree that has been observed directly in other
experimental studies. Those studies were discussed in detail in Annexe E (Bailey and Roy,
1994) of ICRP66. Based on that discussion, ICRP66 concluded that, for particles with a
physical  diameter of 2.5 jim  or less,  only 50% of the number deposited in the tracheobronchial
airways is cleared rapidly. The remaining 50% is cleared at a rate that is indistinguishable
experimentally from particles deposited in the alveolar-interstitial airways. For larger particles,
the fraction of the tracheobronchial deposition that is cleared slowly is found to decrease steeply
with particle size. The dashed curves shown in Figure 10A-2 make allowance for slow clearance
of a part of the tracheobronchial deposition. It is seen that, by making this allowance, the  fit of
the predicted "fast-cleared" fraction to the measured values is improved.
     Figure 10A-3 compares the experimental data and theoretical predictions of the
complementary "slow-cleared" fraction of lung deposition.  For particles with aerodynamic
diameter 5  jam or greater, the fit between predicted and measured values is generally good.
Allowance for part of the predicted tracheobronchiolar deposition being cleared slowly is again
seen to improve the predictions for smaller particles.
                                         10A-10

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10A.3.2   Comparison with Data for Polystyrene Particles
     The GSF Laboratory used a so-called "academic" breathing pattern, in which the subject
inhaled and exhaled at a closely controlled rate. Other investigators exposed their subjects under
so-called "spontaneous" breathing conditions, where the subject maintains a more natural
variation in flow rate through the breathing cycle, but is trained to achieve a relatively constant
tidal volume and respiratory frequency. In this manner, Foord et al. (1978) measured the
fractional deposition of 99mTc-labelled polystyrene particles in the mouth and lungs of 15
different subjects. The lung deposition was divided into a "tracheobronchiolar" fraction, which
was assumed to consist of the activity cleared from the lungs within 24 h of inhalation, and the
remaining "pulmonary" fraction.  These authors used three different sizes of particles, i.e.,
2.5-|im, 5-|im, and 7.5-|im diameter, and studied regional deposition for several different
breathing patterns. Figure 10A-4 shows their results for 6 subjects (with an average tidal
volume of 1 L, and a mean respiratory frequency of 10 min"1), together with the deposition of
99mTc-labelled polystyrene particles in the lungs of 12  different subjects measured by Emmett
and Aitken (1982), using the same breathing pattern.
     The figure shows that, after correcting for the  extrathoracic deposition measured for each
test, the recommended lung deposition model accurately matches the trend of tracheobronchiolar
"deposition" with particle size measured by Foord et al (1978).  (See panel labeled "TB"). The
calculated curve here includes ICRP66's recommended allowance for an  assumed fraction of
50% the TB deposition of the 2.5-|im particles not being cleared from the TB region within the
24-h measurement period. The tracheobronchiolar deposition reported by Emmett and Aitken
(1982), i.e., the activity deposited in the lungs that is cleared within 24 h, is generally higher
than that found by Foord et al.  (1978),  with relatively  little variability between the three subjects
studied at each particle size.
     The panel labeled "A" in  Figure 10A-4 shows  the measured values  of activity deposited in
the lungs that was retained longer than 24 h. In this case, the data of Foord et al. are generally
higher than the modeled values, while Emmett and Aitken's values are lower by a similar factor.
Both sets of data show  a similar trend of "slow-cleared" lung deposition with particle size to that
modeled, but with higher or lower absolute values, respectively, for the same breathing pattern.
                                         10A-11

-------
                     0.8
                   §
                   s
                     0.6
                   8
                   ffl
                   .1
                     0.4
                     0.2 ~
                         TB
                                      I
                                                            I
                                     4       6      8      10
                                     Aerodynamic Diameter dim)
12
                                     468
                                     Aerodynamic Diameter (jim)
                                                            10
Figure 10A-4. Comparison of fractional deposition measured by Foord et al. (1978)
              (solid triangles) and Emmett and Aitken (1982) (open triangles) in
              different subjects with values given by the International Commission on
              Radiological Protection (ICRP) Publication 66 (1994) lung model (solid
              curves).  The fractional deposition shown has been adjusted to
              correspond to zero extrathoracic deposition in the tracheobronchial (TB)
              and alveolar (A) regions.  The dashed curves  represent the upper and
              lower 95% confidence bounds of regional deposition predicted for an
              individual subject by the ICRP lung model.

Source:  ICRP Publication 66 (1994).
                                       10A-12

-------
     When the experimental data on thoracic deposition in "fast-" and "slow-cleared" fractions
are pooled, as is done in Figure 10A-4, the deposition model recommended in ICRP66
represents the data as a whole. It is also seen from Figure 10A-4 that ICRP66's estimated 95%
confidence bounds on regional lung deposition predicted for individual subjects include all but 3
of the data points.

10A.3.3   Comparison with Data for Submicron-Sized Particles
     For particles in the submicron, thermodynamic size range (with equivalent diameter
between about 5 nm and 0.2 |im), extrathoracic deposition during mouth breathing (in the oral
cavity and larynx) is small compared to that in the lungs.  Schiller et al. (1986)  measured the
total respiratory tract deposition for several subjects exposed via a mouthpiece to monodisperse,
uncharged spherical particles  of silver over a range of particle diameter extending from 5 nm to
about 0.2 jim. These experimental results were corrected by Gebhart et al. (1989) for the effects
of instrumental dead space, which tended to reduce the measured deposition fraction for
nanometer-sized particles. Egan and Nixon  (1989) compared the resulting mean values of total
thoracic deposition with the values predicted by the theoretical model developed by Egan et al.
(1989).  These authors showed that the theoretically modeled fractional deposition in the lungs
matches the measured values. Figure 10A-5 shows that the calculated values also represent the
data obtained earlier for hydrophobic submicron-sized spheres of aluminosilicate by Tu and
Knutson (1984).

10A.3.4   Influence of "Controlled" Versus "Spontaneous" Breathing
     The data from the GSF Frankfurt Laboratory shown above apply to controlled breathing at
a constant inspiratory and expiratory flow rate, whereas, during normal spontaneous breathing,
the flow rate varies throughout each breath in an approximately sinusoidal manner.  However,
Heyder et al. (1982) showed in a study of 20 different subjects that the mean total deposition for
spontaneous breathing is virtually identical to that for controlled breathing at the same average
flow rate.  Heyder et al.'s data are given in Figure  10A-6, together with the values predicted for a
reference male subject by the ICRP66 lung model. It is seen that, for both controlled and
spontaneous mouth breathing, there is a large amount of variation
                                        10A-13

-------
            80
            70
            60
       £,   50
       §
       s
       to
       g.   40
       8
           30
            20
            10
                  A Subject K-1000 mL
                  • Subject Y-1000 mL
                  ° Subject Y-750 mL
                 	ICRP 66-1000 mL
                 	ICRP66-750mL
                  B
            0
             0.01
                                               I
        0.1
Particle Diameter (urn)
Figure 10A-5. Comparison of total respiratory tract deposition of submicron-sized
              alumino-silicate particles measured by Tu and Knutson (1984) in two
              subjects (at tidal volumes of 1000 mL or 750 mL), with the values
              calculated as a function of particle diameter by Egan et al. (1989).
              The ICRP Publication 66 (1994) lung model reproduces these calculated
              values.

Source: ICRP Publication 66 (1994).
between different subjects, although in any one subject under controlled breathing conditions,
total deposition measurements are highly repeatable (Heyder et al., 1982).
                                       10A-14

-------
                        Spontaneous Breathing
                     1.0
                  o
                  15
                  a
                  o
                    0.8  —
                     0.6  —
                     0.4  —
                     0.2  —
                                  246
                                       Particle Diameter (urn)
                         Controlled Breathing
                      1.0
                      0.8
                      0.6
                      0.4
                      0.2
                           B
Single Subject

Different Subjects

ICRPPublication66
  I	I	i
                        024           68
                                       Particle Diameter (urn)

Figure 10A-6. Comparison of the distributions of total respiratory tract deposition
              measured in 20 different subjects (A) breathing spontaneously at rest or
              (B) breathing at a controlled rate at rest.  In case (A), the individual
              mean flow rate varied from 220 to 740 mL/s, with a collective mean value
              of 380 mL/s. In case (B), the mean flow rate was held constant at
              400 mL/s for each subject.  Each box shown in the figure represents one
              experimental measurement.  Shaded boxes represent repeat
              measurements on a single subject (see inset key in bottom figure).  The
              curves show values predicted by the ICRP Publication 66 (1994) model.

Source:  ICRP Publication 66 (1994).
                                        10A-15

-------
10A.3.5       Comparison with Data for Iron Oxide Particles from New York
               University
     Lippmann (1977) and Chan and Lippmann (1980) reported measurements of lung
deposition and 24-h retention in a large number of different subjects at New York University
(NYU). These studies involved iron oxide particles tagged in aqueous suspension with 99mTc
(Wales et al., 1980). Each subject was allowed to breath normally, and the average tidal volume
and breathing frequency were monitored. Typical values of these respiratory parameters were
500 cm3 s"1 and 15 min"1, respectively.
     Figure 10A-7 shows the values of "fast-" and "slow-cleared" lung deposition obtained in
these studies at NYU (adjusted from the measured value to zero extrathoracic deposition).  In
common with the earlier theoretical lung deposition models described by Yeh and Schum (1980)
and Yu and Diu (1982b), and with the NCRP's currently proposed lung model, ICRP66's
deposition model predicts substantially less bronchial ("fast-cleared") deposition for particles of
aerodynamic diameter larger than 1  jim than is indicated by the bulk of the NYU data.
Likewise, the predicted alveolar ("slow-cleared") deposition for particles of about l-|im
aerodynamic diameter is also low compared to the NYU data.
     These data from NYU provide an excellent measure of intersubject variability in the
deposition efficiencies of the tracheobronchiolar and alveolar-interstitial regions of the lungs.
However, according to ICRP66's review of the literature, the interpretation of the NYU results is
complicated by the possibility that the labeled iron oxide particles used may have grown
hygroscopically in the humid air of the respiratory tract. Monodisperse iron oxide particles are
produced by atomization of an aqueous suspension of colloidal iron oxide with a spinning top
generator (Albert et al., 1964; Lippmann and Albert, 1967; Stahlhofen et al., 1979). The
colloidal suspension is prepared by converting iron chloride in aqueous solution by hydrolysis to
iron oxide.  In order to remove all traces of the dissolvable chloride, the aqueous iron oxide
colloid must be dialyzed extremely thoroughly.
     Gebhart et al. (1988) used light-scattering photometry to examine the effect of the degree
to which a suspension of colloidal iron oxide is dialyzed on the hygroscopicity of the resulting
monodisperse particles, by comparing the physical properties of these particles on inhalation and
exhalation. These authors found that even when the particles are produced from extremely well
dialyzed iron oxide there is a distinct change in light-scattering
                                        10A-16

-------
                                     1               10
                                   Aerodynamic Diameter (urn)
                                100
                    0.1
  1               10
Aerodynamic Diameter (urn)
                         Chan & Lippmann (1980)    •  Lippmann (1977)
Figure 10A-7. Experimental data on deposition efficiency of the tracheobronchial (TB)
              region and fractional deposition in the alveolar (A) region for the large
              group of subjects studied at New York University (NYU). These subjects
              inhaled monodisperse particles of iron oxide through a mouthpiece at a
              tidal volume of approximately 1000 mL and respiratory frequency of
              15/min.   The measured values are normalized to zero extrathoracic
              deposition. The curves show the corresponding values predicted by the
              NCRP (proposed) and ICRP Publication 66 (1994) models. Two curves
              are shown for the ICRP 66 model:  (1) "no growth" represents the values
              calculated on the assumption  that the size  of the iron oxide particles was
              stable in  the respiratory tract, and (2) "with growth" represents the
              partial hygroscopic growth of similar  particles indicated by the
              experimental study of Gebhart et al. (1988). The lower figure (marked
              as "A") also shows the characteristic particle collection efficiency curve
              for a PM10 sampler.

Source:  Adapted from ICRP Publication 66 (1994).
                                      10A-17

-------
properties between the inhaled and exhaled particles.  Since the total respiratory tract deposition
of these particles was indistinguishable from that of oil droplets of the same aerodynamic size in
ambient air, Gebhart et al. (1988) concluded that their measured shift in optical properties was
caused by the presence of a thin film of condensed water on the surface of the exhaled particles.
     Using this same technique on a sample of the dialyzed iron oxide suspension prepared at
NYU by their published method (Wales et al., 1980), Gebhart et al. (1988) found a much greater
shift in light-scattering properties of the final monodisperse particles between inhalation and
exhalation. This observed shift in light-scattering properties was accompanied by increased total
respiratory tract deposition compared with that of oil droplets of the same aerodynamic size in
ambient air. The deposition measured under identical exposure conditions was found to increase
from 44% for the hydrophobic oil droplets to 68% for the iron oxide particles.  The same change
in measured respiratory tract deposition would be obtained by inhaling oil droplets of 3.8-|im
aerodynamic diameter in place of the 2.4-|im-aerodynamic-diameter iron oxide particles.
     The ICRP66 report includes a recommended method for extending the algebraic deposition
model to evaluate regional lung deposition for aerosols that are subject to hygroscopic particle
growth. Figure 10A-7 shows the effect on the modeled fast- and slow-cleared lung deposition
including in the calculation the rate of hygroscopic growth of the NYU iron oxide particles that
was derived from the results of the Gebhart  et al. (1988) study. It is seen that this correction of
the modeled lung deposition improves substantially the overall fit of the predicted values to the
measurements.
                                         10A-18

-------
        APPENDIX 10B
SELECTED MODEL PARAMETERS
             10B-1

-------
              TABLE IQB-l(a). BODY WEIGHT AND RESPIRATORY TRACT REGION SURFACE AREAS
Respiratory Tract Surface Areas
Body Weight (kg) Lung Weight (g)

o
td
K>




73.0
TABLE
Activity
Pattern

Adult male,
general
population
Adult male,
light work
Adult male,
heavy work
1,100
10B-l(b). HUMAN ACTIVITY PATTERNS AND
Sleeping Sitting
(.45 m3/h) (.54 m3/h)
Hours Total m3 Hours Total m3
8 3.6 8 4.32

8 3.6 6.5 3.5

8 3.6 4 2.16

ET (cm2) TB (cm2)
470
2,690
ASSOCIATED RESPIRATORY MINUTE
Activity Light
(1.5m3/h)
Hours Total m3
8 12

8.5 12.75

10 15

Activity Heavy
(3.0m3/h)
Hours Total m3
0 0

1 3

2 6

A(m2)
54.0
VENTILATION
Total/Day
Hours Total m3
24 19.9

24 22.85

24 26.76

international Commission on Radiological Protection (ICRP66, 1994).

-------
       TABLE 10B-2. BODY WEIGHTS, LUNG WEIGHTS, RESPIRATORY MINUTE VENTILATION, AND RESPIRATORY
                      TRACT REGION SURFACE AREA FOR SELECTED LABORATORY ANIMAL SPECIES


Lung
Body Weight Weight13
Species
Mouse (B6C3F1)
Syrian hamster
Rat (F344)
Guinea pig
Monkey
Dog
(kg)
0.037a
0.134a
0.380a
0.890a
2.5C
10.0d
(R)
0.43b
1.54b
4.34b
10.1b
28. Ob
110.0d
Minute
Ventilation13
Minute
Ventilation
per g lung
(L/min) (1/min • g lung)
0.044a
0.057a
0.253a
0.286a
0.789b
2.39b
0.063
0.049
0.040
0.034
0.028
0.022
Respiratory Region Surface Area

ET (cm2
3a
14a
15a
30a
NAe
NAe

) TB (cm
3.5a
20.0a
22.5a
200a
NAe
NAe

2) A(m2)
0.05a
0.30a
0.34a
0.90a
4.3f
42.5f
o
td
aU.S. Environmental Protection Agency (1994, 1988a). Default values for male laboratory animals in chronic bioassays.
bStahl, 1967:  lung weight in g = 11.3 • (kg BW)°"; minute ventilation = 379 • (kg BW)08.
Thalen(1984).
dCuddihyetal. (1972).
"Not available.
fScaled from results of dogs and baboons in Crapo et al. (1983).

-------
                                     8     12     16
                                       Hour of the Day
       24
zu •
To
ID
4A •







Elderly Male (over 65 yr)



••<








^•H








5L
h^M








S






>.6L
^
r








f


















1:
•••*








3.8L
I f









^











13.0L














X,






                                     8     12     16
                                       Hour of the Day
20
                                                                24
                                     8      12      16
                                       Hour of the Day
                                                                24
Figure 10B-1. Daily minute volume pattern for male demographic groups. The average
              rates for each of four time intervals are shown.  Total volume (m3)
              breathed in 24 hours for male worker (18-44 yr) is 19.4; for elderly male
              (over 65 yr) is 18.1; and for compromised subjects is 17.4.
                                       10B-4

-------
                 Female worker (18-44 yr)
                                 8       12       16
                                    Hour of the Day
 20
 24
                 Elderly Female (over 65 yr)
                                8        12       16
                                   Hour of the Day
20
24
Figure 10B-2. Daily minute volume pattern for female demographic groups. The
             average rates for each of four tune intervals are shown. Total volume
             (m3) breathed in 24 hours for female worker (18-44 yr) is 16.5 and for
             elderly female (over 65 yr) is 16.1.
                                     10B-5

-------
                   
-------
       APPENDIX IOC


SELECTED AMBIENT AEROSOL
  PARTICLE DISTRIBUTIONS
            10C-1

-------
 0)
8

7
 E   6
 o
 E   5  -
 3   3  -

                                                                  EAAC_]
                                                                  220
                                                                  245
              Electrical aerosol analyzer^>
     2  -
     1  -
0.002
                0.01
                                           1
10
100
                                        DP (|jm)
Figure 10C-1.  An example of histogram display and fitting to log-normal functions for
              particle-counting size distribution data. Instruments used and the range
              covered by each are shown. Counts are combined into reasonably-sized
              bins and displayed. Lognormal functions, fitted to the data, are shown
              with geometric mass median diameter (MMD) of each mode and the width
              (og) of each mode. Data taken from a study of fine sulfate and other
              particles generated by catalyst equipped cars as part of a cooperative study
              by EPA and General Motors Corporation.  Note the clear separation of the
              nuclei mode (MMD = 0.018 /j,m), the accumulation mode (MMD = 0.21 /j,m)
              and coarse mode (MMD = 4.9 /j,m). Fine particles, as defined by Whitby
              (1978), include the nuclei and accumulation mode.

Source: Wilson et al. (1977).
                                      10C-2

-------
o
                   TABLE 10C-1 DISTRIBUTION OF PARTICLE COUNT, SURFACE AREA OR MASS IN THE
                              TRIMODAL POLYDISPERSE AEROSOL DEFINED IN FIGURE 10C-1
     (The tabulated numbers represent the upper size cut [in jim] for each particle size interval based on the distribution of particle
      count vs. physical diameter [d p{c}], distribution of surface area vs. physical diameter [dp{s|], distribution of mass vs. physical
                            diameter [dn{m}], or distribution of mass vs. Aerodynamic diameter [dae{m}]a.)
Percent of Total Count,
Aerosol Mode
Accumulation11



Intermodal0



Coarse4



Particle Parameter
count; dp{c}
surface; dp{s}
mass; dp{m}
mass; dae{m}
count; dp{c}
surface; dp{s}
mass; dp{m}
mass; dae{m}
count; dp{c}
surface; dp{s}
mass; dp{m}
mass; dq(,{m}
1
0.0053
0.0058
0.0060
0.0056
0.044
0.050
0.053
0.044
0.915
1.06
1.14
1.40
5
0.0073
0.0080
0.0083
0.078
0.066
0.075
0.080
0.066
1.40
1.63
1.75
2.14
10
0.0087
0.0094
0.010
0.093
0.081
0.093
0.099
0.083
1.76
2.04
2.20
2.68
20
0.011
0.012
0.012
0.011
0.105
0.120
0.128
0.108
2.32
2.69
2.89
3.52
Surface Area or Mass Associated with Particles
30
0.012
0.013
0.014
0.013
0.127
0.145
0.154
0.131
2.83
3.28
3.53
4.29
40
0.014
0.015
0.016
0.015
0.149
0.170
0.181
0.155
3.35
3.88
4.18
5.08
50
0.016
0.017
0.018
0.017
0.173
0.197
0.210
0.180
3.93
4.55
4.90
5.95
60
0.018
0.019
0.020
0.019
0.201
0.228
0.244
0.211
4.60
5.34
5.75
6.98
70
0.020
0.022
0.023
0.022
0.235
0.268
0.286
0.248
5.45
6.32
6.81
8.27
Smaller than Size
80
0.024
0.026
0.027
0.025
0.283
0.323
0.345
0.301
6.66
7.71
8.30
10.1
90
0.029
0.032
0.033
0.031
0.367
0.418
0.447
0.437
8.76
10.2
10.9
13.2
Cut
95
0.034
0.037
0.039
0.037
0.454
0.517
0.551
0.485
11.0
12.7
13.7
16.6

99
0.047
0.051
0.054
0.051
0.676
0.768
0.820
0.725
16.8
19.5
20.9
25.3
    ^Values for dae were calculated iterative ly from dp using Equations D. 13 and D. 14 of ICRP Publication 66, Annexe D
     (James et al, 1994).
    bMass median aerodynamic diameter (MMAD) = 0.018 (jm; geometric standard deviation (og) = 1.6; density (p) =1.4 g/cm3.
CMMAD = 0.21
dMMAD = 4.9 ^
                  m; og = 1.8; p = 1.2 g/cm3.
                  ;  o = 1.87; p = 2.2 g/cm3.

-------
     TABLE 10C-2a. DISTRIBUTION OF PARTICLE NUMBER IN THE
   TRIMODAL POLYDISPERSE AEROSOL DEFINED IN FIGURE 10C-1
(Each individual mode of the trimodal aerosol is separated into the size fractions
containing the 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% number fractiles.
   The "nuclei mode" contains about 99.6% of the total number of particles;
 the "accumulation mode" about 0.39%; and the "coarse mode" about Q.01%.)
Mode Number Fractile (%)
Nuclei3 1
5
10
20
30
40
50
60
70
80
90
95
99
Accumulation13 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
1.0
4.0
5.0
10
10
10
10
10
10
10
10
5.0
4.0
0.004
0.0159
0.0198
0.0397
0.0397
0.0397
0.0397
0.0397
0.0397
0.0397
0.0397
0.0198
0.0159
Upper Limit of Particle
Size Interval (|im)
0.0027
0.0038
0.0045
0.0055
0.0064
0.0073
0.0082
0.0092
0.0105
0.0122
0.0149
0.0177
0.0244
0.0156
0.0233
0.0289
0.0374
0.0450
0.0528
0.0613
0.0711
0.0834
0.101
0.130
0.161
0.241
                                10C-4

-------
      TABLE 10C-2a (cont'd). DISTRIBUTION OF PARTICLE NUMBER IN THE
        TRIMODAL POLYDISPERSE AEROSOL DEFINED IN FIGURE 10C-1
     (Each individual mode of the trimodal aerosol is separated into the size fractions
     containing the 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% number fractiles.
        The "nuclei mode" contains about 99.6% of the total number of particles;
      the "accumulation mode" about 0.39%; and the "coarse mode" about Q.01%.)
Mode Number Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
2.7 >
1.1 >
1.3 >
2.7 >
2.7 >
2.7 >
2.7 >
2.7 >
2.7 >
2.7 >
2.7 >
1.3 >
1.1 >
< 10'7
< ID'6
< 10'6
< 10'6
< ID'6
< 10'6
< 10'6
< ID'6
< 10'6
< ID'6
< 10'6
; 10'6
= ID'6
Upper Limit of Particle
Size Interval (|im)
0.283
0.432
0.543
0.716
0.873
1.03
1.21
1.42
1.68
2.05
2.71
3.40
5.21
aMass median diameter (MMD) = 0.018 (jm; geometric standard deviation (og) = 1.6;
density (p) =1.4 g/cm3.
bMMD = 0.21 ^m; og = 1.8; density (p) = 1.2 g/cm3.
CMMD = 4.9 ^m; o = 1.87; density (p) = 2.2 g/cm3.
                                       10C-5

-------
   TABLE 10C-2b. DISTRIBUTION OF PARTICLE SURFACE AREA IN THE
     TRIMODAL POLYDISPERSE AEROSOL DEFINED IN FIGURE 10C-1
   (Each individual mode of the trimodal aerosol is separated into the size fractions
containing the 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% surface area fractiles.
   The "nuclei mode" contains about 77.4% of the total particle surface area; the
     'accumulation mode" about 21.9%; and the "coarse mode" about Q.64%.)
Mode Surface Area Fractile (%)
Nuclei3 1
5
10
20
30
40
50
60
70
80
90
95
99
Accumulation13 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.78
3.1
3.9
7.8
7.8
7.8
7.8
7.8
7.8
7.8
7.8
3.9
3.1
0.22
0.89
1.1
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
1.1
0.89
Upper Limit of Particle
Size Interval (|im)
0.0043
0.0059
0.0070
0.0086
0.0100
0.0113
0.0127
0.0144
0.0163
0.0189
0.0233
0.0277
0.0381
0.0312
0.0465
0.0575
0.0746
0.0899
0.105
0.122
0.142
0.167
0.201
0.260
0.322
0.481
                                   10C-6

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  TABLE 10C-2b (cont'd).  DISTRIBUTION OF PARTICLE SURFACE AREA IN THE
        TRIMODAL POLYDISPERSE AEROSOL DEFINED IN FIGURE 10C-1
     (Each individual mode of the trimodal aerosol is separated into the size fractions
  containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% surface area fractiles.
      The "nuclei mode" contains about 77.4% of the total particle surface area; the
        'accumulation mode" about 21.9%; and the "coarse mode" about Q.64%.)
Mode Number Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.006
0.026
0.032
0.064
0.064
0.064
0.064
0.064
0.064
0.064
0.064
0.032
0.026
Upper Limit of Particle
Size Interval (|im)
0.618
0.947
1.19
1.57
1.91
2.27
2.65
3.11
3.69
4.50
5.92
7.44
11.4
aMass median diameter (MMD) = 0.018 (jm; geometric standard deviation (og) = 1.6;
density (p) =1.4 g/cm3.
bMMD = 0.21 ^m; og = 1.8; density (p) = 1.2 g/cm3.
CMMD = 4.9 ^m; o = 1.87; density (p) = 2.2 g/cm3.
                                       10C-7

-------
      TABLE 10C-2c.  DISTRIBUTION OF PARTICLE MASS IN THE
   TRIMODAL POLYDISPERSE AEROSOL DEFINED IN FIGURE 10C-1
(Each individual mode of the trimodal aerosol is separated into the size fractions
 containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% mass fractiles.
The "nuclei mode" contains 15.6% of the total particle mass; the "accumulation
            mode" 38.7%; and the "coarse mode" about 45.7%.)
Mode Mass Fractile (%)
Nuclei3 1
5
10
20
30
40
50
60
70
80
90
95
99
Accumulation13 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.16
0.63
0.79
1.58
1.58
1.58
1.58
1.58
1.58
1.58
1.58
0.79
0.63
0.39
1.56
1.95
3.91
3.91
3.91
3.91
3.91
3.91
3.91
3.91
1.95
1.56
Upper Limit of Particle
Size Interval (|im)
0.0053
0.0073
0.0087
0.0107
0.0124
0.0141
0.0159
0.0179
0.0203
0.0236
0.0290
0.0345
0.0474
0.0312
0.0465
0.0575
0.0746
0.0899
0.105
0.122
0.142
0.167
0.201
0.260
0.322
0.481
                                10C-8

-------
       TABLE 10C-2c (cont'd). DISTRIBUTION OF PARTICLE MASS IN THE
        TRIMODAL POLYDISPERSE AEROSOL DEFINED IN FIGURE 10C-1
     (Each individual mode of the trimodal aerosol is separated into the size fractions
      containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% mass fractiles.
     The "nuclei mode" contains 15.6% of the total  particle mass; the "accumulation
               mode" about 38.7%; and the "coarse mode" about 45.7%.)
Mode Number Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.46
1.85
2.31
4.62
4.62
4.62
4.62
4.62
4.62
4.62
4.62
2.31
1.85
Upper Limit of Particle
Size Interval (|im)
0.915
1.40
1.76
2.32
2.83
3.35
3.93
4.60
5.45
6.66
8.76
11.0
16.9
aMass median diameter (MMD) = 0.018 (jm; geometric standard deviation (og) = 1.6;
density (p) =1.4 g/cm3.
bMMD = 0.21 ^m; og = 1.8; density (p) = 1.2 g/cm3.
CMMD = 4.9 ^m; o = 1.87; density (p) = 2.2 g/cm3!.
                                       10C-9

-------
            0)
            o
              90.0
                                    Philadelphia-WRAC
                                  1.0                10.0
                                 Aerodynamic Diameter, pe (|jm)
                                     100.0
                                       Phoenix-WRAC
                         Mode
                          1
                          2
                          3
 MMAD   oq  %Mass
 0.188    1.54    22.4
 1.70    1.90    13.8
16.4     2.79    63.9
                                  1.0                10.0
                                 Aerodynamic Diameter, pe (|jm)
                                     100.0
Figure 10C-2.  Impactor size distribution measurement generated by Lundgren et al. with
               the Wide Range Aerosol Classifier:  (a) Philadelphia and (b) Phoenix. Note
               the much larger, small size tail to the coarse mode in the dryer environment
               of Phoenix.


Source: Lundgren and Hausknecht (1982).
                                        10C-10

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o
O
                  TABLE 10C-3.  DISTRIBUTION OF PARTICLE COUNT, SURFACE AREA OR MASS IN THE
                 TRIMODAL POLYDISPERSE AEROSOL FOR PHILADELPHIA DEFINED IN FIGURE 10C-2(a)
     (The tabulated numbers represent the upper size cut [in jim] for each particle size interval based on the distribution of particle
     count vs. aerodynamic diameter [dae{c}], distribution of surface area vs. aerodynamic diameter [dae{s|], distribution of mass vs.
                  aerodynamic diameter [dae{m}], or distribution of mass vs. equivalent physical diameter [dn{m}]a.)
Percent of Total Count,
Aerosol Mode
Accumulation11



Intermodal0



Coarse4



Particle Parameter
count; dae{c}
surface; dae{s}
mass; dae{m}
mass; dp{m}
count; dae{c}
surface; dae{s}
mass; dae{m}
mass; dp{m}
count; dae{c}
surface; dae{s}
mass; dae{m}
Mass; dp{m}
1
0.152
0.162
0.167
0.185
1.53
1.54
1.55
1.67
3.43
4.29
4.80
5.16
5
0.201
0.214
0.221
0.243
1.70
1.72
1.73
1.86
5.80
7.25
8.12
8.73
10
0.233
0.249
0.257
0.282
1.79
1.80
1.81
1.95
7.67
9.60
10.7
11.5
20
0.280
0.298
0.308
0.336
1.92
1.93
1.94
2.09
10.8
13.5
15.1
16.2
Surface Area or Mass Associated with Particles Smaller than Size Cut
30
0.319
0.340
0.351
0.383
2.01
2.03
2.04
2.20
13.8
17.2
19.2
20.6
40
0.357
0.381
0.393
0.428
2.09
2.11
2.12
2.28
16.9
21.2
23.7
25.5
50
0.396
0.422
0.436
0.474
2.17
2.19
2.20
2.37
20.6
25.7
28.8
30.9
60
0.440
0.469
0.484
0.526
2.26
2.28
2.29
2.47
25.0
31.3
35.0
37.6
70
0.492
0.525
0.541
0.587
2.35
2.37
2.38
2.56
30.8
38.6
43.2
46.4
80
0.561
0.597
0.618
0.670
2.47
2.49
2.50
2.69
39.4
49.2
55.1
59.2
90
0.673
0.717
0.741
0.802
2.63
2.66
2.67
2.87
55.3
69.0
77.3
83.0
95
0.781
0.831
0.860
0.930
2.78
2.80
2.81
3.02
73.1
91.4
102.1
109.7
99
1.03
1.10
1.13
1.22
3.06
3.09
3.11
3.34
122.5
153.5
171.5
184.2
    ^Values for dp were calculated iteratively from dae using Equations D. 13 and D. 14 of ICRP Publication 66, Annexe D (James et al., 1994).
    bMass median aerodynamic diameter (MMAD) = 0.436 (jm; geometric standard deviation (og) = 1.51; density (p) =1.3 g/cm3.
    CMMAD  = 2.20 ^m; og = 1.16; p = 1.3 g/cm3.
    dMMAD  = 28.8 pm; o = 2.16; p = 1.3 g/cm3.

-------
        TABLE 10C-4a. DISTRIBUTION OF PARTICLE NUMBER IN THE
     TRIMODAL POLYDISPERSE PHILADELPHIA AEROSOL DEFINED IN
FIGURE 10C-2a (Each individual mode of the trimodal aerosol is separated into the size
   fractions containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% number
   fractiles. The "accumulation mode" contains  about 99.95% of the total number of
 particles; the "intermodal mode" about 0.05%;  and the "coarse mode" about Q.004%.)
Mode Number Fractile (%)
Accumulation" 1
5
10
20
30
40
50
60
70
80
90
95
99
Intermodalb 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
1.0
4.0
5.0
10
10
10
10
10
10
10
10
5.0
4.0
4.8 x 1C'4
1.9 x 1C'3
2.4 x 1C'3
4.8 x 1Q-3
4.8 x 1Q-3
4.8 x 1C'3
4.8 x 1C'3
4.8 x 1C)'3
4.8 x 1C)'3
4.8 x icr3
4.8 x icr3
2.4 x icr3
1.9 x icr3
Upper Limit of Particle
Size Interval (|im)
0.0912
0.121
0.140
0.168
0.192
0.215
0.238
0.264
0.296
0.337
0.404
0.469
0.623
1.43
1.60
1.68
1.79
1.88
1.96
2.03
2.12
2.20
2.31
2.47
2.59
2.89
                                  10C-12

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      TABLE 10C-4a (cont'd). DISTRIBUTION OF PARTICLE NUMBER IN THE
       TRIMODAL POLYDISPERSE PHILADELPHIA AEROSOL DEFINED IN
 FIGURE 10C-2a (Each individual mode of the trimodal aerosol is separated into the size
    fractions containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% number
    fractiles. The "accumulation mode" contains about 99.95% of the total number of
  particles; the "intermodal mode" about 0.05%; and the "coarse mode" about Q.004%.)
Mode Number Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
4.4 x lO'5
1.8 x lO'4
2.2 x 1Q-4
4.4 x lO'4
4.4 x lO'4
4.4 x lO'4
4.4 x 1Q-4
4.4 x lO'4
4.4 x lO'4
4.4 x lO'4
4.4 x 1Q-4
2.2 x lO'4
1.8 x lO'4
Upper Limit of Particle
Size Interval (|im)
0.579
0.979
1.30
1.82
2.32
2.86
3.48
4.22
5.21
6.65
9.34
12.3
20.9
aMass median aerodynamic diameter (MMAD) = 0.436 (jm; geometric standard deviation (og) = 1.51;
density (p) =1.3 g/cm3.
bMMAD = 2.20 ^m; og =1.16; density (p) = 1.3 g/cm3.
CMMAD = 28.8 pm; og = 2.16; density (p) = 1.3 g/cm3.
                                      10C-13

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    TABLE 10C-4b. DISTRIBUTION OF PARTICLE SURFACE AREA IN THE
     TRIMODAL POLYDISPERSE PHILADELPHIA AEROSOL DEFINED IN
FIGURE 10C-2a (Each individual mode of the trimodal aerosol is separated into the size
 fractions containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% surface area
 fractiles. The "accumulation mode" contains about 95.4% of the total particle surface
    area; the "intermodal mode" about 2.5%; and the "coarse mode" about 2.1%.)
Mode Surface Area Fractile (%)
Accumulation" 1
5
10
20
30
40
50
60
70
80
90
95
99
Intermodalb 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.96
3.9
4.8
9.6
9.6
9.6
9.6
9.6
9.6
9.6
9.6
4.8
3.9
0.025
0.10
0.13
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.13
0.10
Upper Limit of Particle
Size Interval (|im)
0.128
0.170
0.197
0.236
0.269
0.301
0.334
0.371
0.415
0.473
0.568
0.659
0.875
1.50
1.66
1.75
1.88
1.96
2.05
2.13
2.21
2.30
2.41
2.57
2.73
3.02
                                   10C-14

-------
  TABLE 10C-4b (cont'd). DISTRIBUTION OF PARTICLE SURFACE AREA IN THE
       TRIMODAL POLYDISPERSE PHILADELPHIA AEROSOL DEFINED IN
 FIGURE 10C-2a (Each individual mode of the trimodal aerosol is separated into the size
  fractions containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% surface area
  fractiles. The "accumulation mode" contains about 95.4% of the total particle surface
      area; the "intermodal mode" about 2.5%; and the "coarse mode" about 2.1%.)
Mode Surface Area Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.02
0.08
0.11
0.21
0.21
0.21
0.21
0.21
0.21
0.21
0.21
0.11
0.08
Upper Limit of Particle
Size Interval (|im)
1.90
3.20
4.24
5.95
7.60
9.37
11.4
13.8
17.0
21.8
30.5
40.4
68.1
aMass median aerodynamic diameter (MMAD) = 0.436 (jm; geometric standard deviation (og) = 1.51;
density (p) =1.3 g/cm3.
bMMAD = 2.20 Mm; og =1.16; density (p) = 1.3 g/cm3.
CMMAD = 28.8 pm; o  = 2.16; density (p) = 1.3 g/cm3.
                                      10C-15

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         TABLE 10C-4c. DISTRIBUTION OF PARTICLE MASS IN THE
     TRIMODAL POLYDISPERSE PHILADELPHIA AEROSOL DEFINED IN
FIGURE 10C-2a (Each individual mode of the trimodal aerosol is separated into the size
fractions containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% mass fractiles.
  The "accumulation mode" contains 48.2% of the total particle mass; the "intermodal
                   mode" 7.4%; and the "coarse mode" 44.3%.)
Mode Mass Fractile (%)
Accumulation" 1
5
10
20
30
40
50
60
70
80
90
95
99
Intermodalb 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.49
2.0
2.4
4.9
4.9
4.9
4.9
4.9
4.9
4.9
4.9
2.4
2.0
0.07
0.30
0.37
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.37
0.30
Upper Limit of Particle
Size Interval (|im)
0.152
0.201
0.233
0.280
0.319
0.357
0.396
0.440
0.492
0.561
0.673
0.782
1.04
1.53
1.70
1.79
1.92
2.01
2.09
2.17
2.26
2.35
2.47
2.63
2.78
3.06
                                   10C-16

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       TABLE 10C-4c (cont'd). DISTRIBUTION OF PARTICLE MASS IN THE
       TRIMODAL POLYDISPERSE PHILADELPHIA AEROSOL DEFINED IN
 FIGURE 10C-2a (Each individual mode of the trimodal aerosol is separated into the size
 fractions containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% mass fractiles.
   The "accumulation mode" contains 48.2% of the total particle mass; the "intermodal
                     mode" 7.4%; and the "coarse mode" 44.3%.)
Mode Mass Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.45
1.8
2.2
4.5
4.5
4.5
4.5
4.5
4.5
4.5
4.5
2.2
1.8
Upper Limit of Particle
Size Interval (|im)
3.43
5.80
7.67
10.8
13.7
16.9
20.6
25.0
30.8
39.2
55.0
72.4
118.7
aMass median aerodynamic diameter (MMAD) = 0.436 (jm; geometric standard deviation (og) = 1.51;
density (p) =1.3 g/cm3.
bMMAD = 2.20 Mm; og =1.16; density (p) = 1.3 g/cm3.
CMMAD = 28.8 pm; o = 2.16; density (p) = 1.3 g/cm3.
                                       10C-17

-------
o
O
i
oo
                TABLE 10C-5. DISTRIBUTION OF PARTICLE COUNT, SURFACE AREA OR MASS IN THE TRIMODAL
          POLYDISPERSE AEROSOL FOR PHOENIX DEFINED IN FIGURE 10C-2(b) (The tabulated numbers represent the upper
           size cut [in um] for each particle size interval based on the distribution of particle count vs. aerodynamic diameter [dae{c|],
            distribution of surface area vs. aerodynamic diameter [dae{s|], distribution of mass vs. aerodynamic diameter [d^jm}], or
                                       distribution of mass vs. equivalent physical diameter [dn{m}]a.)
Percent of Total Count,
Aerosol Mode
Accumulation11



Intermodal0



Coarse4



Particle Parameter
count; dae{c}
surface; dae{s}
mass; dae{m}
mass; dp{m}
count; dae{c}
surface; dae{s}
mass; dae{m}
mass; dp{m}
count; dae{c}
surface; dae{s}
mass; dae{m}
mass; dp{m}
1
0.062
0.066
0.069
0.062
0.302
0.353
0.381
0.353
0.831
1.24
1.51
1.41
5
0.083
0.089
0.092
0.083
0.469
0.548
0.592
0.552
1.67
2.49
3.03
2.34
10
0.097
0.104
0.108
0.098
0.592
0.691
0.747
0.697
2.43
3.61
4.40
4.13
20
0.118
0.126
0.131
0.119
0.785
0.916
0.991
0.926
3.81
5.67
6.92
6.50
Surface Area or Mass Associated with Particles Smaller than Size Cut
30
0.135
0.145
0.150
0.137
0.962
1.12
1.21
1.13
5.28
7.85
9.58
8.99
40
0.152
0.163
0.169
0.155
1.14
1.34
1.45
1.36
6.97
10.4
12.7
11.9
50
0.169
0.182
0.188
0.172
1.35
1.57
1.70
1.59
9.04
13.4
16.4
15.4
60
0.189
0.203
0.210
0.193
1.58
1.85
2.00
1.87
11.7
17.4
21.3
20.0
70
0.212
0.228
0.236
0.217
1.89
2.20
2.38
2.23
15.5
23.0
28.1
26.4
80
0.243
0.261
0.271
0.250
2.31
2.70
2.91
2.73
21.4
31.9
38.9
36.5
90
0.295
0.316
0.327
0.303
3.06
3.58
3.87
3.63
33.7
50.0
61.1
57.4
95
0.345
0.369
0.383
0.355
3.87
4.52
4.89
4.59
48.8
72.6
88.4
83.0
99
0.461
0.495
0.511
0.475
5.96
6.95
7.52
7.06
97.4
144.8
176.9
166.2
        ^Values for dp were calculated iteratively from dae using Equations D. 13 and D. 14 of ICRP Publication 66, Annexe D (James et al., 1994).
        bMass median aerodynamic diameter (MMAD) = 0.188 (jm; geometric standard deviation (og) = 1.54; density (p) = 1.7 g/cm3.
        CMMAD  = 1.70 ^m; og = 1.90; p = 1.7 g/cm3.
        dMMAD  = 16.4 ^m; o = 2.79; p = 1.7 g/cm3.

-------
       TABLE 10C-6a.  DISTRIBUTION OF PARTICLE NUMBER IN THE
TRIMODAL POLYDISPERSE PHOENIX AEROSOL DEFINED IN FIGURE 10C-2b
   (Each individual mode of the trimodal aerosol is separated into the size fractions
  containing the 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% number fractiles.
 The "accumulation mode" contains about 99.6% of the total number of particles; the
        "intermodal mode" about 0.3%; and the "coarse mode" about Q.1%.)
Mode Number Fractile (%)
Accumulation3 1
5
10
20
30
40
50
60
70
80
90
95
99
Intermodalb 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
1.0
4.0
5.0
10
10
10
10
10
10
10
10
5.0
4.0
0.0034
0.014
0.017
0.034
0.034
0.034
0.034
0.034
0.034
0.034
0.034
0.017
0.014
Upper Limit of Particle
Size Interval (|im)
0.0353
0.0475
0.0556
0.0672
0.0771
0.0867
0.0967
0.108
0.122
0.139
0.169
0.197
0.264
0.0878
0.136
0.172
0.228
0.280
0.333
0.391
0.461
0.548
0.673
0.891
1.13
1.74
                                  10C-19

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      TABLE 10C-6a (cont'd). DISTRIBUTION OF PARTICLE NUMBER IN THE
  TRIMODAL POLYDISPERSE PHOENIX AEROSOL DEFINED IN FIGURE 10C-2b
     (Each individual mode of the trimodal aerosol is separated into the size fractions
    containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% number fractiles.
   The "accumulation mode" contains about 99.6% of the total number of particles; the
          "intermodal mode" about 0.3%; and the "coarse mode" about Q.1%.)
Mode Number Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
9.3 >
3.7 >
4.6 >
9.3 >
9.3 >
9.3 >
9.3 >
9.3 >
9.3 >
9.3 >
9.3 >
4.6 >
3.7 >
< ID'4
< 10'3
< 10'3
< 10'3
< 10'3
< 10'3
< 10'3
< 10'3
< 10'3
< 10'3
< 10'3
< 10'3
< 10'3
Upper Limit of Particle
Size Interval (|im)
0.0353
0.0711
0.103
0.162
0.224
0.296
0.385
0.499
0.658
0.912
1.43
2.08
4.18
aMass median aerodynamic diameter (MMAD) = 0.188 (jm; geometric standard deviation (og) = 1.54;
density (p) =1.7 g/cm3.
bMMAD = 1.70 ^m; og = 1.90; density (p) = 1.7 g/cm3.
CMMAD = 16.4 ^m; o = 2.79; density (p) = 1.7 g/cm3.
                                       10C-20

-------
   TABLE 10C-6b. DISTRIBUTION OF PARTICLE SURFACE AREA IN THE
TRIMODAL POLYDISPERSE PHOENIX AEROSOL DEFINED IN FIGURE 10C-2b
   (Each individual mode of the trimodal aerosol is separated into the size fractions
containing the 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% surface area fractiles.
The "accumulation mode" contains about 85.5% of the total particle surface area; the
        "intermodal mode" about 7.4%; and the "coarse mode" about 7.0%.)
Mode Surface Area Fractile (%)
Accumulation" 1
5
10
20
30
40
50
60
70
80
90
95
99
Intermodalb 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.86
3.5
4.3
8.6
8.6
8.6
8.6
8.6
8.6
8.6
8.6
4.3
3.5
0.075
0.30
0.37
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.37
0.30
Upper Limit of Particle
Size Interval (|im)
0.0514
0.0689
0.0807
0.0977
0.112
0.126
0.141
0.157
0.176
0.202
0.244
0.285
0.385
0.202
0.311
0.392
0.520
0.637
0.758
0.892
1.05
1.25
1.53
2.03
2.57
3.97
                                  10C-21

-------
  TABLE 10C-6b (cont'd).  DISTRIBUTION OF PARTICLE SURFACE AREA IN THE
  TRIMODAL POLYDISPERSE PHOENIX AEROSOL DEFINED IN FIGURE 10C-2b
     (Each individual mode of the trimodal aerosol is separated into the size fractions
  containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% surface area fractiles.
    The "accumulation mode" contains about 85.5% of the total particle surface area;
        the "intermodal mode" about 7.4%; and the "coarse mode" about 7.0%.)
Surface Area
Mode Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.07
0.29
0.36
0.71
0.71
0.71
0.71
0.71
0.71
0.71
0.71
0.36
0.29
Upper Limit of Particle
Size Interval (|im)
0.290
0.583
0.847
1.33
1.84
2.43
3.16
4.09
5.40
7.48
11.8
17.1
34.4
aMass median aerodynamic diameter (MMAD) = 0.188 (jm; geometric standard deviation (og) = 1.54;
density (p) =1.7 g/cm3.
bMMAD = 1.70 Mm; og = 1.90; density (p) = 1.7 g/cm3.
CMMAD = 16.4 ^m; o = 2.79; density (p) = 1.7 g/cm3.
                                       10C-22

-------
         TABLE 10C-6c. DISTRIBUTION OF PARTICLE MASS IN THE
TRIMODAL POLYDISPERSE PHOENIX AEROSOL DEFINED IN FIGURE 10C-2b
   (Each individual mode of the trimodal aerosol is separated into the size fractions
    containing the 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% mass fractiles.
 The "accumulation mode" contains 22.4% of the total particle mass; the "intermodal
                 mode" 13.8%; and the "coarse mode" 63.9%.)
Mode Mass Fractile (%)
Accumulation3 1
5
10
20
30
40
50
60
70
80
90
95
99
Intermodalb 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.23
0.91
1.1
2.3
2.3
2.3
2.3
2.3
2.3
2.3
2.3
1.1
0.91
0.14
0.56
0.70
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
0.70
0.56
Upper Limit of Particle
Size Interval (|im)
0.0618
0.0832
0.0973
0.118
0.135
0.152
0.169
0.189
0.213
0.243
0.295
0.345
0.462
0.302
0.469
0.592
0.785
0.962
1.14
1.35
1.58
1.89
2.31
3.06
3.87
6.00
                                  10C-23

-------
       TABLE 10C-6c (cont'd). DISTRIBUTION OF PARTICLE MASS IN THE
  TRIMODAL POLYDISPERSE PHOENIX AEROSOL DEFINED IN FIGURE 10C-2b
     (Each individual mode of the trimodal aerosol is separated into the size fractions
      containing the 1, 5,10, 20, 30, 40, 50, 60, 70, 80, 90, 95, and 99% mass fractiles.
   The "accumulation mode" contains 22.4% of the total particle mass; the "intermodal
                     mode"  13.8%; and the "coarse mode" 63.9%.)
Mode Mass Fractile (%)
Coarse0 1
5
10
20
30
40
50
60
70
80
90
95
99
Percent of Trimodal
Aerosol
0.65
2.6
3.2
6.5
6.5
6.5
6.5
6.5
6.5
6.5
6.5
3.2
2.6
Upper Limit of Particle
Size Interval (|im)
0.831
1.67
2.43
3.81
5.27
6.96
9.03
11.7
15.5
21.4
33.5
48.4
94.1













aMass median aerodynamic diameter (MMAD) = 0.188 (jm; geometric standard deviation (og) = 1.54;
density (p) =1.7 g/cm3.
bMMAD = 1.70 Mm; og = 1.90; density (p) = 1.7 g/cm3.
CMMAD = 16.4 urn; o = 2.79; density (p) = 1.7 g/cm3.
                                       10C-24

-------
               11.  TOXICOLOGICAL STUDIES OF
                       PARTICULATE  MATTER

11.1  INTRODUCTION
     This chapter assesses results of exposure to paniculate matter (PM) in controlled human
clinical studies, selected occupational studies, and animal toxicology studies. It focuses mainly
on those studies published since the 1982 Air Quality Criteria Document for Particulate Matter
and Sulfur Oxides (U.S. Environmental Protection Agency, 1982), emphasizing coverage of
selected constituents of ambient air PM that may contribute to those types of health effects found
by epidemiological studies discussed in Chapter 12 of this document.  The data discussed in
Chapter 12 indicate that increased levels of PM in the ambient atmosphere are associated with
increased mortality risk, especially among the elderly (aged 65+ years) and individuals with
preexisting cardiopulmonary diseases,  such as chronic obstructive pulmonary disease (COPD),
pneumonia, and chronic heart disease.  The epidemiology studies also provide evidence for
associations of ambient PM exposures with increased risk of respiratory  and cardiovascular
morbidity effects (e.g., increased hospital admissions or emergency room visits for asthma or
other respiratory problems, increased incidence of respiratory symptoms, or alterations in
pulmonary function).
     Chronic obstructive pulmonary disease is defined as a disease state characterized by the
presence of airflow obstruction due to  chronic bronchitis or emphysema; the airflow obstruction
is generally progressive, may be accompanied by airway hyperreactivity, and may be partially
reversible (American Thoracic Society, 1995). The biological responses occurring in the
respiratory tract following controlled PM inhalation encompass a continuum of changes,
including changes in pulmonary function, respiratory symptoms (i.e., wheeze, coughing, etc.),
inflammation, and tumor formation. The responses observed are dependent on the
physicochemical characteristics of the  parti culate matter, the total exposure and the health status
of the host. However, many of the responses are usually seen only at distinctly higher level
exposures characteristic of occupational and laboratory animal studies but not at typically much
lower ambient particle concentrations.
                                         11-1

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     Particulate matter is a broad term that encompasses thousands of chemical species, many of
which have not been investigated in controlled laboratory animal or human studies.  However, a
full discussion of all the types of particles that have been studied is well beyond the scope of this
chapter.  Thus,  criteria were used to select topics for presentation. High priority was placed on
studies that: (1) may elucidate health effects of major common constituents of ambient PM
(e.g., sulfates, carbon, silica) and/or (2) contribute to enhanced understanding of the
epidemiological studies (e.g., real-world particles, "surrogate" particles; or particles with low
inherent toxicity that may cause effects due to their generic nature as a particle, such as their
ultrafine size).  Based on these criteria, full summaries of acid aerosols, ultrafme particles, real-
world particles, and "surrogate" particles are provided.
     Diesel exhaust particles generally fit the criteria; but, because they are described in great
detail elsewhere (U.S. Environmental Protection Agency, 1994; Health Effects Institute, 1995),
they are only summarized briefly here. Diesel particles also differ from other particles in this
classification because they are regulated pursuant to mobile source sections of the Clean Air Act
(g/mi emission  standards), although there is still a relationship of these regulations to the PM10
standard.  Medium priority was placed on particles with high inherent toxicity that are of
concern primarily because of point source emissions and more local exposures (as contrasted to
ubiquitous pollutants). Metals having air concentrations greater than 0.5 //g/m3 were placed in
this class.  The  health effects of particles in this prioritization class are summarized  far more
briefly here. It must be emphasized that this prioritization is not related to a judgement or
decision about potency or health risk. For example, it should not be inferred that on an
individual exposure basis, a "high priority" particle  is of more inherent health concern than a
"medium priority" particle.  The split is primarily related to regulatory issues.  The Clean Air
Act requires a criteria document for criteria pollutants. Except for lead, individual metals are
not criteria pollutants.  Rather, they are regulated  as hazardous air pollutants under the Clean Air
Act. Thus, their inclusion here is only intended to be generally instructive because they can be
part of the complex mixture of PM in the ambient air.
     As noted above, lead is a criteria air pollutant that, like paniculate matter, is also regulated
under Sections  108 and 109 of the Clean Air Act. Earlier extensive evaluations in Air Quality
Criteria for Lead (U.S. Environmental Protection  Agency, 1977) led to setting of
                                           11-2

-------
the current National Ambient Air Quality Standard (primary as well as secondary) for lead at
1.5 //g/m3 on a quarterly average basis (Federal Register, 1978 [51594]). Subsequent to
promulgation of that standard, the U.S. Environmental Protection Agency issued a revised Air
Quality Criteria for Lead (1986a) and a Supplement (U.S. Environmental Protection Agency,
1990). These and other such assessments found blood lead levels of 10 //g/dl in young children
and women of child bearing age (due to risk to the fetus in utero) to be associated with
unacceptable risk of slowed prenatal and  postnatal growth and neuropsychological development.
Air levels below 0.50 to 0.75 //g/m3 lead  have been proposed as adequate to protect against such
risk (World Health Organization, 1987).  Typical  ambient air levels of lead in U.S. urban areas
almost invariably now fall below 0.10 to  0.25 //g/m3. The reader is referred to the above-noted
air quality criteria documents/supplement and Federal Register notices concerning the lead
National  Ambient Air Quality Standard for detailed information on particulate lead health
effects.
     In some widespread geographic areas of the United States, silica can be among major
ambient PM constituents and is discussed briefly here.  The reader is referred to more extensive
evaluation of silica elsewhere (U.S. Environmental Protection Agency, 1996). Asbestos fibers
are also well established as a fibrogenic pollutant  and they are known to cause mesothelial
tumors following chronic exposures in laboratory animals. However, asbestos is not discussed
as a separate entity in the present document, but reviews on asbestos effects can be found
elsewhere (U.S. Environmental Protection Agency, 1986b; Mossman and Gee, 1989;  Rom, et
al., 1991; Health Effects Institute, 1991).
     The effects of exposure to combinations of particles or particles and gases are important to
understand because people are not exposed to single ambient air pollutants. The responses to
pollutant mixtures may be different from those of the individual chemical constituents.  Effects
can be additive, antagonistic, or synergistic. Controlled exposure studies of humans or animals
rarely involve more than two pollutants simultaneously or sequentially. Significant exceptions
to this are the bodies of work on diesel and gasoline engine emissions, where the exposure has
been to the specific mixture.  In studies involving more complex mixtures (e.g., ambient air) it is
difficult,  if not impossible, to assess the relative contributions of individual specific components.

-------
The different nature of the data bases also influences the structure of the chapter. For example,
community epidemiology studies that sought associations between health effects and some type
of ambient PM metric are described in Chapter 12 to permit full portrayal and integrated
evaluation of the results. For the metals and diesel particles, discussed to reach a different goal,
epidemiological studies are included here in Chapter 11 to facilitate a full hazard identification,
and as appropriate, exposure-response information. Besides the summary of the effects portion
of the literature, this chapter also attempts to identify and characterize key factors that may have
significant influences on the health effects of PM.
     Most of the investigations reported herein were conducted with laboratory animals, raising
the question of their quantitative extrapolation to humans. Of the dosimetric and species
sensitivity aspects of extrapolation, most is known about the former, which is presented in
Chapter 10.  Both Chapters 10 and 11 must be jointly considered for interpretation. For
example, was one aerosol more toxic than another because it had a greater deposition in a
sensitive lung target site or because it had higher potency?
     Similarly, most particles considered in the laboratory animal toxicology and occupational
studies are mainly in the fine and coarse mode size range. However, the enormous numbers and
huge surface area of the ultrafine particles demonstrate the importance of considering the size of
the particle.  Ultrafine particles with a diameter of 20 nm when inhaled at the same mass
concentration have an approximately 6 orders of magnitude higher number concentration than  a
2.5 //m diameter particle; particle surface area is also greatly increased (Table 11-1).
        TABLE 11-1.  NUMBERS AND SURFACE AREAS OF MONODISPERSE
         PARTICLES OF UNIT DENSITY OF DIFFERENT SIZES AT A MASS
                           CONCENTRATION OF 10
       Particle Diameter             Particle Number            Particle Surface Area
             //m _ per cm3 Air _ //m2 per cm3 Air
0.02
0.1
0.5
1.0
2.5
2,400,000
19,100
153
19
1.2
3,016
600
120
60
24
Source:  Oberdorster et al. (1995a).
                                          11-4

-------
     Most of the laboratory animal and occupational epidemiological studies summarized here
used high paniculate mass concentrations, relative to ambient, even when laboratory animal-to-
human dosimetric differences are considered.  This raises a question about the relevance of, for
example, a rat study at 5,000 //g/m3 in terms of direct extrapolation to humans in ambient
exposure scenarios.
     In spite of these difficulties, the array of laboratory animal studies does illustrate certain
toxicological principles for particles.  To identify but a few here, the data base clearly shows that
the site of respiratory tract deposition (and hence particle size) influences the health outcome and
that toxicity is dependent on the chemical species (e.g., cadmium is different from sulfuric acid,
and cadmium chloride is different from cadmium oxide).
11.2   ACID AEROSOLS
     The ubiquitous presence of acidic aerosols in the ambient air and concern about their
potential health effects led to considerable research over the past 15 years on the response of
humans and laboratory animals to exposure to acid aerosols.  In Section 11.2.1, responses of
both healthy and sensitive humans to acid aerosols and acidic aerosol mixtures with other
pollutants are reviewed.  Human studies primarily consider brief exposures, whereas the
laboratory animal toxicology studies discussed in Section 11.2.2 also consider the effects of
chronic exposure to acid aerosols and acidic aerosol mixtures.
     Section 11.2 focuses mainly on sulfate-related species (e.g., sulfuric acid [H2SO4]).
Information on certain other aerosol species (e.g., nitrates) was reviewed in the previous PM/SOX
CD (U.S. Environmental Protection Agency, 1982), the EPA Acid Aerosols Issue Paper (U.S.
Environmental Protection Agency,  1989), and the Oxides of Nitrogen Criteria Document (U.S.
Environmental Protection Agency,  1993). Those earlier assessments yielded only very limited
information indicative of health effects being associated with exposures to aerosol species such
as sodium nitrate (NaNO3) or ammonium nitrate (NH4NO3) at levels very much in excess of
ambient (i.e., at three orders of magnitude [about 1000 times] above nitrate concentrations
typically found in ambient air).  Ambient levels of airborne nitrate salts are typically less than 5
Mg/m3 and rarely exceed 50 //g/m3 (Sackner et al., 1979). Given that little, if any, important new
information on nitrate-related health
                                          11-5

-------
effects has appeared in the past few years since the above noted assessments were completed,
they are not treated further here, except as components of some particle mixtures discussed later
in the chapter.

