EPA-600/8-79-0221
October 1979
                                        Special Series
                         AIR QUALITY CRITERIA
     FOR CARBON  MONOXIDE
                                        (PREPRINT)
                         Environmental Criteria and Assessment Office
                        Office of Health and Environmental Assessment
                               Office of Research and Development
                              U.S. Environmental Protection Agency
                                               D.C. 20460

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                                    EPA-600/8-79-022
                                        October 1979
    AIR QUALITY CRITERIA
                FOR
       CARBON MONOXIDE
              (Preprint)
U.S. ENVIRONMENTAL PROTECTION AGENCY
  Environmental Criteria and Assessment Office
 Office of Health and Environmental Assessment
     Office of Research and Development
          Washington, B.C. 20460

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                                 NOTICE
     This document is available through the Library Services Office,

MD-35, Environmental Protection Agency, Research Triangle Park, NC, 27711.

It 1s also available from the Superintendent of Documents, U.S. Government

Printing Office, Washington, DC, 20402.  Correspondence relating to the

subject matter of the document should be directed to:

               Project Officer for Carbon Monoxide
               Environmental Criteria and Assessment Office (MD-52)
               Environmental Protection Agency
               Research Triangle Park, NC  27711
                                      11

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                                PREFACE
     This document has been prepared pursuant to Section 108(c) of the
Clean Air Act, as amended, which requires that the Administrator from
time to time review and, as appropriate, modify and reissue criteria
issued pursuant to Section 108(a).   Air quality criteria are required by
Section 108(a) to reflect accurately the latest scientific information
useful in indicating the kind and extent of all identifiable effects on
public health and welfare which may be expected from the presence of a
pollutant in the ambient air, in varying quantities.
     The original criteria document for carbon monoxide was issued
in 1970.  Since that time new information has been developed, and this
document represents the modification and reissuance of the air quality
criteria for carbon monoxide.
     The regulatory purpose of these criteria is to serve as the basis
for national ambient air quality standards promulgated by the Administrator
under Section 109 of the Clean Air Act, as amended.  Accordingly, as
provided by Section 109(d), the Administrator has reviewed the national
ambient air quality standards for carbon monoxide based on these revised
criteria and is proposing appropriate action with respect to those
standards concurrently with the issuance of this document.
     The Agency is pleased to acknowledge the efforts and contributions
of all persons and groups who have contributed, as participating authors
or reviewers, to this document.  In the last analysis, however, the
Environmental Protection Agency is responsible for its content.
                                     iii

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     The studies and data cited comprise the best available basis for

specific standards aimed at protecting human health and the environment

from carbon monoxide (CO) in ambient air.   Various natural processes

such as forest fires, oxidation of atmospheric methane, and biological
                                                                    3
activities maintain a CO background concentration of about 0.05 mg/m

(0.044 ppm).  Additional CO from urban and industrial sources increases
                                               3
global concentrations to approximately 0.2 mg/m  (0.18 ppm) in the
                                                  3
northern hemisphere and to approximately 0.06 mg/m  (0.05 ppm) in the

southern hemisphere.  Within heavily populated areas such as cities,

much higher concentrations of CO are found as a result of the local

combustion of fossil fuels.

     Carbon monoxide is a normal constituent of plant life, which both

metabolizes and produces CO.  It has been shown that adverse effects of

CO to plants and various microorganisms require relatively high levels,

considerably greater than those required for adverse health effects  in

animals and humans.

     In mammals, endogenous sources of CO from metabolic activities

result in levels of blood carboxyhemoglobin (COHb) of about 0.5 percent.

Inhalation of CO from the ambient air may increase COHb to toxic levels,

due to the greater affinity of hemoglobin for CO than for oxygen, thus

creating a lowered oxygen concentration in blood and tissues.  Reductions

of blood oxygen content caused by 5-10 percent COHb may be critical  for

patients suffering from cardiovascular diseases or chronic obstructive

lung disease.
                                      iv

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     Experimental animal studies have indicated deleterious effects upon
the central nervous and cardiovascular systems.  Adverse behavioral and
central nervous system effects have been demonstrated at levels of
12-20 percent COHb, while adverse cardiovascular effects have been
demonstrated at levels as low as 4-7 percent COHb.
                                                                 3
     Human exposures to concentrations of CO as low as 17-21 mg/m
(15-18 ppm) for eight hours, resulting in 2.5-3.0 percent COHb,
adversely affects cardiovascular systems.  Carbon monoxide exposures
of 29-34 mg/m3 (25-30 ppm) for eight hours, resulting in COHb levels
of 4-6 percent, have been shown to affect the central nervous systems of
humans.