11.2.1 Controlled Human Exposure Studies

11.2.1.1   Introduction
     Human clinical exposure studies utilize controlled laboratory conditions to test responses
to atmospheric pollutants.  Advantages include the opportunity to study the species of interest
(i.e., humans), and the ability to carefully control the atmosphere with regard to pollutant
concentration, aerosol characteristics, temperature, and relative humidity.  Concentrations can be
varied while other conditions are held constant to determine exposure-response relationships.
Mixtures of pollutants or sequential exposures to different pollutants can be used to elucidate
interactions.
     Methods of inhalation used in clinical studies include mouthpiece, face mask, head-dome,
and environmental chamber. Breathing through  a mouthpiece alters breathing patterns, and
bypasses the normal filtering and humidifying role of the nasal passages, thereby increasing
delivery of particles to the lower airways.  Environmental chamber and head-dome exposures
allow the assessment of shifts between nasal and oral-nasal breathing that normally occur with
exercise.
     Several factors limit the utility of human clinical studies. To meet legal and ethical
requirements, exposures must be without significant harm. Studies are typically limited to short-
term exposures, since long-term exposures are impractical, and may be more likely to cause
harm.  Sample sizes are small, and therefore may not be representative of populations at risk.
Finally, individuals likely to be at greatest risk (i.e., the very young and very old, those with
severe obstructive lung disease,  or combined heart and lung disease) have not been studied.  The
data from human clinical studies should therefore be used together with information from
laboratory animal exposure studies, epidemiologic studies, and in vitro exposure studies, in the
process of health assessment.
     The endpoints most commonly measured in human clinical studies are symptoms and
pulmonary function tests.  The latter are well standardized, and their use in these studies has
been reviewed (Utell et al., 1993). Effects in clinical studies can be directly compared to
                                          11-6

-------
acute changes in field studies, as has been done extensively in studies of ozone health effects
(U.S. Environmental Protection Agency, 1995).
     Airway responsiveness is another endpoint commonly measured in human clinical studies.
This test measures changes in lung function in response to pharmacologic bronchoconstricting
agents, typically methacholine, carbachol, or histamine (see also Section 11.2.1.4). A
dose-response curve is obtained for the agent, and airway responsiveness is expressed as the dose
of the bronchoconstricting agent resulting in a specific change in lung function:  e.g., the PD20 is
the provocative dose resulting in a 20% fall in forced expiratory volume in 1  sec (FEVj).
Individuals with asthma almost always have hyperresponsive airways, with a PD20 well below
the normal range.  Increase in airway reactivity in response to pollutant exposure could reflect
airway inflammation or edema. However, smaller airway caliber as a consequence of the
exposure will also increase measured responsiveness because of factors related to airways
geometry. It is therefore important to measure responsiveness at a time when spirometric
function has returned to baseline. Likewise, performing airway challenge testing prior to
pollutant exposure may alter subsequent lung  function responses to the pollutant by changing the
baseline airways caliber. Differences among laboratories in the protocols and provocative agents
used for airway challenge make comparison of experimental results problematic.
     Endpoints in human clinical studies have extended beyond measures of air flow and lung
volume. Mucociliary clearance is measured using inhaled radio-labelled aerosols. As reviewed
in the Acid Aerosols Issue Paper (U.S. Environmental Protection Agency,  1989), exposure to
acid aerosols alters mucociliary clearance in humans as well as in several laboratory animal
species. Within the past decade, fiberoptic bronchoscopy has been used to examine the lower
respiratory tract in healthy volunteers exposed to pollutants. Cells that populate the alveolar
space, including alveolar macrophages (AM), lymphocytes, and polymorphonuclear leukocytes
(PMN), can be recovered by bronchoalveolar  lavage (BAL); bronchial epithelial cells can be
sampled using bronchial brushing and endobronchial biopsies. Nasal lavage can be used to
quantitate inflammation in the nose.
     Features of experimental design of particular importance with regard to human clinical
studies are method of exposure, exercise, and  selection of control exposures. Exposure by
mouthpiece reduces humidification of inhaled air that normally occurs in the nasal passages;
                                          11-7

-------
 inhalation of dry cold air into the airways may cause bronchoconstriction in asthmatic subjects.
Exercise plays an important role in enhancing pollutant effects by causing a change from nasal
to oral-nasal breathing, hence decreasing upper airways deposition, and by increasing pollutant
dose through increased minute ventilation (VE).
     Selection of control exposures is of particular importance. Typically, each subject serves
as his/her own control to eliminate intersubject variability.  The control atmosphere depends on
the study objectives and may consist of clean air, or, when acidic aerosols are being tested, a pH
neutral aerosol, such as sodium chloride (NaCl), to distinguish non-specific effects of the aerosol
from pollutant or hydrogen ion (H+) effects. It is important that control exposures be performed
under similar conditions of temperature, relative humidity, VE, and time of day; that control and
pollutant exposure be separated by  sufficient time to avoid carry-over effects; and that the order
of the exposures be randomized among the study group. Double blind procedures (by which
neither the investigators collecting data nor the subjects know the  contents of exposure
atmospheres) should be used to the extent possible.
     Human exposure studies of the effects of acid aerosols were reviewed in the Acid Aerosols
Issue Paper (U.S. Environmental Protection Agency, 1989). That review reached the following
conclusions:
     (1)   In healthy subjects, no effects on spirometry have been observed after exposure to
           concentrations of H2SO4 less than 500 //g/m3, and no  consistent effects have been
           observed at levels up to 1,000 //g/m3 with exposure durations up to 4 h.  Studies of a
           variety of other sulfate and nitrate aerosols have similarly demonstrated an absence
           of spirometric effects on healthy subjects.

     (2)   Combinations of sulfates with ozone or SO2 have not demonstrated synergistic
           or interactive effects.
     (3)   Asthmatic subjects experience modest bronchoconstriction after exposure to -400 to
            1000 //g/m3 H2SO4, and small decrements in spirometry have been observed in
           adolescent asthmatics at concentrations as low as 68 //g/m3 for 30 min.

     (4)   Some  studies suggest that delayed effects may occur in healthy and asthmatic
           subjects following exposure to H2SO4.
     (5)   Effects of sulfate aerosols are related to their acidity,  and neutralization by oral
           ammonia tends to mitigate these effects.
                                           11-8

-------
     (6)   Exposure to H2SO4 at concentrations as low as 100 //g/m3 for 60 min alters
           mucociliary clearance.

     (7)   Airway reactivity increases in healthy and asthmatic subjects following exposure to
           1,000 Mg/m3 H2SO4 for 16 min.

     (8)   Differences in estimated respiratory intake explain  only a portion of the differences
           in responses among studies.

     In the five years since the publication of the Acid Aerosol Issue Paper, several of these
summary statements have been further confirmed. For example, recent studies confirm the
absence of spirometric effects following acute exposure to H2SO4 and other acid aerosols in
healthy subjects, at or below 1,000 //g/m3.  The observation of effects on adolescent asthmatics
at levels as low as 68 //g/m3 has not been confirmed, and studies utilizing longer exposures have
raised further questions about the relationship between dosimetry and health effects. However,
additional evidence  supports the conclusion that lung function effects in asthmatic subjects are
related to hydrogen  ion exposure, which is in part determined by the degree of neutralization by
oral ammonia. Two recent studies examining sequential exposure to H2SO4 and ozone (Linn et
al., 1994; Frampton et al., 1995) suggest that acid aerosols may potentiate the response to ozone
in some asthmatic subjects.  Finally, clinical studies of acid aerosols have been expanded to
include endpoints associated with fiberoptic bronchoscopy and BAL.
     Table 11-2 summarizes, in alphabetical order by author, controlled human exposure studies
of particle exposure published since 1988.  The majority of the human clinical studies  have
focused on the pulmonary function effects of exposure to acid aerosols.  These studies are
therefore summarized separately below, first reviewing studies of effects on healthy subjects,
followed by subjects with asthma. Subsequent sections deal with effects other than lung
function, and with studies of particulate pollutants other than acid aerosols.

11.2.1.2  Pulmonary Function Effects of Sulfuric Acid in Healthy Subjects
     Since 1988, ten studies have examined the effects of H2SO4 exposure on pulmonary
function in healthy subjects.  Exposure levels ranged from 100 //g/m3 to 2,000 //g/m3,  with
exposure durations ranging from 16 min to 6.5 h on  two successive days. All of these  studies
confirmed the findings from previous studies of an absence of spirometric effects on
                                          11-9

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TABLE 11-2. CONTROLLED HUMAN EXPOSURES TO ACID AEROSOLS AND OTHER PARTICLES
Ref.
Anderson
etal.
(1992)



Aris et al.
(1990)




Aris et al.
(1991a)







Aris et al.
(1991b)





Subjects
15 healthy
15 asthmatic
18 to 45 years



19 asthmatic
20 to 40 years




10 healthy
nonsmokers
21 to 31 years
ozone

sensitive



18 asthmatics
23 to 37 years





MMAD2 GSD3
Exposures1 C"m) (/^m)
(1): air
(2):H2S04 =100//g/m3 1.0 2
(3): carbon black
=200 //g/m3
(4): acid-coated carbon
with = 100 ,ug/m3 H2SO4
Mouthpiece study:
HMSA5 0 to 1000 fj.M + H2SO4
50 ijM vs H2S04 50 /Al
Chamber study:
HMSA 1 Mm + H2SO4 5 Mm
vs H2SO4 5 Mm
HN03 500 //g/m3 or H2O, or =6
air followed by ozone
0.2 ppm






Mouthpiece study:
H2SO4 vs NaCl, =3000 //g/m3 0.4 vs =6
with varying particle
size, osmolarity,
relative humidity


Chamber study: H2SO4 vs
NaCl, 960 to 1400 //g/m3
6
with varying water
content
Temp
Duration Exercise (°C)
Ih VE^50 22
L/min




3 min. 100 W on
cycle


1 h =25

2 h 50 min of 22
each h
3 h
40 L/min




22


16 min With and
without
=24
exercise.


100 W on
1 h cycle =27

RH"
(%) Symptoms
50 Healthy
subjects more
symptomatic in
air.


100 HMSA did not
increase
symptoms in
comparison
with H2SO4
alone.
100 No effects of
fog exposure





50

No effects
<10 vs
100





Lung Function Other Effects
Largest No change in
decrements in airway
FVC with air responsiveness
exposure.


No effects on
SRaw6




No direct No change in
effects of fog airway
exposures. responsiveness

Greatest
decrements when

ozone preceded
by air.
Increases in
Sraw with low RH
conditions; no
pollutant-rela
ted effects





Comments
Smoking
status of
subjects
not
stated.







Fog may
have
reduced
ozone

effects on
lung
function.

Postulated
that
effects
seen in
other
studies
due to
secretions
or effects
on larynx


-------
TABLE 11-2 (cont'd). CONTROLLED HUMAN EXPOSURES TO ACID AEROSOLS AND OTHER PARTICLES
Ref.
Avol et al.
(1988a)







Avol et al.
(1988b)






Avol et al.
(1990)




Balmes
etal.
(1988)






Gulp et al.
(1995)




Subjects
21 healthy
21 asthmatic
18 to 45 years






22 healthy
22 asthmatic
18 to 45 years





32 asthmatics
8 to 16 years




12 asthmatics
responsive to
hypoosmolar
saline
aerosol
25 to 41 years



16 healthy
20 to 39 yrs




MMAD2 GSD3 Temp RH"
Exposures1 C^m) C^m) Duration Exercise (°C) (%) Symptoms
Air 0.85 to 2.4 to Ih 10 min x 3 21 50 Healthy: Slight
H2SO4: 0.91 2.5 47 to increase in cough
Healthy: 363, 49 L/min with highest
1128, 1578 concentrations.
//g/m3
Asthmatic: 396, Asthma:
999, 1,460 ,ug/m3 dose-related
increase in lower
resp. symptoms.
H2O 9.7 to Ih 10 minx 3 9 100 Dose-related
H2SO4: 10.7 41 to 46 increase in lower
Healthy: 647, L/min resp. symp. in both
1,100, groups.
2,193//g/m3
Asthmatic: 516,
1,085,
2,034 //g/m3
Air 40 min 30 min 21 48 No pollutant effect
H2SO446, 127, 0.5 1.9 rest, 10
and 134 //g/m3 min
exercise
20L/min/m2

Mouthpiece, At rest -23
5,900 to
87, 100 ,u/m3:
NaCl 30 mOsm
H2SO430mOsm =5 to 6 1.5
HNO3 30 mOsm
H2SO4+HNO3 30 mOsm
H2SO4 300 mOsm

NaCl 1000 //g/m3 0.9 1.9 2 h 10 min x 4 22 40
H2S04 1,000 Mg/m3 =40 L/min




Lung Function Other Effects
Healthy: No
effects on lung
function or
airway
reactivity.

Asthma: iFEVj
0.26 L with H2S04
1,460 //g/m3
Healthy: No No effects on
effects on lung airway
function. responsiveness

Asthma: ipeak
flow 16% at
2,034 //g/m3
H2S04.
No pollutant
effect.
One subject
increased Sraw
14.2% with acid
exposure.
Concentration
of acid aerosol
required to
increase Sraw
by 100% lower
than for NaCl.
No difference
between acid
species.
Mucins from
bronchoscopy:
no effects on
mucin recovery
or changes in
glycoproteins
Comments









Half the
subjects
received
acidic gargle;
no difference
in effects.


Did not
reproduce
findings of
Koenig et al.,
1983.

Exposures did
not mimic
environmental
conditions.
No mitigation
by oral
ammonia.









-------
TABLE 11-2 (cont'd). CONTROLLED HUMAN EXPOSURES TO ACID AEROSOLS AND OTHER PARTICLES
Ref.
Fine et al.
(1987b)




Fine et al.
(1987a)




Frampton
etal.
(1992)




Frampton
etal.
(1995)






Hanley
etal.
(1992)





Subjects
8 asthmatics
22 to 29 yrs




10 asthmatics
22 to 34 yrs




12 healthy
20 to 39 yrs





30 healthy
30 asthmatics
20 to 42 yrs






22 asthmatics
12 to 19 yrs






MMAD2 GSD3 Temp RH"
Exposures1 C"m) C"m) Duration Exercise (°C) (%)
Mouthpiece: 5. 3 to 6. 2 1.6 to 3 min. At rest
Buffered and 1.8
unbuffered HC1
and H2SO4 at
varying pH

Mouthpiece: 5. 6 to 6.1 1.6 to 1 min. At rest
Na2SO3Oto 1.7
10 mg/ml, pH 9,
6.6, 4; buffered
acetic acid pH 4;
SO2 0.25 to 8 ppm
NaCl 1,000 //g/m3 0.9 1.9 2 h 10 min x 4 22 40
H2S04 1,000 //g/m3 =40 L/min





NaClorH2SO4 0.45 4.05 3h 10 min x 6. 21 40
100 //g/m3 0.64 2.50 Healthy: 33
followed by to 40 L/min;
ozone 0.08, 0.12, 3h asthmatics:
or 0. 1 8 ppm 3 1 to 36 L/min




Mouthpiece: 22 65
(1): Air; 40 min. 10 min
H2SO470, 0.72 1.5
130 //g/m3 45 min. 30 min
(2): Air; =30 L./min
H2S04 70 //g/m3
with and without
lemonade
Symptoms
Cough with
inhalation
of
unbuffered
pH2
aerosols






4/12
subjects:
throat
irritation
with acid
exposure.

No
pollutant
effects






No effects







Lung Function
= 50% increase in
airway resistance
with buffered acid
aerosols at pH 2.
Little response to
unbuffered acids.
ForN^Sq,,
bronchoconstriction
greater at
lower pH; no
response to acetic
acid.
No pollutant
effects





Healthy subjects:
no significant
effects.

Asthmatics: ozone
dose-response
following H2SO4
pre-exposure, but
not NaCl
Significant
decreases in FEVj
(=37ml///molH+)
and FVC at 2 to 3
min but not 20 min
after exposure.


Other Effects












BAL findings:
No effects on
cell recovery,
lymphocyte
subsets, AM
function, fluid
proteins.









Significant
correlation
between
baseline
airways
responsiveness
and AFEV/H+
(R2=0.3).
Comments
Titratable
acidity
important
determinant of
response to acid
aerosols.
Suggests
effects related
to release of SO2
or bisulfite,
but not sulfite.

















Large
variability in
oral NH3 levels.






-------
TABLE 11-2 (cont'd). CONTROLLED HUMAN EXPOSURES TO ACID AEROSOLS AND OTHER PARTICLES
Ref.
Koenig
etal.
(1989)



Koenig
etal.
(1992)





Koenig
etal.
(1993)







Koenig
etal.
(1994)





Laube et al.
(1993)









Subjects
9 asthmatics with
exercise-induced
bronchospasm
12 to 18yrs


14 asthmatics
with
exercise-induced
bronchospasm
13 to 18yrs



8 healthy
9 asthmatic
60 to 76 yrs







28 asthmatics
12 to 19 yrs






7 healthy
20 to 3 1 yrs









MMAD2 GSD3
Exposures1 C"m) C"m) Duration Exercise
Mouthpiece: 0.6 1.5 40 min lOmin
Air;
H2S04 68 //g/m3;
SO20.1 ppm;
H2SO4+SO2.
HNO3 0.05 ppm
Mouthpiece: =23 L/min
Air; 0.6 1.5 45 or
H2SO4 35 or 70 //g/m3 90 min





Mouthpiece: 10 min
Air; 40 min 17.5 L/min
(NH4)2SO4 =70 Mg/m3; 0.6 1.5 for
H2SO4 =74 to 82 //g/m3 with asthmatics,
and without lemonade 19.7 for
healthy




Mouthpiece: 90 min x VE 3 x
Air; 2 days resting
ozone 0.12 ppm+NO2 0.3 ppm; 0.6 1.5
ozone 0. 12 ppm+NO2
0.3 ppm+H2SO4 68 //g/m3;
ozone 0. 12 ppm+NO2
0.3 ppm+HNO3 0.05 ppm

Head dome: 1 h 20 min
NaCl =500 //g/m3 10.3
H2SO4 = 500//g/m3 10.9








Temp RH"
(°C) (%) Symptoms Lung Function
25 65 No effects iFEV^/oafter
H2SO4 compared
with 2% after
air.


22 65 JFEVjeo/oafter
H2S04 35 Mg/m3
for 45 min, 3%
after 70 //g/m3
(NS). Smaller
changes after
90 min
exposures.
22 65 No significant
effects.
Correlation
between
increase in
resistance and
oral ammonia
levels in
asthmatics
(R2 = 0.575).
22 65 No No pollutant
pollutant effects
effects





22 to 25 99 No No pollutant
pollutant effects
effects








Other Effects Comments






Responses
unrelated
to CxTx VE















No effects on 6 subjects
airway with
responsiveness moderate or
severe
asthma did
not
complete
protocol
Tracheal
clearance
increased
(4/4 subjects).
Outer zone
clearance
increased
(6/7 subjects).
No effects on
airway
responsiveness

-------
       TABLE 11-2 (cont'd).  CONTROLLED HUMAN EXPOSURES TO ACID AEROSOLS AND OTHER PARTICLES
Ref.
Linn et al.
(1989)




Linn et al.
(1994)








Morrow et
al. (1994)



Utell et al.
(1989)



Subjects
22 healthy
19
asthmatic
18to48yrs


15 healthy
30
asthmatic
18 to 50 yrs






17
asthmatic
20 to 57 yrs
17 COPD
52 to 70 yrs
15
asthmatic
19 to 50 yrs


Exposures1
H20
H2S04 =2,000 Mg/m3




Air;
ozone 0.12 ppm;
H2SO4 100 //g/m31
ozone+H2SO4






NaCl = 100 //g/m3
H2S04 =90 Mg/m3



Mouthpiece:
NaCl 350 //g/m3;
H2S04 350 //g/m3, high
NH3;
H2S04, low NH,
MMAD2 GSD3 Temp
Cum) C«m) Duration Exercise (°C)
20 Ih 40 to 45 =10
10 L/min
1



6.5 h/d 50 minx 6 21
=0.5 ~2 x2d 29 L/min








2h Asthmatics: 21
10 min x
4 COPD: 7 min
x 1

0.80 1.7 30 min 10 min
VE3x
resting


RH"
(%) Symptoms
74 to Increased
100 total score
with larger
acid
particles.

50 Symptoms
unrelated
to
atmosphere






30 No
pollutant
effects.


20 to
25



Lung Function
No pollutant effects





i FEVj & FVC in ozone,
similar for healthy &
asthmatic subjects.
Greater fall in FEVj
for acid+ozone than
ozone alone,
marginally
significant
interaction.

Asthmatics: JFEVj
slightly greater
after acid than after
NaCl.
COPD: No effects.
Greater fall in FEVj
with low NH3 (19%)
than with high NH3
(8%).

Other Effects
No effects on
airway
reactivity



Increased
airway
responsivenes
s with ozone,
marginal
further
increase with
ozone+acid












Comments
4 asthmatic
subjects unable
to complete
exposures
because of
symptoms.
Average subject
lost 100 ml FEVj
with ozone, 189
ml with
ozone+acid

Original
findings
replicated in
13 subjects










'Exposures in environmental chamber unless otherwise stated.
2Mass median aerodynamic diameter.  In some studies expressed as volume median diameter; see text.
3Geometric standard deviation.
"Relative humidity.
5Hydroxymethanesulfonic acid.
'Specific airways resistance.
BAL=Bronchoalveolar lavage.
AM=Alveolar macrophage.

-------
healthy subjects. Exposures at the highest concentrations (i.e. 1,000 //g/m3 or greater) were
associated with mild increases in respiratory symptoms (cough, substernal discomfort, throat
irritation), especially those exposures with particle sizes in the 10 to 20 //m range.
     Two studies reported by Avol and colleagues (Avol et al., 1988a,b) examined effects of
1-h H2SO4 aerosol exposures in an environmental chamber. In the first study (Avol et al.,
1988b), 22 healthy nonsmoking subjects between the ages of 18 and 45 years, some reporting
allergies, were exposed for 1 h to large particle aerosols (volume median diameter (VMD) 9.7 to
10.3 //m, GSD not stated) consisting of H2O (control) or H2SO4 at 647, 1,100, and 2,193 //g/m3.
Three 10-min  periods of moderate exercise (46 L/min) were included. All subjects were
exposed to each atmosphere, separated by one week.  Half the subjects received an acidic gargle
to reduce oral ammonia levels prior to exposure; no difference in effects was observed with or
without the gargle, so data were combined in the analysis.  Healthy  subjects experienced a slight
concentration-related increase in lower respiratory symptoms (cough, sputum, dyspnea, wheeze,
chest tightness, substernal irritation), but no effect was found on spirometry or on airway
reactivity to methacholine measured 1 h after exposure.
     A second study (Avol et al., 1988a) essentially duplicated this protocol for H2SO4 aerosols
with a smaller particle size (MMAD = 0.85 to 0.91 //m, geometric standard deviation [GSD =
2.4 to 2.5]).  Twenty-one healthy subjects, 12 with allergies by skin testing, were exposed on
separate occasions to air and H2SO4 aerosol at each of three concentrations: 363, 1128, 1578
Mg/m3. A slight increase in cough was found at the two highest concentrations of H2SO4, but no
effects were found on spirometry, specific airway resistance (Sraw), or airway reactivity to
methacholine.
     Linn et al. (1989) examined the effects of droplet size on 22 healthy subjects exposed
to nominally 2,000 //g/m3 H2SO4 for 1 h, with three, 10-min exercise periods. Distilled H2O was
used for control aerosols. Aerosol VMDs were 1,10, and 20 //m. Actual exposure
concentrations were 1,496, 2,170, and 2,503 //g/m3.  Results were similar to the previous fog
studies by this group, with no significant effects on lung function or airway reactivity to
methacholine.  Total symptom scores were increased with exposure to 10 //m and 20 //m H2SO4
particles, but not to  1 //m.
                                          11-15

-------
Frampton et al. (1992) exposed 12 healthy nonsmokers to aerosols of NaCl (control) or H2SO4
(MMAD = 0.9//m, GSD = 1.9) at 1,175 //g/m3 for 2 h in an environmental chamber. Four
10-min exercise periods at VE of -40 L/min were included. Subjects brushed their teeth and
rinsed with mouthwash prior to and once during each exposure to reduce oral ammonia levels.
Mild throat irritation was described by 4 of 12 subjects after acid exposure and 3 of 12 subjects
after NaCl exposure.  No effects on lung function were found.
     Five other recent studies (Anderson  et al., 1992; Koenig et al.,  1993; Laube et al., 1993;
Linn et al., 1994; Frampton et al., 1995) have included healthy subjects in exposures to H2SO4
aerosols at levels below 1000 //g/m3; none have shown meaningful effects on lung function.
Anderson et al., (1992) studied the responses of 15 healthy subjects exposed for 1 h in  a chamber
to air, 100 //g/m3 H2SO4, 200 //g/m3 carbon black, and carbon black coated with H2SO4,
(MMAD ~ 1 //m). Lemonade or citrus juice gargles were used to reduce oral ammonia levels.
Exposures containing acid were without effects on symptoms, lung function, or airway
reactivity. Healthy subjects were actually more symptomatic and demonstrated greater increases
in Sraw after air than after pollutant exposure, contrary to expectation. In a study designed to
examine effects of acid fog on pulmonary clearance, Laube et al., (1993) exposed seven healthy
volunteers to NaCl or H2SO4 at 470 //g/m3, MMAD ~ 11 //m, for 1 h with 20 min of exercise.
Acid exposure did not alter symptoms or lung function.  Two chamber studies designed to
examine the effects of combined or sequential exposure to acid aerosols and ozone found no
direct effects of exposure to ~ 100 //g/m3 H2SO4 on lung function of healthy subjects, using
exposure durations of 3 h (Frampton et al., 1995) or 6.5 h for two successive days (Linn et al.,
1994).  Both studies included exercise and acidic mouthwash to minimize oral ammonia. Also
of particular interest, Koenig et al, (1993) studied eight elderly subjects age 60 to 76 years
exposed to air, H2SO4, or ammonium sulfate at approximately 82 //g/m3 H2SO4 for 40 min,
delivered by mouthpiece. No effects were found on spirometry or total respiratory resistance.
     Thus, for young healthy adults, brief exposures to H2SO4 at mass concentrations  more than
an order of magnitude above ambient levels do not alter lung function. Some subjects report
increased lower respiratory symptoms, including cough, at 1000 //g/m3 and higher
                                         11-16

-------
levels, particularly with larger particle sizes (> 5 //m). One small study suggests that the elderly
do not demonstrate decrements in lung function at low H2SO4 exposure levels of (approximately
82 //g/m3). There are no data on the responses to particle exposure for healthy adolescents or
children.

11.2.1.3   Pulmonary Function Effects of Sulfuric Acid in Asthmatic Subjects
     Individuals with asthma often experience bronchoconstriction in response to a variety of
stimuli, including exercise, cold dry air, or exposure to strong odors, smoke, and dusts.
Considerable individual variability exists in the nature of stimuli that provoke a response, and in
the degree of responsiveness. Thus, for clinical studies involving asthmatic subjects, subject
selection and sample size deserve particular consideration. Differences among subjects may
explain, in part, the widely differing results between laboratories studying effects of acid
aerosols. For example, in some studies described below, asthmatic subjects were specifically
selected to have exercise-induced bronchoconstriction (Koenig et al., 1989, 1992, 1994; Hanley
et al., 1992), or responsiveness to hypo-osmolar aerosols (Balmes et al., 1988). The interval for
withholding medications prior to exposure differed among various laboratories and different
studies.  In addition, the severity of asthma differed among studies; severity is often difficult to
compare because published information describing clinical severity and baseline lung function is
often incomplete.  Table 11-3 lists the characteristics of asthmatic subjects exposed to acid
aerosols and other particles.
     Several studies have suggested that asthmatics are more sensitive than healthy subjects to
effects of acid aerosols on lung function. Utell et al., (1982) found significant decrements in
specific airway conductance  (SGaw) in asthmatic subjects exposed by mouthpiece for 16 min to
450 and 1,000 //g/m3 H2SO4  (MMAD 0.5 to 1.0 //m). Moreover, exposure to neutralization
products of H2SO4 produced  smaller decrements in function, roughly in proportion to their
acidity (H2SO4 > NH4HSO4 > NaHSO4).
     The role of H+ in the responsiveness of asthmatics to acid aerosols was explored by Fine et
al. (1987b), who found that titratable acidity and chemical composition, rather than pH alone,
are key determinants of response in asthmatics.  Eight asthmatic subjects were challenged by
mouthpiece for 3 min at rest, with buffered or unbuffered hydrochloric acid (HC1) or H2SO4 at
varying pH levels, and changes in SRaw were measured.  Solutions were
                                          11-17

-------
                 TABLE 11-3. ASTHMA SEVERITY IN STUDIES OF ACID AEROSOLS AND OTHER PARTICLES
oo
Ref.
Anderson
etal.
(1992)




Aris et
al.
(1990)




Aris et
al.
(1991b)









Avol et
al.
(1988a)



Avol et
al.
(1988b)

Subject #
(F/M)
15
(6/9)





19
(8/11)





18











21
(9/12)




22
(9/13)


Age Range
(mean)
19 to
45 years
(29)




20 to
40 years





23 to
37 years










18 to
45 years
(30)



18 to
45 years
(26)

Exposures1
(1): Air
(2):H2SO4«100,ug/m3
(3): carbon black

~ 200 Mg/m
(4): acid-coated
carbon
Mouthpiece study:
HMSAOto l,OOOmM
+ H2SO4 50 mM vs
H2S04 50 mM
Chamber study:
HMSA 1 mM + H2SO4
5 mM vs H2SO4 5 mM
Mouthpiece study:
H2SO4 vs NaCl to test
changes in particle
size, osmolarity (30
to 300 mOsm),
relative humidity
Chamber study: H2SO4
vs NaCl with varying
water content



Air
H2SO4 396, 999, 1,460
//g/m3



H20
H2SO4516, 1,085,
2,034 ^g/rn3

Allergies
Not
stated





Not
stated





Not
stated










Positive
skin
tests in
20


Positive
skin
tests in
18
Medications
Not stated






All but one on
albuterol. 3 on
inhaled
steroids. No
meds 24 h before
study.

Most subjects on
albuterol.
Several on
inhaled
steroids. No
meds 24 h before
study.





11 on no regular
meds; 10 on
regular meds.
3 unable to hold
meds prior to
exposure.
"Majority had
mild extrinsic
disease" . 9 on
regular meds.
FEVj
(% pred.)
Not
stated





82±20
(SD)





79±23
(SD)










Not
stated




Not
stated


FEV/FVC Airway
(%) Responsiveness
69±14 (SD) Methacholine:
PD20 < 56
"breath-units"




Not stated Methacholine:
All responded
to <2 mg/ml




Not stated Methacholine:
All responded
to <1 mg/ml









73±14 (SD) Hyperresponsive
by
methacholine
challenge, not
further
specified
45 to 98 Methacholine:
PD20<295 "dose
units"

Exercise/VE
Intermittent
at ~ 50 L/min





Intermittent,
100 W on
cycle
ergometer



Mouthpiece
study: with
and without
exercise.

Chamber
study :
intermittent
exercise at
100 W on
cycle
ergometer.
10 min x 3
47 to
49 L/mm



10 min x 3 41
to 46 L/min



-------
TABLE ll-Srcont'dX
Ref.
Avol et al.
(1990)



Balmes
etal.
(1988)





Fine et al.
(1987b)




Fine et al.
(1987a)









Frampton
etal.
(1995)




Subject #
(F/M)
32
(12/20)



12
(6/6)






8
(6/2)




10
(5/5)









30
(20/10)





Age Range
(mean)
8 to
16 years



25 to
41 years






22 to
29 years




22 to
34 years
(26.7)








20 to
42 years





ASTHMA SEVERITY IN STUDIES OF ACID AEROSOLS AND OTHER PARTICLES
Exposures1
Air
H2SO446,127, and!34
Mg/m3


Mouthpiece, doubling
outputs, 5,900 to
87,100 ,ug/m3: NaCl
30 mOsm
H2SO4 30 mOsm
HNO3 30 mOsm
H2SO4+HNO3 30 mOsm
H2SO4 300 mOsm
Mouthpiece:
Buffered and
unbuffered HC1 and
H2SO4 at varying pH


Mouthpiece: Na2SO3
Oto 1 0,000 ,ug/ml,
pH 9, 6.6, 4;
buffered acetic acid
pH4;
SO2 0.25 to 8 ppm





NaCl or H2SO4
100 |ig/m3 followed by
ozone 0.08, 0.12, or
0.1 8 ppm



Allergies
All had
history of
allergy


Not stated







Not stated





Not stated










All had
positive
skin
tests.
tlgEin 10.


Medications
1 8 on regular
meds, 2 on no
meds, rest
intermittent.
None on steroids.
All on inhaled
meds, 3 on
inhaled
steroids. No meds
24 h before
study.


6 on inhaled meds
and/or
theophylline, no
steroids. No
meds 1 2 h before
study.
7 on inhaled
meds, no
steroids. No
meds 1 2 h before
study.






All on
intermittent or
daily
bronchodilators.
None on steroids.
Meds held 24 h
before study.
FEVj FEV/ Airway
(% pred.) FVC (%) Responsiveness
Less than Not stated Hyperresponsive
70 in by exercise, cold
25 subjects air, or
methacholine.

94±15 (SD) 61 to 89 Responsive to
hypoosmolar
saline aerosol,
methacholine
<2 mg/ml.



41 to 108 74±11 (SD) Methacholine:
All responded to
<3 mg/ml.



Not stated Not stated 9 subjects had
bronchoconstrict-
ion and greater
response to
aerosol with
lower pH.
Response to NaSO3
aerosols may be
due to release of
SO2 gas in
bisulfiteions.
81±4 (SE) 75±2 (SE) Positive
carbachol
challenge if
normal
spirometry


Exercise/VE
30 min rest,
10 min
exercise
20L/rmn/m2

At rest







At rest





At rest










10 min x 6 for
each exposure






-------
               TABLE 11-3 (cont'd). ASTHMA SEVERITY IN STUDIES OF ACID AEROSOLS AND OTHER PARTICLES
to
o
Ref.
Hanley
etal.
(1992)




Koenig
etal.
(1989)



Koenig
etal.
(1992)









Koenig
etal.
(1993)




Subject # Age Range
(F/M) (mean) Exposures1
22 12 to Mouthpiece:
(7/15) 19years (1): Air orH2SO4
70, 130,ug/m3
(2): AirorH2SO4
70 ,wg/m3, with and
without lemonade

9 12 to Mouthpiece: Air
(3/6) 18 years H2SO4 68 ,ug/m3
SO2 0. 1 ppm
H2S04+S02
HNO3 0.05 ppm

14 13 to Mouthpiece:
(5/9) 18 years Air
H2SO4 35 or
70 Mg/m3








9 60 to Mouthpiece:
(7/2) 76 years (1): Air
(2): (NH4)2S04
«70 Mg/m3
(3&4): H2SO4
-74 ,wg/m3 with and
without lemonade
Allergies
"All had
allergic
asthma".
I IgE in 8.



5
"allergic
asthma"



"Allergic
asthma"










Not
stated





Medications
All but 2 on
meds, no
steroids. No
meds 4 h before
study.


Not stated





Not stated











All on
"bronchodilator
and/or anti-
inflammatory
treatment".
Steroids not
specified.
FEVj FEV/ Airway
(% pred.) FVC(%) Responsiveness
Not Not Methacholine: PD20
stated stated 0.25 to 25 mg/ml;
not available for
3 subjects.
1 8 were responsive
to exercise by
treadmill test
Not Not Methacholine: All
stated stated responded to
<20 mg/ml.
AllhadiFEV1>15%
with treadmill
test
Not Not Methacholine: PD20
stated stated 0.25 to 25 mg/ml;
not available for
1 subject; 8 had
pos. treadmill
tests, 4 history of
exercise
responsiveness, 2
did not meet stated
criteria for
exercise
responsiveness.
75 Not Methacholine:
stated PD20< 10 mg/ml





Exercise/VE
(1): 10 mm
(2): 30 mm
~ SOL. /min




"Moderate",
on
treadmill
for 10 min


Intermittent
~ 23 L/min










10 min
17.5 L/mm






-------
TABLE 11-3 (cont'd). ASTHMA SEVERITY IN STUDIES OF ACID AEROSOLS AND OTHER PARTICLES
Ref.
Koenig
etal.
(1994)








Linn
etal.
(1989)





Linn
etal.
(1994)




Morrow
etal.
(1994)
Subject # Age Range
(F/M) (mean)
28 12 to
(9/19) 19 years









19 18 to
(13/6) 48 years
(29)





30 18 to
(17/13) 50 years
(30)




17 20 to
57 years
(35)
Exposures1
Mouthpiece:
(1): Air
(2): ozone 0.1 2 ppm
+NO2 0.3 ppm
(3): ozone
0.12ppm+NO2
0.3 ppm+H2SO4
68 //g/m3
(4): ozone 0.12 ppm
+NO20.3ppm
+HNO3 0.05 ppm
H20
H2SO4 « 2,000 ,ug/m3






(1): Air
(2): ozone 0.1 2 ppm
(3):H2S04100//g/m3
(4): ozone+H2SO4



NaCl«100//g/m3
H2SO4~90//g/m3

Allergies
"Personal
history
of
allergic
asthma"






"Some"
subjects
had
history
of
allergy


Some
subjects
had
positive
skin
tests.

Positive
skin
tests
FEVj
Medications (% pred.)
3 on no meds, 87
rest on regular
meds. 4 on
inhaled
steroids.






All on Not
bronchodilators stated
at least
weekly. No
regular
steroid use. No
meds 1 2 h
before study.
Wide range of Not
medication stated
usage. Some on
inhaled
steroids. No
meds 4 h before
study.
Requirement Not
for stated
bronchodilators
FEV/FVC Airway
(%) Responsiveness
Not Methacholine:
stated PD20<25 mg/ml.
All but 1
responsive to
exercise by
treadmill test.





70±11 Hyperresponsive-
(SD) ness based on
methacholine
PD20<38 "breath
units", exercise
responsiveness, or
bronchodilator
response.
72 Responsive to
methacholine or
exercise, or
bronchodilator
response


65±8 (SD) Positive carbachol
challenge if
normal spirometry
Exercise/VE
Intermittent
VE3x
resting








Intermittent
40 to
45 L/min





50 min x 6
29 L/min





10 min x 4



-------
                   TABLE 11-3 (cont'd). ASTHMA SEVERITY IN STUDIES OF ACID AEROSOLS AND OTHER PARTICLES
            Ref.
Subject   Age Range

# (F/M)   (mean)      Exposures1
                                                                                     FEV,
Allergies    Medications
                                       FEV/FVC  Airway
(% pred.)   (%)
Responsiveness
           'Exposures in environmental chamber unless otherwise stated.
Exercise/ VE
Utellet 15
al.
(1989)




Yang and 25
Yang (15/10)
(1994)

19 to
50 years





23 to
48 years


Mouthpiece: Not stated
(1): NaCl
350 ,ug/m3
(2): H2S04
350 Mg/m3 high NH3
(3):H2S04lowNH3

Mouthpiece: All TIgE
Bagged polluted
air,
TSP = 202 Mg/m3
All on
intermittent or
daily
bronchodilators.
None on steroids.
Meds held 24 h
before study.
No steroids.
Holding of
medications not
stated.
88±4 (SE) 70±3 (SE) Positive carbachol 10 mm VE 3
challenge if x resting
normal spirometry




Not stated Not stated Hyperresponsive to Rest
methacholine


to
to

-------
buffered with glycine, which, by itself, was found to have no direct effect on lung function.
Aerosol MMAD ranged from 5.3 to 6.2 //m (GSD 1.6 to 1.8), simulating acid fogs.  There was
no group response to unbuffered acid, even at pH 2. However, SRaw increased in seven of eight
subjects after inhalation of H2SO4 and glycine at pH 2, suggesting that titratable acidity or
available FT, rather than pH, plays a role in mediating acid fog-induced bronchoconstriction.
Nevertheless, the response occurred at H2SO4 concentrations estimated in excess of 10,000
Mg/m3, more than an order of magnitude higher than the concentration producing a response in
the study of Utell et al. (1982).
     Fine et al. (1987a) further examined the role of pH in sulfite-induced bronchoconstriction
in asthmatics.  Ten subjects with asthma were challenged with increasing concentrations of
sodium sulfite (Na^C^) at three different pH levels. Challenge with  buffered acetic acid
aerosols at pH 4 was used to control for the airway effects of acid aerosols.  Subjects also
inhaled increasing concentrations of SO2 gas during eucapneic hyperpnea. Exposures consisted
of 1 min of tidal breathing on a mouthpiece at rest. Particle MMAD ranged from  5.6 to 6.1 //m.
Nine often subjects experienced bronchoconstriction with Na^C^with greater responses to
aerosols made from solutions with lower pH. No response was seen following acetic acid. The
authors concluded that bronchoconstriction in response to Na2SO3 aerosols may be caused by the
release of SO2 gas or by bisulfite ions, but not by sulfite ions and not merely by alterations of
airway pH.  These studies of Fine et al., as pointed out by the authors, addressed potential
mechanisms for bronchoconstriction in response to acidic sulfates, but did not attempt to mimic
the effects of environmental exposures.
     Hypo-osmolar aerosols can induce bronchoconstriction in some asthmatics.  To test the
effects of varying osmolarity of acidic aerosols, Balmes et al. (1988) administered aerosols of
NaCl, H2SO4, HNO3, or H2SO4 + HNO3 to 12 asthmatic subjects via mouthpiece.  All solutions
were prepared at an osmolarity of 30 mOsm, and delivered at doubling concentrations until
SRaw increased by 100%.  An additional series of challenges with H2SO4 at 300 mOsm was
performed.  The 12 subjects were selected from a group of 17 asthmatics on the basis of
responsiveness to challenge with hypo-osmolar saline aerosol.  Aerosol particle size was similar
to coastal fogs, with MMAD ranging from 5.3 to 6.1. Delivered nebulizer output  during
exposure was quite high, ranging from 5,900 to
                                          11-23

-------
approximately 87,000 //g/m3.  All hypo-osmolar aerosols caused bronchoconstriction. Lower
concentrations of hypo-osmolar acidic aerosols were required to induce bronchoconstriction than
with NaCl, and there was no difference between acidic species. No bronchoconstriction
occurred with isosmolar H2SO4, even at maximum nebulizer output (estimated H2SO4
concentration greater than 40,000 //g/m3).  The authors concluded that acidity can potentiate
bronchoconstriction caused by hypo-osmolar aerosols. As in the studies of Fine et al. (1987a,b),
these exposures did not mimic environmental conditions.
     Koenig and colleagues have studied the responses of adolescents with allergic asthma to
H2SO4 aerosols with particle sizes in the respirable range,  and concentrations only slightly above
peak, worst-case ambient levels. In one study (Koenig et al., 1983), ten adolescents were
exposed to 110 //g/m3 H2SO4 (MMAD = 0.6 //m) by mouthpiece for a total of 40 min, 30 min at
rest followed by  10 min of exercise. The FEVj decreased 8% after exposure to H2SO4, and 3%
after a similar exposure to NaCl, a statistically significant difference. In another study (Koenig
et al., 1989), nine allergic adolescents were exposed to 68 //g/m3 H2SO4 (MMAD = 0.6 //m) for
30 min at rest followed by  10  min of exercise (VE = 32 L/min).  Although only five subjects
were described as having "allergic asthma", all subjects had exercise-induced
bronchoconstriction; thus all subjects were asthmatic by generally accepted criteria (Sheffer,
1991). Effects were compared with similar exposures to air, 0.1 ppm SO2, 68 //g/m3 H2SO4 +
0.1 ppm SO2, and 0.05 ppm HNO3. The FEVj decreased 6% after exposure to H2SO4 alone, and
4% after exposure to H2SO4 + SO2, compared to a 2% decrease after air. Increases in total
respiratory resistance were not significant.  These results were presented as preliminary findings,
in that a total of 15 subjects were to be studied; formal statistical comparison of H2SO4 versus air
was not presented.  Findings from the full  group of 15 subjects have not been published.  These
studies suggest that allergic asthmatics with exercise-induced bronchoconstriction may be more
sensitive to effects  of H2SO4 than adult asthmatics, and that small changes in lung function may
be observed at exposure levels below 100 //g/m3.
     Two studies reported by Avol et al. (1988a,b) examined effects of H2SO4 aerosols and fogs
on asthmatic subjects. The results for healthy subjects in these studies were described in  Section
11.2.1.2. In the first study, 21 adult asthmatics, 20 of whom had positive skin tests to common
allergens, were exposed to  air or 396, 999, and 1,460 //g/m3 H2SO4
                                         11-24

-------
(MMAD 0.85 to 0.91 //m) for one hour with intermittent exercise. The asthmatic subjects
experienced concentration-related increases in lower respiratory symptoms (most notably,
cough), with some persistence of symptoms at 24 h.  The FEVj decreased by a mean of 0.26 L
after exposure to 999 //g/m3, and 0.28 L after exposure to 1,460 //g/m3. Results using analysis of
variance (ANOVA) were significant for concentration effects on change in FEVj and FVC.
However, decrements at 396 //g/m3 were identical to those seen with air exposure.  The SRaw
approximately doubled following exposure to both air and 396 //g/m3 H2SO4, and approximately
tripled following exposure to 999 and 1,460 //g/m3.  Although absolute change in SRaw related
to concentration was not significant, percent change in  SRaw was not analyzed as was done for
FEVj and FVC; ANOVA of percent change for each of these measures may  have proved more
sensitive. These findings are similar to those of Utell, et al. (1983b), who found significant
effects on SGaw following exposure to 450 and 1,000 //g/m3, and significant effects on FEVj at
1,000 //g/m3 (MMAD = 0.8 //m). However, exposures in the Utell study were performed at rest
for a considerably shorter duration (16 minutes).
     The second study (Avol et al.,  1988b) utilized an  identical protocol  to examine effects of a
large particle aerosol  (MMAD = 10 //m).  Twenty-two  asthmatic subjects were exposed to fogs
containing 516,  1,085 and 2,034 //g/m3 H2SO4, compared with H2O. Although
concentration-related increases in respiratory symptoms were similar to those in the study of
submicron aerosols, no significant effects were found on FEVl3 FVC, or SRaw, even at the
highest concentration of greater than 2,000 //g/m3. The findings from these two studies suggest
that aerosols of  submicron particle size may alter lung function to a greater degree than large
particle aerosols in asthmatic subjects. Deep breaths of air containing acid aerosol would often
provoke cough.  However, the concentrations required  to produce an effect (> 5000 //g/m3)
differ strikingly from the studies of adolescent asthmatics of Koenig and colleagues (1983,
1989).
     Linn et al. (1989) utilized a similar exposure protocol to specifically examine effects of
particle size. Nineteen asthmatic adults were exposed for 1 h to a pure water aerosol or
approximately 2,000 //g/m3 H2SO4 at 3 difference droplet sizes:  1,10,  and 20 //m.  Subjects
exercised for 3 10-min periods at VE of 40 to 45 L/min. Grapefruit juice  gargles were used to
minimize oral ammonia. As in previous studies by this group, symptoms increased in acid
                                         11-25

-------
atmospheres with larger particles. Four of the 19 asthmatic subjects were unable to complete
one or more exposures because of respiratory symptoms. All but one of the aborted exposures
was in an acid aerosol-containing atmosphere: three subjects did not complete the 1 //m acid
exposure, one the 10 //m exposure, and three the 20 //m exposure. The authors reported
significant decrements in lung function in these subjects, requiring administration of a
bronchodilator.  As stated by the authors, "the patterns of these appreciable clinical responses by
asthmatics suggests a causal relationship to acid exposure,  without obvious dependence on
droplet size". These more dramatic responses to acid aerosols are not reflected in the mean
responses, and suggest the existence of a few particularly susceptible individuals.  Mean
responses of FEVj to acid aerosol exposure were about -21%, with responses to exercise in clean
air of about -12%. Some subjects experienced decreases in FEVj in excess of 50%, as a result of
combined exercise and acid aerosol exposure.  Analysis of variance found significant effects of
acid x time on SRaw and FEVj. There was no apparent effect of droplet size.
     Utell et al. (1989) examined the influence of oral ammonia levels on responses to H2SO4.
Fifteen subjects with mild asthma inhaled H2SO4 aerosols (350 //g/m3, MMAD = 0.8 //m) via
mouthpiece for 20 min at rest followed by 10 min of exercise.  Sodium chloride aerosol served
as control. Low oral ammonia levels were achieved using a lemon juice gargle and
toothbrushing prior to exposure, and high levels were achieved by eliminating oral hygiene and
food intake for 12 h prior to exposure.  These procedures achieved a five-fold difference in oral
ammonia levels. The FEVj decreased 19% with low ammonia versus 8% with high ammonia
(p<0.001).  The FEVj also decreased 8% with NaCl aerosol. These findings extended the
authors' previous findings (Utell et al.,  1983b) of decrements in SGaw following exposure to 450
Mg/m3 H2SO4, and demonstrated the importance of oral ammonia in mitigating the clinical
effects of submicron H2SO4 aerosols.
     The findings of Koenig et al. (1989) in adolescent asthmatics prompted an attempt by Avol
and colleagues (1990) to replicate the study using a larger group of subjects.  Thirty-two subjects
with mild asthma, aged 8 to 16 years, were exposed to 46 and 127 //g/m3 H2SO4 (MMAD
~0.5fj,m) for 30 min at rest followed by 10 min of exercise at 20 L/min/m2 body surface area.
Subjects gargled citrus juice prior to exposure to reduce oral ammonia.  Bronchoconstriction
occurred after exercise in all atmospheres, with no statistically
                                         11-26

-------
significant difference between clean air and acid exposures at any concentration.  Because these
exposures were undertaken in an environmental chamber with unencumbered oral/nasal
breathing, in contrast to mouthpiece exposure in the Koenig et al. studies (1983, 1989), a
subsequent study was performed to examine the effects of oral breathing only. Twenty-one of
these subjects were therefore exposed to 134 //g/m3 H2SO4 while breathing chamber air through
an open mouthpiece.  Again, no acid effect was found.  One subject who was "unusually
susceptible to exercise-induced bronchospasm" also showed the largest decrements in lung
function with both exposures to the highest acid concentrations. It is possible that the subjects
in the Koenig et al. (1989) study, all of whom demonstrated exercise-induced
bronchoconstriction during a specific exercise challenge test, represented a more responsive
subgroup of adolescent asthmatics. Only 15 of the 32 subjects in the Avol et al. (1990) study
were known to have exercise-induced bronchoconstriction. Indeed, subsequent data (Hanley et
al., 1992) suggest exercise responsiveness is predictive of H2SO4 responsiveness (see below).
     Aris et al. (1990) examined the effects of hydroxymethanesulfonic acid (HMSA), which
has been identified as a component of west coast acidic fogs. They postulated that HMSA might
cause bronchoconstriction in asthmatics because, at the pH of airway lining fluid, it dissociates
into CH2O and SO2.  In the first part of the study, nine asthmatics were serially challenged by
mouthpiece with 0, 30, 100, 300 and 1,000 //M HMSA in 50 //M H2SO4 (MMAD = 6.1 //m).
The SRaw was measured after each challenge. These findings were compared on a separate day
to a similar series of exposures to 50 //M H2SO4 alone.  No effect was found for HMSA on
symptoms or airways resistance. An environmental chamber exposure study was then performed
in which 10 asthmatic subjects were exposed to 1 mM HMSA + 5 mM H2SO4 for 1 h with
intermittent exercise.  The control was exposure to 5 mM H2SO4 alone.  Three subjects
underwent additional  exposures to NaCl aerosol. Particle MMAD was approximately 7 //m.
Both acid exposures slightly increased respiratory symptoms, but no significant effects on SRaw
were found.
     In a subsequent series of studies, Aris et al. (1991b) examined the effects of varying
particle size, osmolarity, and relative humidity on airways resistance in response to H2SO4
aerosol. To study effects of particle size and  osmolarity, 11 asthmatics inhaled five different
aerosols for 16 min by mouthpiece at rest: (1) H2SO4 at 300 mOsm (VMD approximately
6 jum); (2) H2SO4 30 mOsm (VMD approximately
                                         11-27

-------
6 jum); (3) sodium chloride 30 mOsm (VMD approximately 6 //m); (4) H2SO4 (VMD
approximately 0.4 //m); and (5) H2SO4, (VMD approximately 0.4 //m).  Sulfuric acid
concentrations were high, at approximately 3000 //g/m3.  Airway resistance actually decreased
slightly with all aerosol exposures and there were no significant effects on respiratory  symptoms.
     In a second mouthpiece study, nine subjects were exposed at rest (part 1) to H2SO4 at
approximately 3000 //g/m3, with large (VMD ~6 //m) versus small (0.3 //m) particle size and
low (< 10%) versus high (100%) relative humidity. Sodium chloride aerosols under similar
conditions served as control.  Because these exposures caused no decrements in SRaw, six
subjects underwent exposures to small particle, low humidity H2SO4 versus sodium chloride
while exercising at 40 L/min (part 2).  Although SRaw increased significantly with exercise,
there was no difference between H2SO4 and sodium chloride exposures. These results are shown
in Figure 11-1.  A significant increase in throat irritation was observed with the low humidity,
small particle H2SO4 inhalation in part 1 of this study (n=9) but was not replicated in part 2
(n=6).
     Finally, an environmental chamber exposure study was undertaken to examine effects of
H2SO4 fogs (VMD approximately 6 //m) with varying water content on airways resistance. Ten
subjects were exposed for 1  h with intermittent exercise to H2SO4 and NaCl at low (0.5 //g/m3)
and high (1.8 //g/m3) liquid water content.  The mean sulfate concentrations were 960 //g/m3 for
low water content fogs and 1,400 //g/m3 for high liquid water content fog. Surprisingly, SRaw
decreased slightly with most exposures,  with no significant difference among the 4 atmospheres.
The authors speculated that the decrements in pulmonary function following exposure to acid
aerosols in previous studies may have been due to increases in  airway secretions or effects on the
larynx rather than bronchoconstriction.
     Responsiveness of adolescent asthmatic subjects to H2SO4 aerosols was further explored by
Hanley et al. (1992).  Fourteen allergic asthmatics aged 12 to 19 years inhaled air or H2SO4 at
targeted concentrations of 70 and 130 //g/m3, for 30 min at rest and 10 min with exercise. In a
second protocol, nine subjects were exposed to targeted concentrations of 70 //g/m3 H2SO4, with
and without drinking lemonade to reduce oral ammonia.  Actual exposure concentrations ranged
from 51 to 176 //g/m3 H2SO4. Exposures lasted 45 min,  including two 15-min exercise periods.
Aerosol MMAD was 0.72 //m.  For the purposes of
                                         11-28

-------
   LowRH
Small Particle
    NaCI
                                          LowRH
                                       Small Particle
  High RH
Large Particle
     S04
                                                  DPre
                                                  • Post
                                       LowRH
                                    Small Particle
                          LowRH
                        Small Particle
                           NaCI
                                                           ^    T

Figure 11-1.  Mean plus or minus standard error of the mean specific airway resistance

             (SR,,W) before and after a 16-min exposure for (A) nine subjects who inhaled

             low relative-humidity (RH) sodium chloride (NaCI), low-RH sulfuric acid

             (H2SO4), and high-RH H2SO4 aerosols at rest, and (B) six subjects who

             inhaled low-RH NaCI and low-RH H2SO4 aerosols during exercise.


Source: Aris et al. (1991b).
                    11-29

-------
this document, mean changes in FEVj were calculated from individual subject data provided in
the published report.  In the first protocol, FEVj fell 0.05 ± 0.08 L after air and 0.15 ± 0.14 L
after nominal 70 //g/m3 H2SO4. In the second protocol, FEVj fell 0.00 ± 0.23 L without
lemonade gargle and 0.13± 0.09 L with lemonade gargle. Results from the 22 subjects exposed
in the two protocols were combined for the published analyses, and changes in pulmonary
function were regressed against FT concentration for each subject. Decrements in FEVj and
FVC were statistically significant at 2 to 3 min after exposure, but not at 20 min after exposure.
Changes in Vmax50 and total respiratory resistance were not significantly different. The findings
corresponded to a fall in FEVj of approximately 37 ml///M FT. A significant correlation was
found between exercise-induced bronchoconstriction, determined prior to exposure using a
treadmill test, and the slope of A FEV1/H+. A similar observation linking baseline airways
reactivity to H2SO4 responsiveness had been made previously by Utell et al. (1983b).
     Koenig et al. (1992) examined the effects of more prolonged mouthpiece exposures to
H2SO4 (MMAD = 0.6//m). Fourteen allergic asthmatic subjects aged 13 to 18, with
exercise-induced bronchoconstriction, were exposed to air or 35 and 70 //g/m3 H2SO4, for
45 min and 90 min, on separate occasions.  Oral ammonia was reduced by drinking lemonade.
The exposures included alternate 15-min periods of exercise at three times resting VE. The
largest decrements in FEVj (6%) actually occurred with the shorter exposure to the lower
concentration of H2SO4 (35 //g/m3). Changes following exposure to 70 //g/m3 and following 90
min exposures were not significant. The authors concluded that duration of exposure did not
play a role in the response to H2SO4 aerosols. However, the absence of a concentration response
in the studies suggests that the statistical findings may be due to chance. Therefore, the study
does not appear to demonstrate a convincing effect of H2SO4 at these exposure levels.
     Anderson et al. (1992) included 15 asthmatic adults in a study comparing the effects of
exposure for 1 h to air, 100 //g/m3 H2SO4, 200 //g/m3 carbon black particles, and acid-coated
carbon black (MMAD ~ 1.0//m). Decrements in FEVj were observed for all exposures,
averaging about 9%.  Analysis of variance for FVC showed a significant interaction of acid,
carbon, and time factors (p =  0.02), but the largest decrements actually occurred with air
exposure.
                                         11-30

-------
     In the only study of elderly asthmatics, Koenig et al. (1993) exposed nine subjects,  60 to
76 years of age, by mouthpiece to air, (NH4)2SO4, or 70 //g/m3 H2SO4 (MMAD = 0.6//m), with
and without lemonade gargle.  Exposures were 30 min at rest followed by 10 min of mild
exercise (VE = 17.5 L/min). Greater increases in total respiratory resistance occurred following
H2SO4 without lemonade than following the other atmospheres, but the difference between
atmospheres was not significant.
     In a study comparing effects of H2SO4 exposure in subjects with asthma and COPD,
Morrow et al. (1994) exposed  17 allergic asthmatic subjects in an environmental chamber to 90
Mg/m3 H2SO4 or NaCl (MMAD<1 //m) for 2 h with intermittent exercise.  Pulmonary function
was measured after each of four 10 min exercise periods, and again 24 h after exposure, before
and after exercise.  Decrements in FEVj were consistently greater in H2SO4 than NaCl, although
the difference was statistically significant only following the second exercise period. FEVj
decreased ~ 18% after H2SO4 compared with  ~ 14% after NaCl (p = 0.02).  Reductions in SGaw
were significantly different only following the fourth exercise period (p = 0.009). No changes
were found in symptoms or arterial oxygen saturation, and there were no significant changes in
lung function 24 h after exposure.
     Finally, two recent studies have examined combined exposures to H2SO4 and ozone, one
using a combined pollutant atmosphere for 6 h per day over 2 days, (Linn et al., 1994) and the
other using sequential 3 h exposures to H2SO4 followed 1 day later by ozone (Frampton et al.,
1995).  These reports will be discussed in detail in section 11.2.1.7.  However, neither study
found any significant changes in lung function in asthmatics exposed to 100 //g/m3 H2SO4 alone.
     In summary, asthmatic subjects appear to be more sensitive than healthy subjects to the
effects of acid aerosols on lung function, but the effective concentrations differ widely among
laboratories.  Although the reasons for these differences remain largely unclear, subject selection
and differences in neutralization of acid by NH3 may be important factors. Adolescent
asthmatics may be more sensitive than adults, and may experience small decrements in lung
function in response to acid aerosols at exposure levels only slightly above peak ambient levels.
Even in studies reporting an overall absence of effects on lung function, some individual
asthmatic subjects appear to demonstrate clinically important effects. Submicron aerosols
appear to have greater effects on spirometry and airway
                                         11-31

-------
resistance than particles in the 10//-20 //m range.  However, respiratory symptoms (cough,
irritation, etc.) are observed with both large and small aerosols.