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                                ABSTRACT
     This document is an evaluation and assessment of scientific



information relative to determination of health and welfare experts



associated with exposure to various concentrations of carbon monoxide in



ambient air.   The document is not intended as a complete, detailed



literature review.  It does not cite every published article relating to



carbon monoxide in the environment and their effects.   The literature



through 1978 has been reviewed thoroughly for information relative to



criteria.  An attempt has been made to identify the major discrepancies



in our current knowledge, again relative to criteria.



     Though the emphasis is on presentation of health and welfare effects



data, other scientific data are presented and evaluated in order to



provide a better understanding of the pollutants in the environment.



To this end, separate chapters are included which discuss properties  and



principles of formation, emissions, analytical methods of measurement,



observed ambient concentrations, the global cycle, effects on vegetation



and microorganisms, mammalian metabolism, effects on experimental animals,



and effects on humans.
                                      vi

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                              TABLE OF CONTENTS
LIST OF FIGURES 	
LIST OF TABLES 	
LIST OF ABBREVIATIONS AND SYMBOLS
 1.   SUMMARY AND CONCLUSIONS 	      1-1
     1.1  INTRODUCTION	      1-1
    ,1.2  PROPERTIES AND PRINCIPLES OF FORMATION OF
          CARBON MONOXIDE 	      1-2
     1.3  ESTIMATION OF CARBON MONOXIDE EMISSIONS FROM
          TECHNOLOGICAL SOURCES 	      1-2
    ,1.4  ANALYTICAL METHODS 	      1-3
    ,1.5  CARBON MONOXIDE CONCENTRATIONS IN AMBIENT AIR 	      1-4
     1.6  THE GLOBAL CYCLE OF CARBON MONOXIDE 	      1-6
     1.7  EFFECTS OF CARBON MONOXIDE ON VEGETATION AND
          CERTAIN MICROORGANISMS 	      1-7
     1.8  METABOLISM OF CARBON MONOXIDE IN MAMMALS 	      1-8
     1.9  EFFECTS OF CARBON MONOXIDE ON EXPERIMENTAL
          ANIMALS 	      1-9
     1.10 EFFECTS OF LOW-LEVEL CARBON MONOXIDE EXPOSURE
          ON HUMANS	      1-10

 2.   INTRODUCTION 	      2-1

 3.   PROPERTIES AND PRINCIPLES OF FORMATION OF
     CARBON MONOXIDE 	      3-1
     3.1  INTRODUCTION 	      3-1
     3 2  PHYSICAL PROPERTIES                                     3-2
     3.3  GASEOUS CHEMICAL REACTIONS OF CARBON MONOXIDE 	      3-3
     3.4  PRINCIPLES OF FORMATION^	      3-7
          3.4.1  General Combustion Processes 	      3-10
          3.4.2  Combustion Engines 	      3-11
                 3.4.2.1  Mobile Combustion Engines 	      3-11
                 3.4.2.2  Internal Combustion Engines -
                          (Gasoline Fueled, Spark-
                          Ignition Engines) 	      3-11
                 3.4.2.3  Internal Combustion Engines -
                          (Diesel Engines) 	      3-14
                 3.4.2.4  Stationary Combustion Sources -
                          (Steam Boilers) 	      3-14
     3.5  NON-COMBUSTION INDUSTRIAL SOURCES	      3-15

 4.   ESTIMATION OF CARBON MONOXIDE EMISSIONS FROM
     TECHNOLOGICAL SOURCES 	      4-1
     4.1  NATIONAL EMISSION LEVELS 	      4-2
                                      vii

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    4.2  EMISSIONS AND EMISSION FACTORS BY SOURCE TYPE 	      4-6
         4.2.1.  Mobile Combustion Sources 	      4-6
         4.2.2  Combustion for Power and Heat	      4-7
         4.2.3  Technological Processes Producing CO 	      4-8
         4.2.4  Solid Waste Combustion 	      4-8
         4.2.5  Miscellaneous Combustion 	      4-8
    4.3  ESTIMATION OF FUTURE EMISSION LEVELS 	      4-9