11.2.1.4  Effects of Acid Aerosols on Airway Responsiveness
     Human airways may undergo bronchoconstriction in response to a variety of stimuli.
Airway responsiveness can be quantitated by measuring changes in expiratory flow or airways
resistance in response to inhalation challenge. Typically, the challenging agent is a non-specific
pharmacologic bronchoconstrictor such as methacholine or histamine. Other agents include
carbamylcholine (carbachol), cold dry air, sulfur dioxide, hypo-osmolar aerosols, or exercise. In
allergic subjects, airway challenge with specific allergens can be performed, although the
responses are variable, and late phase reactions can result in bronchoconstriction beginning 4 to
8 h after challenge and lasting 24 h or more.  Although many individuals with airway
hyperresponsiveness do not have asthma, virtually all asthmatics have airway
hyperresponsiveness, possibly reflecting underlying airway inflammation.  Changes in clinical
status are often accompanied by changes in airway responsiveness. Thus alterations in airway
responsiveness may be  clinically significant,  even in the absence of direct effects on lung
function (Godfrey, 1993; Weiss et al., 1993). Molfino et  al. (1992) have provided a brief review
of air pollution effects on allergic bronchial responsiveness.
     As noted in section 11.2.1.3, two studies (Utell et al., 1983b; Hanley et al., 1992) have
suggested that the degree of baseline airway responsiveness may predict responsiveness to acid
aerosol exposure in asthmatic subjects.  This  section will deal only with studies examining
changes in airway responsiveness with exposure to particles.
     Despite the absence of effects on lung function in healthy subjects, Utell et al. (1983a)
observed, in healthy nonsmokers, an increase in airway responsiveness to carbachol following
exposure to 450 //g/m3 H2SO4 (MMAD = 0.8). The increase occurred 24 h, but not immediately,
after exposure. In addition, some subjects reported throat irritation between 12 and 24 h after
exposure to H2SO4.  These findings suggested the possibility of delayed effects.  These
investigators also observed increases in airway responsiveness among asthmatic subjects
following exposure to 450 and  1000 //g/m3, but not  100 //g/m3 H2SO4. These findings have been
reviewed (Utell et al., 1991).
                                          11-32

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     Avol et al. (1988a,b) included airway responsiveness as an outcome measure in their
studies of healthy and asthmatic subjects exposed to varying concentrations of H2SO4.
No effects on responsiveness were reported, with either acidic fogs or submicron aerosols, at
H2SO4 concentrations as high as 2000 //g/m3. However, airway challenge was performed using
only two concentrations of methacholine. This limited challenge may have been insufficiently
sensitive to detect small changes in airway responsiveness.
     Using a similar 2-dose methacholine challenge protocol, Linn et al. (1989) found no
change in airway responsiveness of healthy subjects following exposure to 2000 //g/m3 H2SO4
for 1 h, at particle sizes ranging from 1 to 20 //m. Anderson et al. (1992), in their study of
responses to 100 //g/m3 H2SO4, 200 //g/m3 carbon black, and acid coated carbon, found no
effects on airway responsiveness in healthy or asthmatic subjects. In this study, a conventional
methacholine challenge was used, administering doubling increases in methacholine
concentration until FEVj decreased more than 20%.
     In a study primarily designed to examine effects of acid fog exposure on mucociliary
clearance, Laube et al. (1993) examined changes in airway responsiveness to methacholine in
7 asthmatic subjects exposed to 500 //g/m3 H2SO4 or NaCl (MMAD ~ 10 //m) for 1 h with 20
min of exercise. Responsiveness was measured at screening and  30 min after each exposure. No
difference was observed between H2SO4 and NaCl exposures.
     A recent  study (Linn et al., 1994) has suggested that exposure to ozone with H2SO4 may
enhance the increase in airway responsiveness seen with ozone exposure alone.  Fifteen healthy
and 30 asthmatic subjects were exposed to air, 0.12 ppm ozone, 100 //g/m3 H2SO4 (MMAD
-0.5), and ozone + H2SO4 for 6.5 h on 2 successive days, with intermittent exercise. Airway
responsiveness was measured after each exposure day using a conventional methacholine
incremental challenge, and compared with baseline measured on  a separate day.  An ANOVA
using data from all subjects found an increase in airway responsiveness in association with ozone
exposure (p=0.003), but showed no significant change following  exposure to air or H2SO4 alone.
Multiple comparisons did not reveal significant differences in airway responsiveness between
ozone and ozone + H2SO4 in healthy or asthmatic subjects. However, asthmatic subjects showed
the greatest increase in airway responsiveness following the first  day of ozone + H2SO4, and
ANOVA revealed a significant interaction of clinical status, ozone, acid, and day (p=0.03).
Decreases in FEVj following methacholine
                                         11-33

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challenge for healthy subjects were 8% after air, 6% after H2SO4, 9% after ozone, and 13% after
ozone + H2SO4. Changes were smaller following the second exposure day, suggesting
attenuation of responsiveness with repeated exposure, as seen in previous studies of ozone alone
(U.S. Environmental Protection Agency, 1995). These studies suggest that exposure to low
concentrations of H2SO4 may enhance ozone-induced increases in airway responsiveness in both
healthy and asthmatic subjects.
     Koenig et al. (1994) sought to determine whether exposure to H2SO4 or HNO3 enhanced
changes in lung function or airway responsiveness seen with exposure to ozone + nitrogen
dioxide (NO2).  Adolescent asthmatic subjects were exposed to air, 0.12 ppm ozone + 0.3 ppm
NO2, ozone + NO2 + 73 //g/m3 H2SO4 (MMAD = 0.6), and ozone + NO2 + 0.05 ppm HNO3.
Exposures were by mouthpiece for 90 min, with intermittent exercise, on two consecutive days.
Airway responsiveness was measured by methacholine challenge at screening and on the day
following the second pollutant exposure. No effects on airway responsiveness were found for
any atmosphere. However, challenge following pollutant exposure utilized only doses of
methacholine well below the level causing significant reductions in FEVj for these subjects at
baseline, making it unlikely that small or transient changes in responsiveness would be detected.
Six subjects did not complete the protocol because of illness, symptoms, and other factors which
may or may not have been related to pollutant exposure; these data were not included in the
analysis.
     In summary, the data suggest that there is little, if any, effect of low concentration acid
aerosol exposure (regardless of particle size) on airway responsiveness in healthy or asthmatic
subjects.  Observations of possible delayed increases in responsiveness in healthy subjects
exposed to 450 //g/m3 H2SO4 (Utell et al., 1983a), and H2SO4 enhancement of ozone effects on
airway responsiveness in healthy and asthmatic subjects (Linn et al., 1994) require confirmation
in additional studies, utilizing standard challenge protocols.

11.2.1.5  Effects of Acid Aerosols on Lung Clearance Mechanisms
     Brief (1-  to 2-h) exposures to H2SO4 aerosols have shown consistent effects  on mucociliary
clearance in three species:  donkeys, rabbits, and humans. The direction and magnitude of the
effect are dependent on the concentration and duration of the acid aerosol
                                         11-34

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 exposure, the size of the acid particle, and the size of the tracer particle.  Clearance studies in
animals are discussed in Section 11.2.2.5.
     Initial studies in healthy nonsmokers by Leikauf et al. (1981) found that exposure to 110
Mg/m3 H2SO4 (MMAD «0.5//m) for 1 h at rest accelerated bronchial mucociliary clearance of
7.5 //m tracer particles, while a similar exposure to 980 //g/m3 H2SO4 slowed clearance.  A
second study (Leikauf et al., 1984) utilizing a smaller tracer particle (4.2 //m) to assess more
peripheral airways, found slowing of clearance with both 108 and 983 //g/m3 H2SO4, in
comparison with distilled water aerosol.  Spektor et al. (1989) extended these studies, exposing
ten healthy subjects to H2SO4 (MMAD = 0.5//m) or distilled water aerosols for up to 2 h. Two
different 4.2 //m tracer aerosols were used, one administered before and the other after exposure.
Following a 2 h exposure to 100 //g/m3 H2SO4, clearance halftime tripled compared with control,
with reduced clearance rates still evident 3 h after exposure.  These findings suggested that brief,
resting exposures to H2SO4  at ~ 100 //g/m3 accelerate clearance in large bronchi but slow
clearance in more peripheral airways in a dose-dependent fashion.
     Data from studies in asthmatics are less clear.  Spektor et al. (1985) exposed ten  asthmatic
subjects to 0, 110, 319, and 911 //g/m3 H2SO4 (MMAD = 0.5//m) for 1 h. The effects  were
difficult to interpret because of inhomogeneous distribution of the tracer aerosol in the more
severe asthmatics. However, clearance was decreased following the highest concentration of
acid exposure in the six subjects with the mildest asthma (not dependent  on regular medications).
These responses were similar to those of healthy subjects reported above.
     Laube  et al. (1993) recently examined the effects of acid fog on mucociliary clearance in
asthmatics.  Seven nonsmoking subjects with mild asthma (baseline FEVj 90 to 118% predicted)
were exposed in a head dome to 500 //g/m3 H2SO4 or NaCl (MMAD ~ 10 //m) for 1 h with 20
min  of exercise.  Mucociliary clearance was measured using inhalation of a technetium-99M
sulfur colloid aerosol after exposure to the test aerosol. Tracheal clearance was measured in four
subjects, and was increased in all four after H2SO4 exposure (no statistical analysis was
performed because of the small number of subjects).  Outer zone lung clearance was increased in
six of seven  subjects after H2SO4 exposure (p < 0.05). The
                                          11-35

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dose of H+ inhaled orally correlated significantly with the change in outer zone lung clearance
(r = 0.79, p = 0.05).

11.2.1.6  Effects of Acid Aerosols Studied by Bronchoscopy and Airway Lavage
     Fiberoptic bronchoscopy with BAL has proved a useful technique for sampling the lower
airways of humans in clinical studies of oxidant air pollutants.  The type and number of cells
recovered in BAL fluid reflect changes in alveolar and distal airway cell populations, providing
a relatively sensitive measure of inflammation. Increases in serum proteins recovered in BAL
fluid can be a result of increased epithelial permeability, a consequence of injury and/or
inflammation. Alveolar macrophages obtained by BAL can be assessed in vitro for functional
changes important in inflammation and host defense.  In addition, proximal airway cells and
secretions can be recovered using airway washes or proximal airway lavage (Eschenbacher and
Gravelyn, 1987).
     Only one study has utilized bronchoscopy to evaluate the effects of exposure to acid
aerosols. Frampton et al. (1992) exposed 12 healthy nonsmokers to aerosols of NaCl (control)
or H2SO4 (MMAD = 0.9, GSD = 1.9) at 1000 //g/m3 for 2 h. Four 10-min exercise periods at
-40 L/min were included.  Subjects brushed their teeth and rinsed with mouthwash prior to and
once during each exposure to reduce oral ammonia levels. Fiberoptic bronchoscopy with BAL
was performed 18 h after exposure.  No evidence for airway inflammation was found.  Markers
for changes in host defense, including lymphocyte subset distribution, antibody-dependent
cellular cytotoxicity of alveolar macrophages, and alveolar macrophage inactivation of influenza
virus, were not significantly different between H2SO4  and NaCl exposures.
     In an effort to define possible effects of H2SO4 exposure on airway mucus, Gulp et al.
(1995) determined the composition of mucins recovered during bronchoscopy of subjects studied
by Frampton et al. (1992),  as well as from some subjects not exposed.  Secretions were lipid
extracted from airway wash samples and analyzed with regard to glycoprotein content, protein
staining profiles, and amino acid and carbohydrate composition. Mucin composition was similar
when non-exposed subjects were compared with NaCl-exposed subjects, indicating that aerosol
exposure per se did not alter mucus composition. No  differences were found between H2SO4
and NaCl exposure with regard to absolute yields
                                         11-36

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of high-density material, proportion of glycoproteins, presence of glycoprotein degradation
products, carbohydrate composition, or protein composition.
     In these studies, bronchoscopy was performed 18 h after exposure in order to detect
delayed effects. Transient effects of exposure to acid aerosols on alveolar macrophage function
or mucous composition have therefore not been excluded.

11.2.1.7  Human Exposure Studies of Acid Aerosol Mixtures
     In human subjects, previous studies have suggested that exposure to H2SO4 does not
potentiate responses to other pollutants.  A number of more recent studies have also failed to
find interactions in effects of pollutant mixtures that include H2SO4.  Anderson et al. (1992)
found no effects on lung function following exposure to 200 //g/m3 carbon black alone, or
carbon particles coated with H2SO4.  Aris et al. (1990) found no effects on airways resistance of
exposure to mixtures of hydroxymethanesulfonic acid and H2SO4. Balmes et al. (1988) found no
differences between the effects of H2SO4 and HNO3 exposure in asthmatics, and no interaction
with exposure to both aerosols by mouthpiece. Koenig et al. (1989) found that exposure of
adolescent asthmatic subjects to 68 //g/m3 H2SO4 with 0.1 ppm SO2 did not increase the
responses seen with H2SO4 alone.
     In one recent study funded by the Health Effects Institute, 28 adolescent asthmatic subjects
were exposed to air, 0.12 ppm ozone + 0.3 ppm NO2, ozone + NO2 + 68 //g/m3 H2SO4, and
ozone + NO2 + 0.05 ppm HNO3 (Koenig et al., 1994). Exposures were by mouthpiece for 90
min, with intermittent exercise, on two consecutive days.  No significant effects on lung function
were seen for any of the atmospheres. However, six subjects did not complete the study protocol
for a variety of reasons; these subjects were characterized by the authors as having moderate to
severe asthma, based on results of methacholine challenge. Although the reasons for withdrawal
of these subjects were  not clearly related to exposures, all discontinued participation following
exposure to pollutants  rather than to clean air. As noted in the published comments of the
Health Effects Institute Health Review Committee accompanying the Koenig et al. report, "...the
conclusions of the study may have been based on a group of subjects more tolerant to oxidants,
acid aerosols, or both,  than those constituting the original study group" (Koenig et al., 1994,
page 103).
                                          11-37

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     Two recent studies suggest that exposure to 100 //g/m3 H2SO4 may enhance airway effects
of exposure to ozone. Linn et al. (1994) exposed 15 healthy and 30 asthmatic subjects to air,
0.12 ppm ozone, 100 //g/m3  H2SO4 (MMAD «0.5 //m), and ozone + H2SO4 for 6.5 h on two
consecutive days. Each subject received all 4 pairs of exposures, each separated by one week.
Subjects were exposed in small groups in an environmental chamber, with six, 50-min exercise
periods each day. Acidic gargles were used to reduce oral ammonia.  Lung function and
methacholine responsiveness were measured at the end of each exposure day. Reductions in
FEVj and FVC, and increases in airway responsiveness, were observed in association with ozone
exposure in both healthy and asthmatic subjects.  Some subjects in both the asthmatic and
nonasthmatic group demonstrated greater declines in lung function after the first day of acid +
ozone than after ozone alone (Figure 11-2), although the group mean differences were only
marginally significant by ANOVA.  From these data, a "hypothetical average subject", under the
specific conditions of the study, would be expected to lose 100 ml FEVj during ozone exposure
relative to clean air exposure, and would lose 189 ml FEVj during ozone + H2SO4 exposure.
When the responsive subjects were re-studied months later, increased responsiveness to acid +
ozone compared with ozone was again demonstrated, although individual responses to O3 +
H2SO4 in the original and repeat studies were not significantly correlated.
100 -
-100 -
2
S
= -200 -
-300 -
-400 -

0-6
H
• f -f



i i i
1 2
Clean
6-4
T
H *"" i/
{""A T...J 0 T
T f.f ^
/\ 1
i ^
i

i i i i i i i
12 12 1
s''[


i
2
Acid Ozone Ozone+Acid
                           |A"--AAsthmatics   O— OlMonasthmatics
Figure 11-2.  Decrements in forced expiratory volume in 1 s (plus or minus standard
             error) following 6.5-h exposures on 2 successive days.
Source: Linn et al. (1994).
                                         11-38

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     Frampton et al. (1995) exposed 30 healthy and 30 asthmatic subjects to 100 //g/m3 H2SO4
or NaCl for 3 h followed the next day by 0.08, 0.12, or 0.18 ppm ozone for 3 h. All exposures
included intermittent exercise. Each subject received two of the three ozone exposure levels.
Exposure to H2SO4 or NaCl did not alter lung functions.  As shown in  Table 11-4, changes in
spirometry following exposure to ozone were small, consistent with the relatively low
concentrations, short exposure duration, and moderate exercise levels (VE 30.6 to 36.2 L/min
for a total  of 60 min). Figure 11-3 shows the percentage changes in FVC 4 h after ozone
exposure;  these changes were similar to those found immediately after exposure.  With H2SO4
pre-exposure, FVC decreased following ozone in a concentration-response fashion. The
ANO VA revealed significant main effects of ozone exposure as well as a significant interaction
between aerosol and ozone exposure for effects on FEVj and FVC among the asthmatic subjects,
but not the healthy subjects. Four-way  ANOVA revealed an interaction between ozone and
aerosol for the entire group (p=0.0022)  and a difference between healthy subjects and subjects
with asthma (p=0.0048). Surprisingly,  the largest decrements in FVC with the NaCl
preexposure were found with 0.08 ppm ozone, whereas no effect was seen at 0.18.  With 0.18
ppm ozone preceded by H2SO4, the responses were similar to those seen at 0.08 with NaCl.  The
authors concluded that, for asthmatic subjects, H2SO4 alters the response to ozone in comparison
with NaCl pre-exposure. Interpretation of these findings would be facilitated by a similar study
including air as a further control pre-exposure atmosphere. However, considered together, these
two  studies (Frampton et al., 1995 and Linn et al., 1994) suggest that H2SO4 aerosol exposure
may enhance airway responsiveness to ozone.

11.2.1.8   Summary and Conclusions
     Controlled human studies offer the opportunity to study the responses of human subjects
under carefully controlled conditions, but are limited to short-term exposures to pollutant
atmospheres without severe health risks. Outcome measures are limited by safety issues, but
have been extended beyond measures of lung function and symptoms to include mucociliary
clearance, BAL, and airway biopsies.
     Human clinical studies of particle exposure remain almost completely limited to the study
of acid aerosols, primarily of H2SO4, with the majority of these focussing on
                                         11-39

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      TABLE 11-4. PULMONARY FUNCTION RESPONSES AFTER AEROSOL AND OZONE EXPOSURES IN
                                      SUBJECTS WITH ASTHMA3
Time of Measurement
0.08 ppm Ozone
Baseline
After exercise
Immediately after exposure
2 Hours after exposure
4 Hours after exposure
0.12 ppm Ozone
Baseline
After exercise
Immediately after exposure
2 Hours after exposure
4 Hours after exposure
0.18 ppm Ozone
Baseline
After exercise
Immediately after exposure
2 Hours after exposure
4 Hours after exposure
FVC
NaCl

3.80±0.17
3.64 ±0.17
3. 51 ±0.18
3.67 ±0.17
3.67±0.15

3. 97 ±0.22
3.72 ±0.20
3. 72 ±0.21
3. 91 ±0.22
3. 87 ±0.22

3. 89 ±0.23
3.76 ±0.23
3. 76 ±0.23
3. 81 ±0.25
3. 90 ±0.24
(L)
H2S04

3.73±0.17
3.59±0.18
3.64 ±0.17
3. 70 ±0.16
3.74±0.18

3. 95 ±0.22
3.76±0.19
3.76 ±0.20
3. 85 ±0.21
3. 87 ±0.21

3. 99 ±0.22
3. 71 ±0.22
3.74 ±0.24
3. 87 ±0.23
3. 84 ±0.25
FEVj
NaCl

2.85±0.11
2.84 ±0.12
2.73 ±0.12
2.91 ±0.12
2.92 ±0.10

2.98 ±0.17
2.94 ±0.17
2.90 ±0.19
3.10±0.18
3. 07 ±0.18

2.92 ±0.16
2.90 ±0.19
2.90 ±0.19
3. 03 ±0.19
3. 06 ±0.17
(L)
H2S04

2.79 ±0.10
2.72 ±0.12
2.79±0.11
2.89±0.11
2.92 ±0.13

3. 05 ±0.17
3.01 ±0.16
2.97 ±0.18
3. 08 ±0.17
3. 04 ±0.18

3. 04 ±0.17
2.99 ±0.16
2.96 ±0.18
3. 03 ±0.17
2.99 ±0.18
sGaw (cm H2O/L/sec)
NaCl H2S04

0.204 ±0.021 0.209 ±0.020
-
0.176 ±0.024 0.177 ±0.022
-
-

0.220 ±0.015 0.236 ±0.020
-
0.186 ±0.019 0.209 ±0.025
-
-

0.183 ±0.016 0.207 ±0.016
-
0.170±0.016 0.179±0.018
-
-
1 Values are expressed as means ± SEM.

-------
                     0.2T
                     0.1"
                 O    o
                 o
                 O)
                 IS
                 £
                 O
                    -0.1"
                    -0.2"
                    -0.3
                                NaCI
                                H2S04
                                    0.08
0.12
0.18
                                          ppm Ozone
Figure 11-3. Asthmatic subjects.  The absolute change in FVC (means ± SE) 4-h after
             exposure to each of the three ozone concentrations for the NaCI and H2SO4
             aerosol preexposure conditions.
Source: Framptonet al. (1995).
symptoms and pulmonary function. Only two studies (Frampton et al., 1992; Gulp et al., 1995)
have utilized BAL to examine effects of particle exposure in humans. No studies have
examined effects of particle or acid aerosol exposure on airway inflammation in asthmatic
subjects. There are no studies examining the effects of particle exposure on antigen challenge in
allergic or asthmatic subjects.
     Ten studies since 1988 have confirmed previous findings that healthy subjects do not
experience decrements in lung function following single exposures to H2SO4 of various particle
sizes at levels up to 2,000 //g/m3 for 1 h, even with exercise and use of acidic gargles to
minimize neutralization by oral ammonia. Mild lower respiratory symptoms occur at exposure
concentrations in the mg/m3 range, particularly with larger particle sizes. Acid aerosols alter
mucociliary  clearance in healthy subjects at levels as low as 100 //g/m3, with effects dependent
on exposure concentration, acid aerosol particle size, and the region of the lung being studied.
     Asthmatic subjects appear to be more sensitive than healthy subjects to the effects of acid
aerosols on lung function, but the effective  concentration differs widely among studies.
                                          11-41

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Adolescent asthmatics may be more sensitive than adults and may experience small decrements
in lung function in response to H2SO4 at exposure levels only slightly above peak ambient levels.
Although the reasons for the inconsistency among studies remain largely unclear, subject
selection and acid neutralization by NH3 may be important factors.  Even in studies reporting an
overall absence of effects on lung function, occasional asthmatic subjects appear to demonstrate
clinically important effects. Two studies from different laboratories have suggested that
responsiveness to acid aerosols may correlate with degree of baseline airway
hyperresponsiveness.  There is a need to identify determinants of responsiveness to H2SO4
exposure in asthmatic subjects. In very limited studies, elderly and individuals with chronic
obstructive pulmonary disease do not appear to be particularly susceptible to the effects of
submicron acid aerosols on lung function.
     Two recent studies have examined the effects of exposure to both H2SO4 aerosols and
ozone on lung  function in healthy and asthmatic subjects. Both studies found evidence that 100
Mg/m3 H2SO4 may potentiate the response to ozone, in contrast with previous studies.
     Human studies of particles other than acid aerosols provide insufficient data to draw
conclusions regarding health effects. However, available data suggest that inhalation of inert
particles in the respirable range, including three studies of carbon particles, have little or no
effect on symptoms or lung function in healthy subjects at levels above peak ambient
concentrations.

11.2.2  Laboratory Animal Studies

11.2.2.1  Introduction
     This section reviews the effects of acidic aerosols on laboratory animals. Almost all of the
available data have been derived from studies using acidic sulfates, namely ammonium bisulfate
(NH4HSO4) and sulfuric acid (H2SO4).

11.2.2.2  Mortality
     The previous CD (U.S. Environmental Protection Agency, 1982) examined animal studies
of the acute lethality of acid aerosols (mainly H2SO4), and there are few new data to add here.
As for other toxicologic endpoints, large interspecies differences occurred, with the guinea pig
being the most sensitive, compared to the mouse, rat and rabbit. But high
                                          11-42

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concentrations of H2SO4, generally in excess of 10,000 //g/m3, were required for lethality, even
in a species as sensitive as the guinea pig. Also, within a particular species of experimental
animal, the H2SO4 concentration required for lethality was dependent upon particle size, with
smaller particles being less effective than larger ones. As noted in the previous CD, the cause of
death due to acute, high-level H2SO4 exposure was laryngeal or bronchial spasm. Since these are
irritant responses, differences in the deposition pattern of smaller and larger acid droplets may
account for the aforementioned particle size dependence of lethal concentration; larger particles
deposit to a greater extent in the larynx and upper bronchial tree, where the bulk of irritant
receptors are located.  As acid particle size is reduced, deeper pulmonary damage occurs prior to
death. Lesions commonly seen are focal atelectasis, hemorrhage, congestion, pulmonary and
perivascular edema, and desquamation of bronchiolar epithelium; hyperinflation is also often
evident.
      Few data allow assessment of lethality for acid sulfate aerosols other than H2SO4.  Pattle
et al.  (1956) noted that if sufficient ammonium carbonate was added into the chamber where
guinea pigs were exposed to H2SO4 so as to provide excess NH3, protection was afforded to acid
levels which would have produced 50% mortality in the absence of NH3.  This implies that
H2SO4 is more acutely toxic than its neutralization products [i.e., NH4HSO4 and/or (NH4)2SO4].
Pepelko et al. (1980a) found no mortality among rats exposed for 8 h/day for 3  days to
(NH4)2SO4 at 1,000,000 to 1,200,000 //g/m3 (2 to 3 //m, MMAD); but 40 and 17% mortality
occurred in guinea pigs exposed once for 8 h to 800,000 to 900,000, or 600,000 to 700,000
Mg/m3, respectively, of similarly sized-particles. Death was ascribed to  airway constriction,
rather than to extensive lung damage.  As with H2SO4, guinea pigs were more sensitive than
other species.
      In summary, very high concentrations of acid sulfates are required to cause mortality in
otherwise healthy animals, with variations in effective concentrations depending on acid particle
size and the animal species tested.

11.2.2.3  Pulmonary Mechanical Function
      Many studies examining the  toxicology of inhaled acid aerosols at sublethal levels used
changes in pulmonary function as  indices of response. A survey of the database since
                                          11-43

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publication of the previous CD (U.S. Environmental Protection Agency, 1982) is presented in
Table 11-5.
     One of the major exposure parameters which affects response is particle size.  Studies by
Amdur (1974) and Amdur et al. (1978a,b), summarized in the previous CD, showed that the
irritant potency of H2SO4, (NH4)2SO4, or NH4HSO4, as measured by pulmonary resistance in
guinea pigs, increased with decreasing particle size (i.e., the degree of response per unit mass of
sulfate [SO4 ] at any specific exposure concentration increased as particle size decreased, at least
within the size range of 1 to 0.1 //m). If this is compared to the relationship between particle
size and mortality, it is evident that the relative toxicity of different particle sizes also depends
upon the exposure concentration. At high concentrations above the threshold for lethality, large
particles were more effective in eliciting response, while at  lower (sublethal) levels, smaller
particles were more effective.
     Pulmonary functional responses to H2SO4 described previously suggested a major site of
action to be the conducting airways, as evidenced by exposure-induced alterations in airflow
resistance. However, some earlier data also suggested that high exposure levels may affect more
distal lung regions, as evidenced by changes in pulmonary diffusing capacity (DLCO) noted in
dogs exposed to 889 //g/m3 (MMAD = 0.5//m) (Lewis et al., 1973). Deep lung effects  of H2SO4
are also evident from studies of morphologic and lung defense endpoints, discussed in
subsequent sections.
     Studies reported in the previous CD (U.S. Environmental Protection Agency, 1982)
indicated that the particle size of the acid aerosol affected the temporal pattern of any pulmonary
function response. For example, the response to 100 //g/m3 H2SO4 at 1  //m was  slight and
rapidly reversible, while that with 0.3 //m droplets was greater and more persistent. At any
particular size, however, the degree of change in resistance  and compliance in guinea pigs was
observed to be concentration related.
     Although the earlier studies by Amdur and colleagues appeared to provide a reasonable
picture of the relative effects of acid particle size and exposure concentration on the
bronchoconstrictive response of guinea pigs at sublethal exposure levels, there is some conflict
between these results and reports by others discussed in the previous CD (U.S. Environmental
Protection Agency, 1982). Whereas the Amdur work  supported a concentration dependence for
respiratory mechanics alterations (i.e., animals in each
                                          11-44

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         TABLE 11-5. EFFECTS OF ACIDIC SULFATE PARTICLES ON PULMONARY MECHANICAL FUNCTION
Particle
H2S04
H2S04
H2S04
H2S04
H2S04
H2S04
H2S04
(NH4)2S04
(NH4)2S04
Species, Gender,
Strain, Age, or
Body Weight
Rat
Rat
Rat
Guinea pig, M
Hartley
Rabbit, M
NZW
Guinea pig, M
Hartley,
260-325 g
Guinea pig, M
Hartley,
290-410 g
Guinea pig, M
Hartley, 10 wk
Rat, M
SD, 14 wk
Exposure
Technique (RH)
Whole body
Whole body
Whole body
Whole body
Nose-only (50%)
Nose-only (50%)
Head-only (50%)
Whole body
(50-60%)
Whole body
(50-60%)
Mass Concentration
(//g/m3)
2,370
6,350
6,590
1,000, 3,200
250
300
200
1,000
1,000
Particle Characteristics
Size (//m); ag
0.5 (MMD)
0.44 (MMD)
0.31 (MMD)
0.54 (MMD); 1.32
0.3 (MMAD); 1.6
0.08 (MMD); 1.3
0.06 (MMD); 1.4
0.4 (MMAD); 2.2
0.4 (MMAD); 2.3

Exposure Duration
14 weeks
6 weeks
13 weeks
24 h/d, 3-30 d
1 h/day, 5 days/week,
up to 12 mo
Ih
Ih
6 h/day, 5 days/week,
1 or 4 weeks
6 h/day, 5 days/week,
1 or 4 weeks
Observed Effect
NC: VT, f, RL, Cd, pH, PaCO2
iPaC02
TpH
Hypo- to hyperresponsive
airways
NC: RL
Hyperresponsive by 4 mo
NC: VC, 1C, VA, TLC;
i DLco, (3 h post exp)
NC: RL
NC: RV; TFRC, VC, TLC,
DLco, Cd, AN2
TRV, TFRC, AN2
Reference
Lewkowski et al. (1979)
Lewkowski et al. (1979)
Lewkowski et al. (1979)
Kobayashi and Shinozaki
(1993)
Gearhart and
Schlesinger(1986)
Chenetal. (1991)
Chen et al. (1992b)
Loscutoffetal. (1985)
Loscutoffetal. (1985)
Key to abbreviations:
 NC: No significant change
 T:  Significant increase
 i:  Significant decrease
 Cd: Dynamic compliance
 DLco: Diffusing capacity, CO
 f: Respiratory frequency
 FRC: Functional residual capacity
 1C: Inspiratory capacity
 AN2:  Change in distribution of ventilation as measured by nitrogen washout technique
 PaCO2:  Partial pressure of CO2 in arterial blood
 pH: Arterial pH
 RL: Pulmonary resistance
 RV: Residual volume
 TLC: Total lung capacity
 VT: Tidal volume
 VA: Alveolar volume
 VC: Vital capacity

-------
exposure group responded uniformly and the degree of response was related to the exposure
concentration), others found that individual guinea pigs exposed to H2SO4 at similar sizes
showed an "all-or-none" constrictive response (i.e., in atmospheres above a threshold
concentration), some animals manifested major changes in pulmonary mechanics ("responders"),
while others were not affected at all ("nonresponders") (Silbaugh et al., 1981b). As the exposure
concentration was increased further, the percentage of the group which was affected (i.e., the
ratio of responders to nonresponders) increased, producing an apparent concentration response
relationship. However, the magnitude of the change in pulmonary function was similar for all
responders, regardless of exposure concentration.  Sensitivity to this all-or-none response may be
related to an animal's baseline airway caliber prior to H2SO4 exposure, because responders had
higher pre-exposure values for resistance and lower values for compliance,  compared to
nonresponders. In any case, the threshold concentration for the all-or-none response was fairly
high (>10,000 //g/m3 H2SO4).  Reasons for the discrepancy with the studies of Amdur and
colleagues are not known; they may involve differences in guinea pig strains,  ages, or exposure
conditions, or differences in techniques used to measure functional parameters.  In any case, the
dyspneic response of the guinea pig responders is  similar to asthma episodes in humans, in both
its rapidity of onset and in the associated characteristic obstructive pulmonary function changes.
     A more recent approach used to evaluate the acute pulmonary functional response to
H2SO4 involves co-inhalation of CO2 (Wong and Alarie, 1982; Matijak-Schaper et al., 1983;
Schaper et al.,  1984). This procedure assesses the response to irritants by measuring a decrease
in tidal volume (VT) (based upon changes in inspiratory volume and pressure) which is routinely
increased above normal by adding 10% CO2 to the exposure atmosphere. Although the exact
mechanism underlying a reduction in response to CO2 is not clear, the assumption is that the
change in ventilatory response after irritant exposure is due to direct stimulation of irritant
receptors. A concentration-dependent decrease in CO2-enhanced ventilation has been found in
guinea pigs following 1-h exposures to H2SO4 (~ 1 //m, MMD) at levels >40,100 //g/m3 (Wong
and Alarie, 1982).  Subsequently, Schaper et al. (1984) exposed guinea pigs for 0.5 h to H2SO4
at 1,800 to 54,900 //g/m3 (0.6 //m, AED).  At concentrations >10,000 //g/m3, the level of
response (i.e., the maximum decrease in ventilatory response to CO2) increased as a function of
exposure concentration.
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At concentrations below 10,000 //g/m3, there was no clear relationship between exposure
concentration and response; any effects were transient, occurring only at the onset of acid
exposure.
     The results of the studies with CO2 differ from those of both Silbaugh et al. (1981b) and
Amdur and colleagues, in that there was neither an "all or none" response as seen by the former,
nor was there a concentration-response relationship observed at H2SO4 concentrations <10,000
Mg/m3, as reported by the latter.  In addition, Amdur and colleagues observed sustained changes
in lung function, rather than a fading response, at low concentrations. The reasons for these
differences are unknown, but may partly reflect inherent sensitivity differences in the
measurement techniques used as noted above.
     The specific mechanisms underlying acid sulfate-induced pulmonary functional changes
are not known, but may be due to irritant receptor stimulation resulting from direct contact by
deposited acid particles or from humoral mediators released as a result of exposure. In terms of
the latter, a possible candidate in mediation of the bronchoconstrictive response, at least in
guinea pigs, is histamine (Charles and Menzel, 1975).  On the other hand, evidence for a direct
response to H2SO4 in altering pulmonary function was found using the CO2 co-inhalation
procedure.  Schaper and Alarie (1985) noted that the responses to histamine and H2SO4 differed
in both their magnitude and temporal  relationship,  suggesting direct action of the inhaled acid, or
a role of other humoral factors.
     Whatever the underlying mechanism, the results of pulmonary function studies indicate
that H2SO4 is a bronchoactive agent that can alter lung mechanics of exposed animals primarily
by constriction of smooth muscle; however, the threshold concentration for this response is quite
variable, depending upon the animal species and measurement procedure used.  In general,
exposure to H2SO4 at levels <1,000 //g/m3 does not produce physiologically significant changes
in standard tests of pulmonary mechanics, except in the guinea pig. Although in this species
such effects may be markers of exposure, any health significance in normal individuals is not
clear. On the other hand, all subgroups of an exposed population may not be equally sensitive.
                                          11-47

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Airway Responsiveness
     Some lung diseases (e.g., asthma) involve a change in airway "responsiveness", which is an
alteration in the degree of reactivity to exogenous (or endogenous) bronchoactive agents,
resulting in increased airway resistance at levels of these agents which would not affect airways
of normal individuals. Such altered airways are called hyperresponsive. The use of
pharmacologic agents capable of inducing smooth muscle contraction, a technique known as
bronchoprovocation challenge testing, can assess the state of airway responsiveness after
exposure to a nonspecific stimulus such as an inhaled irritant.  Human asthmatics and, to some
extent, chronic bronchitis, typically have hyperresponsive airways, but the exact role of this in
the pathogenesis of airway disease is uncertain. Hyperresponsiveness may be a predisposing
factor in clinical disease, or it may be a reflection of other changes in the airways which precede
it. In any case, current evidence supports the hypothesis that an increase in airway
responsiveness is a factor in the pathogenesis of obstructive airway disease (O'Connor et al.,
1989).
     The ability of H2SO4 aerosols to alter airway responsiveness has been assessed in a number
of studies. Silbaugh et al. (1981a) exposed guinea pigs for 1 h to 4,000 to 40,000 //g/m3 H2SO4
(1.01 //m, MMAD) and examined the subsequent response to inhaled  histamine.  Some of the
animals showed an increase in pulmonary resistance and a decrease in compliance at H2SO4
concentrations > 19,000 //g/m3 without provocation challenge; only the animals showing this
constrictive response during acid exposure also had major increases in histamine sensitivity.
This suggested that airway constriction may have been a prerequisite for the development of
hyperresponsiveness.  On the other hand, Chen et al. (1992b) found bronchial
hyperresponsiveness, but no change in baseline resistance, in guinea pigs exposed for 1 h to 200
//g/m3 H2SO4 (0.06 //m, MMD). Perhaps the smaller size of this aerosol was responsible for
producing effects at a lower concentration.
     Kobayashi and Shinozaki (1993) exposed guinea pigs to fairly high H2SO4 levels, namely
1,000 and 3,200  //g/m3 (0.54 //m), 24 h/day for 3, 7, 14 or 30 days, and examined airway
response to inhaled histamine.  Unlike the study of Silbaugh et al. (1981a) and similar to that of
Chen et al. (1992b), acid exposure did not change the baseline resistance measured prior to
bronchoprovocation challenge. Exposure to 3,200 //g/m3 of acid resulted in airway
hyporesponsiveness at 3 days, hyperresponsiveness at 14 days and a return to normal levels of
responsiveness by 30 days of exposure.  Thus, acid exposure resulted in a transient alteration in
airway function.  The authors speculated  that the hyporesponsiveness, and eventual return to
                                          11-48

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normal, was due to changes in mucous secretion in the airways, which would affect the ability of
the inhaled histamine challenge aerosol to contact airway receptors.
     Airway responsiveness following chronic exposure to H2SO4 was examined by Gearhart
and Schlesinger (1986), who exposed rabbits to 250 //g/m3 H2SO4 (0.3 //m, MMD) for 1 h/day, 5
days/week, and assessed responsiveness after 4, 8 and 12 mo of exposure, using acetylcholine
administered intravenously rather than inhaled. Hyperresponsiveness was evident at 4 mo, and a
further increase was found by 8 mo; the response at 12 mo was similar to that at 8 mo, indicating
a stabilization of effect.  There was no change in baseline resistance. Thus, repeated exposures
to H2SO4 produced hyperresponsive airways in previously normal animals.
     The mechanism which underlies H2SO4-induced airway hyperresponsiveness is not clear.
However, some recent studies have suggested possibilities. One may involve an increased
sensitivity to mediators involved in airway smooth muscle control. For example, guinea pigs
exposed to H2SO4 showed a small degree of enhanced response to histamine, but a much more
pronounced sensitivity to substance P, a neuropeptide having effects on bronchial muscle tone
(Stengel et al., 1993). El-Fawal and Schlesinger (1994) exposed rabbits for 3 h to 50 to 500
//g/m3 H2SO4 (0.3 //m), following which bronchial airways were examined in vitro for
responsiveness to  acetylcholine and histamine. Exposures at >75 //g/m3 produced increased
responsiveness to  both constrictor agents. Detailed examination of the response in tracheal
segments suggested that  the acid effect may result from interference with airway
contractile/dilatory homeostatic processes, in that there was a potentiation of the response of
airway constrictor receptors and a diminution  of the response of dilatory receptors.

11.2.2.4  Pulmonary Morphology and Biochemistry
     Morphologic alterations associated with exposure to acid aerosols are summarized in
Table 11-6.
                                         11-49

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TABLE 11-6. EFFECTS OF ACIDIC SULFATE PARTICLES ON RESPIRATORY TRACT MORPHOLOGY
Particle
H2S04
H2S04
H2S04
H2S04
H2S04
H2S04
H2S04
H2S04
H2S04
H2S04
Species, Gender,
Strain, Age, or
Body Weight
Guinea pig
Guinea pig, M/F
Hartley, 2-3 mo
Rabbit, M
mixed,
2.5-2.7 kg
Rabbit, M
mixed,
2.5-2.7 kg
Rabbit, M
NZ White, 3-3. 5 kg
Rat
Rat
Rat
Rhesus monkey
Guinea Pig
Exposure
Technique (RH)
Whole body
(70-90%)
Whole body (80%)
Oral tube or
nose- only (80%)
Nose-only (80%)
Nose-only (60%)
Whole body
(40-60%)
Whole body (50%)
Whole body
(<60%)
Whole body
(<60%)
Whole body
(<60%)
Mass
Concentration
C"g/m3)
32,600
1,200, 9,000,
27,000
250-500
250
125
2,000
700-1,200
45,000
68,000
172,000
150,000
361,000
502,000
30,000
38,000
71,000
Particle Characteristics
Size (//m); an
1 (MMAD); 1.49
0.8-1 (MMAD); 1.5-1.6
0.3 (MMAD); 1.6
0.3 (MMAD); 1.6
0.3 (MMD); 1.6
0.3 (MMD); =2
0.03-0.04 (CMD); 1.8-2.1
0.52(CMD)
0.4 (MMAD)
0.45 (CMD)
0.3-0.5 (CMD)
0.43 (MMAD); 1.6
0.48 (MMAD); 1.5
0.31 (MMAD); 1.6
0.31 (MMAD); 1.6
0.52 (CMD)

Duration
4h
6h
1 h/day,
5 days/week,
4 weeks
1 h/day,
5 days/week
up to 52 weeks
2 h/day,
5 days/week
up to 12 mo
8 h/day,
82 days
Continuous,
up to 180 days
11 days
6 days
7 days
3 days
7 days
7 days
7 days
7 days
4 days
Observed Effect
Focal atelectasis; epithelial
desquamation in terminal bronchioles
At 27,000 lig/m3: interstitial edema only
in "responders"; no change in
"nonresponders" oral 1,000 and 10,000
//g/m3. Concentration-dependent increase
in height of tracheal mucus layer at all
concentrations.
Increased epithelial thickness in small
airways; increase in secretory cells in
mid
to small airways
Increase in secretory cell no. density
throughout bronchial tree increase in
number of small airways
No bronchial inflammation; increase in
secretory cell number density in small
airways at 12 mo
Some hypertrophy of epithelial cells,
mainly at alveolar duct level; no effect
on turnover rate of terminal bronchiolar
epithelial or Type II cells
No effect
No effect in nasal passages, trachea,
bronchi, alveolar region
No effect
At 71,000 //g/m3: focal edema, necrosis of
alveolar septa, inflammatory cell
infiltration; necrosis of bronchiolar
epithelium; focal epithelial necrosis in
larger bronchi; ciliary denudation. At
38,000 //g/m3: minimal effects; some
change in density and length of cilia
Reference
Brownstein
(1980)
Wolff etal.
(1986)
Schlesinger
et al. (1983)
Gearhart and
Schlesinger
(1988)
Schlesinger
et al. (1992b)
Juhos et al.
(1978)
Moore and
Schwartz (1981)
Schwartz et al.
(1977)
Schwartz et al.
(1977)
Schwartz et al.
(1977)

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TABLE 11-6 (cont'd). EFFECTS OF ACIDIC SULFATE PARTICLES ON RESPIRATORY TRACT MORPHOLOGY
Particle
H2S04
H2S04
H2S04
H2S04
H2S04
(NH4)2S04
(NH4)2S04
(NH4)2S04
(NH4)2S04
(NH4)2S04
(NH4)2S04
Species, Gender,
Strain, Age, or
Body Weight
Mouse
Rat
Rat, M/F,
F344/Crl
12-16 weeks
Rat, M
Fischer,
250-300 g
Guinea pig
Guinea pig, M,
Hartley
adult
Rat, M,
SD/Crl,
70-75 g
Hamster, M,
Syrian,
10 weeks
Rat, M,
adult
Rat, M, SD
adult
Rat
Exposure
Technique (RH)
Whole body
(<60%)
Whole body
Whole body (80%)
Whole body (55%)
Whole body (55%)
Whole body
Whole body
Whole body
Whole body
Whole body
Nose- only
Mass
Concentration
(«g/m3)
140,000
170,000
1,000-100,000
1,100, 11,000,
96,000
10,000
30,000
100,000
10,000
30,000
100,000
1,030
5000
187
300,000
1,030
70
Particle Characteristics
Size (//m); a.
0.32 (MMAD); 1.4
0.62 (MMAD); 1.7
0.6-1.1 (MMAD); 1.7-1.8
0.8-1 (MMAD); 1.6-1.8
0.89(MMD)
0.83 (MMD)
0.72 (MMD)
0.89 (MMD)
0.83 (MMD)
0.72 (MMD)
0.42 (MMD); 2.25
0.8-1 (MMD); 1.8-2.0
0.3 (MMD); 2.02
1-2 (MMAD)
0.42 (MMAD); 2.25
0.2 (MMAD)
Exposure
Duration
14 days
10 days
6h
6h
5 days
5 days
5 days
5 days
5 days
5 days
6 h/day,
5 days/week,
20 days
7 days
6 h/day,
5 days/week,
15 weeks
8 h/day,
1-14 days
6 h/day,
5 days/week,
20 days
4 h/day,
4 days/week,
8 weeks
Observed Effect
Lesions in larynx and upper trachea;
epithelial ulceration, edema,
inflammatory infiltration
At 100,000 //g/m3: some cilia loss;
ulceration of larynx. <100,000
//g/m3: no effect
Laceration of larynx and cilia loss
in bronchi at 96,000 //g/m3; no deep
lung lesions; some thickening of
mucus lining in trachea at 1 1,000 and
96,000 A^g/m3
No effect
No effect
} Mortality
}
Interstitial thickening;
hypertrophy and hyperplasia of Type
II cells and secretory
cells in bronchioli
No effect (proximal acinar region)
Emphysematic lesions; no hyperplasia
of bronchial glands or metaplasia of
goblet cells
No effect
Interstitial thickening
Increased alveolar septal thickness;
decreased average alveolar diameter
Reference
Schwartz et al. (1977)
Henderson et al.
(1980a)
Wolff etal. (1986)
Cavender et al.
(1977b)
Cavender et al.
(1977b)
Busch et al. (1984)
Last et al. (1983)
Godleski et al. (1984)
Pepelko et al. (1980a)
Busch et al. (1984)
Kleinman et al. (1995)

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     Single or multiple exposures to H2SO4 at fairly high levels (>1,000 //g/m3) produce a
number of characteristic morphologic responses (e.g., alveolitis, bronchial and/or bronchiolar
epithelial desquamation, and edema).  As with other endpoints, the sensitivity to H2SO4 is
dependent upon the animal species. Comparative sensitivities of the rat, mouse, rhesus monkey
and guinea pig were examined by Schwartz et al. (1977), using concentrations of H2SO4 >30,000
Mg/m3 at comparable particle sizes (0.3 to 0.6 //m) and assessing airways from the larynx to the
deep lung.  Both the rat and monkey were quite resistant, while the guinea pig and mouse were
the more sensitive species. The nature of the lesions in the latter pair were similar, but differed
in location; this was, perhaps, a reflection of differences in the deposition pattern of the acid
droplets. Mice would tend to have greater deposition in the upper respiratory airways than
would the guinea pig (Schlesinger, 1985), which could account for the laryngeal and upper
tracheal location of the lesions seen in the mice. The relative sensitivity of the guinea pig and
relative resistance of the rat to acid sulfates is supported by results from other morphological
studies (Busch et al., 1984; Cavender et al., 1977b; Wolff et al., 1986).
     Repeated or chronic exposures to H2SO4 at concentrations < 1,000 //g/m3 produce a
response characterized by hypertrophy and hyperplasia of epithelial secretory cells.
In morphometric studies of rabbits exposed to 125 to 500 //g/m3 H2SO4 (0.3 //m) for 1 to
2 h/day, 5 d/week (Schlesinger et al.,  1983; Gearhart and Schlesinger, 1988; Schlesinger et al.,
1992b), increases in the relative number density of secretory cells (as determined by
histochemical staining) have been found to extend to the bronchiolar level, where these cells are
normally rare or absent.  Depending upon the study, the changes began within 4 weeks of
exposure and persisted for up to 3 mo following the end of exposure.  The mechanism
underlying increases in secretory cell numbers at low H2SO4 exposure levels is also unknown; it
may involve an increase in secretory activity of existing cells, or a transition from another cell
type.
     An increase in the relative number of smaller airways (<0.25 mm) in rabbits was found by
4 mo of exposure to 250 //g/m3 (0.3 //m) for 1 h/day, 5  days/week (Gearhart and Schlesinger,
1988).  Changes in airway size distribution due to irritant exposure, specifically  cigarette
smoke, has been reported in humans (Petty et al.,  1983; Cosio et al., 1977), and this seems to be
an early change relevant to clinical small airways disease.
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     The specific pathogenesis of acid-induced lesions is not known. As with pulmonary
mechanics, both a direct effect of deposited acid droplets on the epithelium and/or indirect
effects, perhaps mediated by humoral factors, may be involved. For example, similar lesions
have been produced in guinea pig lungs by exposure to either histamine or H2SO4 (Cavender
et al., 1977a).  In addition, some lesions may be secondary to reflex bronchoconstriction, to
which guinea pigs are very vulnerable, rather than primary effects separable from constriction.
Thus, damage at the small bronchi and bronchiolar level may be due not only to direct acid
droplet-induced injury, but to indirect, reflex-mediated injury as well (Brownstein, 1980).
     Morphologic and cellular damage to the respiratory tract following exposure to acid
aerosols may be determined by methods other than direct microscopic observation. Analysis of
bronchoalveolar lavage fluid can also provide valuable information, and this procedure has seen
increasing use since publication of the previous CD. Levels of cytoplasm!c enzymes, such as
lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6PD), are markers of
cytotoxicity; increases in lavageable protein suggest increased permeability of the alveolar
epithelial barrier; levels of membrane  enzymes, such as alkaline phosphatase, are markers of
disrupted membranes; the presence of fibrin degradation products (FDP) provides evidence of
general damage; and sialic acid, a component of mucoglycoprotein, indicates mucus-secretory
activity.  (It should, however, be noted that lavage analysis may not be able to provide
identification of the site of injury nor indicate effects in the interstitial tissue.)
     Henderson et al. (1980b) exposed rats for 6 h to H2SO4 (0.6 //m, MMAD) at 1,500, 9,500,
and 98,200 //g/m3,  and found FDP in blood serum after exposure at all concentrations. No FDP
was found in lavage fluid, but since the washing procedure did not include the upper respiratory
tract (i.e., anterior to and including the larynx), FDP in the serum was concluded to be an
indicator of upper airway injury. A concentration-dependent increase in sialic acid content of
the lavage fluid was also observed, indicating increased secretory activity within the
tracheobronchial tree.
     Chen et al. (1992a) exposed guinea pigs to fine (0.3  //m) and ultrafme (0.04 //m) aerosols
of H2SO4 at 300 //g/m3 for 3 h/day for 1 or 4 days. Animals were sacrificed 24 h after each of
these exposures. Following the single exposure to either size, lavage fluid showed increases in
LDH and total protein, and the change in LDH was evident at 24 h with
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the fine, but not the ultrafine, particles. These responses did not occur following the 4 day
exposure.
     Wolff et al. (1986) exposed both rats and guinea pigs for 6 h to H2SO4 (0.8 to 1 //m,
MMAD), at concentrations of 1,100 to 96,000 //g/m3 for rats and 1,200 to 27,000 //g/m3 for
guinea pigs. No changes in lavageable LDH, protein, or sialic acid were found in the rat.
However, some of the guinea pigs exhibited bronchoconstriction after exposure to 27,000 //g/m3,
and only these animals showed increased levels of lavageable protein, sialic acid and LDH.
In other studies, no changes in lavageable protein were found in the lungs of rats exposed for 3
days to 1,000 //g/m3 (0.4 to 0.5 //m, MMAD) H2SO4 (Warren and Last, 1987), nor for 2 days to
5,000 //g/m3 (0.5 //m, MMAD) (NH4)2SO4 (Warren et al., 1986).
     An important group of biological mediators of the inflammatory response, as well as of
smooth muscle tone, are the eicosanoids,  (e.g., prostaglandins and leukotrienes). Modulation of
these mediators could be involved in damage to the respiratory tract due to inhaled particles.
Preziosi and Ciabattoni (1987) exposed isolated, perfused guinea pig lungs for 10 min to
aerosols of H2SO4 (no concentration or particle sizes were given). An increase in thromboxane
B2 but no change in leukotriene B4 in the  perfusate was found. Schlesinger et al. (1990b)
exposed rabbits to 250 to 1,000 //g/m3 H2SO4 (0.3 //m) for 1 h/day for 5 days.  Lungs were
lavaged and the fluid assayed for eicosanoids. A concentration-dependent decrease in levels of
prostaglandins E2 and F2a and thromboxane B2 were noted, while there was no change in
leukotriene B4.  The effects, which were determined to be due to the hydrogen ion rather than the
sulfate ion, indicate that acid sulfates can upset the normally delicate balance of eicosanoid
synthesis/metabolism which is necessary  to maintain pulmonary  homeostasis.  Since some of the
prostaglandins are involved in regulation of muscle tone, this imbalance may be involved in the
development of airway hyperresponsiveness found with exposure to acid  sulfates.
     Other biochemical markers of pulmonary damage have been used to assess the toxicity of
acid sulfate particles. The proline content of the lungs may provide an index of collagen
metabolism. No change in soluble proline content was found in rat lungs after exposure for 7
days to 4,840 //g/m3 (0.5 //m, MMAD) (NH4)2SO4, nor due to a 7 day exposure to 1,000 //g/m3
(0.5 //m) H2SO4 (Last et al., 1986). A series of studies assessed collagen  synthesis in rat lung
minces after in vivo exposure; this is a possible indicator of the potential
                                         11-54

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for pollutants to produce fibrosis. Exposure for 7 days to H2SO4 at 40, 100, 500, and
1,000 //g/m3 (0.4 to 0.5 //m, MMAD) resulted in an increase in collagen synthesis rate only at
100 //g/m3; higher levels had no effect (Warren and Last, 1987). No effect on collagen synthesis
by rat lung minces was found due to 7-day exposures to (NH4)2SO4 at 5,000 //g/m3 (0.8 to 1 //m,
MMAD) (Last et al.,  1983).
     Other parameters of pulmonary damage are changes in lung DNA, RNA, or total protein
content. No significant changes in any of these parameters were found in rats after exposure to
1,000 //g/m3 H2SO4 (<1 //m) for 3 days (Last and Cross, 1978), nor in protein content in rats
exposed for up to 9 days to a similar concentration of H2SO4 (Warren and Last, 1987).

11.2.2.5   Pulmonary Defenses
     Responses to air pollutants often depend upon their interaction with an array of
non-specific and specific respiratory tract defenses. The former consists of nonselective
mechanisms protecting against a wide variety of inhaled materials; the latter requires antigenic
stimulation of the immune system for activation. Although these systems may function
independently, they are linked, and response to an immunologic insult may enhance the
subsequent response to nonspecific materials. The overall efficiency of lung defenses
determines the local residence times for inhaled deposited material, which has a major influence
upon the degree of pulmonary response; furthermore, either depression or over-activity of these
systems may be involved in the pathogenesis of lung diseases.
     Studies of altered lung defenses resulting from inhaled acid aerosols have concentrated on
conducting and respiratory region clearance function and nonspecific activity of macrophages;
there are only a few studies  of effects upon immunologic competence.
     Clearance Function:  Clearance, a major nonspecific defense mechanism, is the physical
removal of material that deposits on airway surfaces. As discussed in Chapter 10, the
mechanisms involved are regionally distinct. In the tracheobronchial region, clearance occurs
via the mucociliary system,  whereby a mucus "blanket" overlying the ciliated epithelium is
moved by the coordinated beating of the cilia towards the oropharynx. In the alveolar region of
the lungs, clearance occurs via a number of mechanisms and pathways, but the major one for
both microbes and nonviable particles is the alveolar macrophage (AM).
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These cells exist freely within the fluid lining of the alveolar epithelium, where they move by
ameboid motion.  The phagocytic ingestion of deposited particles helps prevent particle
penetration through the alveolar epithelium and subsequent translocation to other sites.  These
cells contain proteolytic enzymes, which digest a wide variety of organic materials, and they also
kill bacteria through oxidative mechanisms. In addition, AMs are involved in the induction  and
expression of immune reactions.  Thus, the AM provides a link between the lung's non-specific
and specific defense systems. These cells also are in the effector chain for lung damage (e.g., by
release of proinflammatory cytokines).
     Mucociliary Transport: The assessment of acid effects upon mucociliary clearance often
involved examination only of mucus transport rates in the trachea, since this is a readily
accessible airway and tracheal mucociliary clearance measurements are more straightforward to
perform than are those aimed at assessing clearance from the entire tracheobronchial tree. Table
11-7 outlines studies of acid sulfate effects upon tracheal mucociliary clearance.
     Although many of the studies involved fairly high concentrations of acid aerosols, most
demonstrated a lack of effect. The most likely explanation for this is that the sizes of the
aerosols were such that significant tracheal deposition did not occur. This is supported by the
results of Wolff et al. (1981), who found tracheal transport rates  in dogs to be depressed only
when using 0.9 //m  H2SO4; no effect was seen with a 0.3 //m aerosol at an equivalent mass
concentration. In addition, the use of tracheal clearance rate as a sole toxicologic endpoint may
be misleading, inasmuch as a number of studies have demonstrated alterations in bronchial
clearance patterns in the absence of changes in tracheal mucous transport.
     Studies assessing the effects of acid aerosols upon bronchial mucociliary clearance are also
outlined in Table 11-7. Responses following acute exposure to H2SO4 indicate that the nature of
clearance change (i.e., a slowing  or speeding) is concentration (C) and exposure-duration (t)
dependent; stimulation of clearance generally occurs after low Ct exposures, and retardation
generally occurs at higher Ct levels. However, the actual Ct needed to alter clearance rate may
depend upon the anatomic location within the bronchial tree from which clearance is being
measured, in relation to the region which is most affected by the  deposited acid. Studies in
humans indicated that low H2SO4 concentrations (i.e., ~ 100 to 500 //g/m3) may accelerate
clearance, compared to unexposed subjects, from the large proximal airways
                                          11-56

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TABLE 11-7. EFFECTS OF ACIDIC SULFATE PARTICLES ON RESPIRATORY TRACT CLEARANCE

Particle

H2S04
H2S04
H2S04
H2S04
H2S04
H2SO4

NH4HS04
(NH4)2S04
(NH4)2S04

H2S04
H2S04
H2S04
H2S04
Species, Gender,
Strain, Age, or
Body Weight
Tracheal
Dog, M/F
Beagle,
3 years
Donkey, M/F
adult
Rat
Rat
Rat, M/F
F344/Crl
12-16 weeks
Guinea pig, M/F
Hartley
2-3 mo
Sheep
Donkey
Sheep
Bronchial
Rabbit, M
NZW/mixed,
2. 5-3 kg
Rabbit, M
mixed
2.5-2.7 kg
Rabbit, M
NZW
2. 5-3 kg
Rabbit, M
NZW
2. 5-3 kg
Exposure Technique
(RH)

Nose-only (80%)
Nasopharyngeal
catheter (45%)
Whole body (82%)
Nose-only (80%)
Whole body (80%)
Whole body (80%)

Head-only (20-30%)
Nasopharyngeal
catheter (45%)
Head-only (20-30%)

Oral tube (75%)
Oral tube or
nose-only (80%)
Nose-only (80%)
Nose-only (60%)
Mass Concentration
(//g/m3)

1,000
5,000
1,000
500
200-1,400
1,000-100,000
10,000-100,000
1,100, 11,000,96,000
1,400, 9,000, 27,000

1,000
300-3,000
1,100

100-2,200
250-500
250
125
Particle Characteristics
Size (//m); ag

0.3 (MMAD); 1.2
0.3 (MMAD); 1.2
0.9 (MMAD); 1.3
0.9 (MMAD); 1.3
0.4 (MMAD); 1.5
0.6-0.8 (MMAD); 1.5-2.6
0.4-0.6 (MMAD); 1.3-1.4
0.9-1 (MMAD); 1.6-1.8
0.8-0.9 (MMAD); 1.5-1.6

0.1(CMD);2.1
0.4 (MMAD); 1.5
0.1 (CMD);2.1

0.3 (MMAD); 1.6
0.3 (MMAD); 1.6
0.3 (MMAD); 1.6
0.3 (MMD); 1.6

Exposure
Duration

Ih
Ih
Ih
Ih
Ih
6h
0.5 h
6h
6h

4h
Ih
4h

Ih
1 h/days,
5 days/week,
4 weeks
1 h/day,
5 days/week,
12 mo
2 h/day,
5 days/week up to
12 mo

Observed Effect

NC
NC
i
i
NC
T
T
T at 96,000 //g/m3
i at 1,400 //g/m3

NC
NC
NC

T,i (depending
on concentration
and duration)
T ; persistent
i by 1 week;
progressive
slowing after
19 weeks;
persistent
T followed by i
PE; persistent

Reference

Wolff etal. (1981)
Schlesinger et al. (1978)
Wolff etal. (1980)
Wolff etal. (1986)

Sackner et al. (1981)
Schlesinger et al. (1978)
Sackner et al. (1981)

Chen and Schlesinger
(1983); Schlesinger et al.
(1984)
Schlesinger et al. (1983)
Gearhart and Schlesinger
(1988)
Schlesinger etal. (1992b)

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TABLE 11-7 (cont'd). EFFECTS OF ACIDIC SULFATE PARTICLES ON RESPIRATORY TRACT CLEARANCE
Particle

H2S04


H2S04




H2S04

NH4HSO4

(NH4)2S04

(NH4)2S04


H2S04

H2S04
H2S04
Species, Gender,
Strain, Age, or Exposure Technique Mass Concentration
Body Weight (RH) C"g/m3)
Bronchial
Rabbit, M oral tube 250; 250; 500
mixed nose-only
6 mo

Donkey Nasopharyngeal 200-1,400
catheter (45%)




Rat, M Nose-only (39%; 85%) 3,600
SD
200 g
Rabbit, M Oral tube (78%) 600-1,700
mixed
2.5-2.7 kg
Rabbit, M Oral tube (78%) 2,000
mixed
2.5-2.7 kg
Rat, M Nose-only (39%; 85%) 3,600
SD
200 g
Alveolar
Rat, M Whole body (30-80%) 3,600
SD
200 g
Rabbit, M Oral tube 1,000
NZW
2. 5-3 kg
Rabbit, M Nose-only (80%) 250
NZW
2. 5-3 kg
Particle Characteristics
Size (//m); ag Duration
0.3 (MMAD); 1.6 1 h/day,
5 days/week,
4 weeks

0.4 (MMAD); 1.5 Ih




1.0 (MMAD); 1.9-2.3 4h

0.4 (MMAD); 1.6 Ih

0.4 (MMAD); 1.6 Ih

0.4 (MMAD); 1.9-2.3 4h

1.0 4h

0.3 (MMAD); 1.5 1 h
0.3 (MMAD); 1.6 1 h/day,
5 days/week,
1, 57, 240 day
Observed Effect
T only some days at
250/oral and
500/nasal;
persistent T up to
14 days PE for all.
i in some animals at
all
concentrations;
progressive
slowing in some
animals with
continued
exposures.
NC

i at 1,700 A^g/m3

NC

NC

NC

T
T
Reference
Schlesinger et al. (1983)


Schlesinger et al. (1978)




Phalen et al. (1980)

Schlesinger (1984)

Schlesinger (1984)

Phalen et al. (1980)

Phalen et al. (1980)

Naumann and Schlesinger
(1986)
Schlesinger and Gearhart
(1986)

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      TABLE 11-7 (cont'd).  EFFECTS OF ACIDIC SULFATE PARTICLES ON RESPIRATORY TRACT CLEARANCE
Particle
Species, Gender,
 Strain, Age, or
 Body Weight
Exposure Technique
      (RH)
Mass Concentration
    (//g/m3)
                                                                           Particle Characteristics
                                                                              Size (//m); a
                                                                                                      Exposure
                                                                                                      Duration
                                                                                                                   Observed Effect
                                                                                                                                           Reference
        Alveolar (cont'd)
               Rabbit, M
                 NZW
                3-3.5 kg
                Nose-only (80%)
                                                          500
                                              0.3 (MMAD); 1.6
                                                  2 h/day,
                                                  14 days
Schlesinger and Gearhart
(1987)
Key to abbreviations:
 NC: No significant change
 T: Significant increase
 i: Significant decrease
 PE: Post exposure

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where little acid deposits, while slowing clearance from the distal ciliated airways where there is
greater acid deposition. At higher concentrations, mucociliary clearance from both the proximal
and distal bronchial tree becomes depressed (Leikauf et al., 1984).
     Comparison of responses to H2SO4 show interspecies differences in the sensitivity of
mucociliary clearance to acid aerosols.  As an example, the acceleration of tracheal transport
found by Wolff et al. (1986) in the rat with ~ 100,000 //g/m3 H2SO4 seems anomalous since, in
other species, levels > 1,000 //g/m3 depress mucociliary function. The reasons for this apparent
discrepancy are not known. The rat is less susceptible to the lethal effects of H2SO4, and it does
not have strong bronchoconstrictive reflex responses following H2SO4 exposures. These
characteristics suggest that the mucociliary system of the rat may also differ in sensitivity from
the other species studied, a view supported by the lack  of effect of H2SO4 on bronchial clearance
found by Phalen et al. (1980) following exposure at 3,600 //g/m3 for 4 h and by the similarity in
bronchial clearance response in donkeys and rabbits to single  1-h exposures of H2SO4 (Table
11-7).  Although the lack of response of tracheal transport in the guinea pig at H2SO4 levels
>1,000 //g/m3 is also surprising, its response at 1,000 //g/m3 is  also different from that of the rat
and more in line with other species (Wolff, 1986).
     The relative potency of acid sulfate aerosols, in terms of altering mucociliary clearance, is
related to their acidity (H+ content).  Schlesinger (1984) exposed rabbits for 1 h to
submicrometer aerosols of NH4HSO4, (NH4)2SO4, and Na^CV Exposure to NH4HSO4 at
concentrations of -600 to 1,700 //g/m3 significantly depressed clearance rate only at the highest
exposure level. No significant effects were observed with the other sulfur oxides at levels up to
«2,000 //g/m3.  When these results are compared to those from a study using H2SO4 (Schlesinger
et al., 1984), the ranking of potency was H2SO4 > NH4HSO4 >  (NH4)2SO4, Na2SO4; this strongly
suggests a relation between the hydrogen ion concentration and the extent of alteration in
bronchial mucociliary clearance.
     The mechanism by which deposited acid aerosol alters clearance is not certain.  The
effective functioning of mucociliary transport depends  upon optimal beating of cilia and the
presence of mucus having appropriate physicochemical properties, and both ciliary beating as
well as mucus viscosity may be affected by acid deposition. At alkaline pH, mucus is more fluid
than at acid pH, so a small increase in viscosity due to deposited acid could "stiffen"
                                          11-60

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the mucus blanket, perhaps promoting the clearance mechanism and, thus, increasing its
efficiency (Holma et al., 1977).  Such a scenario may occur at low H2SO4 exposure
concentrations, where ciliary activity would not be directly affected by the acid, and is
consistent with clearance acceleration observed at these concentrations with acute exposure.
However, the exact relation between mucus viscosity and transport rate is not certain.
     High concentrations of H2SO4 may affect ciliary beating, as discussed in the previous CD
(U.S. Environmental Protection Agency, 1982; Schiff et al.,  1979; Grose et al., 1980).  An
additional mechanism by which deposited acid may affect mucociliary clearance is via altering
the rate and/or amount of mucus secreted. A small increase in mucus production could facilitate
clearance, while more excessive production could result in a thickened mucus  layer which would
be ineffectively coupled to ciliary beat.  Finally, the airways actively transport ions, and the
interaction between transepithelial ion transport and consequent fluid movement is important in
maintaining the mucus lining. A change in ion transport due to deposited acid particles may
alter the depth and/or composition of the sol layer (Nathanson and Nadel, 1984), perhaps
affecting clearance rate.  In any  case, the pathological significance of transient alterations in
bronchial clearance rates in healthy individuals is not certain, but such changes are an indication
of a lung defense response.  On  the other hand, persistent impairment of clearance may lead to
the inception or progression of acute or chronic respiratory disease and, as such, may be a
plausible link between inhaled acid aerosols and respiratory disease.
     Short-term exposures to acid aerosols may lead to persistent clearance changes, as
indicated previously (Schlesinger et al., 1978). The effects of long-term exposures were
investigated by Schlesinger et al. (1983), who exposed rabbits to 250 or 500 //g/m3 H2SO4
(0.3 //m, MMAD) for 1 h/day, 5 days/week for 4 weeks, during which time bronchial
mucociliary clearance was monitored.  Clearance was accelerated on individual days during the
course of the acid exposures, especially at 500 //g/m3. In addition, clearance was significantly
faster, compared to preexposure levels,  during a 2 week follow- up period after acid exposures
had ceased.
     Another long-term exposure at relatively low H2SO4 levels was  conducted by Gearhart and
Schlesinger (1988). Rabbits were exposed to 250 //g/m3 H2SO4 for 1  h/day, 5  days/week for up
to 52 weeks, and some animals were also provided a 3 mo follow-up
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period in clean air. Clearance was slower during the first month of exposure and this slowing
was maintained throughout the rest of the exposure period. After cessation of exposure,
clearance became extremely slow and did not return to normal by the end of the follow-up
period. Differences in the nature of clearance change between this study and that of Schlesinger
et al. (1983) may be due to differences in exposure protocol daily (duration) and/or
concentration. In both studies, however, and as discussed earlier, histologic analyses indicated
the development of increased numbers of epithelial secretory cells, especially in small airways,
the likely consequence of which would be an increase in mucus production. In addition, the
slowing of clearance seen by Gearhart and Schlesinger (1988) was also associated with a shift in
the histochemistry of mucus towards a greater content of acidic glycoproteins; this would tend to
make mucus more viscous.
     The longest duration study at the lowest concentration of H2SO4 yet reported is that of
Schlesinger et al. (1992b), in which rabbits were  exposed to 125 //g/m3 H2SO4 for 2 h/day,
5 days/week for up to 52 weeks. The variability of measured bronchial clearance time was
increased with acid exposure, and acceleration of clearance was noted at various times during the
one-year exposure period. However, following a 6-mo observation period after exposures had
ceased, a trend towards slowing  of clearance was noted (compared to both control and rates
during acid exposure). In addition, and consistent with previous studies, an increase in the
number density of epithelial secretory cells was observed in small airways (<0.5 mm) following
12 mo of acid exposure. This histological change had resolved by the end of the 6-mo
post-exposure period.
     Alveolar Region Clearance and Alveolar Macrophage Function: Only a few studies
have examined the ability of acid aerosols to alter clearance of particles from the alveolar region
of the lungs (Table 11-7). Rats exposed to 3,600 //g/m3 H2SO4 (l//m) for 4 h showed no change
in clearance (Phalen et al., 1980).  On the other hand, acceleration of clearance was seen in
rabbits exposed for 1 h to 1,000 //g/m3 H2SO4 (0.3 //m, MMAD) (Naumann and Schlesinger,
1986).
     Two studies involving repeated exposures to acid aerosols have been reported. In one,
rabbits were exposed to 250 //g/m3 (0.3 //m, MMAD) H2SO4 for 1 h/day,  5 days/week,  and inert
tracer particles were administered on days 1, 57 and 240 following the start of the acid exposures
(Schlesinger and Gearhart, 1986).  Clearance (measured for 14 days after each
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tracer exposure) was accelerated during the first test, and this acceleration was maintained
throughout the acid exposure period. In the other study (Schlesinger and Gearhart, 1987),
rabbits were exposed 2 h/day for 14 days to 500 //g/m3 H2SO4 (0.3 //m, MMAD); retardation of
early alveolar region clearance of tracer particles administered on the first day of exposure was
noted.  The results of these two studies suggest a graded response, whereby a low exposure
concentration accelerates early alveolar region clearance and a high level retards it, such as was
seen with mucociliary transport following acute H2SO4 exposure.
     The mechanisms responsible for the altered alveolar region clearance patterns seen in the
above studies are not known.  Observed clearance is the net consequence of a number of
differential underlying responses, which can include change in mucociliary transport rates and
altered functioning of AMs.
     A number of studies have examined the functional response of AMs following acidic
sulfate aerosol exposures. To adequately perform their role in clearance, AMs must be
competent in a number of functions, including phagocytosis, mobility and attachment to a
surface. Alterations in any one, or combination, of these individual functions may affect
clearance function. Naumann and Schlesinger (1986) noted a reduction in surface adherence and
an enhancement of phagocytosis in AMs obtained by lavage from rabbits following a 1-h
exposure to 1,000 //g/m3 H2SO4 (0.3 //m). The acid exposure produced no change in the
viability or numbers of recoverable AMs.
     In a study with repeated H2SO4 exposures, AMs were lavaged from rabbits exposed to
500 //g/m3 H2SO4 (0.3 //m) for 2 h/day for up to  13 consecutive days (Schlesinger, 1987).
Macrophage counts increased after 2 of the daily exposures, but returned to control levels
thereafter. Neutrophil counts remained at control levels throughout the study, suggesting no
acute inflammatory response.  Random mobility of AMs decreased after 6 and 13 of the daily
exposures.  The number of phagocytically active AMs and the level of such activity increased
after 2 exposures, but phagocytosis became depressed by the end of the exposure series.
Although such studies demonstrate that H2SO4 can alter AM function, they have not as yet been
able to provide a complete understanding of the cellular mechanisms which may underly the
changes in pulmonary region clearance observed with exposure to acid  aerosols.
     The relative potency of acidic sulfate  aerosols in terms of altering AM numbers or function
has been examined. Aranyi et al. (1983) found no change in total or differential
                                         11-63

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counts of free cells lavaged from mice exposed to 1,000 //g/m3 (NH4)2SO4 for 3 h/day for
20 days; this suggests a lack of inflammatory response to this sulfate aerosol. Additional studies
seem to suggest that the response to acid sulfates of AM is a function of the H+. Schlesinger
et al. (1990a) examined phagocytic activity of AMs recovered from rabbits exposed for 1 h/day
for 5 days to either 250 to 2,000 Aig/m3 H2SO4 (0.3//m) or 500 to 4,000 Aig/m3 NH4HSO4 (0.3
Aim); the  levels were chosen such that the H+ concentration in the exposure atmospheres were
equivalent for both sulfate species. Phagocytic activity of AMs was reduced following exposure
to > 1,000 Aig/m3 H2SO4 or to 4,000 Aig/m3 NH4HSO4; exposure to 2,000 Aig/m3 NH4HSO4
resulted in increased phagocytic activity. While these exposure concentrations were quite high,
the interesting observation was that for a given level of sulfate, the response to H2SO4 was
greater than that to NH4HSO4. However, even when the data were assessed in terms of H+
concentration in the exposure atmosphere, it was noted that exposure to the same concentrations
of H+ did not result in identical responses for the two different acid sulfate species; H+ appeared
to be more effective as the H2SO4 species. On the other hand, when AMs were incubated in
acidic environments in vitro, the phagocytic activity response was identical, regardless of the
sulfate species used, as long as the pH was the same.  These results  suggested an enhanced
potency of H2SO4 during inhalation exposures. Experimental evidence provided by Schlesinger
and Chen (1994) indicated that this difference noted in vivo was likely a reflection of different
degrees of neutralization by respiratory tract ammonia of the two species of inhaled acid
aerosols.  It was shown that, for a given concentration of ammonia and within a given residence
time within the respiratory tract, more total H+ remained available from inhaled sulfuric acid
than from inhaled ammonium bisulfate when the exposure atmospheres had the same total H+
concentration.  Thus, the greater observed potency of inhaled sulfuric acid compared to
ammonium bisulfate for exposure atmospheres containing the same total IT" concentration is
likely due to a greater degree of neutralization of the latter, and a resultant greater loss ofH+
prior to particle deposition onto airway surfaces. Thus, the respiratory "fate" of inhaled acid
sulfate particles should be considered in assessing the relationship between exposure atmosphere
and biological  response, since a lower IT" concentration will likely deposit onto lung tissue than
is inhaled at the mouth or nose.
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     Interspecies differences in the effects of acid sulfates on AM function were examined by
Schlesinger et al. (1992a). Based upon in vitro exposures of AM to acidic media, a ranking of
response in order of decreasing sensitivity to acidic challenge  and subsequent effect on
phagocytic activity was found to be: guinea pig>rat>rabbit>human.
     As noted with other endpoints, the effect of H2SO4 upon AM function may be dependent
upon particle size.  Chen et al. (1992a) observed that 300 //g/m3 H2SO4 enhanced the phagocytic
activity of AMs recovered from guinea pigs after 4 days (3 h/day) of exposure to fine particles
(0.3 //m), while an identical exposure to ultrafine particles (0.04 //m) depressed phagocytic
function.
     The effects of acid sulfates upon the intracellular pH of AMs has been examined, because
this may be one of the determinants of the rate of many cellular functions (Nucitelli and Deamer,
1982). Internal pH of AMs recovered from guinea pigs exposed to 300 //g/m3 H2SO4 was
depressed after a single 3-h exposure to both 0.3 and 0.04 //m particles, but the depression
persisted for 24 h following exposure to the smaller size (Chen et al., 1992a).  A depression in
pH was also noted 24 h following 4 days of exposure to the ultrafine, but not the fine,  aerosol.
Thus, acid exposure produced a change in intracellular pH of the  AMs and the effect was
particle size dependent.
     It is possible that this and other differences in response between fine and ultrafine particles
reflect, to some extent, differences in the number of particles in aerosols of these two size
modes, in that at a given mass concentration of acid sulfate, there are a greater number of
ultrafine than fine particles. To examine this possibility, Chen et al. (1995) noted that changes
in intracellular pH of macrophages obtained following inhalation exposure to H2SO4 aerosols
were dependent both upon the number of particles as well as upon the total mass concentration
of H+ in the exposure atmosphere, with a threshold existing for both exposure parameters.  The
role of size in modulating toxicity due to PM is discussed further in Section 11.4.  It should,
however, be noted that aside from number, differences in deposition and neutralization may also
affect differential responses to fine and ultrafine particles.
     A possible mechanism underlying the acid-induced alterations in intracellular pH was
examined by Qu et al.  (1993), who  exposed guinea pigs to 969 //g/m3 H2SO4 (0.3 //m MMD, og
1.73) for 3 h or to 974 //g/m3 for 3 h/day for 5  days. Macrophages were
                                          11-65

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obtained following the end of each exposure protocol and examined for the ability of internal
pH to recover from an added intracellular acid load.  Both H2SO4 exposures resulted in a
depression of internal pH recovery compared to air control.  Subsequent analysis indicated that
this alteration in internal pH regulation was attributable to effects on the Na+/H+ exchanger
located in the cell membrane.
     Macrophages are the source of numerous biologically active chemicals, and the effects of
acid sulfate upon some of these have been investigated. Zelikoff and Schlesinger (1992)
exposed rabbits to 50 - 500 //g/m3 H2SO4 (0.3 //m) for 2 h.  AM recovered by lavage following
exposure were assessed for effects on tumor necrosis factor (TNF) release/activity and
production of superoxide radical, both of which are biological mediators involved in host
defense.  Exposure to H2SO4 at > 75 //g/m3 produced a reduction in TNF cytotoxic activity, as
well as a reduction in stimulated production of superoxide radical.  Subsequently, Zelikoff et al.
(1994) exposed rabbits for 2 h/day for 4 days to sulfuric acid at 500, 750 or 1,000 //g/m3.  AM
recovered from animals exposed at the highest acid level showed a reduction in TNF and
interleukin (IL)-la production/activity, both immediately and 24 h following the last exposure.
On the other hand, increased release of TNF from macrophages obtained from guinea pigs was
observed immediately following a single 3 h exposure, and 24 h  following a 3 h/day 4 day
exposure, to 300 //g/m3 H2SO4 (0.3 //m or 0.04 //m) (Chen et al., 1992a); in addition, production
of hydrogen peroxide by these cells was enhanced immediately after the 4  day exposure. These
differences in TNF may reflect interspecies differences in response to acid exposure and/or
differences in experimental conditions.

Resistance to Infectious Disease
     The development of an infectious disease requires both the presence of the appropriate
pathogen, as well  as host vulnerability. There are numerous anti-microbial host defenses with
different specific functions for different microbes (e.g., there are some differences in defenses
against viruses and bacteria).  The AM represents the main defense against gram positive
bacteria depositing in the alveolar region of the lungs.  The ability of acid aerosols to modify
resistance to bacterial infection could result from a decreased ability to clear microbes, and
a resultant increase in their residence time, due to alterations in AM function.  To test this
possibility, a rodent infectivity model has been frequently used.  In this
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technique, mice are challenged with a bacterial aerosol after exposure to the pollutant of interest;
mortality rate and/or survival time are then examined within a particular postexposure time
period.  Any decrease in the latter or increase in the former indicates impaired defense against
respiratory infection. A number of studies which have used the infectivity model (primarily
with Streptococcus sp.) to assess effects of acid aerosols were discussed in the previous CD
(U.S. Environmental Protection Agency, 1982).  It was evident that acute exposures to H2SO4
aerosols at concentrations up to 5,000 //g/m3 were not very effective in enhancing susceptibility
to this bacterially-mediated respiratory disease in the murine model.  More recent studies with
mice, shown in Table 11-8, continue to support this conclusion.
     However, a study using another animal suggests that H2SO4 may indeed alter antimicrobial
defense. Zelikoff et al. (1994) exposed rabbits for 2 h/day for 4 days to 500, 750,
or 1,000 //g/m3 H2SO4.  Intracellular killing of a bacterium, Staphylococcus aureus, by AMs
recovered by lavage 24 h following the last exposure at the two highest acid concentrations was
reduced; bacterial uptake was also reduced at the same time point, but only at the highest acid
level. Thus, repeated H2SO4 exposures may reduce host resistance to bacteria in the rabbit, in
contrast to no effect on this endpoint in the mouse.

Specific Immune Response
     Most of the database involving effects of acid aerosols on lung defense is concerned with
non-specific mechanisms.  Little is known about the effects of these pollutants on humoral
(antibody) or cell-mediated immunity.  Since numerous potential antigens are present in inhaled
air, the possibility exists that acid sulfates may enhance immunologic reaction and, thus, produce
a more severe response, and one with greater pulmonary pathogenic potential. Pinto et al.
(1979) found that mice which inhaled H2SO4 for 0.5 h daily and were then exposed weekly to a
particulate antigen (sheep red blood cells) exhibited higher serum and bronchial lavage antibody
liters than did animals exposed to the antigen alone; unfortunately, neither the exposure mass
concentration nor particle size of the H2SO4 was described. The combination of acid with
antigen also produced morphologic damage,  characterized by mononuclear cell infiltration
around the bronchi and blood vessels, while
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                      TABLE 11-8. EFFECTS OF ACID SULFATES ON BACTERIAL INFECTIVITY IN VIVO
Particle
H2S04
H2S04
(NH4)2S04
Species, Gender,
Strain, Age, or
Body Weight
Mouse, F
CD-I
30 days
Mouse, F
CD-I
30 days
Mouse, F
CD-I
30 days
Exposure Mass Concentration
Technique (RH) (/ig/m3)
Head-only (31%) 543
Head-only (31%) 365
Whole body 1,000
Particle Characteristics
Exposure Duration Observed References
Size (//m); a. Effect
0.08 (VMD); 2.3 2h NC Grose etal. (1982)
0.06 (VMD); 2.3 2 h/day, 5 days NC Grose et al. (1982)
Submicrometer 3 h/day, 20 days NC Aranyi et al. (1983)
         NC: No change
oo

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exposure to acid or antigen alone did not.  Thus, the apparent adjuvant effect of H2SO4 may be a
factor promoting lung inflammation.
     Osebold et al. (1980) exposed mice to 1,000 //g/m3 H2SO4 (0.04 //m, CMD) to determine
whether this enhanced the sensitization to an inhaled antigen (ovalbumin). The exposure
regimen involved intermittent 4 day exposures, up to 16 total days of exposure; no  increase in
sensitization compared to controls was found. Kitabatake et al. (1979) exposed guinea pigs to
1,910 //g/m3 H2SO4 (<1 //m, MMAD) for 0.5 h twice per week for 4 weeks, followed by up to
10 additional paired treatments with the H2SO4 for 0.5 h  each; the animals were then exposed to
aerosolized albumin for another 0.5 h. The breathing pattern of the  animals was monitored for
evidence of dypsnea.  Enhanced sensitization was found  after ~4 of the albumin exposures. A
subsequent challenge with acetylcholine suggested hyperresponsive airways.
     Fujimaki et al. (1992) exposed guinea pigs to 300,  1,000, and  3,200 //g/m3 H2SO4 for 2 or
4 weeks, following which lung mast cell suspensions were examined for antigen-induced
histamine release. Exposure for 2 weeks at the two highest concentrations resulted in enhanced
histamine release, but this response dissipated by 4 weeks of exposure. Thus, H2SO4, at high
concentrations, may affect the functional properties of mast  cells; these cells are involved in
allergic responses, including bronchoconstriction.

11.2.3
         Mixtures  Containing Acidic Sulfate Particles
     Most of the toxicological data concerning effects of PM are derived from exposures using
single compounds.  Although such information is essential, it is also important to study
responses which result from inhalation of typical combinations of materials, because population
exposures are generally to mixtures.  Toxicological interaction provides a basis whereby ambient
pollutants may show  synergism (effect greater than the sum  of the parts) or antagonism (effect
less than the sum of the parts). Thus, the lack of any toxic effect following exposure to an
individual pollutant should always be interpreted with caution, because mixtures may act
differently than expected from the same pollutants acting separately. Most toxicologic studies of
pollutant mixtures involved exposures to mixtures containing only two materials. These are
summarized first below for mixtures containing
                                         11-69

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acidic aerosols (see Table 11-9); complex acid aerosol mixture studies (i.e., those using more
than 2 compounds) are then discussed.
     The extent of any toxicological interaction involving acidic sulfate aerosols has been
shown to depend on the endpoint being examined, as well as on the co-inhalant. Most studies of
interactions using acidic sulfates employed ozone (O3) as the co-pollutant. Depending upon the
exposure regimen, endpoint, and animal species,  either additivity, synergism, or antagonism has
been observed.  These studies are summarized in the O3 criteria document (U.S. Environmental
Protection Agency, 1995). Interaction studies of H2SO4 and nitrogen dioxide (NO2) are
discussed in the nitrogen oxides criteria document pollutant (U.S. Environmental Protection
Agency,  1993). The nature of interactions was dependent on the protocol; no unifying principles
emerged. It is important to recognize that the nature of particle-pollutant interactions are
specific for a given endpoint and set of exposure conditions and no attempt should be made to
generalize from those specific observations discussed in the O3 and NOX criteria documents.
     Kitabatake et al.  (1979) exposed guinea pigs to H2SO4 aerosol (average 1910 //g/m3) or
SO2 + H2SO4 aerosol (average 145 ppm and  1890 //g/m3) for 30 min, twice a week for 4 weeks
prior to albumin exposure. After the preexposures, the guinea pigs were treated 10 times with
paired exposures to the sulfur oxides for 30 min followed by treatment with the antigen
(albumin) aerosol for another 30 min. The results indicate that exposures to high concentrations
of sulfur  oxides (SO2 + H2SO4 aerosol or H2SO4 aerosol alone) may increase hyperreactivity to
albumin in guinea pigs.
     In a study designed to determine if effects of exposure to H2SO4 aerosol were exacerbated
in the presence of other particulate matter, Henderson et al. (1980a) exposed rats to H2SO4
aerosol (MMAD = .8 //m, og = 1.7) in the presence or absence of 70,000 //g/m3 fly ash (MMAD
= 6.0 //m, og = 2.0). Lung damage in the rats was determined  by BAL one day after exposure to
the fly ash and 1,000, 10,000,  or 100,000 //g/m3 H2SO4 for 6 h. BAL from animals exposed to
high levels of sulfuric acid alone, to the ash alone, or to both showed an increase in sialic acid
and in acid phosphatase activity. Lactate dehydrogenase and glutathione reductase activities
were elevated in the combined exposures. The presence of a separate paniculate aerosol did not
greatly modify the response of the rat lung to H2SO4.
                                         11-70

-------
TABLE 11-9. TOXICOLOGIC EFFECTS OF MIXTURES CONTAINING ACIDIC AEROSOLS
Co-Pollutant
Chemical //g/m3 ppm
ZnO (0.05 //m,
MMAD,
ag=1.86)

ZnO (0.05 CMD,
ag = 2)





O3 0.15
ZnO up to
2,760 //g/m
3 (0.05 fj.m
MMAD,
ag = 2.0)




SO2 145







Fly ash 70,000
(6 fj.m,
MMAD)





Acid Particle
Chemical
H2S04



H2S04
(coated
on
particles)



H2SO4 pure
H2S04
(coated
on
particle)

H2S04



H.SO,







H2S04







, , , , Exposure
,ug/mj(//m) . *,
Exposure Regime Conditions
25 or 84 3 h Nose-only



24 or 84 Nose-only






300 (0.08)
20-30 //g/m3 1 h Head-only
(0.05//mMMAD,
a = 2.0)


202 //g/m3
(0.06//mMMAD,
a = 1.36)

1,890 0.5 h, twice Head-only
(<1 //m, weekly for
MMAD) 4 weeks;
then 0.5 h twice
weekly with
antigen
or constrictor
challenge
1,000, 6 h Chamber
10,000,
100,000
(0.8//m,
MMAD,
ag= 1.7-1.8)


Species, Gender
Strain, Age and
Body Weight Endpoints
GP, M Hartley BAL eicosanoids
250-300 g PE


Guinea pig, M, Pulmonary
Hartley 260-325 function
g





Guinea pig Airway
responsiveness
to acetylcholine






Guinea pig Sensitization to
inhaled antigen
(albumin);
responsitivity
to acetylcholine



Rat Lavage indices
(LDH, acid
phosphatase,
glutathione
reductase)




Response to
Mixture Interaction Reference
Concentration Chen et al.
dependent T in (1989)
PGF2a compared to
ZnO alone
Animals Acid layered on Chen et al.
exposed to particle enhanced (1991)
acid had response to
greater subsequent O3 or
decrease in acid exposure
lung volume
and DLCO

Acid-coated Chen et al.
particles caused (1992b)
hyperresponsiveness


Similar changes at
10 x concentration
of coated
particles
Enhanced response Kitabatake et al.
compared (1979)
to H2SO4 alone





Minimal Henderson et al.
interaction: (1980a)
response largely
due to H2SO4;
increase in LDH and
glutathione
reductase only in
combined exposure

-------
                 TABLE 11-9 (cont'd). TOXICOLOGIC EFFECTS OF MIXTURES CONTAINING ACIDIC AEROSOLS
to
Co-Pollutant
Chemical
HN03
(vapor)
Diesel
exhaust

HN03
(vapor)
Diesel
exhaust






ZnO









//g/m3 ppm
380

460(0.15)


380

550
(0.1 5 Aim
MMAD)





up to
2500 Aig/m3
(0.05 //m
emd,
ag = 2)





Acid Particle Species, Gender
_, . , , , , Exposure Strain, Age and
Chemical Aig/m3 (Aim) F ' , 6.
Exposure Regime Conditions Bodv Weight bndpomts
H2SO4 180 5h/day, 5 days Rat, M, Macrophage
(no size Sprague-Dawley phagocytosis;
stated) receptor
activity

H2SO4 180 5h/day, 5 days Nose-only Rat, M, Macrophage
(no size Sprague-Dawley, phagocytosis;
stated) 6 wk morphology;
tracheobronchial
and
mucociliary
clearance



H2SO4 20-30 Aig 3 h/day for 5 Guinea pig Pulmonary
(coated days function
on ZnO
particles)







Response to
Mixture Interaction
Macrophage Not determined
phagocytosis,
Fc receptor
activity
decreased
No change in Not
cell turnover in determinable
nose, trachea,
alveolar
epithelium; no
deep lung
lesions;
J phagocytosis;
no clearance
effects
Reductions in
total lung vol.
vital capacity,
DLCO severity
inc. with
increasing
exposure
duration, inc.
protein, PMNs in
BAL

Reference
Prasad et al.
(1988)



Prasad et al.
(1990)








Amdur and Chen
(1989)









-------
     A few studies have examined the effects of exposure to multicomponent (complex)
atmospheres containing acidic sulfate particles.  Studies of mixtures containing O3 or NO2 are
summarized elsewhere (U.S. Environmental Protection Agency, 1993, 1995).
     A series of studies discussed in the previous PM/SOX CD (U.S. Environmental Protection
Agency, 1982) involved exposure of dogs to simulated auto exhaust atmospheres (e.g., Hyde
et al., 1978) for 16 h/day for 68 mo followed by a 32- to 36-mo period in clean air.  The mixture
consisted of 90 //g/m3 H2SO4+ 1,100 //g/m3 SO2, with and without irradiated auto exhaust
(which results in production of oxidants) and nonirradiated auto exhaust. The results were
dependent on the time of examination, exposure, and the endpoint.  The primary finding was that
groups exposed to SO2 and H2SO4 showed emphysema like changes, observed 32- to 36-mo
postexposure. The authors considered the  specific changes to be analogous to an incipient stage
of human centrilobular emphysema.  SO2 alone would be unlikely to produce such a deep lung
response.  Also, from the pulmonary function results, it did not appear that auto exhaust
exacerbated the effects of the SO2-H2SO4 mixture.
     Prasad et al. (1988) exposed rats for 5 h/day for 5 days to an atmosphere consisting of 460
Mg/m3 diluted diesel exhaust (0.15 //m), 380 //g/m3 HNO3 vapor, and 180 //g/m2 H2SO4 (present
as a surface coat on the  diesel particles). Reduced activity of macrophage surface (Fc) receptors
and phagocytosis were noted, but interaction could not be determined since the individual
components were not tested separately. In another related study, Prasad et al. (1990) examined
particle clearance, lung  histology and macrophage phagocytic activity following nose-only
exposures of rats (Sprague-Dawley, M, 6 weeks) for 5 h/day for 5 days to atmospheres
consisting of 380 //g/m3 HNO3 vapor, 550  //g/m3 diluted diesel exhaust, and 180 //g/m3 H2SO4
coated on the diesel particles (0.15 //m). There was no change in tracheobronchial or pulmonary
clearance of tracer particles with this mixture, compared to air controls. While no deep lung
lesions nor any change in turnover rate of epithelial cells from the nose, trachea or alveolar
region were noted, there was a decrease in  the percentage of total macrophages  assessed which
had internalized diesel particles following exposure to the mixture, compared to cells recovered
from animals exposed to the diesel particles alone. Furthermore, phagocytosis was depressed up
to 3 days following exposure to the mixture.
                                         11-73

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The enhanced effect of the particles with the surface acid coat is consistent with studies,
described below, with other acid-coated particles.
     Amdur and Chen (1989) exposed guinea pigs to simulated primary emissions from coal
combustion processes, produced by mixing ZnO, SO2, and water in a high temperature
combustion furnace.  The animals were exposed 3 h/day for 5 days to ultrafme (0.05 //m CMD,
og=2) aerosols of zinc oxide (ZnO) at up to 2,500 //g/m3 having a surface coating of H2SO4
resulting from this process (ZnO had no effect in this  study). Levels of SO2 in the effluent
ranged from 0.2 to 1 ppm. Acid sulfate concentrations as low as 20 to 30 //g/m3 as equivalent
H2SO4 delivered in this manner resulted in significant reductions in total lung volume, vital
capacity, and DLco. The effects appeared to be cumulative, in that the severity was increased
with increasing exposure duration. These exposures also resulted in an increase in the protein
content of pulmonary lavage fluid and an increase in PMNs. The investigators noted that much
higher exposure levels of pure H2SO4 aerosol were needed to produce comparable results,
suggesting that the physical  state of the associated acid in the pollutant mixture was an important
determinant of response.  But one confounder in these studies was that the number concentration
was greater for the coated particles than for the pure acid particles and, as mentioned earlier,
both number and mass concentrations of the exposure atmosphere likely play roles in the
biological responses.
     Other studies have examined responses to acid-coated particles. Chen et al. (1989)
exposed (nose-only) guinea  pigs (male, Hartley, 250 to 300g) for 3 h to ultrafme ZnO (0.05 //m,
og=1.86) onto which was coated 25 or 84 //g/m3 H2SO4.  Selected eicosanoids were examined in
lavage fluid obtained at 0, 72,  and 96 h post-exposure. Immediately following exposure,
animals exposed to the higher  acid concentration showed increased levels of prostaglandin F2a
compared to those found in animals exposed to ZnO alone. Levels of prostaglandins El and
6-keto-PGF 1 a, thromboxane B2 and leukotriene B4 were similar to those found in animals
exposed to the metal alone.  During the post-exposure period, changes in prostaglandin El,
leukotriene B4 and thromboxane B2 were noted.  But the authors suggested that there was no
causal relationship between  these changes and alterations in pulmonary function noted earlier
(Amdur et al., 1986).
     Chen et al. (1992b) exposed guinea pigs to acid-coated ZnO for 1 h, and examined airway
responsiveness to acetylcholine administered 1.5 h after exposure. In this study, the
                                         11-74

-------
equivalent concentrations of H2SO4 were 20 and 30 //g/m3 coated on the 0.05 //m ZnO particles.
Animals were also exposed to pure H2SO4 droplets at 202 //g/m3 and having a similar size as the
coated particles (0.06 //m, og=l .36).  Hyperresponsiveness was found in animals exposed to the
acid-coated particles, but not in those exposed to furnace gases (particle-free control) or to the
ZnO alone. A similar quantitative change was noted in those animals exposed to the pure
droplet at about 10 times the concentration of the coated particles (Amdur and Chen,  1989).
     Amdur and Chen (1989) exposed guinea pigs for 3 h or for 3 h/day for 5 days to a similar
atmosphere as above and examined pulmonary function. Levels of 30 //g/m3 H2SO4 produced a
significant depression in diffusing capacity (DLco). Repeated exposures at the equivalent of
21 //g/m3 H2SO4 resulted in reduced DLco after the 4th exposure day; at the higher (30//g/m3)
level of coated acid, DLco decreased  gradually from the first exposure day.
     The interaction of acid coated particles with ozone was examined by Chen et al. (1991).
Guinea pigs (male, Hartley, 260 to 325 g) were exposed (nose-only) to sulfuric acid coated ZnO
particles (0.050 //m CMD, og=2) at 24 or 84 //g/m3 H2SO4 or pure acid (0.08 //m) at 300 //g/m3
for 2 h, followed by 2 h rest period and 1 h additional  exposure (whole body) to air or 0.15 ppm
O3. Other animals were exposed to acid coated ZnO having an equivalent acid concentration (24
//g/m3) for 3 h/day for 5 days.  This was followed by exposure for 1 h to 0.15 ppm O3 on day 9,
or to two additional 3 h exposures to 24 //g/m3 H2SO4  layered-ZnO on days 8 and 9. In the
single exposure series, animals exposed only to the higher coated acid concentration followed by
ozone showed greater than additive changes in vital capacity and DLco, while those exposed
first to the pure acid droplet did not show any change greater than that due to ozone alone.
Animals exposed repeatedly and then to the two added acid exposures showed greater reductions
in lung volumes and DLco than did those that did not receive the additional acid exposures.
Finally, animals exposed to ozone after acid showed reduced lung volumes and DLco not
observed in animals exposed to either ozone alone or acid alone.  In terms of acid alone, neither
single exposure to the coated acid affected the endpoints, while exposure to the pure acid
decreased DLco. The investigators concluded that single or multiple exposures to the acid-
coated ZnO resulted in an enhanced response to subsequent exposures to acid or ozone and that
the manner in which the acid was
                                         11-75

-------
delivered (i.e., as a pure droplet or as a surface coating) affected whether or not any interaction
occurred.  However, it is likely that the number concentration of particles was greater in the zinc
oxide aerosol than in the pure acid aerosol, and the interaction may reflect this greater particle
number. It should also be noted that ZnO itself may have produced some biological response, or
contributed to any interaction with the acid, in some of the studies reported for some endpoints.
     Wong et al. (1994) exposed rats (M; F-344, nose-only) for 4 h/day, 4 days/week for
8 weeks to a complex mixture consisting of 350 //g/m3 California road dust (5 //m MMAD) + 65
Mg/m3 (NH4)2SO4 (0.3 //m) + 365 //g/m3 NH4NO3 (0.6//m) + O3 (0.2 ppm), as well as to O3
alone.  Animals were sacrificed at 4 or 17 days after the last exposure to assess stress inducible
heat shock protein as an indicator of early pulmonary injury. An increase in heat shock protein
was observed with the mixture at both time points,  but the effect of O3 was greater than that due
to the mixture.
     Mannix et al. (1982) examined the effects of a 4 h exposure of rats to a SO2-sulfate mix,
consisting of SO2 (13,000 //g/m3) plus 1,500 //g/m3 (0.5 //m, MMAD) of an aerosol containing
(NH4)2SO4 and Fe2(SO4)3. No change in particle clearance from the tracheobronchial tree or
pulmonary region was found.
11.3   METALS
11.3.1 Introduction

     The metals discussed in this section are generally present in the ambient atmosphere of
U.S. urban areas in concentrations greater than 0.5 //g/m3 (see Chapter 3, Table 3-10) and
include arsenic, cadmium, copper, iron, lead, vanadium,  and zinc.  While other metals are
present in the ambient air, they are found at concentrations less than 0.5 //g/m3 and are not
reviewed here.  There are no reported toxicological studies of acute effects of inhaled metals at
or below this concentration.
     The information presented has primarily been obtained from occupational and laboratory
animal studies.  Both of these data sources have limitations that affect their usefulness to
ambient particulate matter discussion.  In the occupational studies, the exposures are not well-
characterized and may be confounded by exposure to other materials
                                          11-76

-------
such as PAH, toxic gases, and other respirable particulate. Moreover, the concentrations of
metals experienced in occupational settings as well as the exposure concentrations and the doses
administered in the laboratory animal studies are generally hundreds to several thousand times
greater than the concentrations found in the ambient air (about 1-14 //g/m3).
     These sections are intended as general summaries of each metal since the majority, with
the exception of lead, do not have current documentation or health risk standards. However,
review articles and criteria documents from other agencies are cited as sources of additional
information. While there are many studies available using higher concentrations and other
routes of administration than inhalation, a select summary only of the effects of inhaling metals
on humans and animals is presented in Table 11-10 where an attempt was made, where possible,
to focus on those studies that reported effects at the lowest exposures.  Each section briefly
discusses data on acute and chronic effects from inhaling metals in humans and laboratory
animals.  Endpoints (developmental effects and other non-respiratory endpoints) not
immediately related to the epidemiological findings presented in Chapter 12 are not included in
this discussion but are presented in the references cited. End points seen with routes of exposure
other than inhalation  are not discussed.

11.3.2 Arsenic

     Human Data:  The toxicity data on inhalation exposures to arsenic are limited in number
and quality. Long-term occupational exposure to arsenic leads to  a range of health effects such
as lung cancer,  skin changes and peripheral nerve damage in workers.  Most of the available
human inhalation data on arsenic are based on occupational exposures  to arsenic trioxide.
     In humans, acute  symptoms are seen after airborne exposure to high levels of arsenic
trioxide in an occupational setting.  Symptoms include  severe irritation of the nasal mucosa,
larynx, and bronchi (Holmqvist, 1951; Pinto and McGill, 1953).  It is not clear if these effects
were chemically related to arsenic or a result of irritation due to the dusts inhaled.  Irritation of
mucous membranes of the nose and throat leading to hoarseness, laryngitis,  bronchitis,  or
rhinitis and sometimes perforation of the nasal septa have been reported in workers exposed to
arsenic dusts (Pinto and McGill, 1953), but effect levels cannot be set due to  insufficient
exposure data.  Increased peripheral vasospastic disorders and Raynaud's
                                          11-77

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                                               TABLE 11-10.  RESPIRATORY SYSTEM EFFECTS OF INHALED
                                                    METALS ON HUMANS AND LABORATORY ANIMALS
Metal
(Ambient
Concentrations)3
Arsenic
(0.002-2.32
Mg/m3)
Subjects
In humans
In animals

Resp. tract irritation, laryngitis,
100-1,000 ,ug/m3.
Decreased bactericidal activity,
Effectsb
bronchitis, rhinitis. Effects absent at
inc mortality in streptococcal assay at 500-940
References
Agency for Toxic
Substances and
Disease Registry
(1993)
Aranyietal. (1985)
              Cadmium
              (0.0002-7.0
oo
In humans     Acute exposure: resp. tract irritation, bronchiolitis, alveolitis, impaired
              lung function, and emphysema; mild and reversible symptoms with exposure to 200-
              500 //g/m3.  Chronic exposure: kidneys and resp. tract affected; effects include
              proteinuria and emphysema, with exposure to 20 ,wg/m3 for 27 years.
In animals     Mild  inflammation; AM and epithelial hyperplasia in rat at 500 //g/m3 for 3 h;
              lesions repaired at 7-15 days postexposure. Effects similar to humans. Dose-
              dependent fibrotic lesions in lungs of rats exposed to 300-1,000 ,ug/m3 for 12
              weeks.
              Hyperplasia of terminal bronchioles, cell flattening, inflammation and
              proliferation of fibroblasts in rat at >300 ,wg/m3, 6 h/day, 5 days/week, 62 days.
              BAL  fluid changes at 1,600 ,ug/m3, 3 h/day, 5 days/week, 1-6 weeks indicative of
              lung damage.  Aggregates of PMNs in interstitium, thickening of alveolar septa.
              Effects peaked at 2 weeks, then dec.
              Inc number and size of AM in rat at 100 ,ug/m3, 22 h/day, 7 days/week, 30 days,
              returning to normal 2 mo postexposure.
              In rabbit at 400 ,ug/m3, 6 h/day, 5 days/week, 4-6 weeks, inc lung weight,
              interstitial infiltration of PMNs and lymphocytes, intraalveolar accumulation
              of large, vacuolated macrophages, inc  phospholipid content.
              In mouse at 30-90 ,ug/m3, 8 or,  19 h/day, 5 days/week, 42-69 weeks inc incidence of
              alveolar lipoproteinosis, interstitial fibrosis, broncho alveolar hyperplasia.
Agency for Toxic
Substances and
Disease Registry
(1989)
Buckley and Bassett
(1987)
                                                                                                                                        Kutzmanetal. (1986)
                                                                                                                                        Hart (1986)
                                                                                                                                        Glaseretal. (1986a)

                                                                                                                                        Johansson et al.
                                                                                                                                        (1984)

                                                                                                                                        Heinrich et al.
                                                                                                                                        (1989a)

-------
TABLE 11-10 (cont'd). RESPIRATORY SYSTEM EFFECTS OF INHALED METALS
              ON HUMANS AND LABORATORY ANIMALS
Metal
(Ambient
Concentrations)3
Copper
(0.003-5.14
Mg/m3)
Iron
(0.13-13.80
Subjects Effectsb
In humans Subjective symptoms and clinical tests (CBC, LDH determination, urinalysis) after
outbreak of metal fume fever: fever, dyspnea, chills, headache, nausea, myalgia,
cough, shortness of breath, sweet metallic taste, vomiting, 1-10 h occup exposure.
Complaints of discomfort similar to onset of common cold; chills or warmth;
stuffiness of the head, 75-120 //g/m3, few weeks occup exposure.
In Mild respiratory tract effects in hamster: Decreased cilia beating frequency and
animals abnormal epithelium at 3,300 //g/m3, 3 h/day.
In mouse exposed for 3 h/day, 5 days/week, 1 -2 weeks slight alveolar thickening and
irregularities after 5 exposures at 120 ,ug/m3, extensive thickening with many walls
fused into irregular masses and dec mean survival time after 10 exposures at
130 ,ug/m3. Dec bactericidal activity in both exposure groups.
In humans Subjective symptoms, chest X ray: siderosis in 3 males. Note: concurrent exposure
to several other chemicals; > 10,000 ,ug/m3, 2 mo-12 years (occup).
34% prevalence of siderosis; complaints of chronic coughing and breathlessness,
3,500-269,000 ,ug/m3, 10 year (avg).
In Respiratory tract cell injury (not specified) in hamsters, alveolar fibrosis,
animals 14,000 //g/m3, 1 mo.
Impaired respiration in rats, blood nasal discharge at 6,800 and 22,000 ,ug/m3, 6
h/day 5 days/week, 4 weeks.
References
Agency for Toxic
Substances and
Disease Registry
(1990)
Agency for Toxic
Substances and
Disease Registry
(1990)
Agency for Toxic
Substances and
Disease Registry
(1990)
Sentz and Rakow
(1969)
Teculescu and Albu
(1973)
Creasia and
Nettesheim(1974)
BASF Corporation
(1991)

-------
                                    TABLE 11-10 (cont'd).  RESPIRATORY SYSTEM EFFECTS OF INHALED METALS
                                                          ON HUMANS AND LABORATORY ANIMALS
                     Metal
                   (Ambient
                Concentrations)3
   Subjects
Effectsb
References
              Vanadium
              (0.0004-1.46
oo
o
In humans     Bronchial irritation (cough, mucous formation) postexposure at 60 //g/m3.
              Cough at 100, 600 Mg/m3 8 h lasted about 1 week.

              Productive cough, runny nose, sore throat, wheezing, 100-300 ,ug/m3, 2 years
              (occup).
In humans     Rhinitis, nasal discharge, irritated throat, bronchopneumonia,
              "asthmatic" bronchitis, est <6,500, 1-2 years (occup)
In animals     Alveolar proteinosis in rat at 17,000 //g/m3, 6 h/day, 5 days/week, 2 weeks;
              dose-related inc lung weight, inc accumulation of macrophages, collagen
              deposition, lung lipid content, and Type II pneumocytes.
              Reduced lung function in monkey at 2,500 //g/m3, 6 h, inc pulmonary
              resistance; inc leukocytes in bronchoalveolar lavage.
              In rat, nasal discharge (sometimes containing blood), difficulty
              breathing, dec BW; hemorrhages in lung, heart, liver, kidney, brain.
              bronchitis, focal interstitial pneumonia in lungs.  Effects mainly in lungs
              at low concentration. Mild signs of toxicity at 2,800 //g/m3.
In rats         Capillary congestion, perivascular edema, hemorrhages in lungs.  Also focal
              edema and bronchitis in some cases, lymphocyte infiltration of interstitial
              spaces, constriction of small bronchi, 1,700-2,800 //g/m3, 2 h/every other
              day, 3 mo.
                                            Zenz and Berg (1967)


                                            Lewis (1959)

                                            Sjoberg (1950)

                                            Lee and Gillies
                                            (1986)

                                            Knechtetal. (1985)

                                            Roshchm(1967a)



                                            Roshchm (1967a)

-------
                                    TABLE 11-10 (cont'd).  RESPIRATORY SYSTEM EFFECTS OF INHALED METALS
                                                           ON HUMANS AND LABORATORY ANIMALS
                     Metal
                    (Ambient
                 Concentrations)3
   Subjects
Effectsb
References
              Zinc
              (0.015-8.328
oo
In humans      Symptoms metal fume fever: Nausea, chills, shortness of breath and chest
               pains at 320,000-580,000 ,wg/m3, 1-3 h.
               Fever, chills, chest tightness, muscle/joint pain, sore throat, headache at
               4-8 h postexposure; inc airway resistance of 16%, 4,900 ,ug/m3, 2 h/day, 1 day
               (face mask).
               Significant correlation between change in peak expiratory flow rate and dust
               concentration, 6-8 h workshift.
               BAL fluid changes; inc number of leukocytes, T cells, T suppressor cells, and
               NK cells; me PMN leukocytes, with 77,000-153,000 ,ug/m3, 15-30 mm (occup).
               Miminal substernal irritation and throat irritation during exposure, 3.6
               ,ug/m3, 2 h.
In animals      BAL fluid: Inc protein, LDH, and p-glucuronidase, inflammation at 2,200
               ,ug/m3, 3 h/day 1 day in rat.
               BAL fluid: Inc protein, LDH, and P-glucuronidase (suggesting altered
               macrophage function), inflammation at 2,200 ,ug/m3, 3 h/day 1 day in guinea
               Pig-
               Impaired lung function (dec compliance and lung volume, inc pulmonary
               resistance, dec CO diffusing capacity at 3,700 //g/m3, 3 h/day 6 day in guinea
               Pig-
               Inc lung weight; inflammation, and increased interstitial thickening,
               fibroblasts, and interstitial infiltrates at 4,300 //g/m3.
               Dec pulmonary compliance, followed by inc during 2-h postexposure, at 730
               ,ug/m3, 1 h in guinea pig.
                                             Agency for Toxic
                                             Substances and
                                             Disease Registry
                                             (1994)
                                             Gordon et al. (1992)
                                             Marquart et al.
                                             (1989)
                                             Blanc etal. (1991)

                                             Lmnetal. (1981)

                                             Gordon etal. (1992)
                                                                                                                                   Lam etal. (1985)
                                                                                                                                   Amduretal. (1982)
             ^Ambient air concentration range associated with metal particulate matter in the United States atmosphere (see Chapter 1, Table 1 -4).
             bAbbreviations: dec = decreased; inc = increased; occup = occupational; PAH = polycyclic aromatic hydrocarbons; ALK = alkaline phosphatase;
              BAL = bronchoalveolar lavage; AM = pulmonary alveolar macrophage; PMN = polymorphonuclear leukocyte; res = respiratory.

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phenomenon were found in Swedish arsenic workers exposed to airborne arsenic dusts
(Lagerkvist et al., 1986).
     Laboratory Animal Data: Limited acute data were available on the inhalation toxicity of
arsenic in animals. Aranyi et al. (1985) exposed mice to an aerosol of arsenic trioxide for 3 h at
levels of 0, 270, 500, or 940 //g arsenic/m3. Additional groups were exposed for 3 h/day for 5
or 20 days. At the end of exposure, mice were challenged with an aerosol exposure of viable
streptococci, and death of exposed and controls was recorded over 14 days. Separate groups
were challenged with aerosols of35S-\abQ\QdKlebsiellapneumoniae to evaluate macrophage
function (bacterial killing) in a 3-h period.  In the streptococcal assay, a concentration-related
increase in mortality  occurred.  Bactericidal activity was markedly decreased after a single
exposure to 940 //g arsenic/m3, but no consistent or significant effects were seen at lower
exposure levels after  one or several exposures.
     In a chronic inhalation study, male Wistar rats (20 to 40/group) were continuously exposed
to 0, 60, or 200 //g arsenic/m3 as arsenic trioxide for 18 mo (Glaser et al., 1986b). No effects on
body weight, hematology, clinical chemistry, or macroscopic and microscopic examination
outcomes were observed.

11.3.3  Cadmium

     Recent reviews and health criteria documents have detailed the toxicological and
carcinogenic effects of cadmium by different routes of administration including inhalation
(Oberdorster, 1989a,b; Waalkes and Oberdorster, 1990; International Agency for Research on
Cancer, 1993).  Acute and chronic health effects observed after cadmium exposure were mostly
related to occupational settings and occurred after exposures to concentrations far exceeding
those occurring environmentally. Average airborne cadmium concentrations in rural  areas range
from 0.0002 to 0.006 //g/m3, and in urban areas concentrations from 0.002 to  0.025 //g/m3 have
been found which can increase in industrial areas by a factor of 3 to 5.  Health effects at these
low airborne concentrations of cadmium have not been  reported; the following summary
indicates that health effects observed in humans and animals are correlated with higher
occupational exposure concentrations ranging up to the mg/m3 levels. Thus, exposure to much
lower ambient environmental airborne concentrations of cadmium
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are unlikely to contribute to acute health effects.  It should also be considered that exposure to
cadmium occurring in cigarette smoke by far exceeds background ambient air concentrations.
When evaluating health effects of inhaled cadmium compounds it should be considered that in
vivo solubility of the different cadmium compounds is different from their water solubility. For
example, CdO and CdS are both insoluble in water, yet CdO is rapidly soluble in the lung,
possibly in the acidic milieu of alveolar macrophages after phagocytosis, whereas CdS is highly
insoluble in the lung, behaving more like a low toxicity particle (Oberdorster, 1989b).

11.3.3.1   Health Effects

     Human Data: Table 11-10 summarizes data from studies of occupationally-exposed
workers which show that the main target organs for cadmium toxicity are the kidney and the
respiratory tract.  This table is restricted to those studies where exposures to airborne cadmium
concentrations were less than 100 //g/m3 since it is felt that effects observed from exposures to
higher airborne cadmium concentrations are irrelevant for low concentrations of environmental
cadmium and particulate matter. With respect to renal damage, these low environmental
concentrations will not lead to significant accumulation of cadmium in the kidney to reach the
critical concentration of 200 //g/g which will result in symptoms of kidney damage, e.g.,
proteinuria. Earlier studies found evidence of proteinuria after occupational exposures to 50
Mg/m3 for up to 12 years (Kjellstrom et al., 1977). More recent analyses found the threshold of
cadmium exposure for proteinuria at close to 1,000 //g/m3 x year (Blinder et al.,  1985a,b; Mason
et al., 1988).  Obviously, these exposure concentrations are far above those encountered
environmentally and will not be considered further in the context of this document.
     Acute respiratory effects of inhaled cadmium have been reported as pneumonitis and
edema if exposure concentrations exceed 1,000 //g/m3 for periods of 1 h or more. Chronic
cadmium exposures resulting in emphysema and dyspnea have also been reported when
exposure concentrations are very high, exceeding for extended periods of time several hundred
Mg/m3. Chronic exposure concentrations below 100 //g/m3 at occupational settings have been
associated with induction of lung tumors (International Agency for Research on Cancer, 1993).
Recent analyses of English and Swedish cohorts as well as an American
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cohort found a statistically significant excess risk of lung cancer in the highest exposure groups
(Blinder et al., 1985c; Sorahan, 1987; Thun et al., 1985). Based on these studies, IARC
determined that cadmium is a human carcinogen. However, environmentally encountered
airborne cadmium concentrations are too low to induce lung cancer, unless it is postulated that a
combination of cadmium plus other air contaminants results in a synergistic carcinogenic effect.
Excess of prostate cancer due to occupational inhalation of cadmium observed in earlier
epidemiological studies have not been confirmed in later studies (IARC, 1993).
     Laboratory Animal Data: Health effects of inhaled cadmium compounds are summarized
in Table 11-10. Like with the human studies, only those studies are listed where exposure
concentrations below 100 //g/m3 were used. These studies in laboratory animals confirm that
inhalation exposure to cadmium compounds can result in respiratory tract injury. Very high
exposure concentrations (mg/m3) are needed to cause acute effects such as lung edema and
alveolar epithelial cell necrosis, whereas lower exposure concentrations at -50 - 100 //g/m3 can
induce chronic inflammatory responses including bronchoalveolar hyperplasia, proliferation of
connective tissue leading to interstitial fibrosis (Takenaka et al., 1983). The most striking effect
at low exposure concentrations in rats is that different cadmium compounds were shown to cause
lung cancer (Takenaka et al., 1983; Glaser et al., 1990).  These studies reported primary lung
tumors (bronchoalveolar adenoma, adenocarcinoma, squamous cell tumors) following exposure
to CdCl2, CdSO4, CdS and CdO inhaled as dust or fume. Exposure concentrations were as low
as 10 //g/m3, adding to the evidence from human occupational exposure studies that inhaled Cd-
compounds can induce lung tumors. In contrast to rats, mice and hamsters exposed to the
different cadmium compounds at similar concentrations did not induce lung tumors (Heinrich et
al.,  1989a). The reason for the significant species differences may be the different inducibility
of metallothionein (MT) as well as different baseline levels of MT in the lungs of mice and rats
which was demonstrated by Oberdorster et al. (1994a). These authors found that a four-week
inhalation exposure to CdCl2 aerosols at an exposure concentration of 100 //g/m3 caused greater
and more persistent inflammation and cell proliferation in the lungs of mice than in rats.  At the
same time MT was induced to a greater degree in mice, possibly protecting the lungs of this
species from the cytotoxic effects of inhaled cadmium.
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In summary, these studies demonstrate that measured low environmental cadmium
concentrations alone are not likely to be causally associated with acute effects on mortality and
morbidity observed in epidemiological studies; nor are they likely to cause long-term chronic
effects.  Cadmium exposure at relatively high exposure concentrations has been shown to lead to
a decreased immune response in mice (Graham et al., 1978; Krzystyniak et al., 1987) which
could suggest that people with a compromised immune system may also be affected more than
healthy people by exposure to cadmium. However, environmental low level cadmium
concentrations have not been shown to induce these effects.

11.3.4  Copper

     Human Data: The data on human exposure to copper by inhalation are limited. The
major target organ appears to be the respiratory system, but the data are limited to occupational
studies.  Data are primarily based  on subjective symptoms without indications of pulmonary
function changes as a result of occupational exposure to copper. The observed symptoms may
also be due to exposure to copper  by both oral and inhalation routes since exposures were
confounded. The lack of control workers is also a limitation in evaluating the human data
available for copper exposure by inhalation.  A combination of respiratory symptoms has been
reported following acute inhalation exposure to copper in humans. Armstrong et al. (1983)
reported the following symptoms  (in order of number of workers affected): fever, dyspnea,
chills, headache, nausea, myalgia, cough, shortness of breath, a sweet metallic taste and vomiting
in factory workers accidentally exposed to copper dust or fumes for 1 to 10 h as a result of
cutting pipes known to contain copper. These symptoms are consistent with metal fume fever,
an acute disease induced by inhalation of metal oxides that temporarily impairs pulmonary
function but does not progress to chronic lung disease (Stokinger, 198la). Airborne copper
concentration during the exposure period was not reported.  It was reported that 5 of 12 workers
hospitalized following the acute exposure had urine copper levels greater than 50 //g/L.   Since
the major route of excretion of copper is biliary, the elevated urine copper levels reported
suggest that the exposure concentration was relatively high. Copper levels were not determined
for control workers in this study which limits the interpretation of the urinary copper values as
an indicator of copper inhalation exposure.  Armstrong et al. (1983) also reported evidence of
minimal elevation of serum
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lactate dehydrogenase (in 3 of 14 workers evaluated) and leukocytosis (in 21 of 24 workers
evaluated). Nonspecific complaints of discomfort and chills were reported among several
workers within a few weeks of beginning operation of a copper plate polishing operation.
Exposure levels of 75 to 120 //g/m3 were measured (Gleason, 1968).
     In a epidemiological study by Suciu et al. (1981), factory workers exposed to copper dust
received annual physical and clinical examinations during a 4 year exposure period.  The
reported air copper levels were not reported for the first year, were 464,000 //g Cu/m3 in the
second year; 132,000 //g Cu/m3 in the third year; and 111,000 //g Cu/m3 in the fourth year.
Although inhalation was considered to be the major route of exposure for these workers, it was
likely that a portion of the airborne copper was trapped in the upper respiratory tract and
swallowed. This assumption was made based on the gastrointestinal effects that were observed
in these workers in addition to the respiratory effects. Respiratory effects reported included
symptoms of coughing, sneezing, yellowish-green expectoration, dyspnea, and thoracic pain.
Radiography revealed linear pulmonary fibrosis and in some cases nodulation. Limitations of
this study include the absence of a control group, poor description of study design and the lack
of statistical analysis of data.
     Respiratory effects were also noted in a report by Askergren and Mellgren (1975). Nose
and throat examinations were performed in sheet-metal workers exposed to copper dust.  Six of
11 workers had nasal mucosa characterized by increased vascularity and superficial epistatic
vessels. This was accompanied by symptoms of runny nose and mucosal irritation in the mouth
and eyes. However, the levels of airborne copper were not measured.
     Laboratory Animal Data:  As with human exposure,  the respiratory system appears to be
the primary site of injury following inhalation exposure to copper.  Drummond et al. (1986)
reported a decrease in tracheal cilia beating frequency following a single exposure to 3,300 //g
Cu/m3 (as a copper sulfate aerosol) in hamsters,  but not in mice exposed to the same level.
Alveolar thickening was observed in mice exposed repeatedly and the severity of the effect
increased with the duration of exposure. Histological examination of the trachea revealed
abnormal epithelium in mice at 5 exposures at 120 //g Cu/m3, extensive thickening and
decreased mean survival time after 10 exposures at 130 //g Cu/m3.
     Immunological effects were observed in mice (Drummond et al., 1986) and in rabbits
(Johansson et al., 1983) exposed to copper sulfate aerosols. Mice exposed to either a single
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concentration of 560 //g Cu/m3 or 10 exposures to 130 //g Cu/m3, and simultaneously challenged
with an aerosol of Streptococcus zooepidemicus had decreased survival time (Drummond et al.,
1986). Decreased bactericidal activity was also observed in mice after exposure to an aerosol of
Klebsiellapneumonia after single or repeated exposures to copper sulfate aerosols (Drummond
et al., 1986), suggesting that copper can inhibit the function of alveolar macrophages.  After
inhalation exposure, Johansson et al. (1983) also observed a slight increase in the amount of
lamellated cytoplasmic inclusions in alveolar macrophages. Exposures of rabbits to copper
chloride  aerosols for 4 to 6 weeks resulted in a minor increase in volume density of alveolar
Type 2 cells and minor levels of lymphocytic or eosinophilic inflammatory infiltrates (Johansson
etal., 1984).