5.   ANALYTICAL METHODS FOR MEASUREMENT OF CARBON MONOXIDE ..      5-1
    5.1  INTRODUCTION 	      5-1
         5.1.1  Overview of Techniques for Measurement
                of CO in Air 	      5-2
         5.1.2  Calibration Requirements 	      5-3
    5.2  PREPARATION OF CARBON MONOXIDE GAS STANDARDS 	      5-3
         5.2.1  Gravimetric Method	      5-3
         5.2.2  Volumetric Gas Dilution Methods 	      5-5
         5.2.3  Other Methods 	      5-7
    5.3  MEASURING CARBON MONOXIDE IN AIR 	      5-8
         5.3.1  Sampling Techniques 	      5-8
         5.3.2  Sampling Schedules 	      5-16
         5.3.3  Recommended Analytical Methods for
                CO Measurements 	      5-18
         5.3.4  Continuous Measurement Methods 	      5-21
                5.3.4.1  Nondispersive Infrared Photometry..      5-21
                5.3.4.2  Gas Chromatography - Flame
                         lonization 	      5-24
                5.3.4.3  Electrochemical Analyzers 	      5-25
                         5.3.4.3.1  Controlled-potential
                                    Electrochemical Analysis.     5-25
                         5.3.4.3.2  Galvanic Analyzer	      5-26
                         5.3.4.3.3  Coulometric Analyzer ...      5-27
                5.3.4.4  Mercury Replacement 	      5-27
                5.3.4.5  Dual Isotope Fluorescence 	      5-29
                5.3.4.6  Catalytic Combustion-Thermal
                         Detection 	      5-29
                5.3.4.7  Second-Derivative Spectrometry 	      5-30
                5.3.4.8  Fourier Transform Spectroscopy 	      5-30
                5.3.4.9  Gas Filter Correlation Spectroscopy.     5-31
         5.3.5  Intermittent Analysis 	      5-32
                5.3.5.1  Colorimetric Analysis 	      5-32
                         5.3.5.1.1  Colored Silver Sol Method.    5-32
                         5.3.5.1.2  National Bureau of
                                    Standards Colorimetric
                                    Indicating Gel 	      5-33
                         5.3.5.1.3  Length-of-stain Indicator
                                    Tube 	      5-33
                5.3.5.2  Frontal Analysis 	      5-34
                                    V111

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6.










5.4 MEASURING CARBON MONOXIDE IN BLOOD 	
5. 4. 1 Other Methods 	
5.4.1.1 Gasometric 	
5.4.1.2 Infrared Spectrometry 	
5.4.1.3 Catalytic Oxidation 	
5.4.1.4 Electrochemical Sensors 	
5.4.1.5 Gas Chromatography 	
5.4.1.6 Colorimetric Palladium Chloride
Reacti on 	
5.4.2 Equilibrium Methods 	
OBSERVED CARBON MONOXIDE CONCENTRATIONS 	
6.1
6.2
6.3








6.4




6.5




6.6
6.7
THE
7.1
7.2








SITE SELECTION 	
UNITED STATES DATA BASE 	
TECHNIQUES OF DATA ANALYSIS 	
6. 3.1 Introduction 	
6.3.2 Calculation of Population Statistics 	
6.3.3 Frequency Analysis 	 	 	
6.3.4 Comparing CO Data to National
Ambient Air Quality Standards 	
6.3.5 Averaging Time Analysis 	
6. 3.6 Trend Analyses 	
6.3.7 Special Analyses 	
URBAN LEVELS OF CARBON MONOXIDE 	
6.4.1 Comparison to NAAQS 	
6. 4. 2 Hourly Patterns 	
6.4.3 Seasonal Patterns 	
6.4.4 Annual Patterns 	
SPECIAL CARBON MONOXIDE EXPOSURE SITUATIONS 	
6.5.1 Variations with Type of Vehicle Traffic 	
6.5.2 Car Passenger Exposure to Carbon Monoxide ..
6.5.3 Occupational Exposure 	
6.5.4 Indoor Carbon Monoxide Exposure 	
EFFECTS OF METEOROLOGY AND TOPOGRAPHY 	
CARBON MONOXIDE DISPERSION MODELS 	
GLOBAL CYCLE OF CARBON MONOXIDE 	
INTRODUCTION 	
GLOBAL SOURCES 	
7.2.1 Technological Sources 	
7.2.2 Natural Sources 	
7.2.2.1 Forest Fires and Agricultural
Burni ng 	
7.2.2.2 Carbon Monoxide Production from
Oceans 	
7.2.2.3 Oxidation of Natural Hydrocarbons .
7.2.2.4 Emission by Plants 	
5-34
5-35
5-40
5-41
5-41
5-41
5-41