11.3.5 Iron

     Human Data: Most of the available human inhalation data on iron are based on
occupational exposures to iron oxide,  with effects limited to respiratory symptoms and
dysfunction. There are no acute human inhalation data on the effects of iron exposure.  Health
effects information via inhalation route is limited to iron pentacarbonyl. No information was
located on the soluble iron salts including ferric chloride, ferric nitrate, and ferric sulfate.
     Occupational exposure occurs from mining of iron ores, consisting mainly  of oxide forms.
During the mining and during smelting and welding process, workers are often exposed to dust
containing iron oxides and silica, as well as other metals and substances.  It is known that
exposure to iron oxides results in roentgenological changes in the lung due to deposition of
inhaled iron particles (Doig and McLaughlin, 1936; Musk et al., 1988; Plamenac et al., 1974),
designated variously as siderosis, iron pneumoconiosis, hematite pneumoconiosis, iron
pigmentation of the lung, and arc welder lung (Blinder, 1986).  Siderosis is prevalent in 5 to
15% of iron workers exposed for more than 5 years  (Buckell et al., 1946; Schuler et al., 1962;
Sentz and Rakow, 1969). Exposure levels were reported to exceed 10,000 //g iron/m3 by Sentz
and Rakow (1969); but no exposure data were presented for the other studies. A Romanian
study (Teculescu and Albu, 1973) reported a 34% prevalence of siderosis in  workers exposed to
ferric oxide dust (3,500 to 269,000 //g/m3); but radiological evidence of lung fibrosis was not
observed. Complaints of
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chronic coughing were reported by 80% of the workers.  Morgan (1978) found a male subject
exposed chronically to ferric oxide (magnetite; Fe3O4) had symptoms of coughing and sputum
for 8-9 years and exhibited an abnormal chest x-ray, but pulmonary function tests revealed no
abnormalities. Stokinger (1984) reviewed the literature on occupational exposure to iron oxide
fumes, and concluded that most investigators considered the roentgenological pulmonary
changes,  secondary to inhalation of iron dust (i.e., siderosis), as benign and did not suspect them
to progress to fibrosis. Although several case reports have described iron oxide workers, with
coughing and shortness of breath, exhibiting diffuse fibrosis in their chest x-rays (Charr, 1956;
Friede and Rachow, 1961; Stanescu et al., 1967), concurrent exposure to other chemicals may
have contributed to this finding (Chan-Yeung et al., 1982; Sitas et al., 1989).
     Several studies report high incidence of lung cancer mortality among workers exposed to
iron oxide in mines and smelters; but, in all cases, there was simultaneous exposure to other
potentially carcinogenic substances (Boyd et al., 1970; Faulds, 1957). Improvements in dust
control and ventilation of mines after 1967 have also resulted in reduction of lung cancer
mortality in iron ore mine workers (Kinlen and Willows,  1988).
     Iron oxide particles have been used both as a tracer and as a carrier particle for radioactive
tracers (e.g., Te) in human (Leikauf et al., 1984; Gerrard et al., 1986; Ilowite et al., 1989;
Bennett et al., 1992; Bennett and Zeman, 1994; Bennett et al., 1993) and laboratory animal
studies (Okuhata et al., 1994, Brain et al., 1994; Warheit and Hartsky, 1993; Domes and
Valberg,  1992; Warheit et al., 1991a,c; Bellmann  et al., 1991; Lehnert and Morrow, 1985;  Brain
et al., 1984; Valberg, 1984;  Skornik  and Brain, 1983) to measure different aspects of pulmonary
deposition and clearance. In general, the exposures were brief and the concentrations of iron
used in these  studies were extremely high compared to those found in the ambient atmosphere.
There were no reported acute effects of exposure to these iron oxide particles.
     Laboratory Animal Data: Two acute inhalation studies reported clinical signs relating to
respiratory distress in rats exposed to iron pentacarbonyl for 4 h or 1 mo (BASF Corporation,
1991; Bio/Dynamics Incorporated, 1988).  However, histopathology was not performed on the
lungs.  Acute exposure of rats to 500,000 //g iron/m3 as iron oxide for greater than 30 min also
resulted in coughing, respiratory difficulties, and nasal irritation
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(Hewitt and Hicks, 1972 as cited in Blinder, 1986) and histopathology of the lungs revealed iron
oxide particles in macrophage cells.  Ten intratracheal installations of ferric oxide in hamsters
produced loss of ciliated cells, and hyperplasia and proliferation of non-ciliated epithelial cells in
the lungs (Port et al., 1973). Intratracheal instillation of iron oxides in female rats produced
tumors in 70% of the animals but did not reduce the life-span (Pott et al., 1994).  At a longer
duration of 1  mo, hamsters inhaling  14,000 //g iron/m3 as ferric oxide dust (MMAD of 0.11 //m)
revealed respiratory tract cell injury  and alveolar fibrosis (Creasia and Nettesheim, 1974).
      See also the discussion below on transition metals (Section 11.3.8) regarding ferric iron
(Fe3+) complexed on the surface of silicates. There it is noted, for example that newly emerging
studies by Ohio et al. (1992) and others suggest that Fe3+ complexed on the surface of silicate
particles may be responsible for inflammatory responses associated with silicate inhalation.

11.3.6  Vanadium

     Human Data:  Acute and chronic inhalation studies in humans are generally limited to
occupational  case studies and epidemiology studies in workers engaged in the industrial
production and use of vanadium. Based on these studies, the respiratory tract is the primary
target of vanadium inhalation.  Most of the reported exposures are to vanadium pentoxide dusts.
     Acute and chronic respiratory effects were most commonly seen following exposure to
vanadium pentoxide dusts.  Mild respiratory distress (cough, wheezing, chest pain, runny nose,
or sore throat) was observed in workers exposed to vanadium pentoxide dusts or vanadium in
fuel oil smoke for as few as 5 h (Levy et al., 1984; Musk and Tees, 1982; Thomas and Stiebris,
1956; Zenz et al., 1962) or as long as 6 years (Lewis, 1959; Orris et al., 1983; Sjoberg, 1956;
Vintinner et al., 1955; Wyers, 1946). Most clinical signs reflect the irritative effects of
vanadium on  the respiratory tract; only at concentrations > 1,000 //g vanadium/m3 were more
serious effects on the lower respiratory tract observed (bronchitis, pneumonitis).  Rhinitis,
pharyngitis, bronchitis, chronic productive cough, wheezing, shortness of breath, and fatigue
were reported by workers following chronic inhalation of vanadium pentoxide dusts (Sjoberg,
1956; Vintinner et al., 1955; Wyers, 1946).
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Two volunteers exposed to 60 //g vanadium/m3 as vanadium pentoxide reported a delay of 7 to
24 h in the onset of mucus formation and coughing (Zenz and Berg, 1967).
     Vanadium induced asthma in vanadium pentoxide refinery workers without previous
history of asthma, with symptoms continuing for 8 weeks following cessation of exposure (Musk
and Tees, 1982). Increased neutrophils in the nasal mucosa were reported in chronically
exposed workers (Kiviluoto,  1980; Kiviluoto et al., 1979, 1981c).
     Chronic occupational exposure to vanadium dusts was also associated with some
electrocardiographic changes (Sjoberg, 1950).  Vanadium dusts had no effect on hematology
following acute exposure (Zenz and Berg, 1967)  or chronic exposure (Kiviluoto et al., 1981a;
Sjoberg,  1950; Vintinner et al., 1955). Blood pressure and  gross neurologic signs were not
affected following chronic exposure to vanadium pentoxide dusts at levels up to 58,800 //g
vanadium/m3 (Vintinner et al., 1955), although other authors reported anemia or leukopenia
(Roshchin,  1964; Watanabe et al., 1966). Based on serum biochemistry and urinalysis, there
was no indication of kidney or liver toxicity in workers chronically exposed to 200 to 58,800 //g
vanadium/m3 as vanadium dusts (Kiviluoto et al., 1981a,b;  Sjoberg, 1950; Vintinner et al.,
1955).  Vanadium green discoloration of the tongue resulting from direct deposition of
vanadium is often reported (Orris et al.,  1983; Lewis, 1959; Musk and Tees,  1982).
     Laboratory Animal Data:  Acute and chronic laboratory animal studies support the
respiratory tract as the main target of inhaled vanadium compounds.  The animal data indicate
that vanadium toxicity increases with increasing compound valency, and that vanadium is toxic
both as a cation and as an anion (Venugopal and Luckey, 1978).
     The mechanism of vanadium's effect on the respiratory system is similar to that of other
metals. In vitro tests show that vanadium damages alveolar macrophages (Castranova et al.,
1984; Sheridan et al., 1978; Waters et al., 1974; Wei and Misra, 1982) by affecting the integrity
of the alveolar membrane, thus impairing the cells' phagocytotic ability, viability, and resistance
to bacterial infection. Cytotoxicity, tested on rabbit alveolar macrophages in vitro, was directly
related to solubility in the order V2O5 > V2O3 > VO2.  Dissolved vanadium pentoxide (6 //g/ml)
also reduces phagocytosis (Waters, 1977).
     Respiratory effects in laboratory animals following acute inhalation of vanadium
compounds include increased pulmonary resistance and significantly increased
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polymorphonuclear leukocytes in bronchioalveolar lavage fluid.  These effects were observed in
monkeys 24 h following a 6-h inhalation exposure to 2,800 //g vanadium/m3 as vanadium
pentoxide (Knecht et al., 1985).  In addition, increased lung weight and alveolar proteinosis were
observed in rats after inhaling bismuth orthovanadate 6 h daily for two weeks (Lee and Gillies,
1986). Rabbits exposed to high concentrations of vanadium pentoxide dust for 1 to 3 days
exhibited dyspnea and mucosal discharge from the nose and eyes (Sjoberg, 1950).  In a follow-
up experiment, rabbits had difficulty breathing following a daily 1-h exposure for 8 mo
(Sjoberg, 1950).
     The effects of acute exposure to 5,600 to 39,200 //g vanadium/m3 as vanadium pentoxide
fume or 44,800 to 392,000 //g vanadium/m3 as vanadium pentoxide dust were investigated by
Roshchin (1967a); the exposure duration was not described in the available literature.  For
vanadium pentoxide fume, "mild toxicity" occurred at 5,600 //g vanadium/m3, and deaths were
observed at the high level.  The vanadium pentoxide dust was described as one-fifth as toxic as
the fume. Effects at the lower levels were mostly observed in the lungs. These included
irritation of respiratory mucosa, perivascular and focal edema, bronchitis,  and interstitial
pneumonia. In a subchronic experiment, rats were exposed to vanadium pentoxide fume (1,700
to 2,800 (j,g vanadium/m3) or vanadium pentoxide dust (5,600 to 17,000 //g vanadium/m3) for 2
h every other day for 3 to 4 mo (Roshchin, 1967a).  Histopathological effects were limited to the
lungs and were similar to those observed following acute exposure. The study author concluded
that vanadium inhalation resulted in irritation of the respiratory mucosa, hemorrhagic
inflammation, a spastic effect on smooth muscle of the bronchi, and vascular changes in internal
organs (at higher levels). Similar effects were observed with the trivalent vanadium compounds
vanadium trioxide and vanadium trichloride, although vanadium trichloride caused more severe
histological changes in internal organs (Roshchin, 1967b); further details were not available.
     Rats exposed to vanadium pentoxide condensation aerosol (15 //g vanadium/m3)
continuously for 70 days developed marked lung congestion, focal lung hemorrhages, and
extensive bronchitis (Pazynich, 1966).
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11.3.7 Zinc

     Inhalation of zinc compounds, most notably zinc oxide fumes, can result in significant
pulmonary irritation and inflammation referred to as metal fume fever. However, zinc is an
essential element with low intrinsic toxicity, and exposure concentrations have to be in the
mg/m3 range to induce these symptoms which are accompanied by increased inflammatory cell
and protein levels in pulmonary lavage both in experimental animals and humans (Gordon et al.,
1992). A number of studies in experimental animals and also in humans occupationally-exposed
to zinc fumes have been reported, and almost all of these were related to high exposure
concentrations which are irrelevant for low environmental exposure levels.  A recent review of
the toxicity of inhaled metal compounds including zinc in the respiratory tract (Gordon, 1995)
describes a number of studies  from which it can be concluded that inhaled zinc compounds
including zinc oxide are rapidly solubilized in the lung and do not appear to accumulate in the
respiratory tract. Elevated levels of zinc can be found in blood and urine of exposed workers as
well as in exposed animals. Occupational exposures at concentrations below 50 //g/m3 have not
resulted in the occurrence of metal fume fever (Marquart et al., 1989; Linn et al., 1981).  Higher
exposure concentrations inhaled repeatedly result in the development of tolerance after initial
symptoms of zinc fume fever  subside (Gordon et al., 1992). Effects observed after acute high
level exposures include dyspnea, cough, pleuritic chest pain, bilateral diffuse infiltrations,
pneumothorax and acute pneumonitis from respiratory tract irritations. However, exposure
concentrations have to be extremely high for the more severe symptoms to occur which has no
relevance for ambient low level paniculate pollutants.

11.3.8 Transition Metals

     An area of current investigation is the potential for the particle-associated transition metals
to induce oxidant injury. The  transition metals are characterized by being electronically stable in
more than one oxidation state  and, as a result, have the ability to catalyze the oxidative
deterioration of biological macromolecules.  Considering that the transition metals can catalyze
the oxidative deterioration of biological macromolecules it is plausible that inhalation of PM
containing these metals could  cause oxidative injury to the
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respiratory tract.  However, the data available thus far is derived from studies using in vitro
systems and intratracheal administration and can not be used for risk estimation.
     Iron, the best studied of the transition metals, has the ability to catalyze the formation of
reactive oxygen species (ROS) and initiate lipid peroxidation (Aust, 1989; Minotti and Aust,
1987; Imlay et al., 1988; Halliwell and Gutteridige, 1986). Guilianelli et al. (1993) studied the
importance of iron to the toxicity of iron-containing particles in cultured tracheal epithelial cells.
Nemalite, the most cytotoxic of the three minerals tested, contained the most surface Fe2+.
Moreover, pretreatment with the iron chealating compound desferrioxamine, reduced the toxic
effects of nemalite.
     Garrett et al. (198la) exposed rabbit alveolar macrophages in vitro to fly ash with and
without surface coatings of various metal oxides.  Cellular viability and cellular adenosine
triphosphate content were reduced only with the metal-coated ash particles.  Berg and
co-workers (1993) measured the release of ROS from bovine alveolar macrophages stimulated
with heavy metal-containing dusts <4 //m in diameter. Dusts, derived from waste incineration,
sewage sludge incineration, an electric power station, and from two factories, incubated with
alveolar macrophages caused a concentration-dependent increase in ROS release. The ratio of
superoxide anion (O2:) and hydrogen peroxide (!M)2) secreted varied, depending on the dust,
but the release of H2O2 correlated best, in descending order, with the content of iron, manganese,
chromium, vanadium, and arsenic in the dusts. The positioning of iron first in this array is
consistent with other studies examining the biological effects of iron coating the surface of
particles.
     Certain particles, including silica, crocidolite, kaolinite, and talc, complex considerable
concentrations of ferric iron  (Fe3+) onto their surfaces. The potential biological importance of
iron complexation was assessed by Ghio and co-workers (1992) who examined the effects of
surface Fe3+ on several indices of oxidative  injury.  Three varieties of silicate dusts were studied:
(1) iron-loaded, (2) unmodified,  and (3) desferrioxamine-treated. The ability of silicates to
catalyze oxidant generation in an ascorbate/H2O2 system in vitro, to trigger respiratory  burst
activity and leukotriene B4 release by alveolar macrophages, and  induce lung inflammation in
the rat following intra-tracheal instillation all increased in proportion to the amount of Fe3+
complexed onto their surfaces.  Ghio and Hatch (1993)  noted that an extracellular accumulation
of surfactant following instillation of silica  into the lungs of rats
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was associated with the concentration of Fe3+ complexed to the surface of the particles, and that
surfactant-enriched material was a target for oxidants, the production of which was catalyzed by
Fe3+. Moreover, iron, drawn from body stores, has been shown to complex to the surface of
intratracheally instilled silica particles and increase concentrations of iron in bronchoalveolar
lavage fluid, lung tissue and plasma, and decrease antioxidant molecules in lung tissue, including
ascorbate, urate, and glutathione (Ohio et al., 1994).
     Surface complexed iron has been implicated in pulmonary injury due to a variety of
environmental particles (Costa et al., 1994a,b; Tepper et al., 1994). Three particle types (Mt. St.
Helen's volcanic ash, ambient particles of Dusseldorf, Germany, and residual oil fly ash), which
represented a range of inflammatory potential, were intratracheally instilled into rats.  Both the
degree of acute inflammation (as measured by assessing PMNs, eosinophils, LDH and protein in
lavage) and nonspecific bronchial responsiveness correlated with the iron (specifically Fe+3)
loading of the particles.  An interesting observation was that surface iron was correlated with
particle acidity, yet when instillation of H2SO4 at comparable pH was performed, the lavage
analysis indicated much less inflammation with the pure acid compared to the high surface iron
particles. In fact, neutralization of the fly ash instillate (which could occur if similar particles
were inhaled, due to endogeneous respiratory tract ammonia) actually enhanced particle toxicity,
while the pulmonary response diminished when iron was removed from the fly ash by acid
washing. These preliminary results generally support the notion that oxidant generation by iron
present on the surface of particles may increase lung injury; but, clearly, other factors are likely
to contribute to this response.
     Tepper et al. (1994) reported that the concentration of iron (Fe3+) complexed on the surface
of a particle was associated with the ability of the particle to support electron transfer and to
generate oxidants in vitro and to increase lung inflammation and airway hyperresponsiveness in
vivo. Particles with or without iron complexed on the surface were instilled into the lungs of
rats and evaluated for their potential to produce inflammation and airway hyperactivity. The
effects of a high-iron particle  (coal fly ash) before and after surface iron was removed by acid
washing and the effects of an inert particle (titanium), with or without iron added to the particle
surface, were evaluated. The  effects of pretreating the rats with drugs to reduce iron-associated
ROS formation also were studied. Although coal ash caused considerable inflammation and
hyperactivity, acid washing to remove surface iron
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reduced the deleterious effects of the particle.  However, compared to titanium alone, instillation
of a titanium particle coated with iron did not increase lung injury. Pretreatment with
allopurinol partially blocked lung inflammation, but desferrioxamine and an anti-neutrophil
antibody were less effective. The authors concluded that the results generally support the
hypothesis that ROS generation by iron on the surface of particles may exacerbate lung injury.
     The inflammatory potential of 10 different metal-containing dusts of either natural or
anthropogenic origin was evaluated following intratracheal instillation in rats (Pritchard et al.,
1995). Measurements included (1) oxidized products  of deoxyribose catalyzed by particulates,
(2) induction of a neutrophilic alveolitis after particulate instillation, (3) increments in airway
reactivity after particulate instillation, and (4) mortality  after exposures to both dust and a
microbial agent. Except for titanium, in vitro generation of oxidized products of deoxyribose
increased with ionizable concentrations of all metals associated with the particles. After
intratracheal instillation of the dusts in rats, the neutrophil influx and lavage protein both
increased with ionizable concentrations of the same metals. Changes in airway reactivity
following instillation of the dusts also appeared to be associated with the ionizable
concentrations of these metals.  Similarly, mortality after instillation of particles in mice
followed by exposure to aerosolized Streptococcus zooepidemicus reflected metal
concentrations. The authors concluded that in vitro measures of oxidant production and in vivo
indices of lung injury increased with increasing concentrations of the metals instilled
intratracheally.
     Thus, it is clear that ROS produced through chemical reactions involving iron can initiate
lipid peroxidation, cell injury, and ultimately cell death. It may be possible that other transition
metals, by virtue of their ability to redox between valence  states, also can generate ROS in the
presence of precursor oxidants and reducing agents. However, it has not been established in
inhalation studies that these reactions  can occur in vivo.

11.3.9 Summary

     Data from occupational studies and laboratory animal studies indicate that acute exposures
to high levels or chronic exposures to low levels (albeit high compared to ambient levels) of
metal particulate can have an effect on the respiratory tract. However, it is
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doubtful that the metals at concentrations present in the ambient atmosphere (1 to 14 //g/m3)
could have a significant acute effect in healthy individuals.
     Acute and chronic inhalation exposures to arsenic, cadmium, copper, iron,  and vanadium
are associated with respiratory effects, and, in the case of cadmium, renal effects. However, in
general, the levels used in the laboratory animal studies or experienced in occupational settings
are considerably higher (at least 10-fold and as much as 103- or 104-fold) than those found in the
ambient environment, and the results of these studies provide little insight into the morbidity and
mortality studies discussed in Chapter 12. This is not unexpected because of the patterns of
exposure and the total exposures, as well as differences in the populations exposed.  Some of the
effects noted in the human occupational studies such as respiratory tract irritation, bronchitis,
impaired pulmonary function, cough,  wheezing, are also observed in the epidemiological studies
discussed in Chapter 12 and may indicate a general effect of PM.  However, these effects are
evident at exposures much greater than experienced in the ambient atmosphere.  Nevertheless,
the toxicological studies of the metals do not appear to provide insight into the effects observed
in the epidemiological studies discussed in Chapter 12. While  studies examining the potential
for the transition metals to cause lung injury have been conducted in vitro and in animals by
intratracheal instillation are interesting, these results thus far are of limited value.
11.4  ULTRAFINE PARTICLES
     This section on ultrafine particles is designed to provide an overview of current concepts
concerning the potential pulmonary toxicity of this class of particulates.  The occurrence of
ultrafine particles in the ambient environment as well as their sources are reviewed in Chapters 3
and 6.  Studies assessing the comparative toxicity of particles of different sizes using
intratracheal instillation are reviewed in Section 11.9.1.  Particles used in toxicological studies
are mainly in the fine and coarse mode size range. This section addresses the hypothesis that
ultrafine particles can cause acute lung injury and focuses on experimental  studies in which
ultrafine particles generated as fumes were used.  The ultrafine (nucleation mode) particle phase
has a median diameter of -20 nm (see Figure 3-13).  Ultrafine particles with a diameter of 20
nm have an approximately 6 order of magnitude
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higher number concentration than a 2.5 //m diameter particle when inhaled at the same mass
concentration; particle surface area is also highly increased (Table 11-1).
     At present, no toxicological studies with relevant ambient ultrafine particles have been
performed. Although ultrafine particles have been used in animal inhalation studies, the studies
did not focus on two potentially important aspects of ultrafine particles which are addressed in
this chapter; their presence in the exposure atmosphere as single particles rather than aggregates
and their low solubility. Single ultrafine particles occur regularly in the  urban atmosphere at
high number concentrations (5 x 104 - 3 x 10s particles/cm3) but very low mass concentrations
(Brand et al., 1991; 1992;  Castellani, 1993). These single ultrafine particles are not very stable
and eventually aggregate with larger particles but they are always freshly-generated by a number
of natural anthropogenic sources (e.g., gas to particle conversion; combustion processes;
incinerator emissions). Because results of studies with relevant ambient ultrafine particles at
relevant low mass concentrations (10 to 50 //g/m3) are not available in the literature, effects of
single ultrafine particles generated as polymer fumes are discussed  in this section. Obviously,
polymer fume particles do not occur in the ambient atmosphere and they serve only as a
surrogate to indicate the toxic potential that some inhaled ultrafine particles may have. The
hypothesis that other ultrafine particles have this toxic potential as well needs still to be tested
but cannot  be refuted at this time since studies with ultrafine copper oxide particles described in
this section also indicate their potential to cause acute effects. Human exposure to very fine acid
aerosols (~ 100 nm; 1,500  //g/m3) have also been conducted (Horvath et al., 1987). No
pulmonary function or symptom responses were observed suggesting that the soluble nature of
these particles or their tendency to either grow or aggregate may be responsible for the fact that
they did not induce responses similar to other (less soluble) ultrafine particles.
     Inhalation studies in rats with aggregated ultrafine particles have shown that these particles
still required high concentrations (in the mg/m3 range) and repeated exposures to  produce effects
in laboratory animals, although they were more active than larger-sized particles of the same
composition. These particles included ultrafine TiO2 aggregates (Ferin et al., 1992; Oberdorster
et al., 1992; Heinrich, 1994), aggregated carbon black particles (Heinrich, et al., 1995; Mauderly
et al., 1994a; Nikula et al., 1995), and diesel soot (White and Garg, 1981; Rudell  et al., 1990).
Effects observed after subchronic or chronic exposure
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of rats included chronic pulmonary inflammation, pulmonary fibrosis, and induction of lung
tumors. No acute effects were observed, even at the highest exposure concentrations. Although
the studies with TiO2 and carbon black involved particles of ultrafine size (-20 nm), they were
inhaled as aggregates which are considerably larger than single 20 nm ultrafine particles. Thus,
these results may not fully reflect the toxicity of single 20 nm particles.
     From these studies with aggregate ultrafine particles, it appeared that particle surface area
is an important parameter for expressing exposure-response and dose-response relationships of
inhaled highly insoluble particles. The significantly increased pulmonary inflammatory response
of aggregated ultrafine particles is presumably because of their highly increased surface area.  If
the dose for particles of different sizes is expressed relative to their surface area, then responses
elicited by ultrafines would be comparable with those for larger-sized particles (Oberdorster et
al., 1992,  1994b).  The finding that ultrafine particles can penetrate into the interstitium more
easily than larger-sized particles (Takenaka et al., 1986; Ferin et al., 1992) is also very
important.  Transport across the epithelium appears to be  facilitated if ultrafine aggregates
deaggregate upon deposition and are present as single particles.
     As stated above, acute pulmonary effects were not observed after inhalation of aggregates
of ultrafine particles. In contrast,  specific types of inhaled single ultrafine particles described
below can induce severe acute lung injury at low inhaled mass concentrations relative to
aggregated ultrafine particles (Oberdorster, 1995).  Such model  ultrafine particles can be
generated by heating of polytetrafluoroethylene (Teflon®; PTFE); the resulting condensation
aerosol consists of single ultrafine particles.  More than 25 years ago  it was recognized that the
toxicity of pyrolysis products of PTFE is associated with the particulate phase rather than with
gas phase constituents (Waritz and Kwon, 1968).  It was demonstrated more recently that these
particles are of ultrafine size (Lee and Seidel, 1991a,b; Seidel et al., 1991). These particles form
upon heating of Teflon® to a critical temperature of -420 to 450 °C and have diameters from
<10 - 60 nm (median diameter of -26 nm) (Oberdorster et al., 1995a). The toxicity of PTFE
fumes has been recognized dating back to the 1950's, when exposures of rabbits, guinea pigs,
rats, mice, cats, and dogs resulted in acute mortality (Treon et al., 1955).  Further studies in
experimental animals by several
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investigators (Scheel et al., 1968; Coleman et al., 1968; Griffith et al., 1973; Lee et al., 1976;
Alarie and Anderson, 1981) confirmed that these fumes are highly toxic to birds and mammals.
Extensive pulmonary epithelial and interstitial damage and alveolar flooding occurred after only
short-durations of exposure. Accidental exposures of humans to fumes generated from polymers
also demonstrated the high toxicity of these fumes for humans (Nuttall et al., 1964; Goldstein et
al., 1987; Dahlqvist et al., 1992). Associated effects include pulmonary edema, nausea and
headaches, together characterized by the term "polymer fume fever" in analogy to the
well-known symptoms of metal fume fever (Rose, 1992).
     The toxicity of polymer fumes was initially thought to be associated with toxic gas phase
products, such as hydrogen fluoride (HF), carbonyl fluoride, and perfluoroisobutylene (PFIB).
However, detailed studies by Waritz and Kwon (1968) as well as more recent studies have
shown that the high toxicity is associated with the paniculate phase.  For example, HF studies
showed that concentrations as  high as  1300 ppm are needed to cause effects in the upper
respiratory tract of exposed rats; effects did not occur in the lung periphery where the fume
particles have been shown to be most effective (Stavert et al., 1991). Concentrations of HF in
fumes generated at the critical  temperature are only ~ 10 ppm, and therefore, cannot be
responsible for the observed toxicity of the fumes (Oberdorster et al., 1995a).  The more toxic
gas phase compounds,  carbonyl fluoride and PFIB are generated only at temperatures
approaching 500°C when heating PTFE (Coleman et al., 1968; Waritz and Kwon, 1968).
Furthermore, rat inhalation studies with PFIB alone showed that lung pathology was detected
only when a high concentration of 90,000 //g/m3 was exceeded (Lehnert et al., 1993). Further
proof that the particles of polymer fumes represent the toxic entity is provided by studies in
which the particulate phase was removed by filters and subsequently the gas phase compounds
did not show toxicity in exposed rats (Waritz and Kwon, 1968; Warheit et al.,  1990; Lee and
Seidel, 199 la).
     It has also been suggested that highly toxic radicals on the surface of the polymer fume
particles may cause the acute effects.  However, studies by Seidel et al. (1991) with fumes from
different polymers showed similar toxicities to the lung regardless as to whether significant
amounts of radicals could be detected  on those particles or not.  Although  this  still does not
exclude that some reactive  toxic compounds may be attached to the particle surface,
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all of these studies provide strong evidence that the ultrafine particles are the cause of the PTFE
fume-associated, acute lung injury. It has also been shown that aging of the fumes leading to
particle aggregation diminishes their toxicity, indicating that the presence of ultrafine particles as
singlets is highly important for the toxicity of these particles (Lee and Seidel, 1991b; Warheit et
al., 1990).
     To exclude the possibility that oxygen-derived radicals from the generation process may be
responsible for the observed pulmonary toxicity, PTFE particles were generated in a nitrogen
atmosphere (Waritz and Kwon, 1968) or in an argon gas atmosphere (Oberdorster et al., 1995b).
Results showed that the inhaled PTFE fumes generated in this way showed the same high
pulmonary toxicity in rats that was observed with PTFE fumes generated in air. The toxicity
consisted of severe hemorrhagic, pulmonary edema and influx of PMNs into the alveolar space
within 4 h after a 15-min exposure of healthy rats to an ultrafine particle mass concentration of
about 40 to 50 //g/m3; this was accompanied by high mortality (Oberdorster et al., 1995a;
Johnston et al., 1995). It was  also determined by these investigators that a number concentration
of 1 x  10s PTFE particles/cm3 is equivalent to a mass concentration of ~ 10 //g/m3. Pulmonary
lavage data showed that up to 80% of lavageable cells consisted of PMNs.  Acute mortality was
also observed in up to 50% of rats exposed to these concentrations of 5 x io5 particles/cm3.
Epithelial as well as endothelial  cell damage occurred, resulting in both interstitial  and alveolar
edema. The authors concluded that freshly-generated ultrafine PTFE particles inhaled as
singlets at low mass concentrations can cause severe acute lung injury and that ultrafine
particles, in general, penetrate readily through epithelial-endothelial barriers.
     Additional results from studies with ultrafine PTFE particles directed at evaluating
mechanistic events in the lung by using in situ hybridization techniques on lung tissue showed
that the highly inflammatory reaction was characterized by significant increases in message for
the pro-inflammatory cytokine TNFa and the low molecular weight protein metallothionein
(Johnston et al., 1995). Furthermore, increases in abundance for messages encoding IL-la,
IL-lp, IL-6, TNFa and the antioxidants MnSOD and metallothionein were found in RNA
extracted from lung tissues. In addition to the increase in message of these pro-inflammatory
cytokines and antioxidants, abundance for message of inducible NOS was also increased,
whereas message for VEGF (vascular endothelial growth factor) was
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decreased in the acute phase (Johnston et al., 1995). The authors suggested that the acute lung
damage affecting epithelial and endothelial barrier functions may be due to the activities of
reactive oxygen species originating from activated inflammatory cells and reactive nitrogen
species produced via inducible NOS.
     In another effort to evaluate acute effects and disposition of inhaled ultrafme particles
Stearns et al. (1994) exposed hamsters for 60 minutes to ultrafme CuO, Cu2O and Cu(OH)2
particles (11 nm diameter, og = 1.8; approximately 109 particles/cm3). A marked 4-fold increase
in pulmonary resistance was found which persisted for 24 hours. Immediately after exposure,
using electron spectroscopic imaging, copper oxide particles were found not only on and within
airway mucus and extracellular alveolar lining layers but also in airway and alveolar epithelial
cells, in the pulmonary interstitium and in alveolar macrophages. These particles were even
found in the alveolar capillaries and in pulmonary lymphatics. In addition, animals at 24 hours
post-exposure showed evidence of a pulmonary inflammatory response, including the
appearance of neutrophils and eosinophils.
     Roth et al. (1994) demonstrated in human subjects that clearance of ultrafme particles is
delayed.  These workers exposed three male subjects to ultrafme particles (18 nm CMD; 27 nm
MMD) of1U In-labeled indium oxide for two or three breathing cycles and measured
radioactivity present in the head, chest, and stomach immediately after inhalation and for 4 to 8
days at ensuing intervals. The clearance curves showed a fast clearance for particles deposited in
the thorax with  a mean value of 7% and a slow clearance fraction with a mean value of 93%.
The half-life of the slow phase appeared to be on the order of 40 days, indicating greater
persistence of the ultrafme particles rather than the larger particles (>2 jim) in the lung.
     Hatch et al. (1994) evaluated to what extent ultrafme particles (<100 nm) are present in
ambient air by determining their presence in alveolar macrophages of healthy people.  Alveolar
macrophages isolated from lung lavage samples of 7 workers  of an oil-fired power plant, 4
welders of the power plant and 3 university employees (no known occupational or
environmental exposures) were studied by electron energy loss spectroscopy and electron
spectroscopic imaging. Regardless of the occupation, ultrafme particles were observed in
phagolysosomes of macrophages of all volunteers, there was no correlation of ultrafme particle
quantity with occupation.  Spectral analysis of the ultrafme particles revealed a
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variety of metals including cadmium, vanadium, titanium and iron.  This study demonstrates the
presence of large numbers of ultrafine particles in alveolar macrophages of healthy people even
in the absence of specific occupational exposure.  Whether all of these particles have been
inhaled as ultrafines or whether some of them dissolved in the macrophages from larger particles
to the ultrafine size is not known.  However, since ultrafine particles occur in the ambient air
(Chapter 6) their presence in large numbers in alveolar macrophages of people demonstrates that
they are effectively deposited in the deep lung,  although some of them may have been inhaled as
particles adsorbed to larger particles as suggested by the authors. The high deposition efficiency
of inhaled single ultrafine particles in the alveolar region (Chapter 10) contributes to the
plausibility of the suggestion by Hatch et al. (1994) that many of these particles were inhaled as
ultrafines.
     In summary,  certain freshly-generated ultrafine particles, when inhaled as singlets at very
low mass concentrations (<50 //g/m3), can be highly toxic to the lung.  After inhalation and
deposition in the lung, ultrafine particles of low solubility can rapidly penetrate epithelial cell
barriers and penetrate to interstitial and endothelial  sites (Stearns et  al., 1994).  Obviously,
ultrafine particles studied in  experimental animals so far (PTFE-fume, copper oxides) are not
constituents of the ambient atmosphere and it is not clear how well these particles might serve as
surrogates for  ambient ultrafines.
      Mechanisms responsible for a potential high toxicity could include:  (1) high pulmonary
deposition efficiencies of inhaled single ultrafine particles; (2) the large numbers  per unit mass
of these particles; (3) their increased surface area available for reaction;  (4) their rapid
penetration of epithelial layers and access of pulmonary interstitial sites; and (5) the presence of
radicals and perhaps  acids on the particle surface depending on the process of generation of the
particles. Results of studies with model ultrafine particles indicate that particle number or total
particle surface area could be more important than mass concentration (see Table 11-1).
11.5  DIESEL EXHAUST EMISSIONS
     Diesel engines emit both gas phase pollutants (hydrocarbons, oxides of nitrogen, and
carbon monoxide) and carbonaceous PM into the ambient atmosphere.  The concentration of
diesel particulate in the ambient atmosphere although low is ubiquitous. The concentration of
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diesel particulate in the ambient atmosphere has been estimated to be about 1-6 //g/m3 in
Los Angeles (Health Effects Institute, 1995). A description of the diesel engine, its combustion
system, pollutant formation mechanisms and emission factors as well as the cancer and
noncancer health effects of diesel exhaust emissions have been recently reviewed elsewhere in
the Health Assessment Document for Diesel Emissions (U.S. Environmental Protection Agency,
1994) and in Diesel Exhaust:  A Critical Analysis of Emissions, Exposure and Health Effects
(Health Effects Institute, 1995). The endpoints discussed in this section are those associated
with diesel paniculate and directly related to the epidemiological results discussed in Chapter 12.
Other components of diesel exhaust, such as sulfur dioxide (SO2), nitrogen dioxide (NO2),
formaldehyde, acrolein, and sulfuric acid may contribute to some of these potential health
effects. Endpoints not directly related to the epidemiological findings are not included in the
discussion but are presented elsewhere (International Agency for Research on Cancer, 1989;
Claxton,  1983; Lewtas, 1982; Ishinishi et al., 1986; Pepelko and Peirano, 1983; Pepelko et al.,
1980b,c; U.S. Environmental Protection Agency,  1994; Health Effects Institute,  1995).
     Within the text, exposures are expressed in terms of the mass concentration of diesel
particles. Other major measured components in the studies are presented in the tables  which
have additional details about the studies, including references.  The Health Assessment
Document for Diesel Emissions (U.S. Environmental Protection Agency, 1994) that is in
preparation and the Diesel Exhaust Document (Health Effects Institute, 1995) should be
consulted for a complete evaluation of the health effects associated with diesel emissions.

11.5.1 Effects  of Diesel Exhaust on Humans

     It is difficult to study the health effects of diesel exhaust in the general population because
diesel emissions are diluted in the ambient air; hence, exposure is very low.  Thus, populations
occupationally exposed to diesel exhaust are studied to determine the potential health effects in
humans.  The occupations involving potential high exposure to diesel exhaust are miners, truck
drivers, transportation works,  railroad workers, and heavy-equipment operators.  All the
occupational studies considered in this section have a common problem—an inability to measure
accurately the actual exposure to diesel exhaust.
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     The effects of short term exposure to diesel exhaust have been investigated primarily in
occupationally-exposed workers (Table 11-11).  Symptoms of acute exposure to high levels of
diesel exhaust include mucous membrane, eye, and respiratory tract irritation (including chest
tightness and wheezing) and neuropsychological effects of headache, lightheadedness, nausea,
heartburn, vomiting, weakness, and numbness and tingling in the extremities.  Diesel exhaust
odor can cause nausea, headache, and loss of appetite.
     There have been a few experimental exposures of humans to diesel exhaust, but all were
single exposures.  No significant changes in respiratory function were found in subjects exposed
for 1 (Battigelli 1965) or 3.7 (Ulfvarsson et al., 1987) hours to diesel exhaust at approximately
1,000 //g soot/m3 or less.
     Rudell et al. (1990, 1994) exposed eight healthy subjects in an exposure chamber to diluted
exhaust from a diesel engine for one hour, with intermittent exercise. Dilution of the diesel
exhaust was controlled to provide a median NO2 level of approximately 1.6 ppm. Median
particle number was 4.3 x 106/cm3, and median levels of NO and CO were 3.7 and 27 ppm,
respectively (particle size and mass concentration were not provided). There were no effects on
spirometry or on closing volume using  nitrogen washout.  Five of eight subjects experienced
unpleasant smell, eye irritation, and nasal irritation during exposure.  Bronchoalveolar lavage
was performed 18 hours after exposure and was compared with a control BAL performed 3
weeks prior to exposure. There was no control air exposure.  Small but statistically significant
reductions were seen in BAL mast cells, AM phagocytosis of opsonized yeast particles, and
lymphocyte CD4/CD8 ratios. A small increase in recovery of PMNs was also observed. These
findings suggest that diesel exhaust may induce mild airway inflammation in the absence of
spirometric changes.
     In underground miners, bus garage workers, dock workers, and locomotive repairmen
exposed to diesel exhaust, minimal and not statistically significant changes were reported in
respiratory symptoms and pulmonary function over the course of a workshift. In diesel bus
garage workers, there was an increased reporting of burning and watering of the eyes, cough,
labored breathing, chest tightness, and wheezing, but no reductions in pulmonary function
associated with exposure to diesel exhaust. In stevedores pulmonary function was adversely
affected over a workshift exposure to diesel exhaust but normalized after a few days without
exposure.
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        TABLE 11-11.  HUMAN STUDIES OF DIESEL EXHAUST EXPOSURE
      Study
         Description
                  Findings
Kahn et al. (1988)
El Batawi and
Noweir (1966)
Battigelli (1965)
Katz et al. (1960)
Hare and Springer
(1971)
Hare et al. (1974)


Linnell and Scott
(1962)
Battigelli (1965)
Reger (1979)
Ames et al. (1982)
Jorgensen and
Svensson (1970)
13 Cases of acute exposure,
Utah and Colorado coal
miners.


161 Workers, two diesel bus
garages.
Six subjects, eye exposure
chamber, three dilutions.
14 Persons monitoring
diesel exhaust in a train
tunnel.
Volunteer panelists who
evaluated general public's
response to odor of diesel
exhaust.

Odor panel under highly
controlled conditions
determined odor threshold
for diesel exhaust.

13 Volunteers exposed to
three dilutions of diesel
exhaust for 15 min to 1 h.

Five or more VC maneuvers by
each of 60 coal miners
exposed to diesel exhaust
at the beginning and end of
a work shift.

Pulmonary function of
60 diesel-exposed compared
with 90 non-diesel-exposed
coal miners over work
shift.

240 Iron ore miners matched
for diesel exposure,
smoking and age were given
bronchitis questionnaires
and spirometry pre- and
postwork shift.	
Acute reversible sensory irritation,
headache; nervous system effects,
bronchoconstriction were reported at
unknown exposures.

Eye irritation (42%), headache (37%),
dizziness (30%), throat irritation (19%),
and cough and phlegm (11%) were reported in
this order of incidence by workers exposed
in the service and repair of diesel powered
buses.

Time to onset was inversely related and
severity of eye irritation was associated
with the level of exposure to diesel
exhaust.

Three occasions of minor eye and throat
irritation; no correlation established with
concentrations of diesel exhaust
components.

Slight odor intensity, 90% perceived, 60%
objected; slight to moderate odor
intensity, 95% perceived, 75% objected;
almost 75% objected;  almost 95% objected.

In six panelists, the volume of air required
to dilute raw diesel exhaust to an odor
threshold ranged from a factor of 140 to 475.


No significant effects on pulmonary
resistance were observed as measured by
plethysmography.

FEVj, FVC, and PEFR were similar between
diesel and non-diesel-exposed miners.
Smokers had an increased number of
decrements over shift than nonsmokers.
Significant work shift decrements occurred
in miners in both groups who smoked; no
significant differences in ventilatory
function changes between miners exposed to
diesel exhaust and those not exposed.

Among underground (surrogate for diesel
exposure) miners, smokers and older age
groups, frequency of bronchitis was higher.
Pulmonary function was similar between
groups and subgroups except for differences
accountable to age.	
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    TABLE 11-11 (cont'd).  HUMAN STUDIES OF DIESEL EXHAUST EXPOSURE
      Study
         Description
                  Findings
Gamble et al.
(1979)
Gamble et al.
(1987a)
Ulfvarson et al.
(1987)
Battigelli et al.
(1964)
Gamble et al.
(1987b)
200 Salt miners performed
before and after workshift
spirometry. Personal
environmental NO2 and
inhalable particle samples
were collected.

232 Workers in four diesel
bus garages were
administered acute
respiratory questionnaires
and before and after
workshift spirometry.
Compared to lead, acid
battery workers previously
found to be unaffected by
their exposures.

Workshift changes in
pulmonary function were
evaluated in crews of roll-
on/ roll-off ships and car
ferries and bus garage
staff.  Pulmonary function
was evaluated in six
volunteers exposed to
diluted diesel exhaust, 2.1
ppm NO2, and 600 //g/m3
particulate matter.

210 Locomotive repairmen
exposed to diesel exhaust
for an average of 9.6 years
in railroad engine houses
were compared with 154
railroad yard workers of
comparable job status but
no exposure to diesel
exhaust.

283 Male diesel bus garage
workers from four garages
in two cities were examined
for impaired pulmonary
function (FVC, FEV1? and
flow rates). Study
population with a mean
tenure of 9 ± 10 years S.D.
was compared to a
nonexposed "blue collar"
population.	
Smokers had greater but not significant
reductions in spirometry than ex- or
nonsmokers. NO2, but not particulate,
levels
significantly decreased FEV1, FEF25,
FEF50, and FEF75 over the workshift.

Prevalence of burning eyes, headache,
difficult or labored breathing, nausea,
and wheeze were higher in diesel bus workers
than in comparison population.
Pulmonary function was affected
during a workshift exposure to
diesel exhaust, but it normalized after a
few days with no exposure. Decrements
were greater with increasing intervals
between exposures. No effect on pulmonary
function was observed in the experimental
exposure study.
No significant differences in VC, FEVj,
peak flow, nitrogen washout, or diffusion
capacity nor in the prevalence of dyspnea,
cough, or sputum were found between the
diesel exhaust-exposed and nonexposed
groups.
Analyses within the study populations
population showed no association of
respiratory symptoms with tenure. Reduced
FEVj and FEF50 (but not FEF75) were associated
with increasing tenure.  The study
population had a higher incidence of cough,
phlegm, and wheezing unrelated to tenure.
Pulmonary function was not affected in the
total cohort of diesel-exposed of diesel-
exposed but was reduced with 10 or more years
of tenure.
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    TABLE 11-11 (cont'd).  HUMAN STUDIES OF DIESEL EXHAUST EXPOSURE
      Study
         Description
                  Findings
Purdham et al.
(1987)
Reger et al.
(1982)
Ames et al. (1984)
Attfield (1978)
Attfield et al.
(1982)
Respiratory symptoms and
pulmonary function were
evaluated in 17 stevedores
exposed to both diesel and
gasoline exhausts in car
ferry operations; control
group was 11 on-site office
workers.
Differences in respiratory
symptoms and pulmonary
function were assessed in
823 coal miners from six
diesel equipped mines
compared to 823 matched
coal miners not exposed to
diesel exhaust.

Changes in respiratory
symptoms and function were
measured during a 5-year
period in 280 diesel-
exposed and 838 nonexposed
U.S. underground coal
miners.

Respiratory symptoms and
function were assessed in
2,659 miners from
21 underground metal mines
(1,709 miners) and nonmetal
mines (950 miners).  Years
of diesel usage in the mines
were surrogate for exposure
to diesel exhaust.

Respiratory symptoms and
function were assessed in
630 potash miners from six
potash mines using a
questionnaire, chest
radiographs and
spirometry. A thorough
assessment of the
environment of each mine
was made concurrently.	
No differences between the two groups for
respiratory symptoms. Stevedores had lower
baseline lung function consistent with an
obstructive ventilatory defect compared
with controls and those of Sydney, Nova
Scotia, residents. Caution in
interpretation is warranted due to small
sample size. No significant changes in lung
function over workshift nor difference
between two groups.

Underground miners in diesel-use mines
reported more symptoms of cough and phlegm
and had lower pulmonary function.  Similar
trends were noted for surface workers at
diesel-use mines. Pattern was consistent
with small airway disease but factors other
than exposure to diesel exhaust thought to
be responsible.

No decrements in pulmonary function or
increased prevalence of respiratory
symptoms were found attributable to diesel
exhaust. In fact, 5-year incidences of
cough, phlegm, and dyspnea were greater in
miners without exposure to diesel exhaust
than in miners exposed to diesel exhaust.

Questionnaire found an association between
an increased prevalence of cough and
aldehyde exposure; this finding was  not
substantiated by spirometry data. No
adverse symptoms or pulmonary function
decrements were related to exposure to NO2,
CO, CO2, dust, or quartz.
No obvious association indicative of diesel
exposure was found between health indices,
dust exposure, and pollutants. A higher
prevalence of cough and phlegm, but no
differences in FVC and FEVj, were found in
these diesel-exposed potash workers when
compared to predicted values from a logistic
model based on blue- collar staff working in
nondusty jobs.
                                             11-107

-------
    TABLE 11-11 (cont'd).  HUMAN STUDIES OF DIESEL EXHAUST EXPOSURE
       Study
         Description
                  Findings
Gamble et al.
(1983)
Gamble and Jones
(1983)
Edling and Axelson
(1984)
Edling et al.
(1987)
Rudell et al.
(1989,1990,1994)
Respiratory morbidity was
assessed in 259 miners in
5 salt mines by respiratory
symptoms, radiographic
findings and spirometry.
Two mines used diesels
extensively, 2 had limited
use, one used no diesels in
1956,1957,1963, or 1963
through 1967.  Several
working populations were
compared to the salt mine
cohort.

Same as above. Salt miners
were grouped into low,
intermediate and high
exposure categories based
on tenure in jobs with
diesel exposure.
Pilot study of 129 bus
company employees
classified into three
diesel exhaust exposure
categories clerks (0), bus
drivers (1), and bus garage
workers.

Cohort of 694 male bus
garage employees followed
from 1951 through 1983
were evaluated for
mortality
from cardiovascular
disease.  Subcohorts
categorized by levels of
exposure were clerks (0),
bus drivers (1), and bus
garage employees (2).

Eight healthy non-smoking
subjects exposed for 60 min
in chamber to diesel
exhaust  (3.7 ppm NO, 1.5 ppm
NO2, 27  ppm CO, 0.5 mg/m3
formaldehyde, particles
4.3 x 106/cm3). Exercise,
10 of each 20 min (75 W).
After adjustment for age and smoking, salt
miners showed no symptoms, increased
prevalence of cough, phlegm, dyspnea or air
obstruction (FEVj/FVC) compared to
aboveground coal miners, potash workers or
blue collar workers. FEVj, FVC, FEF50, and
FEF75 were uniformly lower for salt miners in
comparison to all the comparison
populations. No changes in pulmonary
function were associated with years of
exposure or cumulative exposure to
inhalable particles or NO2.


A statistically significant dose-related
association of phlegm and diesel exposure
was noted. Changes in pulmonary function
showed no association with diesel tenure.
Age- and smoking-adjusted rates of cough,
phlegm, and dyspnea were 145,169, and 93% of
an external comparison population.
Predicted pulmonary function indices showed
small but significant reductions; there was
no dose-response relationship.

The most heavily exposed group (bus garage
workers) had a fourfold increase in risk of
dying from cardiovascular disease, even
after correction for smoking and allowing
for 10 years of exposure and 15 years or more
of induction latency time.


No increased mortality from cardiovascular
disease was found among the members of these
five bus companies when compared with the
general population or grouped as sub-
cohorts with different levels of exposure.
Odor, eye and nasal irritation in 5/8
subjects. BAL findings small decrease in
mast cells, lymphocyte subsets and
macrophage phagocytosis, small increase in
PMNs.
                                            11-108

-------
     The chronic effects of exposure to diesel exhaust have been evaluated in humans in
epidemiologic studies of occupationally exposed workers. Most of the epidemiologic data
indicate the absence of an excess of chronic respiratory disease associated with exposure to
diesel exhaust. In a few of these studies, a higher prevalence of respiratory symptoms, primarily
cough, phlegm, or dyspnea was observed in the exposed workers. Reductions in several
pulmonary function parameters including FVC and FEVl3 and to a  lesser extent forced
expiratory flow at 50 and 75% of vital capacity (FEF50 and FEF75), have also been reported.
Two studies (Reger et al., 1982; Purdham et al., 1987), each with methodological problems,
detected statistically significant decrements in pulmonary function when compared with matched
controls. These two studies coupled with other reported nonsignificant trends in respiratory
flow-volume measurements suggest that diesel exhaust exposure may impair pulmonary function
among occupational populations.  A preliminary study of the association of cardiovascular
mortality and exposure to diesel exhaust found a risk ratio of 4.0. A more  comprehensive study
by the same investigators, however, found  no significant difference between the observed and
expected number of deaths due to cardiovascular disease.
     The results of the epidemiologic studies addressing noncarcinogenic health effects
resulting from exposure to diesel exhaust must be interpreted cautiously because of a myriad of
methodological problems, including incomplete information on the extent of exposure to diesel
exhaust, the presence of confounding variables (smoking, occupational exposures to other toxic
substances), and the short duration and low intensity of exposure. These limitations restrict
definitive conclusions about diesel exhaust being the cause of any noncarcinogenic health
effects,  observed or reported.

11.5.2  Effects of Diesel Exhaust on Laboratory Animals

     In short-term and chronic exposure studies, toxic effects have been related to high
concentrations of diesel particulate matter. Data from short-term exposures indicate minimal
effects on pulmonary function, even though histological and cytological changes were observed
in the lungs (Table 11-12). Exposures for  several months or longer to levels markedly above
environmental ambient concentrations resulted in accumulation of particles in the lungs,
increases in lung weight, increases in AMs and leukocytes, macrophage aggregation, hyperplasia
of alveolar epithelium, and thickening of the alveolar septa.  Similar
                                         11-109

-------
               TABLE 11-12.  SHORT-TERM EFFECTS OF DIESEL EXHAUST ON LABORATORY ANIMALS
Species/Sex
Rat, F-344, M;
Mouse, A/J;
Hamster, Syrian
Rat, F-344, M,
F; Mouse,
CD-1,M, F
Cat, Inbred, M
Rat, Sprague-
Dawley, M
Guinea Pig,
Hartley, M, F
Rat, F-344, M
Guinea Pig,
Hartley
M, F
Exposure
Period
20 h/day
7 days/week
10-13 weeks
7 h/day
5 days/week
19 weeks
20 h/day
7 days/week
4 weeks
20 h/day
7 days/week
4 weeks
20 h/day
7 days/week
4 weeks
20 h/day
5.5 days/week
4 weeks
20 h/day
7 days/week
8 weeks
Particles
(//g/m3)
1,500
0. 19 //m, MMD

210
1,000
4,400
6,400
6,400
6,800'
6,800'
6,000
6.8//m, MMD
6,300
CxT CO
Og-h/m3) (ppm)
2, 100,000 to 6.9
2,730,000

140,000 —
665,000 —
2,926,000 —
3,584,000 14.6
3,584,000 16.9
3,808,000 16.1'
3,808,000 16.7
2,640,000 —
7,056,000 17.4
NO2 SO2
(ppm) (ppm) Effects
0.49 — Increase in lung wt; increase in
thickness of alveolar walls; no
species difference
— — No effects on lung function; increase
— — in PMNs and proteases and AM
— — aggregation in both species
2. 1 2.1 Few effects on lung function; focal
pneumonitis or alveolitis
2. 49 2.10 Decreased body wt; arterial blood pH
2.76' 1.86' reduced; both vital and total lung
capacities increased
2.9 Exposure started when animals were
4 days old; increase in pulmonary
(<0.01 ppm O3)' flow; bradycardia
— — Macrophage aggregation; increase in
PMNs; Type 2 cell proliferation;
thickened alveolar walls
2.3 Increase in relative lung wt; AM
aggregation; hypertrophy of goblet
(<0.01 ppm O3)" cells; focal hyperplasia of alveolar
epithelium
References
Kaplan et al. (1982)

Mauderly et al. (1981)
Pepelkoetal. (1980d)
Pepelko(1982a)
Wiesteretal. (1980)
White and Garg (1981)
Weisteretal. (1980)
"Irradiated exhaust.
PMN = Polymorphonuclear leukocyte.
AM = Alveolar macrophage.

Source: quoted from U.S. Environmental Protection Agency (1994).

-------
histological changes, as well as reductions in growth rates and alterations in indices of
pulmonary function, have been observed in chronic exposure studies. Chronic studies have been
carried out using rats, mice, guinea pigs, hamsters, cats, and monkeys.  Reduced resistance to
respiratory tract infections has been reported in mice exposed to diesel exhaust.
     Reduced growth rates have been observed most often in studies with exposures of at least
2,000 //g/m3 diesel particulate matter which lasted for 16 h or more per day (Table 11-13).
No effects on growth or survival were noted at levels of 6,000 to 8,000 //g/m3 of PM when the
daily exposures were only 6 to 8 h/day.
     Changes in pulmonary function have been noted in a number of different species
chronically exposed to diesel exhaust (Table 11-14).  The lowest exposure levels that resulted in
impaired pulmonary function varied among the species tested but were in excess of 1,000 //g/m3.
     Histological changes occurring in the respiratory tract tissue of animal exposed chronically
to high concentrations of diesel exhaust include alveolar histiocytosis, macrophage aggregation,
tissue inflammation, increases in polymorphonuclear leukocytes, hyperplasia of bronchiolar and
alveolar Type 2 cells, thickened alveolar septa, edema, fibrosis, and emphysema (Table 11-15).
Biochemical changes in the lung associated with these histopathological findings included
increases in lung DNA, total protein, and activities of alkaline and acid phosphatase, and
glucose-6-phosphate dehydrogenase; increased synthesis of collagen; and release of
inflammatory mediators such as leukotriene  LTB and prostaglandin PGF2a. Some studies have
also suggested that there may be a threshold of exposure to diesel exhaust below which
pathologic changes do not occur. These no-effect levels were reported to be 2,000 //g/m3 for
cynomolgus monkeys, 110 to 350 //g/m3 for rats, and 250 //g/m3 PM for guinea pigs exposed for
7 to 20 h/day, 5 to 5.5 days/week for 104 to  130 weeks.
     The pathological effects of diesel exhaust particulate matter appear to be strongly
dependent on the relative rates of pulmonary deposition and clearance (Table 11-16). At particle
concentrations of about 1,000 //g/m3 or above, pulmonary clearance becomes reduced, with
concomitant focal aggregations of particle-laden AMs.  The principal mechanism of reduced
particle clearance appears to be the result of impaired AM function. This impairment seems to be
nonspecific and applies to insoluble particles deposited in the
                                         11-111

-------
                                TABLE 11-13. EFFECTS OF CHRONIC EXPOSURES TO DIESEL EXHAUST
                                          ON SURVIVAL AND GROWTH OF LABORATORY ANIMALS
Species/Sex
Rat, F-344, M, F;
Monkey,
cynomolgus, M
Rat, F344, M;
Guinea Pig,
Hartley, M

Hamster,
Chinese, M

Rat, Wistar, M


Rat, F-344, M, F;
Mouse CD-I


Rat, Wistar, F;
Mouse, MMRI, F

Rat, F-344
M, F

Rat0
F-344/Jcl.