5-42
5-42
6-1
6-1
6-8
6-13
6-13
6-14
6-18

6-18
6-20
6-20
6-22
6-26
6-26
6-28
6-33
6-33
6-46
6-47
6-48
6-49
6-50
6-53
6-61
7-1
7-1
7-2
7-2
7-4

7-4

7-4
7-5
7-5
                                         IX

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                 7.2.2.5  Methane Oxidation	    ^7-6
                 7.2.2.6  Other Natural  Sources 	      7-9
     7.3  BACKGROUND LEVELS AND FATE OF  CARBON MONOXIDE 	      7-10
          7.3.1  Measured Background Levels of Carbon
                 Monoxide 	      7-10
                 7.3.1.1  Geographic Distribution 	      7-10
                 7.3.1.2  Variation with Height 	      7-12
                 7.3.1.3  Diurnal and Seasonal Variation ....      7-15
          7.3.2  Residence Time and Removal Mechanisms of
                 Atmospheric CO 	      7-16
                 7.3.2.1  Carbon Monoxide Residence Time 	      7-16
                 7.3.2.2  Removal Processes for Carbon
                          Monoxide	      7-17
                          7.3.2.2.1  The Stratosphere as a
                                     Sink for Tropospheric
                                     CO  	      7-17
                          7.3.2.2.2  Soil as a Sink	      7-18
                          7.3.2.2.3  Vegetation 	      7-19
                          7.3.2.2.4  Reaction with Hydroxyl  .      7-20
                          7.3.2.2.5  Other Removal Processes.      7-22
     7.4  SUMMARY 	      7-22

 8.  EFFECTS OF CARBON MONOXIDE ON VEGETATION AND
     SOIL MICROORGANISMS	      8-1
     8.1  INTRODUCTION 		      8-1
     8.2  EFFECTS OF CARBON MONOXIDE ON  PLANTS 	      8-2
          8.2.1  Visible Symptoms 	      8-2
          8.2.2  Growth, Yield, and Reproduction 	      8-4
          8.2.3  Biochemical and Physiological Processes 	      8-6
                 8.2.3.1  Photosynthesis 	      8-8
                 8.2.3.2  Nitrogen Fixation	      8-8
     8.3  REMOVAL OF CO FROM THE ENVIRONMENT	      8-10
          8.3.1  Plants 	      8-11
          8.3.2  Soil Microorganisms 	.A	      8-13
     8.4  PRODUCTION OF CO BY PLANTS 	      8-14
     8.5  SUMMARY 	      8-16

 9.  METABOLISM OF CARBON MONOXIDE IN MAMMALS 	      9-1
     9.1  INTRODUCTION 	      9-1
     9.2  THEORETICAL CONSIDERATIONS 	      9-3
     9.3  ABSORPTION, EXCRETION, AND EQUILIBRATION 	      9-14
     9.4  DISTRIBUTION IN BODY TISSUES 	      9-23
     9.5  SUMMARY 	      9-25

10.  EFFECTS OF CO ON EXPERIMENTAL ANIMALS 	     10-1
     10.1  INTRODUCTION 	     10-1
     10.2  SELECTION OF ANIMAL MODELS 	     10-2
     10.3  NERVOUS SYSTEM AND BEHAVIOR 	     10-4