Exposure
Period
7 h/day
5 days/week
104 weeks
20 h/day
5 days/week
106 weeks

8 h/day
7 days/week
26 weeks
6 h/day
5 days/week
87 weeks
7 h/day
5 days/week
130 weeks

19 h/day
5 days/week
104 weeks
16h/day
5 days/week
104 weeks
16 h/day
6 days/week
130 weeks



Particles
(//g/m3)
2,000
0.23-0.36 urn, MMD

250
750
1,500
0.19 urn, MMD
6,000
12,000

8,300
0.71 urn, MMD

350
3,500
7,000
0.25 urn, MMD
4,240
0.35 urn, MMD

700
2,200
6,600
110"
410"
1,080"
2,310"
3,720e
0.2-0.3 urn, MMD
CxT
(,ug-h/m3)
7,280,000


2,650,000
7,950,000
15,900,000

8,736,000
17,472,000

21,663,000


1,592,000
15,925,000
31,850,000

41,891,0000


5,824,000
18,304,000
54,912,000
1,373,000
5,117,000
13,478,000
28,829,000
46,426,000

CO
(ppm)
11.5


2.7'
4.4'
7.1'

—
—

50.0


2.9
16.5
29.7

12.5


—
—
32.0
1.23
2.12
3.96
7.10
12.9

N02
(ppm)
1.5


0.1"
0.27"
0.5"

—
—

4.0-6.0


0.05
0.34
0.68

1.5


—
—
—
0.08
0.26
0.70
1.41
3.00

S02
(ppm) Effects
0. 8 No effects on growth or survival


— Reduced body weight in rats at 1,500 //g/m3
—
—

— No effect on growth
—

— No effect on growth or mortality rates


— No effect on growth or mortality rates
—
—

1 . 1 Reduced body wts; increased mortality in
mice

— Growth reduced at 2,200 and 6,600 //g/m3
—
—
0.38 Concentration-dependent decrease in body
1.06 weight; earlier deaths in females exposed
2.42 to 3,720 //g/m3, stabilized by 15 mo
4.70
4.57

References
Lewis etal. (1989)


Schreck et al.
(1981)


Vinegar et al.
(1981a,b)

Karagianes
etal. (1981)

Mauderly et al.
(1984, 1987b)


Heinrich et al.
(1986a)

Brightwell et al.
(1986)

Research Committee
for HERP Studies
(1988)



"Estimated from graphically depicted mass concentration data.
'Estimated from graphically presented mass concentration data for NO2 (assuming 90% NO and 10% NO2).
°Data for tests with light-duty engine; similar results with heavy-duty engine.
"Light-duty engine.
'Heavy-duty engine.

Source: Quoted from U.S. Environmental Protection Agency (1994).

-------
                                     TABLE 11-14. EFFECTS OF DIESEL EXHAUST ON
                                  PULMONARY FUNCTION OF LABORATORY ANIMALS
Species/Sex
Rat, F-344
M, F
Monkey, M
Cynomolgus
Rat, F-344, M
Rat, Wistar, F
Hamster,
Chinese, M
Rat, F-344,
M, F

Hamster, Syrian
M, F
Rat, F-344;
Hamster Syrian
Rat, Wistar, F
Cat, inbred, M
Exposure
Period
7 h/day
5 days/week
104 weeks
7 h/day
5 days/week
104 weeks
20 h/day
5.5 days/week
87 weeks
7-8 h/day
5 days/week
104 weeks
8 h/day
7 days/week
26 weeks
7 h/day
5 days/week
130 weeks

19 h/day
5 days/week
120 weeks
16 h/day
5 days/week
104 weeks
19 h/day
5 days/week
140 weeks
8 h/day
7 days/week
124 weeks
Particles
(//g/m3)
2,000
0.23-0.36 urn MMD
2,000
0.23-0.36 urn, MMD
1,500
0.19 urn, MMD
3,900
0.1 urn, MMD
6,000
12,000
350
3,500
7,000
0.23-0.26 urn, MMD
4,240
0.35 urn, MMD
700
2,200
6,600
4,240
0.35 urn, MMD
6,000'
12,000"
CxT
(,ug-h/m3)
7,280,000
7,280,000
14,355,000
14,196,000-
16,224,000
8,736,000
17,472,000
1,593,000
15,925,000
31,850,000

48,336,000
5,824,000
18,304,000
54,912,000
56,392,000
41,664,000
83,328,000
CO
(ppm)
11.5
11.5
7.0
18.5
—
2.9
16.5
29.7

12.5
—
12.5
20.2
33.3
N02
(ppm)
1.5
1.5
0.5
1.2
—
0.05
0.34
0.68

1.5
—
1.5
2.7
4.4
S02
(ppm) Effects
0. 8 No effect on pulmonary function
0.8 Decreased expiratory flow; no effect on
vital or diffusing capabilities
— Increased functional residual capacity,
expiratory volume and flow
3.1 No effect on minute volume, compliance or
resistance
— Decrease in vital capacity, residual
— volume, and diffusing capacity; increase
in static deflation lung volume
— Diffusing capacity, lung compliance
— reduced at 3,500 and 7,000 ,ug/m3

1 . 1 Significant increase in airway
resistance
— Large number of pulmonary function
— changes consistent with obstructive and
— restrictive airway diseases at
6,600 /^g/m3 (no specific data provided)
1.1 Decrease in dynamic lung compliance;
increase in airway resistance
2. 1 Decrease in vital capacity, total lung
5.0 capacity, and diffusing capacity after
2 years; no effect on expiratory flow
References
Lewis et al. (1989)
Lewis et al. (1989)
Gross (1981)
Heinrich et al.
(1982)
Vinegar et al.
(1980, 1981a,b)
Mauderly et al.
(1988)
McClellan et al.
(1986)
Heinrich et al.
(1986a)
Brightwell et al.
(1986)
Heinrich et al.
(1986a)
Pepelko et al.
(1980e, 1981)
Moorman et al.
(1985)
"1 to 61 weeks exposure.
b62 to 124 weeks of exposure.

Source: Quoted from U.S. Environmental Protection Agency (1994).

-------
TABLE 11-15. HISTOPATHOLOGICAL EFFECTS OF DIESEL EXHAUST
          IN THE LUNGS OF LABORATORY ANIMALS
Species/Sex
Rat, F-344, M
Mouse A/3, M;
Hamster,
Syrian, M
Monkey,
Cynomolgus, M
Rat, F-344, M,
F
Rat, Sprague-
Dawley, M;
Mouse, A/HEJ,
M
Hamster,
Chinese, M
Hamster,
Syrian, M, F
Rat, Wistar, M
Rat, F-344, F
Rat, F-344, M,
F; Mouse CD-I,
M, F
Exposure
Period
20 h/day
7 days/week
12-13 weeks
7 h/day
5 days/week
104 weeks
7 h/day
5 days/week
104 weeks
8 h/day
7 days/week
39 weeks
8 h/day
5 days/week
26 weeks
7-8 h/day
5 days/week
120 weeks
6 h/day
5 days/week
87 weeks
8 h/day
7 days/week
104 weeks
7 h/day
5 days/week
130 weeks
Particles
(//g/m3)
1,500
0.19 urn, MMD
2,000
0.23-0.36 urn, MMD
2,000
0.23-0.36 urn, MMD
6,000
6,000
12,000
3,900
0.1 urn, MMD
8,300
0.71 urn, MMD
4,900
350
3,500
7,000
0.23 urn, MMD
CxT
Og-h/m3)
2,520,000-
2,730,000
7,280,000
3,640,000
13,104,000
6,240,000
12,480,000
16,380,000-
18,720,000
21,663,000
28,538,000
1,592,000
15,925,000
31,850,000
CO NO2 SO2
(ppm) (ppm) (ppm) Effects
— — — Inflammatory changes; increase in lung
weight; increase in thickness of
alveolar walls
11.5 1.5 0.8 AM aggregation; no fibrosis,
inflammation or emphysema
11.5 1.5 0.8 Multifocal histiocytosis;
inflammatory changes; Type II cell
proliferation; fibrosis
— — — Increase in lung protein content and
collagen synthesis but a decrease in
overall lung protein synthesis in both
species; prolyl-hydroxylase activity
increased in rats in utero
— — — Inflammatory changes; AM accumulation;
— — — thickened alveolar lining; Type II cell
hyperplasia; edema; increase in
collagen
18.5 1.2 3.1 Inflammatory changes, 60% adenomatous
cell proliferation
50.0 4.0-6.0 — Inflammatory changes; AM aggregation;
aleovar cell hypertrophy; interstitial
fibrosis, emphysema (diagnostic metho-
dology not described)
7.0 1.8 13.1 Type II cell proliferation;
Inflammatory changes; bronchial
hyperplasia; fibrosis
2.9 0.05 — Alveolar and bronchiolar epithelial
16.5 0.34 — metaplasia in rats at 3,500 and 7,000
29.7 0.68 — //g/m3; fibrosis at 7,000 //g/m3 in rats
and mice; inflammatory changes
References
Kaplan et al.
(1982)
Lewis et al.
(1989)
Bhatnagar et al.
(1980)
Pepelko(1982a)
Bhatnagar et al.
(1980)
Pepelko(1982a)
Pepelko(1982b)
Heinrich et al.
(1982)
Karagianes et
al. (1981)
Iwai et al.
(1986)
Mauderly et al.
(1987a,b)
Henderson et al.
(1988)

-------
TABLE 11-15 (cont'd). HISTOPATHOLOGICAL EFFECTS OF DIESEL EXHAUST
              IN THE LUNGS OF LABORATORY ANIMALS
Species/Sex
Rat, M, F,
F-344/Jcl.
Hamster,
Syrian, M, F
Mouse, NMRI, F
Rat, Wistar, F
Guinea Pig,
Hartley, M
Cat, inbred, M
Rat, Wistar, F


Exposure
Period
16 h/day
6 days/week
130 weeks
19 h/day
5 days/week
120 weeks
19 h/day
5 days/week
120 weeks
19 h/day
5 days/week
140 weeks
20 h/day
5.5
days/week
104 weeks
8 h/day
7 days/week
124 weeks
18 h/day
5 days/week
up to 24 mo


Particles
(//g/m3)
110'
410'
1,080'
2,310'
3,720"
4,240
4,240
4,240
250
750
1,500
6,000
6,000C
12,000"
840
2,500
7,000


CxT
Og-h/m3)
1,373,000
5,117,000
13,478,000
28,829,000
46,336,000
48,336,000
48,336,000
56,392,000
2,860,000
8,580,000
17,160,000
68,640,000
41,664,000
83,328,000
7,400,000
21,800,000
61,700,000


CO NO2 SO2
(ppm) (ppm) (ppm) Effects
1.23 0.08 0.38 Inflammatory changes; Type II cell
2.12 0.26 1.06 hyperplasia and lung tumors seen at
3.96 0.70 2.42 >400 ^g/m3; shortening and loss of cilia
7.10 1.41 4.70 in trachea and bronchi
12.9 3.00 4.57
12.5 1.5 1.1 Inflammatory changes; thickened
alveolar septa; bronchioalveolar
hyperplasia; emphysema (diagnostic
methodology not described)
12.5 1.5 1.1 Inflammatory changes; bronchio-
alevolar hyperplasia; alveolar lipo-
proteinosis; fibrosis
12.5 1.5 1.1 Thickened alveolar septa; AM
aggregation; inflammatory changes;
hyperplasia; lung tumors
— — — Minimal response at 250 and
— — — ultrastructural changes at 750 //g/m3;
— — — thickened alveolar membranes; cell
— — — proliferation; fibrosis at
6,000 A^g/m3; increase in PMN at 750
//g/m3 and 1,500 //g/m3
20.2 2.7 2.1 Inflammatory changes; AM aggregation;
33.2 4.4 5.0 bronchiolar epithelial metaplasia;
Type II cell hyperplasia; peri-
bronchiolar fibrosis
2.6 0.3 0.3 No effect on mortality. Reduced body
8.3 1.2 1.1 wt, bronchioalveolar hyperplasia, and
21.2 3.8 3.4 Inc. lung wt. at 2,500 and 7,000 ug/m3
Alveolar clearance rates reduced in all
groups at 3 mo.
BAL showed clear exposure-related
effects in all except lowest diesel
exposure group
References
Research
Committee for
HERP Studies
(1988)
Heinrich et al.
(1986a)
Heinrich et al.
(1986a)
Heinrich et al.
(1986a)
Barnhart et al.
(1981, 1982)
Vostal et al.
(1981)
Plopper et al.
(1983)
Hyde et al.
(1985)
Heinrich et al.
(1995)



-------
    Species/Sex
                           TABLE 11-15 (cont'd).  HISTOPATHOLOGICAL EFFECTS OF DIESEL EXHAUST
                                                   IN THE LUNGS OF LABORATORY ANIMALS
                     Exposure
                      Period
                    Particles
                    0/g/m3)
                   CxT
                 Qg-h/m3)
                  CO
                 (ppm)
 NO2
(ppm)
 S02
(ppm)
                                                                                                                          Effects
                                                                                                                                                   References
  Rats, M, F
  F-344/N
  Mice
  NMRI/C5L
  F
16 h/day
5 day/week
up to 24 mo
18 h/day
5 days/week
up to 24 mo
2,500
6,500
                 10.3
                 26.9
 0.73
 3.78
4,500
39,000,000
                                                                         14.2
                                                                                       2.3
          Higher mortality in males.              Nikula et al.
          Reduced                            (1995)
          body weight in males and females
          at
          6,500 ,ug/m3.  Inc lung weight in
          males and females at 2,500 and
          6,500 //g/m3.  Dose related
          increases in AM hyperplasia,
          alveolar epithelial
          hyperplasia, chronic active
          inflammation, septal fibrosis,
          alveolar proteinosis
          bronchioalveolar metaplasia,
          focal fibrosis  with alveolar
          epithelial hyperplasia,
          squamous metaplasia, and
          squamous cysts

          Reduced body weight, inc. lung         Heinrich et al.
          weight.                             (1995)
"Light-duty engine.
'Heavy-duty engine.
°1 to 61 weeks exposure.
d62 to 124 weeks of exposure.

AM = Alveolar macrophage.
PMN = Polymorphonuclear leukocyte.
Source: U.S. Environmental Protection Agency (1994).

-------
TABLE 11-16. EFFECTS OF EXPOSURE TO DIESEL EXHAUST ON THE PULMONARY
            DEFENSE MECHANISMS OF LABORATORY ANIMALS
Species
Exposure
Period
Particles
(//g/m3)
CxT
G/g-h/m3)
CO NO2 SO2
(ppm) (ppm) (ppm) Effects
Reference
ALVEOLAR MACROPHAGE STATUS
Guinea Pig,
Hartley

Rat, F-344, M




Rat, F-344, M






Rat F-344/Crl,
M, F
Mouse, CD, M,F





Rat






Rat, F-344
M, F


20 h/day
5.5 days/week
8 weeks
7 h/day
5 days/week
104 weeks


20 h/day
5.5 days/week
26, 48, or
52 weeks



7 h/day
5 days/week
104 weeks
(rat),
78 weeks
(mouse)


7 h/day
5 day/week
12 weeks




7 h/day
5 days/week
18 weeks
<0.5 urn, MMD
250
1,500
0.19 urn, MMD
2,000
0.23-0.36 urn MMD



250'
750'
1,500"
0.19 urn, MMD



350
3,500
7,000
0.25 urn, MMD




200
1,000
4,500
0.25um, MMD



150
940
4,100

220,000
1,320,000

7,280,000




715,000-
8,580,000





1,274,000°
12,740,000°
25,480,000°





84,000
420,000
1,890,000




94,500
592,000
2,583,000

2.9 — — No significant changes in absolute numbers of AMs
7.5 — —

11.5 1.5 0.81 Little effect on viability, cell number, oxygen
consumption, membrane integrity, lyzomal enzyme
activity, or protein content of AMs; decreased
cell volume and ruffling of cell membrane and
depressed luminescence of AM
2.9 — — AM cell counts proportional to concentration of
4.8 — — DP at 750 and 1,500 //g/m3; AM increased in lungs in
7. 5 — — response to rate of DP mass entering lung rather
than toral DP burden in lung; increased PMNs were
proportional to inhaled concentrations and/or
duration of exposure; PMNs affiliated with
clusters of aggregated AM rather than DP
2.9 0.05 — Significant increases of AM in rats and mice
16.5 0.34 — exposed to 7,000 //g/m3 DP for 24 and 18 mo, respec-
29.7 0.68 — lively, but not at concentrations of 3,500 or
350 //g/m3 DP for the same exposure durations; PMNs
increased in a dose-dependent fashion in both
rats and mice exposed to 3,500 or 7,000 //g/m3 DP
and were greater in mice than rats
CLEARANCE
— — — Evidence of apparent speeding of tracheal
— — — clearance at the 4,500 //g/m3 level after 1 week of
— — — 99m Tc macroaggregated-albumin and reduced clear-
ance of tracer aerosol in each of the three
exposure levels at 12 weeks; indication of a lower
percentage of ciliated cells at the 1,000 and
4,500 //g/m3 levels
— — — Lung burdens of DP were concentration-related;
— — — clearance half-time of DP almost double in
— — — 4,100 lig/m3 group compared to 150 //g/m3 group

Chen et. al.
(1980)

Castranova et al.
(1985)



Strom (1984)
Vostal et al.
(1982)




Henderson et al.
(1988)






Wolff and Gray
(1980)





Griffis et al.
(1983)



-------
oo
                          TABLE 11-16 (cont'd).  EFFECTS OF EXPOSURE TO DIESEL EXHAUST ON THE PULMONARY
                                                    DEFENSE MECHANISMS OF LABORATORY ANIMALS
Species
Rat, F-344, M





Rat, Sprague-
Dawley

Rat, F-344,
M, F






Exposure
Period
7 h/day
5 days/week
26-104 weeks



4-6 h/day
7 days/week
0.1 to 14.3 weeks
7 h/day
5 days/week
130 weeks





Particles
C"g/m3)
2,000
0.23-0.36 urn
MMD



900
8,000
17,000
350
3,500
7,000
0.25 urn, MMD




CxT
(//g-h/m3)
1,820,000-
7,280,000




2,500-
10,210,000

1,593,000
15,925,000
31,850,000





CO NO2
(ppm) (ppm)
11.5 1.5





— 5.0
— 2.7
— 8.0
2.9 0.1
16.5 0.3
29.7 0.7





S02
(ppm) Effects Reference
0.8 No difference in clearance of 59Fe3O4 particles Lewis et al.
1 day after tracer aerosol administration; (1989)
120 days after exposure tracer aerosol
clearance was enhanced; Lung burden of DP
increased significantly between 12 to 24
months of exposure
0.2 Impairment of tracheal mucociliary clearance Battigelli et al.
0.6 in a concentration-response manner (1966)
1.0
— No changes in tracheal mucociliary clearance Wolff et al.
— after 6, 12, 18, 24, or 30 mo of exposure; (1987)
— increases in lung clearance half-times as
early as 6 mo at 7,000 //g/m3 level and 18 mo at
3,500 //g/m3 level; no changes seen at 350 //g/m3
level; after 24 mo of diesel exposure, long-
term clearance half-times were increased in
the 3,500 and 7,000 //g/m3 groups
                                                                     MICROBIAL-INDUCED MORTALITY
       Mice, CD-I, F             —                 —                  —          —      —       —     No change in mortality in mice exposed
                                                                                                       intratracheally to 100 ug of DP prior to
                                                                                                       exposure to aerosolized Streptococcus sp.

       Mice CD-I, F      7 h/day                 2,000               280,000-       11.5      1.5      0.8     Mortality similar at each exposure duration
                        5 days/week                0.23-0.36        1,820,000                               when challenged with Ao/PR/8/34 influenza
                        4, 12, or             um MMD                                                     virus; in mice exposed for 3 and 6 mo, but not
                        26 weeks                                                                        1 mo, there were increases in the percentages
                                                                                                       of mice having lung consolidation, higher
                                                                                                       virus growth, depressed interferon levels and
                                                                                                       a four-fold reduction in hemaglutin antibody
                                                                                                       levels
Hatch et al.
(1985)


Hahon et al.
(1985)

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                  TABLE 11-16 (cont'd). EFFECTS OF EXPOSURE TO DIESEL EXHAUST ON THE PULMONARY
                                          DEFENSE MECHANISMS OF LABORATORY ANIMALS
Exposure Particles
Species Period (//g/m3)
Mice, CR/CD-1, F 8 h/day 5,300 to 7,900
7 days/week
2 h up to
46 weeks



CxT
Og-h/m3)
11,000-
20,350,000





CO
(ppm)
19
to
22




NO2
(ppm)
1.8
to
3.6




SO2
(ppm)
0.9
to
2.8




Effects
Enhanced susceptibility to lethal effects of
S. pyogenes infections at all exposure
durations (2 and 6 h; 8, 15, 16, 307, and 321
days); inconclusive results with
S. typhimurium because of high mortality rates
in controls; no enhanced mortality when
challenged with A/PR8-3 influenza virus
Reference
Campbell et al.
(1980, 1981)





"Chronic exposure lasted 52 weeks.
""Chronic exposure lasted 48 weeks.
"Calculated for 104-week exposure.
DP = Diesel exhaust particles.
AM = Alveolar macrophage.
PMN = Polymorphonuclear leukocyte.

Source: Quoted from U.S. Environmental Protection Agency (1994).

-------
alveolar region. Other data suggest that the inability of particle-laden AMs to translocate to the
mucociliary escalator is correlated to the average composite particle volume per AM in the lung.
Data from rats indicate that when this particle volume exceeds a critical level, impairment
appears to be initiated. Such data for other laboratory species and humans, unfortunately, are
very limited.
     There is a considerable body of evidence that the major noncancerous health hazards posed
by exposure to diesel exhaust are to the lung. These data also show that the exposures that cause
pulmonary injury are lower than those inducing detectable increases in lung tumors. These same
data further indicate that the inflammatory and proliferative changes in the lung play a key role
in the etiology of pulmonary tumors in exposed rats. A range of no adverse effect levels has
been estimated as 200-400 //g/m3 (Health Effects Institute, 1995).

11.5.3 Species Differences

     The responses to inhaled diesel exhaust as well as other particulate differs markedly among
rodents.  Data on the response to diesel exhaust for a number of species has been reviewed by
Mauderly (1994a). The data indicate that as with cancer, the non-cancer pulmonary effects of
diesel exhaust differ greatly in rats, mice and Syrian hamsters. Thus far, all animals show
epithelial proliferation with chronic high level exposure to diesel exhaust but the changes in the
respiratory bronchioles of cats differ from the changes in the alveolar ducts of rodents.  Rats
appear to have a greater epithelial proliferative response to dusts than do mice.  Guinea pigs
differ from other species in that the inflammatory response to dust is eosinophil-based rather
than neutrophil-based. Thus, it is unclear which of the animals used in inhalation studies is the
best model for predicting the responses of humans to dust exposure. Pepelko and Perrano
(1983) exposed 8 male cats to diluted DE (6000 //g/m3) for 5 days/week for 61  weeks, then to
12,000 //g/m3 for another 27 mo.  At the end of the exposure, a restrictive respiratory function
impairment with nonuniform gas distribution was observed (Moorman et al.,  1985). The
accompanying histopathology included peribronchiolar fibrosis and epithelial metaplasia in
terminal  and respiratory bronchioles (Plopper et al., 1983). The epithelial changes lessened but
the fibrosis worsened during 6 mo after the exposure ended.
                                         11-120

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     The rat is the species for which most information about the noncancer effects of diesel
exhaust (Table 11-15) as well as other inhaled dusts has been obtained. The responses of rats
chronically exposed to carbon black or diesel particulate without the organic fraction, are
essentially identical to their responses to diesel exhaust (Mauderly, 1994b; Heinrich et al., 1995).
Heinrich et al. (1995) also demonstrated that the noncancer responses of rats to titanium dioxide
were also similar qualitatively and quantitatively. Muhle et al. (1991) reported that the
responses to chronically inhaled copying toner, a plastic dust pigmented with carbon black,
titanium dioxide and silica were also similar qualitatively to titanium dioxide and diesel exhaust.
Similar responses resulting from chronic exposure of rats to a range of other dusts including oil
shale dusts (Mauderly et al., 1994b), talc (National Toxicology Program,  1993), and coal dust
(Martin et al.,  1977) have been described.
     Few studies have examined the effects of exposure to diesel exhaust mixed with other
dusts.  The response of rats chronically exposed to diesel exhaust soot and mineral dust was
studied by Mauderly et al. (1994b).  Male and female F344 rats were exposed 7 hours/day
5 days/week for 30 mo to diesel exhaust, raw or retorted oil shale dust, or additive combinations
of diesel exhaust and shale dust. The diesel exhaust soot accumulated more rapidly in the lungs
than did the shale dust, due to differences in particle  size, but the lung burdens  of the two types
of dust were additive. The long-term effects on lung weight and density,  and BALF
constituents, were greater than additive, the effects on respiratory function were approximately
additive, and the effects  on particle clearance were less than additive.  The noncancer health
effects of the combined exposures were more closely correlated with the total lung dust burden
than with the combined dust exposure concentrations.
     Lewis et al. (1989) studied the effects of diesel  exhaust and mineral  dust in rats and
cynomolgus monkeys exposed to either diesel exhaust or coal dust at 2,000 //g  respirable
particles/m3, or to a combination of 1,000 //g/m3 of each material. Lung burdens of the dusts
were approximately additive in rats but were not measured in the monkeys. Local
histopathological responses were similar and approximately additive for the two dusts in both
species.
                                         11-121

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11.5.4  Effects of Mixtures Containing Diesel Exhaust

     Mauderly (1993) reviewed the results of studies in which laboratory animals were exposed
to complex mixtures. In a study of diesel and coal dust, rats were exposed for 24 mo to
atmospheres containing diesel exhaust at 2000 //g/m3 coal dust at the same concentration, and a
combination of diesel exhaust and coal dust at 1000 //g/m3 each. Among the health end points
evaluated, the effects of diesel exhaust and coal dust were similar with coal dust being slightly
less toxic. No synergistic interactions between the exposure materials were noted. In another
study of diesel and shale oil dust, Mauderly et al. (1994b) exposed rats by inhalation for 7 h/day
5 days/week for up to 30 mo to raw or retorted oil shale dusts at 5,000 //g/m3, to diesel exhaust
at 3,500 //g/m3 or to additive combinations at total particulate concentrations of 8,500 //g/m3.
The three agents all accumulated progressively in the lungs and caused similar pneumoconiotic
responses.  The magnitude of effects was more closely correlated to particle lung burdens  than
to exposure concentrations.  The effects of diesel exhaust and shale dusts generally were less
than additive for delay of particle clearance; additive for respiratory function impairment; and
greater than additive for lung collagen, airway fluid indicators of inflammation, and lung
tumors.
     Mauderly (1989) discussed the susceptibility of the aging lung to inhaled pollutants.
Although the data is extremely limited in that only two particulate pollutants are discussed, it
appears that the aging lung might be more sensitive to  particulate pollution. Rats were exposed
repeatedly for 6 mo to diluted, whole diesel exhaust at a concentration of 3,500 //g/m3.  The
results indicated that rats exposed between 6 and 12  mo were more sensitive then rats born in the
chambers and exposed up to 6 mo of age.  The results indicated that mice exposed as adults were
more susceptible than mice exposed at the onset of breeding age but while  lung maturation was
still underway.

11.5.5  Particle Effect in Diesel Exhaust Studies

     Diesel PM is composed of an insoluble carbon core with a surface coating of relatively
soluble organic constituents. Studies of diesel particle composition have shown that the
insoluble carbon core makes up about 80% of the particle mass and that the organic phase
                                         11-122

-------
can be resolved into a more slowly dissolving component and a more quickly dissolving
component.
     The relative contribution of the carbon core of the diesel particles versus organics adsorbed
to the surface of the particles to cancer induction and the uncertainty involved has been reviewed
(Health Effects Institute, 1995).  The primary evidence for the importance of the adsorbed
organics is the presence of known carcinogens among these chemicals.  These include poly cyclic
aromatics as well as nitroaromatics.  Organic extracts of particles have also been shown to
induce tumors in a variety of injection, intratracheal instillation and skin painting studies, and
Grimmer et al. (1987) has, in fact, shown that the great majority of the carcinogenic potential
following intratracheal  instillation resided in the fraction containing four- to seven-ring PAHs.
     Evidence for the importance of the carbon core is provided by studies of Kawabata et al.
(1986), that showed induction of lung tumors following intratracheal  instillation of CB that
contained no more than traces of organics and studies of Heinrich et al. (1995) that indicated that
exposure via inhalation to CB (Printex 90) particles induced lung tumors at concentrations
similar to those effective in diesel studies. Other particles of low solubility such as titanium
dioxide (Lee et al., 1986) have also been shown to induce lung tumors, although at much higher
concentrations than necessary for carbon particles or diesel exhaust.  Pyrolyzed pitch, on the
other hand, essentially lacking a carbon core but having PAH concentrations at least three orders
of magnitude greater than diesel exhaust, was no more effective in tumor induction than was
diesel exhaust (Heinrich et al., 1986b).  These studies suggest that the insoluble carbon core of
the particle is at least as important as the organic components and possibly more so for lung
tumor induction at high particle concentrations (>2,000 //g/m3).
     Diesel soot and carbon black appear to elicit similar responses in animal inhalation studies
(Mauderly et al., 1994a; Heinrich et al., 1995; Nikula et al., 1995). Macrophage accumulation,
epithelial histopathology, and reduced clearance have been observed in rodents exposed to high
concentrations of chemically inert particles (Morrow, 1992), furthering the possibility that the
toxicity of diesel particles results from the carbon core rather than the associated organics.
However, the organic component of diesel particles consists of a large number of poly cyclic
aromatic hydrocarbons and heterocyclic compounds and their
                                         11-123

-------
derivatives.  A large number of specific compounds have been identified. These components of
diesel particles may also be responsible for the pulmonary toxicity of diesel particles. It is not
possible to separate the carbon core from the adsorbed organics in order to compare the toxicity.
As an approach to this question, a study has been performed in which rats were exposed to either
diesel exhaust or to carbon black, an inert analog of the carbon core of diesel particles.  Rats
were exposed for 16 h/day,  5 days/week, for up to 24  mo to either 2,500 or 6,500 //g/m3 of either
particle (Nikula et al., 1995). Although the study is primarily concerned with the role of particle
associated organics in the carcinogenicity of diesel exhaust, non-neoplastic effects are also
mentioned. Both diesel exhaust and carbon black exposure resulted in macrophage hyperplasia,
epithelial hyperplasia, bronchiolar-alveolar metaplasia, and focal fibrosis. In general, the
number and intensity of the lesions seems to correspond to the exposure time and concentration
and that the morphological characteristics of the lesions were similar in the animals exposed to
diesel and to carbon black.  The results suggest that the chronic noncancer effects of diesel
exhaust exposure are caused by the persistence of the  insoluble carbon core of the particles,
rather than by the extractable organic layer.  These studies have been reviewed (Health Effects
Institute, 1995) and the consensus is that particulate matter is primarily responsible for the rat
lung response to diesel  exhaust.

11.5.6 Gasoline Engine Emissions

     Mauderly (1994c) reviewed the toxicological and epidemiological evidence for health risks
from inhaled gasoline engine emissions.  Although the data bank is more extensive for diesel
exhaust, animal studies have shown that heavy, chronic exposure to gasoline engine exhaust can
cause lung pathology and associated physiological effects.
     In female beagle dogs exposed to gasoline engine exhaust for over 5 years (16 h/day,
7 days/week) there was little effect on respiratory function during the exposure.  However,
subsequent tests revealed increases in lung volumes, dead space ventilation, and dynamic lung
compliance, and a decrease in alveolar-capillary gas exchange  efficiency (Hyde et al., 1978).
There were also slight but distinct histopathological changes in the tracheobronchial  and alveolar
regions.
                                         11-124

-------
     The effects of gasoline engine exhaust on the lungs of rodents were evaluated in a series of
studies in rats and Syrian golden hamsters exposed for up to 24 mo to two dilutions of gasoline
engine exhaust with particle concentrations of approximately 50 or 100 //g/m3 (Bellman et al.,
1983; Muhle et al., 1984; Heinrich et al., 1986a).  While gasoline engine exhaust did not cause
any substantial histopathology or alterations of lavage fluid in either species, gasoline engine
exhaust in the higher concentration increased lung weight, retarded particle clearance, reduced
lung compliance, and increased acetylcholine sensitivity in rats.  No significant changes in
function were found at either concentration in the hamster, or at the lower concentration in the
rat. In rats and hamsters exposed to gasoline engine exhaust and diesel engine exhaust (16
h/day, 5 days/week, for 24 mo), there were no significant changes in respiratory function
(Brightwell et al., 1989).
     While the laboratory animal toxicological data base is limited there is some indication that
long term exposure to gasoline engine exhaust can produce effects on the respiratory tract. It is
unclear to what extent the other constituents of gasoline engine exhaust may have contributed to
the effects.

11.5.7 Summary

     In summary, diesel particulate is a widespread pollutant that is present in low
concentrations in the ambient atmosphere (1 to 6 //g/m3 in Los Angeles). Data from
occupational  studies and laboratory animal studies indicate that acute exposures to high levels or
chronic exposures to low levels (albeit high compared to ambient levels) of diesel particulate can
have an effect on the respiratory tract. However, it is doubtful that the diesel particulate at
concentrations present in the ambient atmosphere could have a significant effect.
     Acute and chronic inhalation exposures to diesel particulate are associated with respiratory
effects.  However, in general, the levels used in the laboratory animal studies or experienced in
occupational  settings are considerably higher than those experienced in the ambient environment
and the results of these studies provide little insight into the morbidity and mortality studies
discussed in Chapter 12.  This is not unexpected because of the patterns of exposure and the total
exposures,  as well as differences in the populations exposed.  Some of the effects noted in the
occupational  studies such as respiratory tract irritation, bronchitis,
                                          11-125

-------
impaired pulmonary function, cough, wheezing, are also observed in the epidemiological studies
discussed in Chapter 12. Although these responses were specific to diesel exhaust, the effects
appear to be due to the particles, per se. However, these effects are evident at exposures much
higher than those experienced in the ambient atmosphere.  Accordingly, the toxicological studies
of specific diesel particulate do not appear to provide insight into the effects observed in the
epidemiological studies discussed in Chapter 12 which relate to PM in general.
11.6  SILICA
     This section on silica particle toxicity is designed to give an overview of current concepts
regarding the pulmonary toxicity of these environmental pollutants as they relate to different
species, different polymorphs (crystalline vs. amorphous), and biological mechanisms of action.
No attempt has been made to review all of the relevant animal   toxicity data, which is
voluminous.  Silica is well established as a fibrogenic pollutant which causes lung tumors
following chronic exposures in rats.  A review of the literature on the effects of silica can be
found elsewhere (U.S. Environmental Protection Agency,  1996).
      The pulmonary response to inhaled silica has long been considered to be a major
occupational hazard, causing disability and deaths among workers in a variety of industries.
Some of the processes and work environments which are frequently associated with silica
exposure include mining, sandblasting of abrasive materials, quarrying and tunneling,
stonecutting, glass and pottery manufacturing, metal casting, boiler scaling, and vitreous
enameling (Ziskind et al., 1976).

11.6.1 Physical and Chemical Properties of Silica

     Silica is one of the most common substances to which workers are exposed. Silica particle
emissions in the  environment can arise from natural, industrial, and farming activities.  There are
only limited data on ambient air concentrations of either crystalline or amorphous silica
particles, due in part, to the limits in accurately quantifying crystalline silica and to the inability,
under existing measurement methods, of separating the identity of crystalline silica from other
particulate matter.  Davis et al., (1984) used radiographic
                                         11-126

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diffraction to determine the inhalable composition and concentration of quartz in ambient
aerosols collected on dichotomous filters at 25 U.S. metropolitan areas. They reported the
average weight percentage of quartz in the coarse and fine particle mass to be 4.9 (+ 2.3) and 0.4
(+ 0.7), respectively. Combining the weight percentage data for the coarse fraction and 7 year
average annual arithmetic mean PM10 information available for 17 of the 25 areas, annual
average and high U.S. ambient quartz levels of 3 and 8  //g/m3, respectively,  have been estimated
(U.S. Environmental Protection Agency, 1996).  The actual fraction of quartz in PM10 samples
may be slightly lower than that which was estimated by Davis et al. (1984) in the coarse fraction
of dichotomous filters.  However, these estimated U.S.  levels are considered to be reasonable
upper bound estimates (U.S. Environmental Protection  Agency, 1996). There are at least four
polymorphs or forms of crystalline silica dust. These include quartz, cristobalite, tridymite and
tripoli. Although identical chemically, they differ in their crystal parameters. The basic
structural units of the silica minerals are silicon tetrahedra, arranged in such a manner so that
each oxygen atom is common to two tetrahedra. However, there are considerable differences in
the arrangement of the silicon tetrahedra among the various crystalline forms of silica (Coyle,
1982). Naturally occurring rocks that contain amorphous forms of silica include diatomite or
diatomaceous earth, a hydrate form such as opal, and an unhydrated form, flint (Stokinger,
1981b). Silica is also a component of many naturally occurring silicate minerals in which
various cations and anions are substituted into a crystalline silica matrix.  Examples of such
silicates are kaolin, talc, vermiculite, micas, bentonite, feldspar, asbestos, and Fuller's earth
(Silicosis and Silicate Disease Committee, 1988). Commonly encountered synthetic amorphous
silica, according to their method of preparation, are SiO2 gel (silica G), precipitated SiO2 (silica
P), and fumed SiO2 (silica F). The most outstanding characteristics of synthetic amorphous
silica compounds are their particle size and high  specific surface area, which determine their
numerous applications (Stokinger, 1981b).

11.6.2 Health Effects of Silica

     The  causal relationship between inhalation of dust containing crystalline silica and
pulmonary inflammation and the consequent development of silica-induced  pulmonary fibrosis
(i.e., silicosis) is well established (Spencer, 1977; Morgan et al., 1980; Bowden,
                                         11-127

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1987). During the acute phase of exposure, a pulmonary inflammatory response develops and
may progress to alveolar proteinosis and a granulomatous-type pattern of disease in rats and
other rodent species.  A pattern of nodular fibrosis occurs in chronically exposed animals and
humans (Ziskind, 1976; Spencer, 1977; Morgan et al., 1980; Bowden, 1987). Although there is
experimental evidence that quartz can also cause lung cancer, a clear correlation between
pulmonary fibrosis and neoplasia has been suggested but has not been definitively established.
Acute high occupational exposures can elicit a rapid onset of lung inflammation, leading to
serious, if not fatal, lung dysfunction.
     The pulmonary pathological effects of inhaled crystalline silica are well established,
however, there is a paucity of information on the effects of inhaled amorphous forms of silica on
the respiratory tract.  The limited toxicological information available suggests that the
respiratory tract effects following exposures to amorphous silicates may be reversible in the
absence of continuing exposures (Groth et al., 1981; Schepers, 1981; Goscicki et al., 1978;
Pratt,  1983).  Thus, current evidence suggests that synthetic amorphous silica is not as severe a
hazard as the various polymorphs of crystalline silica.
     Parameters which have been commonly used to assess the respiratory effects of silica
exposure in experimental animals include lung weight, development of pulmonary fibrosis, or
biomarkers for fibrosis, such as collagen content, cytotoxicity, pulmonary inflammation,
biochemical indices of homogenized lung samples or bronchoalveolar lavage samples, and
immunologic responses. Few studies have provided exposure dose-response data from which
definitive effect levels could be derived, thus necessitating comparisons among studies in which
experimental conditions may vary considerably. A review of the published laboratory animal
toxicology studies is available (U.S. Environmental Protection Agency, 1996).

11.6.3 Differences Between Chemical Forms of Silica

     A few  studies have been carried out to compare the effects of inhaled crystalline and
amorphous silica particulates (see Table 11-17). Pratt (1983) exposed guinea pigs for 21  to 24
mo to atmospheric suspensions of either cristobalite crystalline silica, amorphous diatomaceous
earth, or to amorphous volcanic glass. The index of lung pathogenicity was substantially higher
for the cristobalite-exposed animals compared to the other two polymorphs of amorphous silica
particles (Pratt, 1983). Hemenway et al. (1986) exposed
                                         11-128

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            TABLE 11-17. COMPARATIVE INHALATION TOXICITY STUDIES WITH DIFFERENT SILICA POLYMORPHS
to
VO
Particle

Cristobalite

Diatomaceous earth
(amorphous)

Volcanic glass
(amorphous)
Cristobalite


Alpha-quartz

Amorphous silica
(Zeofree 80)
Fumed silica




Precip. silica

Gel silica
Cristobalite

Alpha-quartz
(Mm-U-Sil)

Amorphous silica
(Zeofree 80)

Ludox
(Colloidal silica)
Species, Gender

Guinea pig (GP)

Same


Same

Male Fischer
344 rats

Same

Same

Male SD rats
Male Hartley GP
Male cynomolgus monkeys

Same

Same

Male SD rats

Same


Same


Same

Mass Concentration

151,000//g/m3

100,000 ^g/rn3


>151,000//g/m3

58,000 & 73,000 //g/m3


36,000 & 81, 000 //g/m3

30,000 Mg/m3

1 5,000 ,ug/m3




Same

Same
1 0,000 or 100,000 //g/m3

10,000, 50,000 or 100,000
//g/m3


10,000 or 1 00,000 ,ug/m3


10,000, 50,000 or 150,000
Exposure
Duration
7-8 h/d
5.5 d/wk
2 1-24 mo




6 h/d
8 days





5. 5-6 h/d
5 d/wk
up to 18 mo


Same

Same
6 h/d for 3 days

6 h/d for 3 days


6 h/d for 3 days


6 h/d for 2 or 4 wk

Observed Effect References

Total amount of silica Pratt et al. (1983)
accum. varied inversely
with the pulmonary tissue
damage. Cristobalite
produced the greatest
pulmonary effects.

Cristobalite produced the Hemenway et al. (1986)
most dramatic
inflammation and fibrotic
response. Amorph. silica-
transient inflamm. AQ
initial mild response but
progressive.
Monkeys developed greater Groth et al. (1981)
response to fumed silica
than rats or guinea pig.
Fumed silica produced
greater fibrotic and
pulmonary function
effects compared to gel or
ppt. silica
Exposures to Cristobalite Warheit et al. (1995)
or AQ produced persistent
and progressive pulmonary
inflammation and I
biomarkers of
cytotoxicity. Ludox and
amorphous silica elicited
transient pulmonary
inflammatory responses.


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rats for 8 days to aerosols of one of three silicon dioxide species, a-cristobalite, a-quartz, and
amorphous silica particulates. The greatest measure of lung injury was produced with
cristobalite, which caused substantial inflammation and fibrosis. Exposures to a-quartz
produced mild but progressive effects, while amorphous silica produced transient inflammation.
Warheit and coworkers carried out a number of short-term inhalation studies using cristobalite,
(a-quartz Min-U-Sil), Ludox colloidal silica, a form of precipitated amorphous silica, and
amorphous silica. Rats were exposed to silica aerosols for periods ranging from 3 days to 4
weeks and evaluated by bronchoalveolar lavage and cellular proliferation indices at several
postexposure time periods. Brief exposures to 2 different forms of crystalline silica particles at
100 //g/m3 produced persistent pulmonary inflammation characterized by neutrophil recruitment
and elevated biomarkers of cytotoxicity in BAL fluids. Progressive histopathologic lesions
previously were observed within 1 mo after a 3-day exposure (Warheit et al., 1991a). In
contrast, a 3-day exposure to amorphous  silica, produced transient lung inflammation, and 2 or
4-week exposures to Ludox elicited pulmonary inflammation at 50,000 or 150,000 //g/m3 but not
at 10,000 //g/m3; most elevated biochemical effects were reversible. These results demonstrated
that the crystalline forms of silica dust were substantially more potent in producing pulmonary
toxicity compared to the amorphous or colloidal forms of silica (Warheit et al., 1991a, 1991b,
1995). In addition, the pulmonary effects of inhaled (a-quartz particles in rats were much more
potent than in the study reported by Hemenway and coworkers (1986).

11.6.4  Species Differences

     The fibrogenic effects of crystalline silica exposure may vary depending  on the species
used in experimental studies. Rats appear to be more sensitive to the development of
silica-induced lung injury and lung tumors in comparison to other rodent species such as mice
and hamsters (Saffioti, 1992; Saffioti et al., 1993; Uber and McReynolds,  1982). Warheit et al.,
(1994) reported that inhalation exposure to silica in complement-normal and
complement-deficient mice produced an acute pulmonary inflammatory response which was
mild and transient, compared to the pulmonary effects observed in rats wherein silica produced a
sustained and progressive pulmonary inflammatory response.  In support of these results, mice
intratracheally injected with silica particles had a milder fibrogenic response
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when compared with rats (Hatch et al., 1984).  It seems clear, however, that the silica-induced
response in mice depends upon the strain, as there appear to be low and high responding strains
of mice to silica (Callis et al., 1985; Hubbard, 1989).
     Differences are not only apparent across and within rodent species, but also between
rodents and humans.  Unlike the nodules observed in human radiographs, silicosis is manifested
in rat radiographs as a diffuse "haziness", described as a ground-glass appearance with some
peripheral striation (Kutzman, 1984). In a chronic study by Muhle et al. (1989), the principal
non-neoplastic finding in the silica-exposed rats, extensive subpleural and peribronchiolar
fibrosis, was described as being unlike the nodular fibrosis observed in human silicosis.  Such
interspecies differences and the fact that most of the available laboratory studies only examined
one dose level may limit the utility of laboratory animal data for extrapolation of the silicosis
risk observed in higher exposure conditions of human occupational studies.
     For additional information on the pathogenic development of silica-related lung disease in
humans and experimental animals, the reader is referred to a variety  of informative reviews
(Ziskind et al., 1976; Spencer, 1977; Reiser and Last,  1986; Bowden, 1987; Crouch, 1990;
Goldstein and Fine, 1986; Warheit and Gavett, 1993).
11.7  BIOAEROSOLS
11.7.1 Types of Health Effects Associated with Bioaerosols

     Exposure to biological aerosols can produce three general classes of health effects:
infections, hypersensitivity disease, and toxicoses.  It is possible that these afflictions may make
people more susceptible to air pollutant effects.

11.7.1.1  Infections
     Infections result when a living (micro)organism invades another organism, multiplies using
some component of the host as a nutrient source, and either directly (via digestion) or indirectly
(via release of toxins) causes disease. The number of individual living particles required to
cause disease depends on the virulence (ability to invade the host) of the organism, and on the
status of the host's immune system (Pennington, 1989).  The organisms
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that most commonly cause infectious disease are viruses (e.g., influenza, measles, common
colds) and bacteria (e.g., Legionnaires' disease, tuberculosis). A few fungi can also cause
infections in healthy people (e.g., Histoplasma capsulatuni) or those with damaged immunity
(Q.g.,Aspergillusfumigatus) (Rippon, 1988).
     Particle size is an important consideration for disease.  Some agents can only cause
infection in the upper respiratory tract, and are best transmitted via large droplets (many
common colds).  Others must reach the lower airway to cause infection, and large droplets that
impact in the upper airway are not usually part of the disease process (e.g., Mycobacterium
tuberculosis) (Burge, 1989).  Infectious aerosols must remain alive and be able to invade and
replicate in the host in order to cause disease.  Over time, infectious aerosols decay physically
(becoming less concentrated) and biologically (each remaining cell becoming less able to cause
disease). Airborne infectious diseases are generally caused by relatively resistant organisms that
are highly virulent (Cox, 1987).

11.7.1.2  Hypersensitivity Diseases
     Hypersensitivity diseases are caused by exposure to allergens (a specific type of antigen)
and result from specific responses of the immune system (Pope et al., 1993). They are always
caused by two step processes. Initial exposures induce sensitization (i.e., cause the production of
circulating or fixed immune cells that recognize the agent), and subsequent exposures precipitate
symptoms (the agent reacts with the specific immune cell and releases mediators such as
histamine that result in overt symptoms).  Thus the first exposure to a sensitizing agent does not
cause symptoms.  The kinds of hypersensitivity diseases that are caused by bioaerosols include
asthma, allergic rhinitis and (rarely) allergic dermatitis (the "immediate" or IgE-mediated
diseases), and hypersensitivity pneumonitis (also called allergic alveolitis) which is mediated
primarily by the cellular immune system. Approximately 30% of the US population is affected
by IgE-mediated allergies. The incidence of hypersensitivity pneumonitis remains unknown.
Farmer's lung disease (a form of the disease) probably occurs in less than 3% of the farm
population.
     Very little good data have been accumulated on the actual doses of an allergen (the agent
that stimulates the response) required for either sensitization or symptom  development. For the
IgE-mediated diseases, relatively low level long-term exposure is considered to be
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important for sensitization and higher levels are needed to precipitate symptoms. For
hypersensitivity pneumonitis, intense short term exposures may result in sensitization, while
very low levels may induce symptoms.
     Any allergen could probably cause either type of disease depending on the conditions of
exposure. Pollen and fungal allergens are well-known agents that precipitate hay fever and
asthma symptoms, while proteins released from dust mite fecal particles are apparently highly
effective sensitizers.  Historically, the agents most commonly associated with hypersensitivity
pneumonitis are the thermophilic actinomycetes.  In addition, fungal spores,  bird droppings,
bacterial enzymes, and other agents have been reported to cause the disease.
     Allergen-bearing particles that induce IgE-mediated disease range in size from <0.1 //m
(cat secretions) to 60 //m (some grass pollen).  Apparently allergen-bearing particles must be <5
//m in order to cause hypersensitivity pneumonitis. In both diseases, there may be synergistic
effects between allergens and irritants (i.e., endotoxin, chemical air pollutants) with respect to
sensitization. Note that allergens are always water soluble, and must diffuse out of the allergen-
bearing particle before inducing their effect. It is likely, then, that the larger the particle, the
more slowly the allergen exposure, and hence the response, will occur.

11.7.1.3   Toxicoses
     Microbial toxins are (essentially) chemicals that are produced by living organisms. The
microbial toxicoses are basically similar to the comparable diseases caused by non-biological
toxins. Microbial toxins are known that are mutagenic, teratogenic, tumorigenic, and cytotoxic.
In addition, some (like endotoxin) have adjuvant activity (i.e., they stimulate the immune
system).
     Exposure/response relationships for biological toxins are poorly known with the possible
exception of endotoxin. Endotoxin clearly affects pulmonary function and at high levels may
cause serious disease (Burge, 1995).  Organic dust toxic syndrome has been associated with
massive exposure to endotoxins (along with mycotoxins and other components of grain dust).
The incidence of the  disease (the percent of the farm worker population with at least one attack)
ranges from 1% in Sweden to up to 44% in the United States (Do Pico, 1992).  Grain dust also
causes a less acute disease with prolonged
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exposures at relatively low exposure levels.  Whether a component of the grain itself or of
contaminating bacteria or fungi is actually the toxic agent remains unknown.
     Mycotoxin-related lung disease remains poorly documented. There is some evidence that
exposure to Aspergillus flavus aerosols containing aflatoxin Bl is a risk for lung and esophageal
cancer in peanut handlers (Sorenson et al., 1984) and in farmers handling moldy corn (Baxter et
al., 1981). Exposure to trichothecene toxins contained in Stachybotrys atra has been blamed for
central nervous system symptoms, skin rashes, and pulmonary hemorrhages in specific cases,
although in all cases, exposure was inferred rather than measured (Croft et al., 1986).
     Particle sizes required for disease related to biological toxin exposure depend on the nature
of the disease. Pulmonary effects of endotoxin probably require pulmonary deposition, while
systemic effects could be precipitated by larger particles impacting in the upper airway.  The
fungal spores that have been blamed for mycotoxin-induced airway disease range from about 3
to 5 (j,m in diameter. The location of the mycotoxins in fungal spores is unknown. The toxins
may not be present on the surface of particles, and, in some cases,  must be released from the
particle to be effective. Endotoxin is a part of the outer cell wall.

11.7.2 Ambient Bioaerosols
     Ambient bioaerosols include fungal spores, pollen, bacteria, viruses, endotoxins, and
animal and plant debris.  Bacteria, viruses and endotoxins are mainly found attached to aerosol
particles, while entities in the other categories are found as separate particles. Data for
characterizing ambient concentrations and size distributions of bioaerosols are sparse.  Matthias-
Maser and Jaenicke (1994) found that bioaerosols constituted about 30% of the total number of
particles in samples collected on a clean day in Mainz, Germany. The proportion of particles
that were bioaerosols was higher in the fine size mode (as much as a third) and slightly lower in
the coarse size mode.  In Brisbane, Australia, Glikson et al. (1995) found that fungal spores
dominate the bioaerosol  count in the coarse fraction of PM10 and that the overall contribution of
bioaerosols to total PM10 particulate mass was on the order of 5 to 10%. However, the
cytoplasmic content of spores and pollen was often found to be adhered to particles emitted by
motor vehicles and particles of crustal origin.
                                         11-134

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     Fungal spores range in size from 1.5 jim to > 100 |im, although most are 2 to 4 jim MMAD.
They form the largest and most consistently present component of biological aerosols in ambient
air. Levels vary seasonally, usually being lowest when snow is on the ground.  Fungal spores
often reach levels of 1000 to 10,000 spores/m3 during the summer months (Lacey and
Dutkiewicz, 1994; Madelin, 1994) and may be as high as 100,000/m3 near some anthropogenic
sources (agriculture activities, compost, etc.).
     Asthma mortality has been associated with ambient levels of fungal spores, unadjusted OR
of 2.16 (95% CI = 1.31 to 3.56) per increment of 1000 spores/m3; controlling for time and pollen
counts reduced the RR to 1.2 (95% CI = 1.07 to 1.34) (Targonski et al., 1995). Asthma
mortality in Scotland shows a seasonal peak that follows the peak in ambient pollen levels
(MacKay et al., 1992).  Exposure to fungal spores has also been identified as a possible
precipitating factor in respiratory arrest in asthmatics (O'Hollaren et al., 1991).  Such exposure
can lead to  allergic alveolitis (hypersensitivity pneumonitis) or pulmonary mycoses such as
coccidioidomycosis or histoplasmosis (Lacey and Dutkiewicz, 1994).
     Bioaerosols can contribute to increased mortality and morbidity. Most commonly,
bioaerosols appear to exacerbate allergic rhinitis and asthma. Induction of hypersensitivity
generally requires exposure to concentrations that are substantially higher than in ambient air,
although subsequent antigenic responses require much lower concentrations. Association of
fungal and pollen spores with exacerbations of asthma or allergic rhinitis is well established
(Ayres, 1986) and fungal spore levels may be associated with asthma mortality (Targonski et al.,
1995). The incidence of many other diseases (e.g., cocci dioidomycosis) induced by fungal
spores is relatively low, although there is no doubt about the causal organisms (Lacey and
Dutkiewicz, 1994). The potential for fungal induced diseases is much higher in
immunocompromised patients and those with unusually high exposures, such as military
personnel.
     In addition to fungal spores and pollen, other bioaerosol material can exacerbate asthma
and can also induce responses in nonasthmatics. For example, in grain workers who experience
symptoms,  spirometry decrements, and airway hyperresponsiveness in response to breathing
grain dust, the severity of responses is associated with levels of endotoxin in the bioaerosol
rather than the total dust concentration (Schwartz et al., 1995).  A classic series of studies (Anto
and Sunyer, 1990) proved that airborne dust from soybean husks was
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responsible for asthma epidemics and increased emergency room visits in Barcelona, Spain.
These studies indicate that airborne fragments of biological substances can produce severe health
effects.
     Bacterial aerosol counts may range as high as 30,000 bacteria/m3 downwind of sewage
treatment facilities, composting areas, waterfalls from polluted rivers, or certain agricultural
activities. Typical levels in urban areas range from several hundred to several thousand
bacteria/m3 (Lighthart and Stetzenbach, 1994).  Human pathogenic activity of such bacteria is
not well understood or characterized.  Infective potential of aerosolized bacteria depends on size
(smaller are more effective), virulence, host immune status, and host species sensitivity (Salem
and Gardner,  1994). Aerosolized bacteria can cause bacterial infections of the lung including
tuberculosis and legionnaire's disease. The Legionella pneumophila bacterium is one of the few
infectious agents known to reside outside an infected host and is commonly found in water,
including lakes  and streams.  Levels of bioaerosols (fungi and bacteria) are generally higher in
urban than in rural areas (Lighthart and  Stetzenbach, 1994).
     Exposures to bioaerosols of the above types, while clearly capable of producing serious
health effects (especially at high concentrations often encountered in indoor environments)
appear unlikely to account for observed ambient (outdoor) PM effects on human mortality and
morbidity demonstrated by epidemiology studies reviewed in Chapter 12.  This conclusion is
based on (1) bioaerosols generally represent only a very small percentage (< 5 to 10%) of
measured urban ambient PM mass; (2) they typically have even lower concentrations in ambient
air during winter months, when notable  ambient PM effects have been demonstrated; and they
tend to be in the coarse fraction size range.

11.8  TOXICOLOGY OF OTHER PARTICULATE MATTER
11.8.1  Introduction

     This section reviews the toxicology of other PM within the framework described in the
introduction to the chapter. The particle classes chosen for inclusion here are those which may
actually occur in ambient air or may be  surrogates for these. For example, some of the particles
discussed are considered to be models of "nuisance" or "inert" dusts (i.e., those having low
intrinsic toxicity) and, as such, are likely to be representative of similar ambient
                                         11-136

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PM. In many instances, there are only a few studies examining the response on specific
biological endpoints following inhalation exposure.  In these cases, and where available,
intratracheal instillation studies have been used to compare the toxicity of different particle
types.  While instillation may produce more severe pulmonary damage than would inhalation
(largely due to differences in delivered doses and dose rates), the relative toxicities of different
particles seem to be similar when given by either method  (Driscoll et al., 1991). Thus,
intracheal instillation studies can be used for comparative  potency purposes, but it is not possible
to quantitatively extrapolate the resulting exposure-response data to inhalation exposure-
responses.  In a number of cases, particles with low intrinsic toxicity have been  used in
instillation studies to delineate nonspecific particle effects from effects of known toxicants.
Some of these studies are discussed herein, as they offer the only database for such materials.

11.8.2 Mortality

     Examples of studies in which effects on mortality  were reported using particles >1 //m in
diameter are presented in Table 11-18; all of these studies involved repeated or chronic
exposures to high concentrations of various PM, some of which are considered to be of low
toxicity. While incomplete, the studies are of a variety of materials and indicate that essentially
no treatment-related mortality was induced in any of the studies.
     Recent interest has been focused on the inherent toxicity of a smaller size  class of particles,
namely the ultrafine particles which are discussed in Section 11.4. While the mass concentration
of ultrafine particles in ambient air may be low, their number concentration may be quite high,
as discussed previously.

11.8.3 Pulmonary Mechanical Function

     Assessments of pulmonary mechanical function have generally been carried out with
particles having some inherent toxicity, as well as other studies examining effects of other
particles with low intrinsic toxicity (see Table 11-19).       Wright et al. (1988) instilled rats
(Sprague-Dawley; F; 200g) with 10,000  //g iron oxide (0.1 //m GMD, og = 1.7) or silica
(quartz) (1.3 //m,  og = 2.5). At 1 mo after exposure, they noted no changes in various indices of
pulmonary mechanics (total lung capacity [TLC];
                                          11-137

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                   TABLE 11-18. EFFECTS OF PARTICIPATE MATTER (>1 ^m) ON MORTALITY
1
OJ
oo
Particle

Ti02
Toner
Coal dust
Petroleum coke
(micronized)
Petroleum coke
(micronized)
Volcanic ash
Ti02
Fly ash (coal)
California
road dust
Talc
Species, Gender,
Strain, Age, or
Body Weight

Rat, M/F, F-344,
8 weeks
Rat, M/F, F-344,
8 weeks
Rat, M, Wistar,
18 weeks
Rat, M, SD
Monkey, adult,
cynomologous
Rat, M/F, F-344,
3 mo
Rat, M/F, CD
Rat, M, Wistar,
3 mo
Rat, F-344
Rat, M/F, F-344
Exposure
Technique

Whole body
Whole body
Whole body
Whole body
Whole body
Whole body
Whole body
Whole body
Nose-only
Whole body
Mass Concentratic
C"g/m3)

5,000
16,000
6,600, 14,900
10,000, 30,000
10,000, 30,000
5,000, 50,000
10,000, 50,000,
250,000
270,000
300, 900
6,000, 18,000
Particle Characteristics
Size (//m); ag

l.l(MMAD); 1.5
4 (MMAD)
2.1 (MMAD); 2.7
3.1 (AED); 1.9
3.1 (AED); 1.9
Respirable (unspecified
size)
1. 5-1.7 (MMD)
47% < 3.75 //m
4 (MMAD); 2.2
2.7-3.2 (MMAD); 1.9

Exposure Duration

6 h/day, 5 days/week,
2 years
6 h/days, 5
days/week,
2 years
6 h/day, 5 days/week,
20 mo
6 h/day, 5 days/week,
2 years
6 h/day, 5 days/week,
2 years
6 h/day, 5 days/week,
2 years
6 h/day, 5 days/week,
2 years
6 h/day, 1 5 days
4 h/day, 4 days/week,
8 weeks
6 h/day, 5 days/week,
2 years
Observed Effect'

None
None
None
None
None
None
None
None
None
None
Reference

Muhle et al. (1991)
Muhle et al. (1991)
Karagianes et al.
(1981)
Klonneetal. (1987)
Klonneetal. (1987)
Wehneretal. (1983)
Lee et al. (1985)
Chauhanetal. (1987)
Kleinman et al.
(1995)
National Toxicology
Program (1993)
"Effect indicates "treatment related" mortality.