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      10.3.1  General Activity and Sleep 	     10-4
      10.3.2  Learning and Performance 	     10-5
      10.3.3  Electrophysiological Effects 	     10-7
      10.3.4  Cerebral Blood Supply	     10-8
      10.3.5  CMS Pathology and
              Biochemical Alterations	     10-9
      10.3.6  Summary and Conclusion of Nervous System
              and Behavior in Experimental Animals 	     10-11
10.4  CARDIOVASCULAR SYSTEMS 	     10-19
      10.4.1  Cardiac Performance and Damage 	     10-20
      10.4.2  Cardiac Fibrillation Threshold 	     10-22
      10.4.3  Cholesterol and Sclerosis 	     10-23
      10.4.4  Coronary Blood Flow	     10-24
      10.4.5  Hemoglobin 	     10-25
      10.4.6  Summary and Conclusion of Cardiovascular
              System in Experimental Animals 	     10-27
10.5  OTHER DEPENDENT VARIABLES 	     10-35
      10.5.1  Feeding, Drinking, and Body Weight 	     10-35
      10.5.2  Biochemical Effects and Drugs 	     10-36
      10.5.3  Miscellaneous 	     10-37
      10.5.4  Summary and Conclusions of Other Dependent
              Variables in Experimental Animals 	     10-37
10.6  INTERACTIONS WITH OTHER POLLUTANTS, DRUGS, AND
      OTHER FACTORS  	     10-41
      10.6.1  Other  Pollutants 	     10-42
      10.6.2  Drugs  	     10-43
      10.6.3  Halogenated Hydrocarbons 	     10-44
      10.6.4  Other Variables 	     10-44
      10.6.5  Conclusions About Interactions 	     10-45
10. 7  MECHANISMS 	r.	     10-45
      10.7.1  Hypoxic Hypoxia and CO
              Hypoxi a 	     10-46
      10.7.2  Elimination of Hemoglobin 	     10-49
      10.7.3  Conclusions About Mechanisms 	     10-50
10.8  ADAPTATION, HABITUATION, AND/OR COMPENSATORY
      MECHANISMS 	     10-50
      10.8.1  Adaptation (Long-term) 	     10-51
      10.8.2  Habituation (Short-term) 	     10-53
10.9  SUBJECTS OF SPECIAL RISK	     10-55
      10.9.1  Fetus  and Uterine Exposure 	     10-55
      10.9.2  Impaired Groups 	     10-56
      10.9.3  Drugs  	     10-57
      10.9.4  Unadapted Populations 	     10-58
10.10  SUMMARY 	     10-58
                                 xi

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                                                                 Page

11.   EFFECTS OF LOW-LEVEL CO EXPOSURE ON HUMANS 	    11-1
     11.1  INTRODUCTION 	    11-1
     11.2  NERVOUS SYSTEM AND BEHAVIOR 	    11-4
           11.2.1  Sleep and Activity 	    11-5
           11.2.2  Vigilance 	    11-5
           11.2.3  Sensory and Time Discriminations 	    11-8
           11.2.4  Complex Sensorimotor Tasks and Driving ...    11-10
           11.2.5  Central Nervous System Electrical Activity.   11-13
           11.2.6  Conclusions and Discussion of Nervous
                   System and Behavior in Humans 	    11-14
     11.3  CARDIOVASCULAR SYSTEMS 	    11-21
           11.3.1  Cardiovascular Damage and EKG
                   Abnormalities	    11-21
           11.3.2  Blood Flow and Related Variables 	    11-23
           11.3.3  Angina 	    11-25
           11.3.4  Epidemiological Evidence 	    11-28
           11.3.5  Conclusions and Discussion 	    11-29
     11.4  PULMONARY FUNCTION AND EXERCISE 	    11-34
           11.4.1  Maximal Work	    11-34
           11.4.2  07 Uptake and Heart Rate 	    11-34
           11.4.3  Aerobic Capacity 	    11-36
           11.4.4  Conclusion and Discussion 	    11-42
     11.5  INTERACTIONS WITH OTHER POLLUTANTS AND DRUGS 	    11-42
           11.5.1  Other Air Pollutants 	    11-42
           11.5.2  Other Environmental Parameters 	    11-48
           11.5.3  Alcohol 	    11-49
           11.5.4  Smoking 	    11-49
           11.5.5  Conclusions and Discussion 	<	    11-56
     11.6  HIGH ALTITUDES - MECHANISMS 	    11-58
           11.6.1  Physiological Results 	    11-58
           11.6.2  Behavioral and Central Nervous System 	    11-61
           11.6.3  Conclusions and Discussion of Carbon
                   Monoxide and High Altitude Combinations ..    11-62
     11.7  ADAPTATION, HABITUATION AND COMPENSATORY
           MECHANISMS 	    11-63
           11.7.1  Adaptation and Other Long-Term Effects ...    11-63
           11.7.2  Habituation and Short-Term Effects 	    11-65
     11.8  SPECIAL GROUPS AT RISK	    11-66
           11.8.1  Fetus 	    11-66
           11.8.2  Impaired Groups 	    11-69
           11.8.3  Drugs 	    11-72
           11.8.4  Unadapted Individuals 	    11-72
           11.8.5  Occupational 	    11-73
     11.9  SUMMARY	    11-82