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                                    TABLE 11-19.  EFFECTS OF INHALED PM ON PULMONARY MECHANICAL FUNCTION
VO
Particle
Volcanic ash
Fly ash (coal)
(Illinois # 6)
Fly ash (coal)
(Montana
lignite)
Volcanic ash
Volcanic ash
Coal dust
Ti02
Species, Gender,
Strain, Age, or Body Exposure Mass Concentration
Weight Technique (//g/m3)
Rat, Whole body 9,400
Sprague-Dawley, 40
days
Guinea pig, Hartley, Nose-only 5,800
250-320 g
Guinea pig, Hartley, Nose-only 5,800
250-320 g
Rat, M/F, F-344, Whole body 5,000, 50,000
3 mo
Guinea pig, Hartley, Head 9,400
300-425 g
Rat, Wistar, Whole body 10,000
200-300 g,
conventional and
germ free
Rat, F, F-344, Whole body 5,000
8 weeks
Particle Characteristics
Size (//m); ag Exposure Duration
0.65 (MMAD); 1.78 2 h/days, 5 days
0.21 (MMAD);4.14 Ior2h
0.21 (MMAD); 4. 14 Ior2h
Respirable 6 h/day, 5 days/week,
24 mo
0.65 (MMAD); 1.78 2h
Geometric mean <5 //m 8 h/day, 120 days
— 6 h/day, 5 days/week,
24 mo
Observed Effect'
No changes (f, VT,
Vinsp, Vexp)
2h: iTLC, VC, DLCO
up to 96 h PE 1 h: no
effect
2h: iTLC, VC; no
change in DLCO
Tf for 50,000 //g/m3
by 8 mo; no change
for 5,000 //g/m3
No change in RQW,

-------
functional residual capacity [FRC]; nitrogen [N2] washout; FEV1; or peak expiratory flow
[PEF]) in animals exposed to iron oxide, but silica exposure resulted in changes in the N2
washout curve and decreased compliance.  Begin et al. (1985) instilled into sheep (Male; 25 to
45 kg BW) 100,000 //g latex beads (0.1 //m) or asbestos fibers.  The latex produced no change in
pulmonary function (TLC, residual volume [RV]; vital capacity [VC]; expiratory reserve volume
[ERV]; pulmonary compliance [Cpulm]; pulmonary resistance [Rpulm]; FRC), while the
asbestos produced a reduction in compliance, abnormalities in the N2 washout curve, and
changes in forced expiratory flow measurements.
     There are a few studies of pulmonary function responses following inhalation exposures to
PM. Chen et al. (1990) evaluated pulmonary function of guinea pigs exposed to coal fly ash (5.8
Mg/m3, MMAD = 0.21 //m) produced during combustion of Illinois no. 6 coal (high sulfur) or
Montana lignite (low sulfur).  Total lung capacity (TLC), vital capacity (VC), and diffusing
capacity for carbon monoxide (DLCO) were all significantly reduced below control values at 2h
and 8h postexposure in guinea pigs exposed to Illinois no. 6 ash.  The DLCO was  still 10% below
control values 96h postexposure.  Guinea pigs exposed to the Montana lignite fly ash at
comparable concentration and particle size did not show alterations in diffusing capacity. The
authors suggested that the different effects could be due to sulfuric acid produced during
combustion of the two coals but neutralized by the high alkali content of the Montana lignite.
     Wehner et al. (1983) exposed rats (F-344;  M/F,  3mo) to 5,000 or 50,000 //g/m3 volcanic
ash (Mt. St. Helens) for 6 h/day, 5 days/week for up to 24 mo (Table 11-19). By 12 mo  of
exposure, no changes in lung volume were noted. By 8 mo of exposure, there was an increase in
respiratory frequency in animals exposed at the higher concentration, but no change at the lower
concentration.
     Heinrich et al. (1989b) exposed rats for 6 h/day, 5 days/week up to 24 mo to titanium
dioxide (TiO2) at 5,000 //g/m3 and silica at 1,000 //g/m3. Exposure to silica produced a
reduction in quasistatic lung compliance, tidal volume, (VT), inspiratory capacity (1C), VC, RV,
and TLC.  Diffusion capacity for carbon monoxide (DLco) was also reduced, and the N2
washout curve was altered; these changes indicate a functionally restrictive lung, a finding often
noted in humans occupationally exposed to silicates.  None of these variables were altered by
exposure to TiO2.
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     Acidic sulfates have been associated with alterations in bronchial responsiveness, but there
are few studies with other particles which examined this response. Fedan et al. (1985) exposed
rats (F344, whole body) for 7 h/day, 5 days/week for 2 years to coal dust (size described as
respirable, but not specifically stated) at 2,000 //g/m3, and examined the pharmacological
response of isolated tracheal preparations to various agonists. The coal dust exposure increased
the maximal contractile response of the tracheal smooth muscle to acetylcholine (a
bronchoconstrictor), compared to air exposed control tissue, but did not alter the slope of the
acetylcholine concentration-response curve nor sensitivity (i.e., EC50).  No change in response
to isoproterenol (a bronchodilator) was noted. Wiester et al. (1985) exposed guinea pigs for 2 h
to 9,400 //g/m3 of Mt. St. Helens volcanic ash (0.65 //m).  No changes in pulmonary mechanics
measured during exposure (airway resistance, dynamic compliance, breathing frequency,
maximum inspiratory flow or expiratory minute volume) were noted. However, following
exposure, airway hyporesponsiveness to histamine challenge was observed.
     It should be noted that, as with acidic sulfates, changes in pulmonary function may not be
the most sensitive marker of response to other PM.  For example, inflammatory  changes in
sheep following the instillation of latex particles (100,000 //g in 100 ml fluid) were not
associated with any changes in lung volumes, resistance, or compliance (Begin et al., 1985).

11.8.4 Pulmonary Morphology and Biochemistry

     A considerable amount of the information concerning morphologic alterations from
inhaled particles has been obtained in studies of diesel exhaust, and this is discussed in this
chapter and reviewed elsewhere (U.S. Environmental Protection Agency,  1994; Health Effects
Institute, 1995). In addition, and as previously mentioned with acidic sulfate particles, markers
in lung BAL have been used to assess damage following PM exposure.
     The ability of ambient particles to affect lung  morphology was strongly suggested by
Bohm  et al. (1989). They exposed rats (Wistar, F, 2.5 mo) for 6 mo to the ambient air of two
cities in Brazil, namely Sao Paulo and Cubatao. Although characterization of air pollution levels
was vague, pollution in the former appeared to be dominated by automobile exhaust gases, while
that in the latter by industrially derived paniculate matter. Rats exposed in Cubatao showed
various responses, such as mucus hypersecretion and epithelial
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hyperplasia, in both the upper and lower bronchial tree, while those exposed in Sao Paulo
showed effects generally limited to the upper bronchial tree. Particle concentrations (PM10) were
as high as 164 //g/m3 in Cubatao.  Thus, high PM levels were suggested to be responsible for the
observed effects, although the contribution of other components of the pollutant mix could not
be discounted.
     Some intratracheal instillation studies have compared morphological effects resulting from
exposure to different particles. Wright et al. (1988) instilled 10,000 //g iron oxide (Fe2O3;
0.1 //m GMD, og = 1.7) or 10,000 //g quartz (1.3 //m GMD, og = 2.5) into rats, and examined
the lungs 30 days following each exposure. The iron oxide did not produce any histological or
morphometric changes, while the quartz exposure resulted in aggregations of PMNs and AMs
around small airways, alveolar proteinosis, increased alveolar distances, airspace enlargement,
and increased thickness of respiratory bronchiolar walls.
     Another example of an instillation study which may be used to compare effects from
different types of particles is that of Sanders et al. (1982), who instilled rats (F-344, female,
young  adult) with 40,000 //g of either soil (sandy loam, 1.6 //m CMD), volcanic ash
(Mt. St. Helens, 0.5 to 1.5  //m CMD), or crystalline quartz (1.5 //m CMD).  Mononuclear cell
infiltration was noted with both the soil and ash particles in regions of high particle aggregation.
There was also some Type 2 epithelial cell hyperplasia 7 to 37 days following ash or soil
instillation.  However, the  ash produced a fibrotic response to a greater extent than did the soil,
with indications from the former of a simple pneumoconiosis and moderate lipoproteinosis.
Some foci of particle-laden macrophages were noted in the mediastinal lymph nodes of soil
exposed animals, but the ash-exposed animals showed reactive lymphoid hyperplasia. Quartz
resulted in production of granulomas, deposition of collagen, widespread lipoproproteinosis, and
fibrosis in regional lymph nodes.
     The comparative fibrogenic potential of a number of particle types was examined by
Schreider et al. (1985). Male Sprague-Dawley rats were exposed by intratracheal instillation to
5,000,  15,000, or 45,000 //g of Montmorillonite clay (0.84 //m CMD), quartz (1.1 //m), Mt. St.
Helens volcanic ash (1.2 //m), stack-collected coal fly ash (1.5 //m) or hopper-collected fly ash
(1.9 //m), or to 5,000 or 15,000 //g of a coal-oil ash mixture (3.9 //m). Lung histology was
assessed at 90 days post instillation. Neutrophils were noted in alveoli only with quartz (all
concentrations), stack ash (at high concentration), and
                                         11-142

-------
volcanic ash (low and mid concentrations).  Some fibrosis was produced by all of the particles,
although there were qualitative and quantitative differences among the different exposure
groups. The order of fibrosis potential, from greatest to least, was as follows: quartz > clay >
volcanic ash > hopper coal ash > stack coal ash > oil-coal ash mixture.
     Begin et al. (1985) instilled 100,000 //g of 0.1 //m latex beads or asbestos fibers into the
lungs of sheep (25 to 45 kg) and examined lavage fluid at 1 to 60 days post instillation. The
latex produced only transient alveolitis and transient increases in the number of AMs and PMNs
in lavage beginning at day 1, whereas the asbestos-exposed animals had a persistent
inflammatory response and more severe damage. Callis et al. (1985) instilled silica or latex
particles (0.9 //m) into the lungs of mice.  While the latter produced some increase in protein and
cell number in lavage, the response to the former was much greater. Finally, Lindenschmidt
et al. (1990) instilled rats with either of two inert dusts, (A12O3;  5.3 //m) and TiO2 (2.2 //m)  at
1,000 or 5,000 //g/100g body weight and examined the lungs up to 63 days post instillation.
Both particle types produced similar increases in N-acetylglucosamine and total recovered cells
in lavage, while a minimal Type 2 cell hyperplasia noted with A12O3 was even less severe with
TiO2. However, when results were compared with those for instilled silica, any responses seen
with the inert particles decreased towards control level during the 2-mo study period, while
changes with silica progressed.  This highlights the difference between the inert and fibrogenic
materials. Thus, the instillation studies suggest that there may be some nonspecific particle
effect, but clearly the chemical characteristics of the particle affects the ultimate biological
response.  In any case, levels of particles with low intrinsic toxicity are not associated with major
nonspecific effects.
     The effects of inhaled PM on pulmonary  morphology are  outlined in Table 11-20.  Most of
the studies used fly ash and volcanic ash; TiO2 has also been used to assess effects of a
"nuisance" (low intrinsic toxicity) type of particle.  However, with the exception of the study of
road dust by Kleinman et al. (1995), exposure concentrations ranged  from very high to
extremely high and likely caused overload with long-term exposures.  Responses, when they did
occur, were quite similar for the various particles, characterized by focal aggregates of
particle-laden macrophages with evidence of an inflammatory response; the intensity of both
effects was related to exposure duration and concentration. On the other
                                          11-143

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TABLE 11-20. EFFECTS OF PARTICIPATE MATTER ON RESPIRATORY TRACT MORPHOLOGY
Particle
Coal dust
(micronized
bituminous)
Petroleum coke
(micronized
raw)
Fly ash (coal)
Volcanic ash
(Mt. St.
Helens)
Ti02
Species, Gender,
Strain, Age or Exposure Mass
Body Weight Technique Concentration
C"g/m3)
Rat, M, Whole body 6,600, 14,900
Wistar, 1 8 weeks
Rat, M/F, S-D; Whole body 10,000, 30,000
Monkey,
cynomologous
(mature)
Rat, M/F, Whole body 36,000
F-344, 10-13 mo
Rat, M/F, Whole body 5,000, 50,000
F-344, 3 mo
Rat, F, Whole body 5,000
F-344, 8 weeks
Particle
Characteristics
exposure Duration
Size (//m); ag
2. 1 (MMAD); 2.7 6 h/day, 5 days/week,
20 mo
3.1 (AED); 1.9 6 h/day, 5 days/week,
2 years
3.6 (MMAD); 2 7 h/day for 3 days on
week 1,
5 days/week next
3 weeks,
2 days in week 5
Respirable 6 h/day, 5 days/week,
(no size given) up to 24 mo
6 h/day, 5 days/week,
up to 24 mo
Observed Effect
Accumulation of aggregates of
particles in
AMs immed. after exposure; alveolar
histocytosis, interstitial fibrosis
and emphysema, indication of simple
pneumoconiosis; no lesions in upper
respiratory tract.
Rat: chronic pulmonary inflammation
at 3, 6, 12, and 18 mo observation times
at both cone; focal fibrosis;
sclerosis; squamous alveolar
metaplasia. Monkey: accumulation of
particle-laden AMs; no inflammation
No exposure-related histopathology in
large or small airways; but increased
cell division; slight increase in
number of hypertrophic Type 2 cells by
2 weeks; small areas of thickened
alveolar walls and some perivenous
inflammatory cell infiltration; by 4
weeks, aggregation of AMs with
particles and greater alveolar wall
thickening and inflammation; some
resolution by 42 weeks in pathology.
At 5,000 //g/m3: small aggregations of
particle-laden AMs at 4 mo and some
thickening of alveolar septa.
Aggregates of dust deposits at 8 mo,
and some peribronchiolar lymphoid
hyperplasia which increased by 12 mo.
Enlargement of mediastinal nodes by 12
mo.
At 50,000 //g/m3: more severe lesions;
low to moderate AM accumulation by 4 mo
which increased by 8 mo and stabilized
by 12 mo. Prominent peribronchial and
mediastinal node reaction by 4 mo,
which increased by 8 mo and stabilized
by 12 mo; alveolar proteinosis by 8 mo.
No fibrosis; no bronchiolar
hyperplasia; no accumulation of AMs in
lung tissue.
Reference
Karagianes et al.
(1981)
Klonne et al.
(1987)
Shami et al.
(1984)
Wehner et al.
(1983)
Heinrich et al.
(1989b)

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TABLE 11-20 (cont'd). EFFECTS OF PARTICIPATE MATTER ON RESPIRATORY TRACT MORPHOLOGY


Particle

Fly ash (coal)


Ti02





Volcanic ash


California road
dust

TiO2









Fly ash
(fluidized bed
coal
combustion)
Fly ash (coal)




Fly ash
(fluidized bed
coal
combustion)
Fly ash
(pulverized
coal
combustion)
Species, Gender,
Strain, Age or Exposure Mass
Body Weight Technique Concentration
0/g/m3)
Mice, M, Nose-only 200,000
C57BL/6,
12 weeks
Guinea pig, F, Whole body 23,000
Dunkin-Hartley,
300-350 g



Rat, Whole body 9,400
Sprague-Dawley,
40 days
Rat, F-344 Nose-only 900


Rat, M/F, Whole body 10,000, 50,000,
CD 250,000








Rat, M/F, F-344, Whole body 142,000
12-16 weeks


Hamster, golden, Whole body 2,000,
8 weeks 1,000, 2,000
20,000


Rat, M/F, F-344, Whole body 36,000
12 weeks


Rat, M/F, Whole body 37,000
F-344, 12 weeks


Particle
Characteristics
Exposure Duration Observed Effect
Size (//m); ag
1.6-1.7 (MMAD); 100 min Increased no. of AMs; no other
1.4-1.5 lesions evident by light microscopy.

95% < 1.98 (MMAD) 20 h/day, 14 days At 1 day PE: dust laden cells in
bronchial lymph nodes and BALT; some
thickening of alveolar septa in areas
of high dust cone.; some degenerative
changes in AMs; no PMNs. At 6 d PE:
increased number of dust laden AMs.
0.65 (MMAD); 1.78 2 h/day, 5 days Slight peribronchial and perivascular
mononuclear cell infiltration.

4 (MMAD); 2.2 4 h/day, 4 days/week, T Alveolar septal wall thickness;
8 weeks i Alveolar diameter

1.5-1.7 (MMAD) 6 h/day, 5 days/week, At 10,000 //g/m3: slight alveolar
2 years epithelial
hyperplasia. At 50,000 //g/m3: marked
alveolar epithelial hyperplasia;
bronchioarization of alveoli adjacent
to terminal bronchioles; alveolar
proteinosis.
At 250,000 lig/m3: increased alveolar
hyperplasia and bronchioarization;
deposition of collagen fibers.
3 (MMAD); 2.6 6 h No pathology, except accumulation of
particles.


2.3-2.4 (MMAD); 20 h/day, 7 days/week, Accumulation of particle-laden AMs in
1.5 6 mo proximal alveoli in
concentration/duration dependent
fashion; T PMNs at 20,000 |ig/m3 in
peripheral alveoli.
3.6 (MMAD); 2.0 7 h/day, 5 days/week, Slight enlargement of lung associated lymph
4 weeks nodes due to increased no. of lymphoid cells
(persistent up to 48 weeks PE); small cluster
of particle laden AMs in alveoli.
2.7 (MMAD); 2. 1 7 h/day, 5 days/week, Moderate enlargement of lung
4 weeks associated lymph nodes due to hyperplasia
and cell accumulation (persistent up to
48 weeks PE); small granulomas in lungs.


Reference

Fisher and
Wilson
(1980)
Baskerville
etal.
(1988)



Raub et al.
(1985)

Kleinman
etal.
(1995)
Lee et al.
(1985)








Hackett
(1983)


Negishi
(1994)



Bice et al.
(1987)


Bice et al.
(1987)



-------
           TABLE 11-20 (cont'd). EFFECTS OF PARTICIPATE MATTER ON PULMONARY MORPHOLOGY
Particle
Carbon black

Carbon black

Fly ash (coal)
Shale dust (raw
or spent)


Coal dust

Species, Gender,
Strain, Age or Exposure Mass Concentration •
Body Weight Technique (//g/m3)
Rat, M, Whole body 10,000
F-344,
14-15 weeks

Rat, F, Wistar 6,000
6 weeks

Rat, M, Whole body 270,000
Wistar, 160- 175 g
Monkey, Whole body 10,000, 30,000
cynomolgus, M/F,
2-4. 5 kg
Rat, M/F, F344,
90-95 g

Monkey Whole body 2,000
cynomolgus, M
Rat, M/F, F-344
Mice, M/F CD-I

Particle Characteristics
Size (//m); ag Exposure Duration
2.0/0. 12 7 h/day, 5 days/week,
(MMAD) 12 weeks
(bimodal distr.
with 70% in
smaller mode) 2. 5/2. 3
n/s 1 8 h/day, 5 days/week,
10 mo

47% <3.75 fj.m 6 h/day, 15 days
3.9-4.5; 6 h/day, 5 days/week,
(1.8-2.2) 2 years


8.6 fj,m (MMAD) 7-h/day, 5 days/week,
up to 2 years

Observed Effect
Mild hyperplasia of Type 2 cells;
particle laden AMs in distal
terminal bronchioles and proximal
alveolar ducts.

Moderate to severe hyperplasia in
bronchioalveolar region; some
inflammation; alveolar
lipoproteinosis
Mild infiltration of mononuclear
cells and mild pneumonitis 45 days
PE; numerous particle-laden AMs
outside alveoli up to 105 days PE;
T lung weight by 30 days PE.
Concentration-related accumulation
of AMs; subacute bronchiolotis and
alveolitis
Concentration-related
proliferative bronchiolitis and
alveolitis, chronic inflammation
with spent shale; no
lymph node inflammation;
accumulation of AMs
Type II cell hyperplasia and
pulmonary lipodosis in rats;
increased phagocytosis. Mild
obstructive airway disease in
monkeys.
Reference
Wolff etal.
(1990)

Nolle et al.
(1994)

Chauhan et al.
(1987)
MacFarland et
al. (1982)


Lewis et al.
(1989)

Key to abbreviations:

 NS: Not specified
 PE: Post-exposure
 AM: Alveolar macrophage
 PMNs: Polymorphonuclear leukocytes

-------
hand, the Kleinman et al. (1995) study at relatively low particle concentrations showed a more
diffuse pattern of morphological change and no inflammatory loci.
     There is some evidence for interspecies differences in response to comparable exposure
atmospheres (Klonne et al., 1987). In the study of Shami et al. (1984), increased proliferation of
large and small airway epithelial cells occurred in the absence of overt histopathology following
exposure to fly ash. The authors suggested that this may indicate some potential for the
interaction of fly ash with carcinogens.
     Clark et al. (1990) exposed dogs (mongrel,  15 to 20 kg) for 5 min to wood smoke (from fir
plywood sawdust and kerosene; no specified particle size or exposure  concentration) via an
endotracheal tube.  The lungs were examined for increased extravascular water around the
pulmonary arteries, which was found to occur with smoke exposure but not in air sham controls.
This response was suggested to be due to increased microvascular permeability without any
increase in capillary pressure.  A decrease in lung compliance was also noted with smoke
exposure.
     Table 11-21 outlines  studies in which lavage fluid was analyzed  following inhalation
exposure to PM.  As with morphology, most exposure concentrations were very high, but
effects, when they occurred, indicated inflammation.
     As mentioned earlier, eicosanoids are potent mediators of various biological functions, and
alterations in arachidonic acid metabolism, which may be involved in lung  pathology, can be
assessed in lavage fluid.  Exposure to coal dust (25,000 //g/m3) produced decreases in
prostaglandin E2, and increases in thromboxane A2 and leukotriene B4, perhaps suggesting
smooth muscle constriction, vasoconstriction and increased chemotactic  activity of macrophages
(Kuhnetal., 1990).
     Table 11-22 outlines  studies examining lung biochemistry following particle inhalation,
mostly to fly ash. In some cases, effects on the xenobiotic metabolizing  system of the lungs
were examined. For example, van Bree et al. (1990) exposed rats to coal fly ash (10,000,
30,000, 100,000 //g/m3) and examined cytosolic antioxidant enzymes and the microsomal P-450
linked mixed function oxidase system involved in lung metabolic defense against reactive
oxygen species and xenobiotic compounds. They noted both exposure-related increases and
decreases in different components of this system, which they ascribed  to differential effects of
organic and trace metal components of the ash. Srivastava et al. (1985)
                                         11-147

-------
                    TABLE 11-21. EFFECTS OF PARTICIPATE MATTER ON MARKERS IN LAVAGE FLUID
oo
Particle
Carbon black
Volcanic ash
Ti02
Ti02
Coal dust
California
road dust
Ti02
Fe203
Carbon black
Carbonyl
iron
Carbon
black
Ti02
Coal dust
Species,
Gender, Strain,
Age or Body
Weight
Mouse, F,
Swiss, 20-23
days
Mouse, F,
CD-I, 4-8 weeks
Rat, M, F-344
180-200 g
Rat, HAN
Rat, HAN
Rat, F-344
Rat, M/F, F-344,
8 weeks
Rat, M,
Long-Evans,
225-250 g
Rat, M,
F-344,
14-15 weeks
Rat, M
CrliCDBR,
8 weeks
Mouse, F,
Swiss
20-23 g
Guinea pig, M/F,
400 g
Rat, F, F-344,
180 g
Exposure
Technique
Nose-only
Whole body
Whole body
Whole body
Whole body
Nose-only
Whole body
Nose-only
Whole body
Nose-only
Nose-only
Whole body
Whole body
Mass Concentration
(//g/m3)
10,000
9,400
50,000
50,000
10,000, 50,000
300, 900
5,000
18,000-24,000
10,000
100,000
10,000
24,000
25,000
Particle Characteristics
Size (//m); ag
2.45 (MMAD); 2.54
0.65 (MMAD); 1.8
1 (MMAD); 2.6


4 (MMAD); 2.2
1.1 (MMAD); 1.6
1.45- 1.7 (MMAD);
2.9-3
2.0/0.12
(MMAD)
(bimodal distr.
with 70% in
smaller mode); 2.5/2.3
3.6 (MMAD); 1.7
2.4 (MMD); 2.75
85% < 2 ij,m
4-5

Exposure Duration
4 h/day, 4 days
2h
6 h/day, 5 days
8 h/day, 5 days/week
(up to 15 weeks)
8 h/day, 5 days/week
(up to 1 5 weeks)
4 h/day, 4 days/week,
8 weeks
6 h/day, 5 days/week,
24 mo
2h
7 h/day, 5 days/week,
12 weeks
6 h; 6 h/day, 3 days
4h
8 h/day, 5 days/week,
3 weeks
16 h/day, 7 days/week,
2 weeks
Observed Effect
No change in total cell no. or
differential counts; no change in
albumin
levels.
Increase in PMNs.
No change in: AMs, PMNs, lymphocytes;
LDH; protein; to 63 days PE.
Slight increase in PMNs at 15 weeks.
Increased PMNs (persistent).
T Albumin at 900 //g/m3; no change in
total cells or differential counts
No change in total cell no. in lavage
but T AMs and J PMNs some time points; no
change in LDH, protein,
6-glucuronidase
in lavage.
No change total cell no. or
differential counts.
T PMNs in lavage; T acid
proteinase in lavage.
No change in total cell no,
protein, or LDH.
No change in total cell no. or
differential count at 20 h PE.
No change in LDH, AP, AG, Cathepsin D at
4-24 h PE.
T TxAj, LTB4, protein; I PGE2 at 1 day PE;
TxAj, and LTB4 change persistent for
2 weeks.
Reference
Jakab (1992, 1993)
Grose et al.
(1985)
Driscoll et al.
(1991)
Brown et al.
(1992)
Brown et al.
(1992)
Kleinman et al.
(1995)
Muhle et al.
(1991)
Lehnert and Morrow
(1985)
Wolff etal.
(1990)
Warheit et al.
(1991a)
Jakab and Hemenway
(1993)
Kuhn et al. (1990)
Sjostrand and
Rylander (1984)

-------
                           TABLE 11-21 (cont'd). EFFECTS OF PARTICIPATE MATTER ON MARKERS IN LAVAGE FLUID
Species, Gender, Particle
Strain, Age or Exposure Mass Characteristics
Particle Body Weight Technique Concentration
Og/m3) size (//m); ag
TiO2 Guinea pig, M/F, Whole body 24,000 Most between 0.5-2 (GMD)
400 g
Exposure Duration Observed Effect
8 h/day, 5
days/week,
3 week
No change PMNs; T no. AMs,
eosinophils by 16 weeks
PE.
Reference
Fogelmark et al. (1983)
             Key to abbreviations:
              LDH: lactate dehydrogenase
              AP: acid phosphatase
              AG: N-acetyl-6-d-glucosaminidase
              TxA^ thromboxane A2
              LTB4: Leukotrine B4
              PGE2: Prostaglandin E2
              AM:  alveolar macrophage
              PE: post-exposure
              PMN: polymorphonuclear leukocyte
              T:  increase
              I:  decrease
VO

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                       TABLE 11-22.  EFFECTS OF PARTICIPATE MATTER ON LUNG BIOCHEMISTRY
Particle
Fly ash
(coal)
Carbon black
Fly ash
(fluidized bed
coal)
Carbonyl iron
Fly ash
(fluidized bed
coal
combustion)
Fly ash
(coal)
Fly ash
(coal)
Species,
Gender, Strain,
Age or Body
Weight
Rat, M,
Wistar, 5 weeks
Rat, M,
F-344, 200-250 g
Rat, M/F,
F-344
Rat, M,
CrliCDBR,
8 weeks
Rat, M/F,
F-344,
10-13 weeks
Rat, M,
Wistar,
160-175 g
Rat, M,
Wistar,
160-170 g
Particle
Exposure Mass Concentration Characteristics
1 echmque (//g/nr*)
Size (//m); ag
Whole body 10,000, 30,000, 80-95% mass was
100,000 <42 /an (AED)
Whole body 6,000 0.22 (MMAD)
Whole body 142,000 3 (MMAD); 2.6
Nose-only 100,000 3.6 (MMAD); 2.6
Whole body 36,000 3.6 (MMAD); 2
Whole body 270,000 47% < 3.75 /an
Whole body 270,000 47% <3.75 /an
Exposure Duration
6 h/day, 5
days/week,
4 weeks
20 h/day, 1-14 days
6h
6 h/day, 3 days
7 h/day, 3 days
week 1; 5 days/week
week 2-4; 2 days
week 5
6 h/day, 1 5 days
6 h/day, 1 5 days
Observed Effect
T Cytosolic GSHPX, protein at 30,000
100,000; T G6PDH at 100,000; T lung
microsomal protein, i microsomal BROD
at 30,000/100,000; no change
microsomal P-450 content; induction
of EROD activity at all cone, (all in
lung tissue).
No change in synthesis of lung total
DNA; no change in DNA synthesis of Type
2 cells.
T Labeling of Type 2 cells;
T incorporation of thymidine in AM DNA,
persisting 4 days PE; T labeling airway
epithelial cells,
persistent up to 4 days PE.
No effect on labeling index of lung
parenchymal or airway cells.
T Labeling index of large airway basal
cells and bronchiolar Clara cells at
2 weeks, resolved by 2 weeks PE;
T labeling index of Type 2 cells
by 4 weeks, resolved by 2 weeks PE.
T P-450 content; T activity of aryl
hydrocarbon hydro xylase, glutathione
S-transferase, 8-amino levulinic acid
synthetase; inhibition of
hemeoxygenase.
T Total lung phospholipids;
T phosphatidylcholine up to 45 days PE.
Reference
van Bree et
al. (1990)
Wright (1986)
Hackett
(1983)
Warheit et
al. (1991a)
Shami et al.
(1984)
Chauhan et
al. (1989)
Chauhan and
Misra(1991)
Key to abbreviations:
 GSHPX = glutathione peroxidase
 G6PDH = glucose 6 phosphate dehydrogenase
 BROD = benzoxyresorufin 0-dearylase
 EROD = NADPH-mediated ethoxyresorufin 0-deethylase
 T: increase
 I: decrease
 PE = post exposure
 AM = alveolar macrophage

-------
also found that the effects of fly ash were likely due to chemicals adsorbed onto, or that were
part of, the fly ash particle, rather than to some nonspecific particle effect. This was because the
activity of the lung mixed function oxidase system was induced in rats by instillation of coal fly
ash (<0.5 //m), but not by instillation of glass beads.
     There is some evidence that fly ash exposure can initiate cell division and DNA synthesis
in the lungs (Hackett, 1983; Shami et al., 1984), but exposure levels were very high
(>30,000
11.8.5 Pulmonary Defenses

11.8.5.1   Clearance Function
Mucocttiary Transport
     Grose et al. (1985) exposed (whole-body) rats (Sprague-Dawley CD, M, 60 to 70 days) to
volcanic ash from Mt. St. Helens (0.65 //m, og=1.8) at 9,400 //g/m3 for 2 h.  At 24 h post
exposure,  a depression in ciliary beat frequency in excised tracheas was noted. Whether this
would contribute to any change in mucociliary transport function in the intact animal is
unknown.

Pulmonary Region Clearance and Alveolar Macrophage Function
     A number of studies have examined particle retention following exposure to high
concentrations of inhaled particles, some of which have low intrinsic toxicity. Such exposures
resulted in a phenomenon known as overload, in which the effectiveness of lung clearance
mechanisms is significantly reduced.  This response, which is nonspecific to a wide range of
particles, is discussed in detail in Chapter 10.
     While there are no studies of effects of exposure to nonacidic sulfate particles on alveolar
region clearance, there have been several studies examining AM function following  inhalation
exposures (Table 1 1-23) or with in vitro exposure.  High exposure concentrations of various
particles can depress the phagocytic activity of AMs following inhalation.
     To examine the effects of different fly ashes, Garrett et al. (1981b) incubated rabbit AMs
with < 1,000 //g of either conventional coal combustion fly ash or fluidized bed combustion fly
ash at >3 and <3 //m, for 20 h. While all exposures  caused reductions in cell viability and cell
ATP levels, conventional coal fly ash <3//m produced the greatest
                                         11-151

-------
TABLE 11-23. EFFECTS OF PARTICIPATE MATTER ON ALVEOLAR MACROPHAGE FUNCTION
1
l^ft
to
Particle
Carbon black
Volcanic ash
Ti02
Fly ash
(coal)
Ti02
Coal dust
California
road dust
Iron oxide
(Fe203)
Carbonyl
iron
Carbon black
Ti02
Species, Gender,
Strain, Age, or
Body Weight
Mouse, F,
Swiss, 20-23 g
Mouse, F,
CD-I, 4-8 weeks
Rat, M, F-344
180-200 g
Mouse, F,
BALB/C; C57BL;
6-8 weeks
Rat, HAN
Rat, HAN
Rat, F-344
Rat, M,
Long-Evans,
225-250 g
Rat, M,
CrliCDBR,
8 weeks
Mouse, F,
Swiss, 20-23 g
Guinea pig, M/F
400g
Exposure
Technique
Nose-only
Whole body
Whole body
Whole body
Whole body
Whole body
Nose-only
Nose-only
Nose-only
Nose only
Whole body

(/jg/m3)
10,000
9,400
50,000
535
(fine particle
fraction
< 2. 1 /mi)
50,000
10,000, 50,000
300, 900
18,000-24,000
100,000
10,000
24,000
Particle Characteristics
Size (/mi); ag
2.45 (MMAD); 2.54
0.65 (MMAD); 1.8
1 (MMAD); 2.6
32 %< 2.1 /mi
(bywt)
"respirable fraction"
"respirable fraction"
4 (MMAD)
1.45-1.7 (MMAD); 2.9-3
3.6 (MMAD); 1.7
2.4 (MMD); 2.75
Most between
0.5-2(GMD)

Exposure Duration Observed Effect"
4 h/day, 4 days No change in F -mediated AM
phagocytic activity up to
40 days PE.
2 h No change in viability of
recovered cells; no effect
on AM phagocytosis at 0 or
24 h PE.
6 h/day, 5 days No change in spontaneous/
stimulated release of IL- 1
by AMs up to 63 days PE.
148 days i AM phagocytic activity by
21 days of exposure.
8 h/day, 5 days/week No change in chemotactic
activity of AM.
8 h/day, 5 days/week Decreased AM chemotactic
activity.
4 h/day, 4 days/week, i Production of superoxide
8 weeks at high concentration; no
change in Fc receptor
mediated phagocytic
activity.
2 h No change in AM adherence;
T phagocytic activity of AM
(Fc-mediated) up to 20 days
PE.
6 h; 6 h/day, 3 days No change in AM chemotactic
activity; cell viability ;
slight T AM phagocytic
activity for single exp.
4 h No change in F -receptor
mediated AM phagocytic
activity.
8 h/d, 5 days/week, No change in AM phagocytic
3 weeks activity.
Reference
Jakab (1992, 1993);
Jakab and Hemenway
(1993)
Grose et al. (1985)
Driscoll et al. (1991)
Zarkower et al. (1982)
Brown et al. (1992)
Brown et al. (1992)
Kleinman et al. (1995)
Lehnert and Morrow
(1985)
Warheitetal. (199 la)
Jakab and Hemenway
(1993)
Fogelmark et al.
(1983)

-------
effect.  These results suggest toxicity somewhat dependent on size, as observed previously with
other endpoints.
     There is little available data on complex mixtures of other PM. Pick et al. (1984) exposed
rabbits (NZW, 1.5 to 2 kg) for 0.2 to 2 h to the pyrolysis products derived from Douglas fir
wood (exposure concentrations and particle size were not stated). They noted an increase in the
total number of cells recovered by lavage immediately postexposure, and the magnitude of this
increase was related to the exposure duration. The ratio of AMs, PMNs and lymphocytes was
constant at all exposure durations except for the longest, in which case lymphocyte numbers
increased. A depression in the uptake and intracellular killing of Pseudomonas aeruginosa was
found in AMs obtained from the smoke-exposed animals compared to cells from air controls.
Furthermore, cells from the smoke-exposed animals were smaller, and had reduced  surface
adherence.
     To examine for a nonspecific particle effect on phagocytosis, Finch et al. (1987) exposed
bovine AMs in vitro to TiO2  (1.57 //m MMD, og=2.3) or to glass beads (2.1 //m, og=1.8), the
former at 2.3 or 5 //g/ml, and the latter at 5 or 8.4 //g/ml.  Neither exposure altered phagocytic
activity, but TiO2 did produce some decrease in cell viability.
     Macrophages may contact particles via chemotactic-directed movement.  Constituents of
lung fluid having high chemotactic activity are components of complement, and particles  which
activate complement tend to show greater chemoattractant activity for macrophage accumulation
at sites of particle deposition (Warheit et al., 1988). For example, in an in vitro study,
iron-coated asbestos and carbonyl iron particles activated chemotactic activity in rat serum and
concentrated rat lavage proteins, while volcanic ash did not. When the rats were exposed by
inhalation to 10,000 to 20,000 //g/m3 of these particles, only the volcanic ash failed to produce
an increased number of macrophages on the first alveolar duct bifurcations, the primary
deposition site for these particles and fibers.  Complement proteins on alveolar surfaces are
likely to be derived primarily from normal transudation of serum components from the
pulmonary vasculature (Warheit et al., 1986). The generation of chemotactic factors at particle
deposition sites may facilitate clearance for some particle types, but not for others, such as silica
(Warheit et al., 1988, 1991a).
     In a somewhat related study, Hill et al. (1982) examined the interaction with complement
of coal combustion fly ash particles (2 to 3 //m MMAD) from different sites,
                                         11-153

-------
using serum from dogs. In addition to releasing peptides that are chemotactic for macrophages
and other inflammatory cells, fly ash also induced release of lysosomal enzymes and increased
vascular permeability, all processes involved in inflammation. While the authors noted that
some fly ash samples activated complement, while others did not, they were not able to
determine which component on or in the ash was responsible for this action. A possibility was
suggested to be some metals, such as Mn, which are potent activators of the complement cascade
(Lewetal., 1975).
      Thoren (1992) examined the metabolic activity of AMs by measuring heat exchange rates
after exposing cell monolayers  to TiO2 or manganese dioxide (MnO2) at
0.6 - 4 x 106 particles/ml. The former affected metabolism only at the highest concentration
used, while the latter caused changes at lower concentrations as well.
      The response of AMs to PM is influenced by both physical and chemical characteristics of
the particles with which they come into contact. Shanbhag et al. (1994) exposed a macrophage
cell line (P388D1) to particles of two  different composition (TiO2 or latex) at comparable sizes,
0.15 and 0.45 //m for the former, and  0.11 and 0.49 for the latter. They also used pure titanium
at  1.76 //m for comparison to latex at 1.61 //m. Titanium dioxide decreased cellular
proliferation, depending upon both size and concentration. Similar sizes and concentrations of
latex produced lesser responses. In addition, cells incubated with latex released factors, into the
medium, which produced fibroblast proliferation to a greater extent than did cells incubated with
TiO2 of a similar size and concentration.

11.8.5.2   Resistance to Infectious Disease
      Susceptibility of mice to challenge with several infectious agents has been used to assess
effects of various inhaled particles on microbial defense of the lungs (Table 11-24).  The study
of Jakab (1993) is of particular interest because the infectious agents used were selected based
upon differences in the antimicrobial defense mechanism  most effective in  eliminating each
organism.  Thus, Staphylococcus aureus defense depends primarily upon the integrity of AMs,
while that for Proteus mirabilis involves both AMs and PMNs. Listeria monocytogenes
defenses involve specific  acquired immunity, namely the integrity of the lymphokine-mediated
components of the cell- mediated immune response (e.g.,  AMs and lymphocytes). A number of
host defenses play a role in defense against influenza, including
                                         11-154

-------
TABLE 11-24. EFFECTS OF PARTICIPATE MATTER ON MICROBIAL INFECTIVITY
Particle
Carbon black
Carbon black
Ti02
Coal dust
Volcanic ash
Ti02
Ti02
Species, Gender,
Strain, Age, or
Body Weight
Mouse, F,
Swiss, 20-23 g
Mouse, F, Swiss,
20-23 g
Guinea pig, F,
Dunkin-Hartley
300-350 g
Mouse, F, Swiss
CD-I, 20-24 g
Mouse, F, CD-I,
4-8 weeks
Mouse,
Harlan-Olac,
8 weeks
Mouse,
Harlan-Olac,
8 weeks
Particle
Exposure Mass Characteristics
1 echnique Concentration Exposure Duration Observed Etlect
Og/m3) size ^m). Og
Nose-only 4,700-6,100 2.45 (MMAD); 2.54 4h/day, 4 days No effect on susceptibility to
infection
from S. aureus administered 1 day PE;
no effect on intrapulmonary killing
of
bacteria by AM.
Nose-only 10,000 2.4 (MMAD); 2.75 4h/day, 4 days No change in no. of S. aureus or P.
mirabilis recovered in lung after
bacterial challenge or on
intrapulmonary killing of bacteria
administered 1 d PE; no effect on
proliferation of L. monocytogenes;
no effect on proliferation or
elimination of influenza A virus; no
change in albumin level in lavage 4 h
after bacterial challenge; no change
in PMN in lavage 4 h after challenge.
Whole body 23,000 95% < 1.98 ,um (MMAD) 20 h/day, 14 days No change in susceptibility to
Legionella pneumophila administered
1-6 days PE but AM with heavy particle
burden did not ingest bacteria.
Whole body 2,000 80% <10//m; 50% <5 //m 7 h/day, 5 days/week, No change in susceptibility to
6 mo influenza virus administered after
1, 3 and 6 mo exposure; decrease in
interferon level in lung at 3 mo; no
change in inflammatory response to
virus.
Whole body 9,400 0.65 (MMAD); 1.8 2h No change in susceptibility to
bacteria (Streptococcus) or virus
administered 0 or 24 h PE; no change
in lymphocyte response to mitogens.
Whole body 2,000,20,000 95%<1.98 /rni(UDS) 20 h/day, 2 or 4 weeks i Clearance of P. haemolytica
administered after exposure in
proportion to exposure duration at
20,000 //g/m3 only.
Whole body 20,000 95% <1.98 urn (UDS) 20 h/day, 10 days J Clearance of P. haemolytica,
persistent up to 10 days PE.
Reference
Jakab (1992)
Jakab (1993)
Baskerville
et al. (1988)
Hahon et al.
(1985)
Grose et al.
(1985)
Gilmour et al.
(1989a)
Gilmour et al.
(1989a)

-------
TABLE 11-24 (cont'd). EFFECTS OF PARTICIPATE MATTER ON MICROBIAL INFECTIVITY
Species, Gender, Particle
Strain, Age, or Exposure Mass Characteristics
Particle Body Weight Technique Concentration
Og/m3) size (>m); ag
TiO2 Mouse, Harlan- Whole body 20,000 95% <1.98 //m
Olac, 8 weeks (UDS)




Key to abbreviations :
i : decrease
PE: post-exposure


Exposure Duration Observed Effect

20 h/day, 7 days i Response to bacterial
antigens of
mediastinal lymph node
lymphocytes from mice
inoculated with P. haemolytica
after exposure.





Reference

Gilmour et al.
(1989b)








-------
specific cytotoxic lymphocytes.  However, repeated exposure to 10,000 //g/m3 carbon black did
not alter any of these antimicrobial defense systems.
     Particles of low intrinsic toxicity may impair mechanisms involved in the clearance of
bacteria, perhaps increasing their persistence and resulting in increased infectivity. To examine
this possibility, a study was aimed at determining whether animals (guinea pigs) in which
phagocytic activity was impaired by exposure to a high concentration (23,000 //g/m3) of an
"inert" dust (TiO2) were more susceptible to bacterial infection, in this case due to Legionella
pneumophila (Baskerville et al.,  1988). While those AMs having heavy burdens of TiO2
particles did not phagocytize  the bacteria, there was no increase in infectivity in particle-exposed
compared to air-exposed control animals; this was suggested to be due to the recruitment of
monocytes into the lungs of the TiO2-exposed animals, and these cells were able to phagocytize
the bacteria.
      The studies presented in Table 11-24 indicate that particles inhaled even at high
concentrations did not reduce resistance to microbial infections. However, some changes  were
noted in an instillation study.   Hatch et al. (1985) examined various particles administered by
intratracheal instillation for their ability to alter infectivity in mice subsequently exposed to a
bacterium (Streptococcus sp). The specific particle types and their sizes (VMD) were as
follows: conventional coal combustion fly ash from various sources  (0.5 //m); various samples
of fluidized bed combustion coal fly ash (0.4 to 1.3 //m); various samples of oil combustion fly
ash (0.8-1.3//m); volcanic ash (1.4 and 2.3//m); latex (0.5 and 5 //m); and urban air particles
(0.4 //m) from Dusseldorf, Germany, Washington, DC, and St. Louis, MO. The instillation dose
was 100 //g particles/mouse.  An increase in infectivity was found with  all  oil fly ash samples,
some of the combustion and fluidized bed coal fly ash samples, ambient air particles from
Dusseldorf and Washington, latex, and also from carbon and ferric oxide particles of unstated
size. Exposure to volcanic ash, St. Louis ambient particles, and other coal fly ash samples did
not have an effect. It was postulated that the activity of the fly ash reflected either the speculated
presence of metals or the ability  of the ash to alter the pH of airway fluid. In a corollary to the
above study, rabbit AMs were incubated for 20 h with the various particles and cell viability
assessed.  Viability was reduced by all oil fly ash samples, coal fly ash,  ambient particles from
all three sites,
                                          11-157

-------
volcanic ash and latex.  These results did not totally correlate with the response following
in vivo exposures.
     To examine effects of particles on nonimmunological antiviral defense, Hahon et al.
(1983) exposed monolayers of mammalian cells (rhesus monkey kidney cell line) to coal
combustion fly ash (2.5 //m)  at 500 to 5,000 //g/10 ml medium and assessed effects on
interferon.  Induction of interferon due to infection with influenza and parainfluenza virus was
reduced when the cells were pretreated with the fly ash. This was suggested to be due to either
the matrix itself, or to some surface component which was not extractable with either polar or
nonpolar solvents.
     One study examined the effect of two larger particles on infectivity. Grose et al. (1985)
instilled (42 //g/animal) mice (CD-I, F, 4 to 8 weeks) with two sizes of volcanic ash from Mt.
St. Helens, namely coarse mode (12.1 //m MMAD, og=2.3) and fine mode (2.2 //m MMAD,
og=1.9), followed by challenge with bacteria (Streptococcus sp.) immediately  or 24 h
postexposure. No particle size related difference was noted in susceptibility to bacterial
infection, with both sizes producing a similar increase in infection following bacterial  challenge
at 24 h, but not immediately, after pollutant exposure. However, inhalation exposure to 9,400
     3 volcanic ash (0.65 //m) for 2 h produced no change in infectivity (Table 1 1-24).
11.8.5.3   Iniiminologic Defense
     The few studies on effects of inhaled particles on respiratory tract immune function are
shown in Table 1 1-25. Particles may affect some aspects of immune defense and not others.
For example, fly ash did not produce any change in the cellular immune response, namely
delayed hypersensitivity, but did depress the ability of macrophages to enhance T-cell
mitogenesis (Zarkower et al., 1982).

11.8.6 Systemic Effects

     A few studies have examined systemic effects of inhaled particles. One assessed the ability
of particles to affect systemic immune responses (Eskew et al., 1982).  Mice (F, BALB/C) were
continuously exposed for various times to coal combustion fly ash (32% by wt <2.1 //m), and
the antigenic response of spleen cells to protein derivatives after
                                         11-158

-------
TABLE 11-25. EFFECTS OF PARTICIPATE MATTER ON RESPIRATORY TRACT IMMUNE FUNCTION
Species, Gender,
Strain, Age, or Exposure
Particle Body Weight Technique

Fly ash Rat, M/F, F-344, Whole body
(fluidized bed 12 weeks
coal
combustion)
Fly ash Rat, M/F, Whole body
(pulverized F-344, 12 weeks
coal
combustion)
Fly ash (coal) Mouse, F BALB/C; Whole body
C57BL 6-8 weeks









Key to abbreviations :
AM: macrophage
PE: post-exposure
IL = interleukin
T : increase
i : decrease

Mass
Concentration
C"g/m3)
36,000



37,000



760
(fine particle
fraction, <2. 1
//m)



2,200
(fine particle
fraction, <2. 1
//m)






Particle Characteristics

Exposure Duration Observed Effect
Size (,um); ag
3.6 (MMAD); 2.0 7 h/day, 5 days/week, No effect on humoral immune
4 weeks function.


2.7 (MMAD); 2. 1 7 h/day, 5 days/week, i Antibody response at 48 weeks
4 weeks PE.


32% < 2. 1 /*im 28 days (continuous) i Ability of AMs to stimulate
(by wt) PHA-induced T-lymphocyte
mitogenesis.

160 days (continuous) No change in ability of animals
sensitized with BCG during
exposure to respond to purified
protein derivative challenge
(delayed hypersensitivity
cellular immune response).









Reference

Bice et al.
(1987)


Bice et al.
(1987)


Zarkower et al.
(1982)
















-------
sensitization with BCG (delayed hypersensitivity reaction) was examined, as was the mitogenic
response of spleen cells to concanavalin A or lipopolysaccharide (LPS). Exposure for 1 to
8 weeks to 1,150 //g/m3 reduced the mitogenic response of spleen cells after 3 weeks of
exposure, but not after 5 or 8 weeks and only for concanavalin A. Exposure for 5 mo to 2,220
Mg/m3 increased thymidine incorporation into spleen cells from BCG-sensitized mice. Finally,
exposure for 5 weeks to 871 //g/m3 reduced the number of antibody plaque forming cells in the
spleen  and the hemagglutinin titer.  These results suggest that fly ash has little effect on the
cellular immune response, but depresses the humoral response. The implications of the increase
in thymidine incorporation into the spleen of BCG-sensitized mice was not clear, but may
indicate an increase in resistance to infection.
     In another study of systemic immunity, Mentnech et al. (1984) exposed rats (F344, M,
whole body) to 2,000 //g/m3 coal dust (40% <7//m) for 7 h/day, 5 days/week for 12 or 24 mo.
The number of antibody-producing cells in the spleen 4 days after immunization with sheep red
blood cells was used as a test of effects on humoral immunity, while the proliferative response of
splenic T-lymphocytes to the mitogens concanavalin A and phytohemagglutin was used to assess
cellular immunity. No  changes were found.

11.8.7  Toxicological  Interactions of Other Particulate Matter
         Mixtures

11.8.7.1   Laboratory Animal Toxicology Studies of Particulate Matter Mixtures

     Toxicological interactions with PM may be antagonistic, additive, or synergistic
(Mauderly, 1993). The presence and nature of any interaction seems to depend upon the
concentration of pollutants in the mixture, the exposure duration,  and the endpoint being
examined, and it is not possible to predict a priori from the presence of certain pollutants
whether there will be any interaction.
     Mechanisms responsible for the various forms of interaction are generally not known. The
greatest hazard in terms of potential health effects from pollutant interaction is the possibility  of
synergism, especially if effects occur at all with mixtures which do not occur at all when the
individual constituents are inhaled.  Various broad mechanisms may underly synergism.  One is
physical, the result of adsorption or absorption of one material on a particle and subsequent
transport to more sensitive sites, or sites where this material  would not normally deposit in toxic
amounts.  This may explain the interaction found in studies of
                                         11-160

-------
mixtures of carbon black and formaldehyde, or carbon black and acrolein (Jakab, 1992, 1993),
especially since formaldehye has been shown to be absorbed onto particles (Rothenberg et al.,
1989).
     Somewhat related to this hypothesis is the possibility of reactions on particle surfaces,
forming some secondary products which may be more lexicologically active than the primary
material and which is then carried to some sensitive site. This may explain the results of the
Jakab and Hemenway (1993) study, wherein mice were exposed to carbon black either prior to
or after exposure to O3, and then to both materials simultaneously. Simultaneous exposure
produced evidence of interaction, while exposure to carbon black either before or after O3 did
not produce responses which were different from that due to exposure to O3 alone. The authors'
suggested that this was due to a reaction of O3 on the surface of the carbon black particles in the
presence of adsorbed water, producing surface bound, highly lexicologically active reactive
oxygen species. Production of these species would not occur when the exposures were
sequential.
      Another mechanism may involve a pollutant-induced change in the local
microenvironment of the lung, enhancing the effects of the co-inhalant. Thus, the observed
synergism in rats between O3 and acidic sulfates was  suggested to be due to a shift in the local
microenvironmental pH of the lung following deposition of acid, enhancing the effects of O3 by
producing a change in the reactivity or residence time of reactants, such as radicals, involved in
O3-induced tissue injury (Last et al.,  1984). This hypothesis was examined in a series of studies
(Last et al., 1983, 1984, 1986; Last and Cross, 1978; Warren and Last, 1987; Warren et al.,
1986) in which rats were exposed to various sulfur oxide aerosols [H2SO4, (NH4)2SO4, Na2SO4]
with and without oxidant gases (O3 or NO2), and various biochemical endpoints examined.
Acidic sulfate aerosols alone did not produce any response at concentrations that caused a
response in conjunction with O3  or NO2.  Further evidence that the synergism was due to FT was
the finding that neither Na2SO4 nor NaCl was synergistic with O3  (Last et al., 1986). But if this
was the only explanation for acid/O3 interaction, then the effects of ozone should be consistently
enhanced by the presence of acid in an exposure atmosphere regardless of endpoint examined.
However, in the study of Schlesinger et al. (1992b), in which rabbits were exposed for 3 h to
combinations of 0.1, 0.3, and 0.6 ppm O3 with 50, 75, and  125 //g/m3 H2SO4 (0.3 //m),
antagonism was noted
                                         11-161

-------
when evaluating stimulated production of superoxide anion by AMs harvested by lavage
immediately after exposure to 0.1 or 0.3 ppm ozone in combination with 75 or 125 //g/m3
H2SO4, and also for AM phagocytic activity at all of the ozone/acid combinations; there was no
change in cell viability compared to air control.
     The database for binary mixtures containing PM other than acid sulfates is quite sparse.
But as with acidic sulfates, interaction depends upon pollutant combinations,  exposure regimen
and biological endpoints (see Table 11-26). Some interaction was noted following exposure of
mice to mixtures of 9,400 //g/m3 volcanic ash and 2.5 ppm SO2 (Grose et al.,  1985), in  that
synergism was suggested in terms of immune cell activity and numbers but no interaction was
found with overall bacterial infectivity.  On the other hand, exposure of mice to various
concentrations of carbon black and formaldehyde (HCHO) produced no evidence of interaction
in terms of bacterial infectivity but possible synergism in terms of macrophage phagocytic
activity (Jakab, 1992).
     The infectivity study of Jakab (1993), in which mice were exposed to acrolein and carbon
black (Table 11-26), is of interest because, as mentioned earlier, the microbial agents were
selected on the basis of the defense mechanisms they elicited. The results indicated that while
particle or acrolein exposure alone did not alter infectivity from any of the microbes, exposure to
the mixture did, and also suggested differential effects on different aspects of antimicrobial
defense.  For example, the increase in intracellular killing of P. mirabilis was ascribed to the
increase in PMN levels after bacterial challenge. The reduced effectiveness for L.
monocytogenes and influenza virus were somewhat more persistent, which led the authors to
suggest that the particle/gas mixture had a greater impact upon acquired immune defenses than
on innate defense mediated by AMs and PMNs, this being the major defense  against S. aureus
and P. mirabilis.
     Another complex mixture examined was a combination  of gaseous sulfur (IV), particulate
sulfur (IV) and paniculate  sulfur (VI). A series of studies involved exposures (whole body) of
Beagle dogs (M, 34 mo old) for 22.5 h/day, 7 days/week for up to 290 days to such an
atmosphere, in which respirable sulfur IV (0.6 //m MMAD, og=2) was maintained at a
concentration of 300 Mg/m3 (Heyder et al., 1992; Maier et al., 1992; Kreyling et al., 1992;
Schulz et al., 1992; Takenaka et al., 1992).  Various biological endpoints were examined, and
responses included reductions in nonspecific defense
                                         11-162

-------
TABLE 11-26. TOXICOLOGIC INTERACTIONS TO MIXTURES CONTAINING NON-ACID AEROSOL PARTICLES
Co-pollutant
Chemical //g/m3 ppm
S02 2,500 —
SO2 2,500 —
S02 2,500 —
SO2 2,500 —
HCHO 1,000; 2.4-
3
HCHO — 4.1-
5
SO2 2,500 —
HCHO — 2.4-
3
Particle
Chemical ,ug/rn3 (//m) . AP^U1"
Exposure Regime Conditions
Volcanic 9,400 2h Whole body
ash (0.65 //m,
MMAD,
ag=1.8)
Volcanic 9,400 2 h Whole body
ash (0.65 //m,
MMAD,
ag=1.8)
Volcanic 9,400 2h Whole body
ash (0.65 //m,
MMAD,
ag=1.8)
Volcanic 9,400 2 h/day, 5 days Whole body
ash (0.65 fj.m,
MMAD,
ag=1.8)
C black 1,000; 4h Nose-only
2,400-6,80
0
(2.45 //m,
MMAD,
ag=2.54)
C black 4,800- 4h Nose-only
13,200
Volcanic 9,400 2 h Whole body
ash (0.65 fj.m,
MMAD,
ag=1.8)
C black 2,400-6,80 4h Nose-only
0
(2.45 f^m,
MMAD,
ag=2.54)
Species, Gender
Strain, Age or
Body Weight
Mouse, F,
CD-I,
4-8 weeks
Rat, M,
Sprague-Dawley,
60-70 days
Rat, M,
Sprague-Dawley,
60-70 days
Rat, M,
Sprague-Dawley,
60-70 days
Mouse, F,
Swiss, 20-23 g
Mouse, F,
Swiss, 20-23 g
Rat, M,
Sprague-Dawley,
60-70 days
Mouse, F,
Swiss, 20-23 g
Endpoints
Infectivity to Group C
Streptococcus or virus
given 0 or 24 h after
exposure
Lavaged cell nos. at 0 or
24hPE
AM phagocytosis at
0 or 24 h PE
Splenic lymphocyte
response to mitogen
(phytohemogglutinin)
Infectivity of S. aureus
administered prior to
pollutant; differential
counts in lavage
Infectivity of S. aureus
administered prior to
pollutant; differential
counts in lavage
Tracheal ciliary beat
frequency at 0, 24, 72 h
PE
Infectivity of S. aureus
administered prior to
pollutant; differential
counts in lavage
Response to
Mixture
No change in
susceptibility
to infection
T PMN;
T lymphocytes;
I AM (no change
in total cell
no.)
I phagocytic
activity
Decrease
None
None
Decrease
None
Interaction
None
Possible at 0 h:
effect greater
than either
pollutant
alone; similar to
SO2 alone at 24 h
Possible at 0 hr:
effect greater
than either
pollutant alone;
at 24 h: similar
to SO2 alone
Possible
synergism:
no effect
with either
pollutant alone
None
None
None: same as
ash alone
None
Reference
Grose et al.
(1985)
Grose et al.
(1985)
Grose et al.
(1985)
Grose et al.
(1985)
Jakab
(1992)
Jakab
(1992)
Grose et al.
(1985)
Jakab
(1992)

-------
TABLE 11-26 (cont'd). TOXICOLOGIC INTERACTIONS TO MIXTURES
         CONTAINING NON-ACID AEROSOL PARTICLES
Co-pollutant
Chemical //g/m3 ppm
HCHO — 1

HCHO — 4.1-5

HCHO — 1.8-2.8
5



HCHO — 5

Acrolein — 2.5








Particle
Chemical //g/m3 (//m) Exposure
Exposure Regime Conditions
C black 1,000; and 4h Nose-only
2,400-6,800
(2.45//mMMAD,
ag = 2.54)

C black 4,800-13,200 4h Nose-only
(2.45 Aim,
MMAD,
ag=2.54)

C black 4,700-6,100; 4h/day, 4 days Nose-only
10,000



C black 10,000 4h/day, 4 days Nose-only

C black 10,000 4h/day, 4 days Nose-only
(2.4 //m,
MMAD'
a=2.75)








Species, Gender
Strain, Age or
Body Weight Endpoints
Mouse, F, Infectivity of
Swiss, 20-23 g S. aureus
administered prior
to
pollutant;
differential
counts in lavage
Mouse, F, Infectivity of
Swiss, 20-23 g S. aureus
administered prior
to
pollutant;
differential
counts in lavage
Mouse, F, Infectivity of
Swiss, 20-23 g S. aureus
administered 1 day
after last
pollutant
exposure;
differential
counts in lavage
Mouse, F, Fc-receptor
Swiss, mediated
20-23 g M0 phagocytosis up
to 40 days PE

Mouse, F, Infectivity to
Swiss, 20-23 g S. aureus,
P. mirabilis,
L. monocytogenes;
influenza A virus
administered 1 day
PE






Response to
Mixture
None

None

None



i Phagocytic
activity from
day 25 PE, return
to normal by day 40
PE
i Elimination of
virus; i killing of
L. monocytogenes;

i killing of
S. aureus;
T killing of
P. mirabilis
T PMN count
4 h after
P. mirabilis
challenge;
No change total
cell no. by lavage
after S. aureus
Interaction
None

None

None



Possible
synergism: no
3-day effect of
C black or HCHO
alone
Possible
synergism: no
effect of either
alone
Possible: no
effect of C black
Possible:
greater than
either alone


None

Reference
Jakab (1992)

Jakab (1992)

Jakab (1992)



Jakab (1992)

Jakab (1993)









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TABLE 11-26 (cont'd). TOXICOLOGIC INTERACTIONS TO MIXTURES
         CONTAINING NON-ACID AEROSOL PARTICLES
Co-pollutant

Chemical //g/m3 ppm

S02 2,700 —





Particle

Chemical /^g/m3 (//m) Exposure
Regime
Volcanic 9,400 2 h/day, 5 days
ash (0.65,
MMAD,
ag=1.78)


Species,
Gender
Exposure Strain, Age or Endpoints
Conditions Body Weight
Whole body Rat, Pulmonary
Sprague-Dawley mechanics
(40 days)




Response to
Mixture Interaction

Reduced tidal None: effect due
volume and peak to SO2
expiratory flow;
no effect on
breathing
frequency


Reference

Raub et al.
(1985)





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capabilities of AMs such as phagocytosis and production of reactive oxygen species; increases in
protein and p-N-acetylglucosaminidase in lavage fluid; increased rate of clearance of test
particles from lungs to blood (suggesting a change in the permeability of the epithelium); minor
changes in pulmonary function; and some histopathological effects, such as hyperplasia of
respiratory epithelium of the posterior nasal passages and a slight (but not statistically
significant) decrease in the volume density of alveolar septa.  The exact role played by specific
components of this mixture could not be determined because responses to individual components
were not examined.