APPENDIX A.  Glossary.
                                     xii

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                               LIST OF FIGURES
Figure                                                           Page

 3-1    Effect of air-fuel ratio on exhaust gas carbon
          monoxide concentrations from three test engines ...     3-13
 4-1    Average composite emission factors for carbon
          monoxide 	     4-11
 5-1    Loss of carbon monoxide with time in mild steel
          cyl i nders 	     5-6
 5-2    Carbon monoxide monitoring system 	     5-9
 5-3    SAROAD hourly data form	     5-14
 5-4    Schematic diagram of typical nondispersive infrared
          CO analyzer	     5-22
 6-1    Annual average CO levels in Los Angeles 	     6-12
 6-2    Histogram of 1-hour average CO concentrations 	     6-15
 6-3    Cumulative frequency distribution of 1-hour average
          CO concentrations 	     6-16
 6-4    Concentration vs. averaging time and frequency for
          carbon monoxide from 12/1/63 to 12/1/68 at
          site 662, St.  Louis 	     6-21
 6-5    Predicted 1-hour average ambient CO concentrations
          (mg/m ) in the vicinity of 1-85 in Atlanta,
          Georgia, for 1976	     6-23
 6-6    Measured 8-hour average background CO concentrations
          in Memphis, Tennessee 	     6-24
 6-7    Pollution rose for St. Louis, Missouri 	     6-25
 6-8    Status of carbon monoxide levels, 1973 	     6-27
 6-9    Hourly variations of ambient CO concentrations
          for Baltimore, MD 	     6-29
 6-10   Hourly variations of ambient CO concentrations
          for Denver, CO 	     6-30
 6-11   Hourly variations of ambient CO concentrations
          for Los Angel es, CA	     6-31
 6-12   Hourly variations of traffic volume 	     6-32
 6-13   Seasonal variations of ambient CO concentrations
          for Baltimore, MD 	     6-34
 6-14   Seasonal variations of ambient CO concentrations
          for Denver, CO	     6-35
 6-15   Seasonal variations of ambient CO concentrations
          for Los Angel es, CA 	     6-36
 6-16   Annual variations of ambient CO concentrations for
          Baltimore, MD 	     6-37
 6-17   Annual variations of ambient CO concentrations for
          Denver, CO, SAROAD site #060580002 (former CAMP
          station) 	     6-38
                                     xiii

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Figure                                                           Page

 6-18   Annual variations of ambient CO concentrations for
          Los Angeles, CA, SAROAD site #053900001	      6-39
 6-19   Annual variations of ambient CO concentrations for
          Chicago, IL, SAROAD site #141220002 (former CAMP
          station)	      6-40
 6-20   Annual variations of ambient CO concentrations for
          Cincinnati, OH, SAROAD site #361220003 (former
          CAMP station discontinued in 1973) 	      6-41
 6-21   Annual variations of ambient CO concentrations for
          Philadelphia, PA, SAROAD site #397140002 (former
          CAMP station) 	      6-42
 6-22   Annual variations of ambient CO concentrations for
          St. Louis, MO, SAROAD site #264280002 (former
          CAMP station discontinued in 1973)	      6-43
 6-23   Annual variations of ambient CO concentrations for
          Washington, DC, SAROAD site #090020002 moved in
          1969 and redesignated #090020003 (former CAMP
          station) 	      6-44
 6-24   Effect of terrain roughness on the wind speed
          profile 	      6-55
 6-25   Schematic representation of an elevated inversion ...      6-58
 6-26   Hourly variations in inversion height and wind speed
          for Los Angel es i n summer	      6-60
 6-27   Area segment scheme for spatial partitioning of
          emissions	      6-64
 6-28   Normalized concentrations versus normal distance
          from the road edge for perpendicular wind
          conditions for B and E atmospheric stability
          category	      6-67
 6-29   Normalized concentration versus normal distance to
          the road edge for parallel wind conditions for
          B and E atmospheric stability category 	      6-68
 7-1    Latitude distribution of carbon monoxide 	      7-11
 7-2    Latitudinal profiles of carbon monoxide 	      7-14
 7-3    Carbon monoxide photochemical production and
          destruction rates as a function of average OH
          concentration 	      7-21
 9-1    Oxygen dissociation curve with and without the
          presence of varying concentrations of CO 	      9-5
 9-2    Blood oxygen dissociation curves at various
          COHb val ues 	      9-6
 9-3    Exposure duration, ambient carbon monoxide
          concentrations (resting individuals) 	      9-16
 9-4    Exposure duration, ambient carbon monoxide
          concentrations (exercising individuals) 	      9-19
                                     xiv