11.8.7.2   Human Studies of Particulate Matter Mixtures  Other Than Acid Aerosols
     Few studies have  examined the effects of particles other than acid aerosols, despite the fact
that ambient particulate matter consists of a mixture of soluble and insoluble material of varying
chemical composition.  Human safety considerations limit experimental exposures to particles
considered to be essentially inert and non-carcinogenic. As reviewed in the 1982  Criteria
Document (U.S. Environmental Protection Agency, 1982), Andersen et al. (1979) examined
effects on healthy subjects of exposure to Xerox toner at concentrations ranging from 2,000 to
25,000 //g/m3. These concentrations are not relevant to outdoor environmental exposures.
Nevertheless, the studies were remarkable for the virtual absence of symptomatic or lung
functional responses.
     Utell et al. (1980) exposed healthy young subjects with acute influenza to a NaNO3 aerosol
(0.5 //m) or NaCl (control), and observed significant reductions in specific airway conductance
in response to the NaNO3 aerosol, but not to NaCl aerosol, for up to 1 week following the acute
illness.  These studies suggested that individuals with acute viral illness may experience
bronchoconstriction from particulate nitrate pollutants that do not have effects on healthy
subjects. However, the concentration of particles in these experiments was ~7,000 //g/m3, more
than 100 times greater than peak ambient concentrations.
     Three more recent studies have attempted to examine effects of exposure to carbon black
particles, either alone or in combination with  other pollutants (see Table 11-27).  First, Kulle et
al. (1986) exposed 20 healthy nonsmokers (10 males and 10 females) to air, 0.99 ppm SO2, 517
Mg/m3 activated carbon aerosol (MMAD =1.5 //m, GSD = 1.5),  and  SO2 + activated carbon for
four hours in an environmental chamber. Two 15-minute
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  TABLE 11-27. CONTROLLED HUMAN EXPOSURE STUDIES OF
PARTICULATE MATTER MIXTURES OTHER THAN ACID AEROSOLS
Ref.
Green et
al. (1989)





Kulle et
al. (1986)



Yang and
Yang
(1994)





Subjects
24 healthy
18to35yrs





20 healthy
20 to 35 yrs



30 healthy
25 asthmatic
23 to 48 yrs





MMAD2 GSD3 Temp RH
Exposures1 (/^m) (/^m) Duration Exercise (°C) (%)
Air; activated 1.4 1.8 2h 15 of each 22 65
carbon 510 //g/m3; 30 min.,
HCHO 3.01 ppm; 57 L/min
carbon 510 //g/m3
+ HCHO 3.01 ppm


Air; activated 1.5 1.5 4h 15 minx 2, 35 22 60
carbon 517 //g/m3; L/min
SO2 0.99 ppm;
carbon 517 //g/m3
+ SO2 0.99 ppm.
Mouthpiece: 30 min At rest
Bagged polluted
air,
TSP = 202 //g/m3




Symptoms
Increased
cough with
carbon +
HCHO



No symptoms
related to
carbon
exposure









Lung Function
No direct effects
of carbon.
Additive effects
of carbon + HCHO on
FVC, FEV3, peak
flow; decrements
less than 5%.
No direct or
additive effects
of carbon exposure


Healthy subjects:
no change
Asthmatics: iFEVj
=7%




Other Effects












Increased
airway
responsiveness
in asthmatics
reported; no
allowance for
change in
airway caliber
Comments












No control
exposure







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exercise periods (VE = 35 L/min) were included in the exposure. The exposure days were
separated by one week and were bracketed by control air exposures on the day prior to and the
day following the experimental exposure. Measurements included respiratory symptoms,
spirometry, lung volumes, and airway responsiveness to methacholine.  The carbon aerosol
exposure resulted in no significant effects on symptoms or lung function, and exposure to carbon
+ SO2 did not enhance the very small effects on lung function seen with SO2 alone. Results of
methacholine challenge testing were not provided.
     Second, a separate report from the same laboratory (Green et al., 1989) examined potential
interactions between formaldehyde (HCHO) and carbon exposure.  Twenty-four healthy
nonsmokers without airway hyperresponsiveness were exposed for two hours to air, 3 ppm
HCHO, 510 //g/m3 activated carbon aerosol  (MMAD = 1.4 //m, GSD = 1.8) and HCHO +
carbon. Exposures incorporated exercise (VE = 57 L/min) for 15 of each 30 minutes.  The
exposures were separated by one week. Measurements included symptoms, spirometry, lung
volumes, and serial measurements of peak flow.  There were no significant effects on symptoms
or decrements in lung function with exposure to carbon alone. The combination of carbon and
HCHO increased cough at 20 and 80 minutes of exposure when  compared to either pollutant
alone.  There were also small (less than 5%) but statistically significant decrements in FVC,
FEV3, and peak flow with carbon + HCHO,  compared with either pollutant alone.  The authors
speculated that the enhancement of cough with carbon + HCHO resulted from increased delivery
of HCHO adsorbed to carbon.
     Finally, the studies by Anderson et al.  (1992), summarized previously, were designed to
test the hypothesis that inert particles in ambient air may become coated with acid, thereby
delivering increased concentrations of acid sulfates to "sensitive" areas  of the respiratory tract.
Carbon black particles (MMAD ~ 1 //m, GSD ~2 //m) were coated with H2SO4 using fuming
H2SO4. Electron microscopy findings suggested successful coating of the particles. Fifteen
healthy and 15 asthmatic subjects were exposed for 1 h to acid-coated carbon, with a total
suspended particulate concentration of 358 //g/m3 for asthmatic subjects and 505 //g/m3 for
healthy subjects.  On separate occasions, subjects were also exposed to carbon black alone
(-200 //g/m3, estimated as the difference between total suspended particulate and non-carbon
particulate concentrations), H2SO4 alone (~ 100 //g/m3), and air.
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No adverse effects of particle exposure on lung function or airway responsiveness were observed
for either study group.
     Clinical studies of single particulate pollutants or simple mixtures may not be
representative of effects that occur in response to complex ambient mixtures.  In an attempt to
examine effects of an ambient air pollution atmosphere under controlled laboratory conditions,
Yang and Yang (1994) exposed 25 asthmatic and 30 healthy subjects to polluted air collected in
a motor vehicle tunnel in Taiwan.  This compressed air sample contained 202 //g/m3 particles as
well as 0.488 ppm NO2, 0.112 ppm SO2, and 3.4 ppm carbon monoxide (CO).  The chemical and
size characteristics of the particles were not provided. Mouthpiece exposure to polluted air was
performed at rest for 30 min, and lung function and methacholine responsiveness were assessed
after exposure. Small but significant decrements in FEVj and FVC were observed in asthmatic,
but not healthy subjects when compared with baseline measurements. However, no control
exposure to air was performed, which seriously limits interpretation of these results. The small
decrements in lung function could have resulted from exposure conditions other than the
pollutants, such as humidity or temperature of the inhaled air, which were not specified.
     Thus, few studies have examined effects of particles other than acid aerosols on lung
function, although available data suggest inert particles in the respirable range have little or no
acute effects at levels well above  ambient concentrations. Other than the studies of Rudell et al.
on diesel exhaust discussed in Section 11.5.1, no studies have examined effects on mucociliary
clearance,  epithelial inflammation, or host defense functions of the distal  respiratory tract in
humans.
11.9    PHYSICOCHEMICAL AND HOST FACTORS INFLUENCING PARTICULA
        MATTER TOXICITY
11.9.1  Physicochemical Factors Affecting Particulate Matter
         Toxicity

     The physicochemical factors modulating biological responses to PM are not always clear.
However, the available toxicological database does allow for some speculation as to factors
which may influence biological responses to diverse types of PM. For example, the toxic
potency of inorganic particles may be related to certain physicochemical characteristics.
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While the bulk chemical makeup of a particle would clearly influence its toxicity, responses may
also be driven by chemical species adsorbed onto the particle surface, even for those particles
considered to have low intrinsic toxicity. Furthermore, certain physical properties of particles,
such as size or surface area, and of aerosols, such as number concentration, may be factors in
determining reponses to PM.  This section provides an overview of current hypotheses
concerning particle characteristics which may relate to toxicity.
     Particle Acidity: It should be clear from discussions in Section 11.2 that the deposition of
acidic particles in the respiratory tract can result in various biological effects. The bulk of the
toxicologic database on acidic PM involves sulfate particles, primarily H2SO4 and the available
evidence indicates that the observed responses to these are likely due to the FT, rather than to the
SO4.  Thus, effects observed for this pollutant likely apply to any acidic particle having a
similar deposition pattern  in the respiratory tract, although the specific chemical composition of
different acids may be a factor mediating the quantitative response (Fine et al., 1987a).  In terms
of FT, the irritant potency  of an acid aerosol may be related more to the total available FT
concentration (i.e., titratable acidity in lung fluids following deposition)  rather than to the free
FT concentration as measured by pH (Fine et al., 1987b). In any case, the response to acidic
particles appears to be due to a direct irritant action and/or the subsequent release of humoral
mediators.
     Acidic particles exert their action throughout the respiratory tract, with the response and
location of effect dependent upon particle size and mass concentration.  They have been shown
to alter bronchial responsiveness, mucociliary transport, clearance from the pulmonary region,
regulation of internal cellular pH, production of cytokines and reactive oxygen species,
pulmonary mechanical function, and airway morphology.
     Particles do not have to be pure acid droplets to  elicit health effects.  The acid may be
associated with another particle type. For example, in the study of Chen et al. (1990), guinea
pigs were exposed to two  different fly ashes, one derived from a low sulfur coal and one from a
high sulfur coal  (Table 11-19). Levels of acidic sulfates associated with the fly ash were found
to be proportional to the coal  sulfur content, and greater effects on pulmonary functional
endpoints were noted for the high sulfur fly ash than for the low  sulfur fly ash.
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     Particle Surface Coatings: The presence of surface coatings may make certain particles
more toxic than expected based solely upon particle core composition.  This was noted in studies
of acid-coated metal oxides (Section 11.2.3) and is discussed in greater detail in Section 11.3.8.
Certain surface metals may be especially important in this regard, and because trace metal
species vary geographically, this may account to some extent for  particles in different areas
having different toxic potentials.
     Particle Size: Studies which have examined PM-induced mortality seem to suggest some
inherent potential toxicity of inhaled ultrafine particles (Section 11.4), and other endpoints
appear to show this as well.  This is especially important when considering particles which may
have low inherent toxicity at one size, yet greater potency at another. However, the mechanism
which underlies a size-related difference in toxicity is not known  at this time.
     To compare toxic potency of particles of different sizes, intratracheal instillation has often
been used.  This technique allows the delivery of equivalent doses of different materials and
avoids differences in deposition which would occur if particles of different sizes were inhaled.
While this approach may highlight inherent similarities and differences in responses to particles
of various sizes, in reality, there would be greater deposition of singlet ultrafine particles (in the
size range used in the toxicology studies described) in the lungs, especially within the alveolar
region, than for the larger fine or coarse mode particles.
     The release  of proinflammatory mediators may be involved  in lung disease, and their levels
may be increased with exposure to ultrafine particles. For example, Driscoll and Maurer (1991)
compared effects  of instilled fine (0.3 //m) or ultrafine (0.02 //m)  TiO2, in rat (F344) lungs.
Concentrations were 10,000 //g particles/kg BW.  Lavage was performed up to 28 days
post-exposure, and pathology was assessed at this 28-day time point.  While both size modes
produced an increase in the number of AMs and PMNs in lavage, the increase was greater and
more persistent with the ultrafine particles.  The release of another monokine, tumor necrosis
factor (TNF), by AMs was stimulated with both sizes, but again the response was greater and
more persistent for the ultrafmes. A similar response was noted for fibronectin produced by
AMs. Finally, fine particle exposure resulted in a minimally increased prominence of
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particle-laden macrophages associated with alveolar ducts, while ultrafine particle exposures
produced somewhat of a greater prominence of macrophages, some necrosis of macrophages and
slight interstitial inflammation associated with the alveolar duct region. In addition, increased
collagen occurred only with ultrafine particle exposure.
     Oberdorster et al. (1992) instilled rats with 500 //g TiO2 in either fine (0.25 //m) or
ultrafine (0.02 //m) sizes, and performed lavage 24 h later.  Various indicators of acute
inflammation were altered with the ultrafine particles; this included an increase in the number of
total cells recovered, a decrease in percentage of AMs and increase in percentage of PMNs, and
an increase in protein.  On the other hand, instillation of the fine particles did not cause
statistically significant effects. Thus, the ultrafine particles had greater pulmonary inflammatory
potency than did the larger size particles of this material. The investigators attributed enhanced
toxicity to greater interaction of the ultrafine particles, with their large surface area, with
alveolar and interstitial macrophages, resulting in enhanced release of inflammatory mediators.
They suggested that ultrafine particles of materials of low in vivo solubility appear to enter the
interstitium more readily than do larger size particles of the same material, which accounted for
the increased contact with macrophages in this compartment of the lung. In support of these
results, Driscoll and Maurer (1991) noted that the pulmonary retention of ultrafine TiO2 particles
instilled into rat lungs was greater than for the same mass of fine mode TiO2 particles.
     Not all ultrafine particles will enter the interstitium to the same extent, and this may
influence toxicity. For example, both TiO2 (-20 nm) and carbon black (-20 nm) elicit an
inflammatory response, yet much less of the latter appears to enter the interstitium after exposure
(Oberdorster et al., 1992). Since different particles may induce chemotactic factors to different
extents, it is possible that less chemotoxis with TiO2 results in less contact with and phagocytosis
by macrophages,  a longer residence time at the area of initial deposition, and a resultant greater
translocation into the interstitium.  Similarly, Brown et al. (1992; Table 11-23) noted following
inhalation exposure of rats to TiO2 or coal mine dust that the former did not affect macrophage
chemotaxis, while the latter reduced it; the coal dust also produced a greater inflammatory
response than did the TiO2. This is consistent with less interaction of coal dust with AMs and
greater movement into the interstitium.
     The above studies appear to support the concept of some inherent toxicity of ultrafine
particles compared to larger ones. Both particle size and the resultant surface  area of a unit
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mass of particles likely influences toxic potential.  Surface area is important because, as noted
above, adsorption of certain chemical species on particles may enhance their toxicity, and this
could be an even greater factor for ultrafine particles with their larger surface area per unit mass.
     Other studies have compared effects following exposures to larger than ultrafine particle
sizes, and the results ranged from none detectable to some particle size-related differences.
Raub  et al.  (1985) instilled into rats coarse mode (12.2 //m) and fine mode (2.2 //m) volcanic ash
at two dose levels, 50,000 or 300 //g particles/animal.  The coarse mode produced a change in
end expiratory volume, but no changes in other pulmonary function endpoints (i.e., frequency,
VT, peak inspiratory and expiratory flows, VC, RV, TLC). When lungs were examined 6 mo
after instillation, animals exposed to the low dose of either size fraction showed no changes in
lung weight or hydroxyproline content compared to control, while those exposed to the high
concentration of coarse mode ash showed increased lung weight.  In terms of histopathology,
both size modes produced some focal alveolitis.  Thus, there were essentially no differences in
responses between the two size modes, especially at the low exposure dose.  In a similar study,
Grose et al. (1985) instilled mice with 42 //g/animal of volcanic ash in the same two size
fractions as above, coarse and fine, 24 h prior to challenge with bacteria (Streptococcus sp.).  A
small, but similar, increase in susceptibility to infection was noted with both particle sizes.
      Shanbhag et al. (1994) exposed a mouse macrophage cell line (P388D1) to particles of two
different composition (TiO2 or latex) at comparable sizes, 0.15  and 0.45 //m  for the former, and
0.11 and 0.49 for the latter. They also used pure titanium at 1.76 //m for comparison to latex at
1.61 //m. In order to examine effects of particle surface area, the cells were exposed to a
constant surface area of particles, expressed in terms of mm2 per unit number of cells.  This was
obtained based upon particle size and density and,  therefore, the weight percentage was greater
for larger particles than for smaller ones for the same surface area. Furthermore, because of
particle density differences, the weight percentage for similarly sized particles of different
materials to obtain the same surface area also differed.  The authors noted that at a constant total
particle surface area to cell ratio, the 0.15 and 0.45 //m particles were likely to be less
inflammatory than were the 1.76 //m particles, in that the smaller particles produced lower
elicited levels of interleukin-1 and less cell
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proliferation. These results indicate that the larger particles had greater toxicity than the smaller
ones in this experimental system.  Thus, the exact relationship between particle size and toxicity
is not resolved. It may differ for different size modes and may also depend on the specific
experimental system used.
     Particle Number Concentration: The number concentration of particles within an aerosol
will increase as the size of the constituent particles decrease.  Thus, for a given mass
concentration of a material, there would be greater particle numbers in an ultrafine aerosol than
in a fine aerosol.  As previously discussed (Section 11.2.3), studies have shown various
biological responses, such as reductions in lung volumes and diffusion capacity, alterations in
biochemical markers, and changes in lung tissue morphology, in guinea pigs following exposure
to ultrafine ZnO having a surface layer of H2SO4. These responses were much greater than were
found following exposure to H2SO4 aerosols in pure droplet form yet having a similar mass
concentration.
     A possible contribution to this differential response is that the number concentration of
particles in the exposure atmospheres were different, resulting in different numbers of particles
deposited at target sites. At an equal total sulfate mass concentration, H2SO4 existed on many
more particles when layered on the ZnO carrier particles than when dissolved into aqueous
droplets (i.e., pure acid aerosol); this was because the particle size distribution of the former
aerosol was  smaller than that of the latter. Therefore, it is possible that the greater the number of
particles containing H2SO4, the greater will be the number of cells affected after these particles
deposit in the lungs, and the more severe will be the overall biological response.  While
differences in particle size distributions between the coated and pure acid particles may have
influenced the results to some extent, a recent study (Chen et al., 1995) confirmed that the
number of particles in the exposure atmosphere, not just total mass concentration, is an
important factor in biological responses following acidic sulfate particle  inhalation when
aerosols having the same size distribution were compared.

11.9.2 Host Factors Affecting Participate Matter Toxicity

     Not only do the differences in particle chemistry and morphology influence responses to
inhalation of particulate matter, but also various factors related to host susceptibility. One
obvious example is the differences associated  with species susceptibility as well as differences
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in dosimetry related to animal mass and lung structure and geometry. Host health status,
specifically the presence of pulmonary inflammation or bacterial or viral infection or nutritional
status also may markedly alter responses to PM.  The presence of chronic pulmonary disease is
also a factor in both animals and humans. Age of the animal, especially very young or very old,
can influence susceptibility.
     Host Health Status:  Epidemiological studies suggest there may be subsegments of the
population that are especially susceptible to effects from inhaled particles (see Chapter 12).  One
particular group may be those having lungs compromised by respiratory disease.  However, most
toxicology studies have used healthy adult animals, and there are very few data to allow
examination of the effects of different disease states  upon the biological response to PM.
A number of studies have examined the effects of lung disease on deposition and/or clearance of
inhaled aerosols, and these are discussed in Chapter  10. Alterations in deposition sites and
clearance rates/pathways due to concurrent disease may impact upon dose  delivered from
inhaled particles, and thus influence ultimate toxicity.
     Some work has been performed with sulfate and nitrate aerosols using models of
compromised hosts. Rats and guinea pigs with elastase-induced emphysema were examined to
assess whether repeated exposures (6 h/day, 5 days/week, 20 days) to (NH4)2SO4 (1,000 //g/m3,
0.4 (j,m MMAD) or NH4NO3 (1,000 //g/m3, 0.6 //m MMAD) would alter pulmonary function
compared to saline-treated controls (Loscutoff et al., 1985).  Similarly,  dogs having lungs
impaired by exposure to NO2 were treated with H2SO4 (889 //g/m3, 0.5 //m, 21 h/day, 620 days)
(Lewis et al., 1973). Results of both of these studies indicated that the specific induced disease
state did not enhance the effect of acidic sulfate aerosols in altering pulmonary function; in
some cases, there were actually fewer functional  changes in the diseased lungs than in the
unimpaired animals. It is possible, however, that other types of disease states could result in
enhanced response to inhaled acidic aerosols; as mentioned,  asthma is a likely one, but there are
no data to evaluate whether effects are enhanced  in animal models  of human asthma.
     Few studies have examined effects of other particles in health compromised host models.
Mauderly et al. (1990) exposed young rats having elastase-induced emphysema to whole diesel
exhaust (3,500 //g soot/m3) for 24 mo (7 h/day, 5 days/week).  Various  endpoints were examined
after exposure, including pulmonary function (e.g., respiratory
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pattern, lung compliance, DLco), biochemical components of BAL (e.g., enzymes, protein,
collagen), and histopathology and morphometry. There was no evidence that the diseased lungs
were more susceptible to the diesel exhaust than were normal lungs. In fact, in some cases, there
seemed to be a reduced effect of the diesel exhaust in the emphysematous lungs. But this could
be due to a reduced lung burden in the diseased lungs, resulting from differences in deposition
and/or clearance compared to normal lungs.
     Rats having elastase-induced emphysema were exposed to 9,400 //g/m3 (0.65 //m) Mt. St.
Helens volcanic ash for 2 h/day for 5 days (Raub et al.,  1985; Table 11-19), with and without
2,700 //g/m3 SO2.  Effects on pulmonary mechanics were similar to those noted in normal
animals exposed to the same atmospheres.
     Raabe et al. (1994) exposed rats with elastase-induced emphysema to two particle
atmospheres, a California-type aerosol and a London-type aerosol. The former consisted of 1.1
to 1.5 //m (MMAD; og = 1.7 to 2.4) particles of graphitic carbon, natural clay, NH4HSO4,
(NH4)2SO4, NH4NO3, and trace amounts of metals (PbSO4, VOSO4, MnSO4, and NiSO4). The
latter consisted of 0.8 to 0.9 //m particles (og = 1.7 to 1.8) of NH4HSO4, (NH4)2SO4,  coal fly ash,
and lamp black carbon. The elastase treated rats showed increased lung DNA and RNA, a
general marker for repair of cell damage. Exposure for 3 days (23 h/day) to the London aerosol
produced a further increase not seen in exposed normal  rats. A 30-day exposure to the
California aerosol enhanced small airway lesions in the  elastase-treated animals. These
preliminary results  suggest that the California aerosol and the London aerosol both caused
significant responses in animals with elastase-induced emphysema, but clarification of these
responses must await a more comprehensive treatment of these data.
     Thus, the available toxicological database indicates only limited evidence of enhanced
susceptibility to PM of "compromised" hosts.  However, these studies were  restricted to
emphysema models and it is not known whether other simulated pulmonary diseases would
enhance susceptibility to PM in laboratory animals.
     Species Differences:  The effects of asbestos-free talc at 6,000 or 18,000 //g/m3 (2.7-3.2
//m) were studied in male and female F344 rats and B6C3F1 mice exposed 6 hours/day 5
days/week for 24 mo  (National Toxicology Program, 1993). In rats and mice exposed to the
higher concentration for 24 mo the specific talc lung burdens (mg/g lung)
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were nearly identical. Rats had a greater increase than mice in lung weight as well as greater
elevations of neutrophils, enzymes and protein in BALF. The histopathology of rats, including
accumulations of talc-filled macrophages, inflammation, epithelial hyperplasia and squamous
metaplasia, and focal fibrosis was identical to that described for other dusts.  The histopathology
differed in that the epithelial hyperplasia and metaplasia, and  focal fibrosis observed in rats was
absent in mice. These findings illustrate that differences between the responses of rats and mice
persist across a wide range of different types of inhaled dusts.
     There are a few reports comparing the responses of other species to chronic dust inhalation
(Mauderly, 1994a). Alarie et al. (1973,  1975) studied the response of cynomolgus monkeys and
guinea pigs chronically exposed to coal combustion fly ash in combination with H2SO4.  In the
study (Alarie et al., 1973), monkeys and guinea pigs were exposed 23+ hours/day 7 days/week
for either 52 weeks (guinea pigs) or 78 weeks (monkeys) to approximately 500 //g ash/m3
(MMAD «2.6//m) in combination with 0.1 to 5.0 ppm sulfur  dioxide.  Although particles
accumulated in the lungs in both species (including bronchial and alveolar deposition) and
caused slight inflammation, type II cell proliferation was observed in guinea pigs but not
monkeys.  In the second study (Alarie et al., 1975), guinea pigs and monkeys were exposed 23+
hours/day 7 days/week for 18 mo to approximately 500 //g ash/m3 (MMAD -4-5//m) in
combination with 100 or 1,000 //g sulfuric acid mist/m3. The effects attributed to fly ash were
similar to those described in the first study.  Comparison between guinea pigs and monkeys in
this series of studies is complicated because the concentrations of co-pollutants and fly ash were
not always equivalent and the deposition pattern of the 2.6-5.3 //m fly ash particles is
undoubtedly different in monkeys than in guinea pigs.
     Comparison of Human and Laboratory Animal Response: There are limited data
allowing direct comparisons of responses of humans and laboratory animals to ambient
particulate matter constituents.  Chronic occupational  exposures to high concentrations of
mineral dusts cause pneumoconioses in human lungs,  consisting primarily of fibrotic responses
with many features similar to those observed in animals. Exposure to silica and dusts with high
quartz content causes granulomatous lesions in both human and animal lungs. Merchant et al.
(1986) provided a comprehensive review of the pulmonary responses to coal  dust in coal
workers. The focal collections of dust (macules) and the progressive focal
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fibrosis have many 1989).  features similar to the responses of rats (Martin et al., 1977; Lewis
et al., Although little information is available on the effects of coal dust in other animals,
Heppleston (1954) reported dust accumulations and responses in the lungs of rabbits and ponies
that were similar to the responses seen in humans. Emphysema, a common feature of
pneumoconiosis even in nonsmoking coal workers (Green et al., 1992) is not a prevalent finding
in other species and is usually found only in association with large scars in rats (Mauderly et al.,
1988). Other features including the epithelial hyperplasia of rodents and squamous metaplasia
of rats are not seen in coal workers' pneumoconiosis.
     There are obviously similarities and differences between animals and humans and among
animals in their responses to chronic dust inhalation. It is not yet clear which, if any, animal
species is a good model for predicting noncancer pulmonary responses of humans to chronic
dust exposure.  The most common bioassay species, rats and mice, clearly differ in their
responses, but it is not clear which best represents humans.
     Age of Animals: There is limited information on the effects of inhaled particles as a
function of changes occurring with age in laboratory animals Mauderly (1989). Mauderly et al.
(1987c) exposed rats for 6 mo to diluted, whole diesel exhaust containing 3500 //g/m3 (MMAD
«0.25//m) soot particles. Effects in rats conceived and born in the exposure chambers and
exposed up to 6 mo of age were compared to those of rats exposed between 6 and 12 mo of age.
Soot accumulated in similar amounts in the lungs of both the young and adult groups, but soot-
laden macrophages formed more intraalveolar aggregates in the adults. Tissue responses
adjacent to the aggregated macrophages were greater in the adults than in the young rats. Lung
weight and the cellularity of pulmonary lymph nodes increased  and particle clearance was
delayed in the older group, but not in the younger group. Exposure throughout the period of
lung development did not cause differences between the lung morphology or respiratory function
of exposed and sham-exposed young rats after they reached adulthood (6 mo of age).  These
results indicate that rats with developing lungs  may be  less susceptible than adults to the effects
of diesel exhaust.
     Mauderly (1989) indicates that there is insufficient information on the influence of age on
the effects of inhaled particles.  It is therefore inappropriate to draw conclusions regarding age-
related susceptibility at the present time.
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11.10  POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS FOR THE EFFECT
        CONCENTRATIONS OF PARTICULATE POLLUTION
11.10.1   Physiological Mechanisms
     The pathophysiologic mechanisms by which low level ambient particle concentrations may
increase morbidity and mortality are not clear. Potential mechanisms might be posited through
examining hypotheses considering the pathological mechanisms by which inhaled particles
might alter normal physiological, immunological, and biochemical processes in the lung.
     In the healthy person, air is drawn into the respiratory tract through a branching airway
network.  Although the large airways of the tracheobronchial region continuously branch into
narrower airways the increase in total cross sectional area makes resistance to airflow low. The
inspired air ultimately enters the alveolar or gas exchange region of the lung where the area
available for the diffusion of gases is large and the distances for diffusion across the respiratory
membrane are minimal.
     In the healthy person, the pulmonary circulation is a low resistance system requiring only
about 1/5 of the pressure required to pump blood through the high resistance systemic circuit.
Any changes in the pulmonary vasculature that increase the resistance to blood flow through the
lungs will impose an additional work load on the right ventricle which, if severe enough in a
compromised individual, could result in right heart failure.
     In considering the potential mechanisms by which increases  in ambient PM might affect
morbidity and mortality, it is important to consider the physiological characteristics of the
population most affected.  In general, the population most susceptible to elevations in ambient
PM is older (see chapter 12) and may have preexisting respiratory  disease.  As the healthy older
population (Folkow and Svanborg, 1993; Dice, 1993; Lakatta, 1993) ages, cardiorespiratory
function, including lung volumes, FEVl3 and cardiac output reserve (Kenney, 1989) decline.
Many of the decrements in physiological function associated with  the aging process also may be
associated with pathological changes caused by disease or other environmental stressors
impacting a person over their lifespan.
     There is little information on the extent to which an elderly population might be more
susceptible to the effects of particulate pollution in the ambient environment (Cooper et al.,
1991).  The elderly might be expected to be more susceptible to parti culate pollution because
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of numerous changes in the body's protective mechanisms. While young and healthy animals
might be more adaptable, older animals and those with chronic illness have a more limited
ability to adapt to environmental stressors.

11.10.2   Physiological-Particle Interaction
     Particles inhaled into the respiratory tract deposit at a variety of sites depending on their
size, shape, and the pulmonary ventilation characteristics of the organism. Once deposited, the
particles may be cleared by from the lung, sequestered in the lymphatics, metabolized or
otherwise transformed by mechanisms described in Chapter 10.
     If the particle mass inhaled into the lung is so excessive that the normal pulmonary
clearance mechanisms are overwhelmed, or if repeated insult from toxic particles has somehow
reduced the ability of normal mechanisms to clear particles, then particles, their degradation
products,  and metabolic products associated with the clearance process may accumulate and
present an additional stress to the organism. This stress may affect the entire organism and not
just the respiratory tract.  While a young healthy organism may tolerate or adapt to the
consequences of an excessive particle load, an older organism or one with chronic respiratory
disease or one rendered more susceptible by other stressors (dietary, crowding, thermal, etc.)
may become sicker or may die. Thus, it is possible that death of an organism may be the result
of an accumulation of lifetime stressors (or, the response to these stressors) that is exacerbated
by the addition of an incremental particle load on the system.
     Cardiorespiratory system function may be compromised and become less efficient in older
people or as a result of disease. Inhaled particles could, conceivably, further compromise the
functional status in such individuals.  Because a small increase in environmental particle
concentrations would not be lethal to most subjects, the terminal event(s) must presumably result
from a triggering or exacerbating of a lethal failing of a critical function,  such as ventilation, gas
exchange, pulmonary circulation,  lung fluid balance, or cardiovascular function in subjects
already approaching the limits of tolerance due to preexisting conditions.
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11.10.3   Pathophysiologic Mechanisms
     It is conceivable that inhaled particles, their reaction products, or the physiological
response to deposited particles may further impair ventilation in the chronically ill individual.
Inhaled particles may induce further bronchoconstriction and increase resistance to air flow by
activating airways smooth muscle, as in asthmatics. Inhaled particles may also influence various
airway secretions that could add to and thicken the mucous blanket leading to mucus plugging or
decreased mucociliary clearance.  Increases in airways resistance would increase the work of
breathing and, in turn, the increased effort would require a greater proportion of the inhaled
oxygen for the respiratory muscles and increase the potential risk of respiratory failure.
     Inhaled particles or their pathophysiological reaction products could also  act at the alveolar
capillary membrane. At this site,  inhaled particles could decrease the diffusing capacity of the
lungs by increasing diffusion distances across the respiratory membrane (by increasing the
thickness of the respiratory membrane) and causing abnormal ventilation-perfusion ratios in
parts of the lung by altering ventilation distribution.
     Inhaled particles, especially ultrafine particles could also act at the level of the pulmonary
vasculature. Inhaled particles or the pathophysiological reaction to inhaled particles could elicit
changes in pulmonary vascular resistance that could further alter ventilation perfusion
abnormalities in people with respiratory disease. Particles could also cause alteration of the
distribution of ventilation by causing changes in airway resistance.  Diseases such as emphysema
destroy alveolar walls as well as the pulmonary capillaries they contain.  This causes a
progressive increases in pulmonary  vascular resistance and elevates pulmonary blood pressure.
The generalized systemic hypoxia could result in further pulmonary hypertension and interstitial
edema that would impose an increased workload on the heart.
     Potential mechanisms which might be evoked to explain the phenomenon of particle
related mortality have been considered by Utell and Frampton (1995). Mechanisms which could
conceivably account for the particle-related mortality include:  (1) "premature"  death, that is the
hastening of death for individuals already near death (i.e., hastening of an already certain death
by hours or days); (2) increased susceptibility to infectious disease; and (3) exacerbation of
chronic underlying cardiac or pulmonary disease.
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     Particulate pollution could contribute to daily mortality rates by affecting those at greatest
risk of dying; those individuals for whom death is already imminent.  Elevated concentrations of
particulate matter, which might be only a minor irritant to healthy people, could be the "last
straw" that tips over the precariously balanced physiology of a dying patient. In developing this
possibility, Utell and Frampton (1995) have compared the effect associated with particulate
matter with that associated with temperature deviations.  Time-series analyses have shown
relationships between temperature changes, regardless of the direction change, and increasing
mortality of a magnitude similar to that described for air pollution (Kunst et al., 1993). While
there are a few deaths that can be  attributed to hyperthermia and hypothermia, the excess
mortality due to moderate temperature deviations is associated primarily with the chronically
and terminally ill.  It is this excess mortality that is likely caused by further stress on over-
burdened compensatory mechanisms.
     However, if particulate air pollution simply represents a physiological stress similar to
thermal stress, and the excess mortality is occurring among individuals who would have died
within days or weeks, one would expect to see a "harvesting effect". That is, following the
increase in mortality associated with an increase in particulate pollution mortality should fall
below baseline, because some of those at risk will have already died.  Although Kunst et al.
(1993) have reported such an effect with temperature-related mortality, it has not been evident in
epidemiology studies of ambient particulate exposure. It is possible however, that epidemiologic
studies may  not be sensitive enough to detect a harvesting effect because the overall changes  in
mortality are small. However, even in the 1952 London Fog episode, there was no decline in
mortality following the peak in excess deaths; instead, increased mortality appeared to remain
somewhat elevated in the days after pollution levels had returned to baseline (Logan, 1953).
     Other studies suggest that the effect of particles on mortality cannot be explained solely by
death-bed effects.  In longitudinal studies, Dockery et al. (1993) and Pope et al. (1995) found a
strong association between particulate air pollution and mortality in U.S. cities after adjusting for
cigarette smoking and other risk factors. Moreover, mortality and respiratory illness in the Utah
Valley have been linked with particulate exposure associated with a steel mill. These findings
indicate an effect on annual mortality rates that cannot be explained by hastening  death for
individuals already near death.
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     Particle exposure could increase susceptibility to infection with bacteria or respiratory
viruses, leading to an increased incidence of, and death from, pneumonia in susceptible members
of the population. Potential mechanisms could include effects on mucociliary clearance,
alveolar macrophage function, adherence of microorganisms to epithelia, and other specific or
nonspecific effects on the immune response.  However, pneumonia rarely results in death within
24 h of onset; serious infections of the lower respiratory tract generally take days or weeks to
evolve. This would potentially contribute to morbidity effects from PM that are lagged by
several days or weeks (Chapter 12).  If pollutant exposure increased susceptibility to infectious
disease, it should be possible to detect differences in the incidence of such diseases in
communities with low vs. high particulate concentrations. It might be expected that emergency
room visits and hospitalizations  for pneumonia caused by the relevant agent should be
measurably higher on days with elevated ambient particle concentrations. Examples of this are
evident in data from several cities (see Chapter 12). Laboratory animal studies indicate that PM
exposure can impair host defenses. Exposure to acidic aerosols has been linked with alterations
in mucociliary clearance and macrophage function. However, bacterial infectivity studies with
exposure to non-acidic aerosols and other particulate species have not been shown
experimentally to cause increased infection.
     What chronic disease processes are most likely to be affected by inhaled particulate
matter? To explain the daily mortality statistics, there must be common  conditions that
contribute significantly to overall mortality from respiratory causes.  The most likely candidates
are the chronic airways diseases, particularly chronic obstructive pulmonary disease (COPD).
COPD is the fourth leading cause of death in the US, and is the most common cause of non-
malignant respiratory deaths, accounting for more than 84,000 deaths in 1989 (U.S. Bureau of
the Census,  1992). This group of diseases encompasses both emphysema and chronic bronchitis,
however, information on death certificates does not allow differentiation between these
diagnoses.  The pathophysiology includes chronic inflammation of the distal airways as well as
destruction of the lung parenchyma.  There is loss of supportive elastic tissue, so that the airways
collapse more easily during expiration, obstructing flow. Processes that  enhance airway
inflammation or edema, increase smooth muscle contraction in the conducting airways, or slow
mucociliary clearance could adversely affect gas exchange and host defense. Moreover, the
uneven ventilation-perfusion matching
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characteristics of this disease, with dependence on fewer functioning airways and alveoli for gas
exchange, means inhaled particles may be directed to the few functioning lung units in higher
concentration than in normal lungs (Bates, 1992)
     Asthma is a common chronic respiratory disease that may be exacerbated by air pollution.
Mortality from asthma (about 3% of all respiratory deaths) has been rising in the last 15 years
(Gergen and Weiss, 1992), and air pollution has been implicated as a potential causative factor.
Atmospheric particle levels have been linked with increased hospital admissions for asthma,
worsening of symptoms, decrements in lung function, and increased medication use. The
incidence of asthma is higher among children and young adults. Although asthma deaths are
rare below the age of 35, asthma is the leading cause of non-infectious respiratory mortality
below the age of 55.  Nevertheless, approximately 70% of all asthma-related deaths occur after
age 55 (National Center for Health Statistics, 1993). Death due to asthma may contribute to
overall PM-related mortality but it is doubtful that asthma is  a leading cause.
     Particulate pollutants have been associated with increases in cardiovascular mortality both
in the major air pollution episodes and in the more recent time-series analysis. Bates (1992) has
postulated three ways in which pollutants could affect cardiovascular mortality statistics. These
include:  acute airways disease misdiagnosed as pulmonary edema; increased lung permeability,
leading to pulmonary edema in people with underlying heart disease and increased left atrial
pressure; and, acute bronchiolitis or pneumonia induced by air pollutants precipitating
congestive heart failure in those with pre-existing heart disease. Moreover, the pathophysiology
of many lung diseases is closely intertwined with  cardiac function.  Many individuals with
COPD also have cardiovascular disease caused by: smoking; aging; or pulmonary hypertension
accompanying COPD. Terminal events in patients with end-stage COPD are often cardiac, and
may therefore be misclassified as cardiovascular deaths. Hypoxemia associated with abnormal
gas exchange can precipitate cardiac arrhythmias and sudden death.
     In comparison to healthy people, individuals with respiratory disease have greater
deposition of inhaled aerosols in the fine (PM25) mode. The deposition of particles in the lungs
of a COPD patient may be as much as three-fold greater than in a healthy adult. Thus, the
potential  for greater target tissue dose in susceptible patients  is present. The lungs of
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individuals with chronic lung diseases, such as asthma, bronchitis, emphysema, etc. are often in
a chronic state of inflammation. In addition to the fact that particles can induce an inflammatory
response in the respiratory region, the influence of particles on generation of proinflammatory
cytokines may be enhanced by the prior existence of inflammation. Phagocytosis by alveolar
macrophages is down-regulated both by inflammation and the increased levels of ingested
particles. Therefore, people with lung disease not only have greater particle deposition, but the
conditions that exist in their lungs prior to exposure  are conducive to amplification of the effects
of particles and depression of their clearance.
11.11 SUMMARY AND CONCLUSIONS
11.11.1 Acid Aerosols
     The results of human studies indicate that healthy subjects do not experience decrements in
lung function following single exposures to H2SO4 at levels up to 2,000 //g/m3 for 1 h, even with
exercise and use of acidic gargles to minimize neutralization by oral ammonia. Mild lower
respiratory symptoms (cough, irritation, dyspnea) occur at exposure concentrations in the mg/m3
range.  Acid aerosols alter mucociliary clearance in healthy subjects, with effects dependent on
exposure concentration and the region of the lung being studied.
     Asthmatic subjects appear to be more sensitive than healthy subjects to the effects of acid
aerosols on lung function, but the effective concentration differs widely among studies.
Adolescent asthmatics may be more sensitive than adults, and may experience small decrements
in lung function in response to H2SO4 at exposure levels only slightly above peak ambient levels.
Although the reasons for the inconsistency among studies remain largely unclear, subject
selection and acid neutralization by NH3 may be important factors. Even in studies reporting an
overall absence of effects on lung function, occasional asthmatic subjects appear to demonstrate
clinically important effects. Two studies from different laboratories have suggested that
responsiveness to acid aerosols may correlate with degree of baseline airway
hyperresponsiveness. There is a need to identify determinants of responsiveness to H2SO4
exposure in asthmatic subjects. In very limited studies, elderly and individuals with
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chronic obstructive pulmonary disease do not appear to be particularly susceptible to the effects
of acid aerosols on lung function.
     Two recent studies have examined the effects of exposure to both H2SO4 and ozone on
lung function in healthy and asthmatic subjects.  In contrast with previous studies, both studies
found evidence that 100 //g/m3 H2SO4 may potentiate the response to ozone.
     Human studies of particles other than acid aerosols provide insufficient data to draw
conclusions regarding health effects.  However,  available data suggest that inhalation of inert
particles in the respirable range, including three  studies of carbon particles,  have little or no
effect on symptoms or lung function in healthy subjects at levels above peak ambient
concentrations.
     The bulk of the laboratory animal toxicologic data base on PM involves sulfur oxide
particles, primarily H2SO4, and the available evidence indicates that the observed responses to
these are likely due to H+ rather than to SO4 .
     Acidic sulfates exert their action throughout the respiratory tract, with the response and
location of effect dependent upon  particle size and mass and number concentration.  At very
high concentrations that are not environmentally realistic, mortality will occur following acute
exposure, due primarily to laryngospasm or bronchoconstriction; larger particles are more
effective in this regard than are smaller ones. Extensive pulmonary damage, including edema,
hemorrhage, epithelial desquamation, and atelectasis can also cause mortality, but even in the
most sensitive animal species, concentrations causing mortality are quite high, at least a
thousand-fold greater than current ambient levels.
     Both acute and chronic exposure to H2SO4 at levels well below lethal  ones will produce
functional changes in the respiratory tract. The pathological significance of some of these are
greater than for others. Acute exposure will alter pulmonary function, largely due to
bronchoconstrictive action.  However, attempts to produce  changes in airway resistance in
healthy animals at levels below 1,000 //g/m3 have been largely unsuccessful, except when the
guinea pig has been used. The lowest effective level of H2SO4 producing a  small transient
change in airway resistance in the guinea pig is 100 //g/m3 (1-h exposure).  In general, the
smaller size droplets (submicron) were more effective in altering pulmonary function, especially
at low concentrations. Very low concentrations (< 100 //g/m3) of acid-coated ultrafine particles
are associated with lung function and diffusion decrements, as well as
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airway hyperresponsiveness. Yet even in the guinea pig, there are inconsistencies in the type of
response exhibited towards acid aerosols. Chronic exposure to H2SO4 is also associated with
alterations in pulmonary function (e.g., changes in the distribution of ventilation and in
respiratory rate in monkeys). But, in these cases, the effective concentrations are >500 //g/m3.
Hyperresponsive airways have been induced with repeated exposures to 250 //g/m3 H2SO4 in
rabbits, and have been suggested to occur following single exposures at 75 //g/m3.
     Severe morphologic alterations in the respiratory tract will occur at high (» 1,000 //g/m3)
acid levels. At low (> 100 //g/m3) levels and with chronic exposure, the main response seems to
be hypertrophy and/or hyperplasia of mucus secretory cells in the epithelium; these alterations
may extend to the small bronchi and bronchioles, where secretory cells are normally rare or
absent.
     The lungs have an array of defense mechanisms to detoxify and physically remove inhaled
material, and available evidence indicates that certain of these defenses may be altered by
exposure to H2SO4 levels <1,000 //g/m3.  Defenses such as resistance to bacterial infection may
be altered even by acute exposure to concentrations of H2SO4  around 1,000 //g/m3. However,
the bronchial mucociliary clearance system is very sensitive to inhaled acids; fairly low levels of
H2SO4 produce alterations in mucociliary transport rates in healthy animals.  The lowest level
shown to have such an effect, 100 //g/m3 with repeated exposures,  is well below that which
results in other physiological changes in most experimental animals. Furthermore, exposures to
somewhat higher levels that also alter clearance have been associated with various morphometric
changes in the bronchial tree indicative of mucus hypersecretion.
     Limited data also suggest that exposure to acid aerosols may affect the functioning of
AMs. The lowest level examined in this regard to date is 500 //g/m3 H2SO4. Alveolar region
particle clearance is affected by repeated H2SO4 exposures to as low as 125 //g/m3 (Schlesinger
etal., 1992a).
     The assessment of the toxicology of acid aerosols requires some examination of potential
interactions with other air pollutants.  Such interactions may be antagonistic, additive, or
synergistic. Evidence for interactive effects may depend upon the  sequence of exposure as well
as on the endpoint examined. Low levels of H2SO4 (100 //g/m3) have been
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shown to react synergistically with O3 in simultaneous exposures using biochemical endpoints
(Warren and Last, 1987). In this case, the H2SO4 enhanced the damage due to the O3.  The most
realistic exposures are to multicomponent atmospheres, but the results of these are often
difficult to assess due to chemical interactions of components and a resultant lack of precise
control over the composition of the exposure environment.

11.11.2  Metals
     Data from occupational studies and laboratory animal studies indicate that acute exposures
to high levels or chronic exposures to low levels (albeit high compared to ambient levels) of
metal particulate can have an effect on the respiratory tract.  However,  it is doubtful that the
metals at concentrations present in the ambient atmosphere (1 to 14 //g/m3) could have a
significant acute effect in healthy individuals.
     The toxicity data on inhalation exposures to arsenic are limited in humans and laboratory
animals.  Acute data are largely lacking for this route of exposure. In humans, inhalation
exposure data, primarily limited to long-term  occupational exposure of smelter workers, indicate
that chronic exposure leads to lung cancer. In laboratory animals, intratracheal administration of
arsenic compounds in the lungs have not indicated tumor development  in rats and mice, but
insufficient exposure duration may have been used in these studies. However, respiratory tract
tumors occurred in hamsters exposed to intratracheal  doses of arsenic when a charcoal carbon
carrier dust was used to increase arsenic retention in the lungs.
     Chronic inhalation exposure to arsenic has also been shown to cause  both skin changes
(such as hyperpigmentation and hyperkeratosis) and peripheral  nerve damage in workers;
however, the available inhalation studies in laboratory animals have not evaluated these
endpoints. The laboratory animal inhalation data are  limited and thus do not allow a thorough
comparison of the toxicological and carcinogenic potential of arsenic with the human data.
Species differences in  dosimetry, absorption, clearance, and elimination of arsenic (i.e., strong
affinity to rat hemoglobin) exist between  rats  and other animal species, including humans, which
complicate comparisons of quantitative toxicity.
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     The kidney is clearly the primary target of chronic inhalation exposure to cadmium in the
human; toxicity is dependent on cumulative exposure.  Tubular proteinuria occurs after kidney
levels of cadmium accumulate to a certain level, estimated at 200 jig/g kidney weight.
     The respiratory system is also a target of inhaled cadmium in humans and animals. Intense
irritation occurs following high-level exposure in humans and more mild effects on pulmonary
function (dyspnea, decreased forced vital capacity) occur following chronic low-level exposure.
These effects and their mechanism have been investigated to a greater degree in laboratory
animals, although spirometry has not been conducted in animals. The observed effects
(increased lung weight, inhibition of macrophages and edema) are consistent with the irritation
observed in human studies.  In humans, symptoms reverse with cessation or lessening of
exposure; laboratory animal studies have reported no progression or slight reversal with
continued exposure.
     Rat studies show that several forms of cadmium (cadmium chloride, cadmium oxide dust
or fume, cadmium sulfide, or cadmium sulfate) can cause lung cancer. There is some evidence
that lung cancer has been observed in humans following high occupational exposure, although
confounding exposures were present. Because animal cancer studies  only examined the lung,
they did not address the suggestive evidence of cadmium-related prostate cancer found in several
occupational studies.
     Although both human and laboratory animal data are limited, both data bases support the
respiratory system as a major target of inhaled copper and copper compounds, including copper
sulfate and copper chloride. In humans, the data are limited primarily to subjective reporting of
respiratory symptoms following acute and chronic inhalation exposures to copper fumes or dust
supported with radiographic evidence of pulmonary involvement.  The human data do not
include pulmonary function tests or histopathology of the respiratory  tract. In laboratory animal
studies, supporting evidence exists for the involvement of the respiratory system after copper
inhalation exposure.  Respiratory tract abnormalities in mice repeatedly exposed to copper
sulfate aerosols, and decreased tracheal cilia beating frequency in singly exposed hamsters have
been reported. Respiratory effects, although minor, have also been observed in rabbits; these
included a slight increase in amount of lamellated cytoplasmic inclusions in alveolar
macrophages, and a slight increase in volume density of alveolar Type 2 cells. Although
respiratory effects were observed in both human and
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 laboratory animal studies, direct comparisons are not possible since different parameters were
examined in the different species for which limited data exist.  Immunological effects have been
investigated in only one animal study.  In the one study addressing the issue, immunotoxic
effects observed included: decreased survival time after simultaneous S. zooepidemicus aerosol
challenge, and decreased bactericidal activity after simultaneous K. pneumonia aerosol exposure.

     There is limited information on iron toxicity, with human data primarily from chronic
occupational exposures. Both human and laboratory animal data, mostly qualitative information,
do demonstrate that the respiratory system is the primary target organ for iron oxides following
inhalation exposure. However, the differences in toxicity (if any) for different particle sizes or
valence states of iron have not been well studied. In humans, respiratory effects (coughing,
siderosis) have been reported in workers chronically exposed to iron dust. In laboratory animals,
hyperplasia and alveolar fibrosis have been reported after inhalation or intratracheal
administration of iron oxide. The lack of information on the histopathological changes in the
lungs of exposed workers precludes direct comparison with animal data. Brief exposure to
relatively high concentrations of large iron oxide particles in humans have not been associated
with adverse responses.  The available human and laboratory animal studies are limited and do
not provide conclusive evidence regarding the respiratory carcinogenicity of iron oxide.
     Human and  laboratory animal data confirm the respiratory tract as the primary target of
inhaled vanadium compounds.  Laboratory animal data suggest that vanadium compounds
damage alveolar macrophages, and that toxicity is related to compound solubility and valence.
Because of the difficulty in obtaining clinical signs of respiratory distress in laboratory animals,
most reported animal data consisted of histological findings (increased leukocytes and lung
weights, perivascular edema, alveolar proteinosis, and capillary congestion). Human
occupational case studies and epidemiological studies generally emphasize clinical symptoms of
respiratory distress, including wheezing, chest pain, bronchitis, rhinitis, productive cough, and
fatigue including the possibility of vanadium induced asthma.  No human data were found
describing histopathology following oral or inhalation exposure.
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     No major differences in the pharmacokinetics of zinc in humans and laboratory animals
were evident. Both human and laboratory animal data demonstrate that the respiratory system is
the primary target organ for zinc following inhalation exposure; the toxic compounds most
studied are zinc chloride and zinc oxide.  In humans, the development of metal fume fever,
characterized by respiratory symptoms and pulmonary dysfunction, was observed in workers and
experimental subjects during acute exposures to zinc oxide. An immunological component is
believed to be responsible for these respiratory responses.  Quantitative data on chronic
exposures in humans are not available. Inflammation with altered macrophage function,
morphological changes in the lungs, and impaired pulmonary function (decreased compliance,
total lung capacity, decreased diffusing capacity) were observed in guinea pigs. Rats also
showed altered macrophage function in the lungs. At subchronic durations, histopathological
changes in the lungs (increased macrophages) were observed in rats, mice, and guinea pigs
exposed to zinc chloride.  It is clear that zinc can produce inflammatory response in both  human
and animal species.  Alveologenic carcinomas have been observed in mice exposed to zinc
chloride for 20 weeks; however, human studies have shown no evidence of increased tumor
incidences at exposure levels found in occupational settings. Zinc compounds are  soluble in
lung fluids and do not appear to accumulate in the respiratory tract.
     Studies examining the potential for the transition metals to cause lung injury  by the
generation of ROS have been conducted in vitro and in animals by intratracheal instillation.
While these studies are interesting, the results thus far are of limited value.

11.11.3 Ultrafme Particles
     There are only limited data available from human studies or laboratory animal studies on
ultrafine aerosols. They are present in the ambient environment as singlet particles but represent
an extremely small portion of the mass. However, ultrafine particles are present in high numbers
and have a high collective surface area. There are in vitro studies that show ultrafine particles
have the capacity to cause injury to cells of the respiratory tract.  High levels of ultrafine
particles, as metal or polymer "fume", are associated with toxic respiratory responses in humans
and other mammals. Such exposures are  associated with cough, dyspnea, pulmonary edema, and
acute inflammation. Presence of ultrafine particles,
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especially the metals Cd, V, Ti, Fe, in human alveolar macrophages indicates widespread
exposure to ultrafmes as single particles in ambient air. At concentrations less than 50 //g/m3,
freshly generated insoluble ultrafine particles can be severely toxic to the lung.  There are also
studies on a number of ultrafine particles (diesel, carbon black, acidic aerosols) where the
particles are not present in the exposure atmosphere as singlet particles. Insufficient information
is available at the present time to determine whether ambient ultrafine particles may play a role
in PM-induced mortality.

11.11.4 Diesel Emissions
     Acute toxic effects caused by exposure to diesel exhaust are mainly attributable to the
gaseous components (i.e., mortality from carbon monoxide intoxication and lung injury from
respiratory irritants). When the exhaust is diluted to limit the concentrations of these gases,
acute effects are not seen.
     The focus of the long-term (> 1 year) animal inhalation studies of diesel engine emissions
studies has been on the respiratory tract effects in the alveolar region. Effects in the upper
respiratory tract and in other organs were not found consistently in chronic animal exposures.
Several of these studies are derived from research programs on the toxicology of diesel
emissions that consisted of large-scale chronic exposures, which are represented by multiple
published accounts  of results from various aspects of the overall research program. The
respiratory system response has been well characterized in terms of histopathology,
biochemistry, cytology, pulmonary function, and respiratory tract clearance.  The pathogenic
sequence following the inhalation of diesel exhaust as determined histopathologically and
biochemically begins with the phagocytosis of diesel  particles by AMs.  These activated
macrophages release chemotactic factors that attract neutrophils and additional AMs.  As the
lung burden of diesel particles increases, there is an aggregation of particle-laden AMs in alveoli
adjacent to terminal bronchioles, increases in the number of Type 2 cells lining particle-laden
alveoli, and the presence  of particles within alveolar and peribronchial interstitial tissues and
associated lymph nodes.  The PMNs and macrophages release mediators of inflammation and
oxygen radicals and particle-laden macrophages  are functionally altered resulting in decreased
viability and impaired phagocytosis and clearance of particles.  There is a substantial body of
evidence for an impairment of particulate
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clearance from the bronchioalveolar region of rats following exposure to diesel exhaust.  The
latter series of events may result in the presence of pulmonary inflammatory, fibrotic, or
emphysematous lesions. The noncancer toxicity of diesel emissions is considered to be due to
the particle rather than the gas phase, since the long-term effects seen with whole diesel are not
found or are found to a much lesser extent in animals exposed to similar dilutions of diesel
exhaust filtered to remove most of the particles.  Chronic studies in rodents have demonstrated
pulmonary effects at 200 to 700 //g/m3 (expressed as equivalent continuous exposure to adjust
for protocol differences). A range of no adverse effect levels has been estimated as from 200 to
400 Mg/m3.
     Several epidemiologic studies have evaluated the effects of chronic exposure to diesel
exhaust on occupationally exposed workers.  None of these studies are useful for a quantitative
evaluation of noncancer toxicity because of inadequate exposure characterization, either because
exposures were not well defined or because the possible confounding effects of concurrent
exposures could not be evaluated.

11.11.5  Silica
     Emissions of silica into the environment can arise from natural, industrial, and farming
activities.  There are only limited data on ambient air concentrations of amorphous or crystalline
silica, principally because existing measurement methods are not well suited for distinguishing
silica from other particulate matter.  Using available data on the quartz fraction of coarse dust
(Davis et al., 1984) and average annual  arithmetic mean PM10 measurements for 17 U.S.
metropolitan areas, annual average and  high U.S. ambient quartz levels of 3 and 8 //g/m3,
respectively, have been estimated  (U.S. Environmental Protection Agency, 1996). Davis et al.
(1984) found that most of the quartz was in the fraction between 2.5 to 15 //m MMAD.
     Silica can occur in two chemical forms, amorphous and crystalline.  Crystalline forms
include quartz, which is  the most prevalent; cristobalite, tridymite, and a few other rare forms.
Freshly fractured crystalline silica is more lexicologically reactive than aged forms of crystalline
silica.  Amorphous silica is less well studied but is considered less potent than crystalline silica.
Occupational studies show that chronic  exposure to crystalline silica causes inflammation of the
lung which can progress to fibrosis and  silicosis, a human fibrotic
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disease, which can lead to early mortality. Some occupational studies also show a concurrent
incidence of lung cancer.  The role, if any, of silica-induced lung inflammation, fibrosis, and
silicosis in the development of lung cancer is postulated but not adequately demonstrated.
Crystalline silica interaction with DNA has been shown under in vitro conditions. Chronic
exposure studies in rats also show a similar pattern of lung inflammation, fibrosis, and lung
cancer.  The International  Agency for Research on Cancer (1987) classified crystalline silica as a
"possible" human carcinogen owing to a sufficient level of evidence in animal studies, but with
inadequate evidence in human studies.  The health statistics of the U.S. do not reveal a general
population increase in the  incidence of these silica-related disease, although there is an increase
within segments of the occupational work force.
     These effective occupational exposures are greater and the particle sizes smaller than those
likely to be experienced by the general public, including susceptible populations. Information
gaps still exist for the exposure-response relationship for levels  of exposure within the general
population.

11.11.6 Bioaerosols
     Ambient bioaerosols include fungal spores, pollen, bacteria, viruses, endotoxins, and plant
and animal debris. Such biological aerosols can produce three general classes of health effects:
infections, hypersensitivity reactions, and toxicoses.  Bioaerosols present in the ambient
environment have the potential to cause disease in humans under certain conditions. However, it
is improbable that bioaerosols, at the  concentrations present in the ambient environment, could
account for the observed effects of particulate matter on human mortality and morbidity reported
in PM epidemiological studies.  Moreover, bioaerosols generally represent a rather small fraction
of the measured urban ambient PM mass and are typically present even at lower concentrations
during the winter months when notable ambient PM  effects have been demonstrated.
Bioaerosols also tend to be in the coarse fraction of PM.

11.11.7  "Other Particulate  Matter"
     Toxicologic studies of other particulate matter species besides acid aerosols, metals,
ultrafine particles, diesel emissions, silica, and bioaerosols were discussed in this chapter.
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These studies included exposure to fly ash, volcanic ash, coal dust, carbon black, TiO2, and
miscellaneous other particles, either alone or in mixtures.
     A number of studies of the effects of "Other PM" examined effects of up to 50,000 //g/m3
of respirable particles with inherently low toxicity on mortality and found  no effects. Some mild
pulmonary function effects of 5,000 to 10,000 //g/m3 of similar particles were observed in rats
and guinea pigs. Lung morphology studies revealed focal inflammatory responses, some
epithelial hyperplasia, and fibrotic responses to exposure generally >5,000 //g/m3. Changes in
macrophage clearance after exposure to >10,000 //g/m3 were equivocal (no infectivity effects).
In studies of mixtures of particles and other pollutants, effects were variable depending on the
toxicity of the associated pollutant.  In humans, associated particles may increase responses to
formaldehyde but not to acid aerosol. None of the "other" particles mentioned above are present
in ambient  air in more than trace quantities.  The  relevance of any of these studies to ambient
particulate  standard setting is extremely limited.
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