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Figure                                                           Page

11-1    The maintenance of requested COHb level 1n a subject
          during rest and at various work levels with a
          widely ranging ventilatory exchange.   Control
          level of COHb was 0.6% prior to the administration
          of the initial bolus of CO to raise COHb to desired
          level; a total of 34.2 ml of CO STPD was given 	     11-39
11-2    Relationship between COHb and decrement in maximum
          aerobic power 	     11-41
11-3    Pattern of change in COHb in a typical  cigarette
          smoker	     11-53
                                      xv

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                                LIST OF TABLES
Table                                                            Page

 3-1    Physical properties of carbon monoxide 	     3-4
 3-2    Reported room temperature rate constants for
          the reaction of OH radicals with CO 	     3-6
 3-3    Automobile emission control schedules 	     3-9
 4-1    Summary of National emission estimates, 1970-1977 	     4-3
 4-2    Nationwide emission estimates, 1977 	     4-4
 4-3    Nationwide carbon monoxide emission estimates,
          1970-1977 	     4-5
 4-4    Average vehicle emission factors for two selected
          highway scenarios 	 	     4-10
 5-1    Performance specifications for automated analytical
          methods for carbon monoxide 	     5-19
 5-2    Comparison of representative techniques for
          analysis of CO in blood	     5-36
 6-1    Recommended criteria for siting monitoring stations ..     6-4
 6-2    Specific probe exposure criteria 	     6-5
 6-3    Suggested priorities of carbon monoxide monitoring
          sites 	     6-7
 6-4    Status of CO monitoring in 1977 	     6-12
 7-1    Global carbon monoxide source strength estimates 	     7-8
 8-1    Effects of CO on pi ants 	     8-7
 8-2    Carbon monoxide effects on nitrogen fixation by
          micro-organi sms  	     8-9
 8-3    Production and utilization of CO by plants and
          micro-organisms  	     8-12
 8-4    Soils as a sink for carbon monoxide 	     8-15
 9-1    Percent COHb versus CO pressure 	     9-23
10-1    Summary of effects of CO on central
          nervous system and behavior of animals 	    10-12
10-2    Summary of effects of carbon monoxide on
          cardiovascular systems of animals 	    10-28
10-3    Summary of CO effects upon metabolism	    10-38
11-1    Summary of data on effects of CO on human behavior
          and CNS 	    11-15
11-2    Exercise-induced angina and carbon monoxide 	    11-27
11-3    Summary of data on effects of CO on human
          cardiovascular system 	    11-30
11-4    Summary of data on effects of CO on human pulmonary
          function and exercise 	    11-43
11-5    Approximate physiologically equivalent altitudes
          at equilibrium with ambient CO levels 	    11-59
                                     xvi

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Table                                                            Page

11-6    Carbon monoxide emission estimates - 1968 	    11-74
11-7    Average percent of carboxyhemoglobin saturation
          in smokers and non-smokers in St. Louis 	    11-75
11-8    Average percent of carboxyhemoglobin saturation 	    11-75
11-9    Estimated health effects levels for carbon monoxide
          exposure 	    11-85
                                    xv 11

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                          ABBREVIATIONS AND SYMBOLS
 o
*A
*(A-aDn
      U
AEROS
A/F
Amthauer's I.S.T.
AQCR
Ar
ASHD
BCG
8C
CAMP
CBF
CFFF
CHA
CHI)
Cm3
cm
CNS
CNV
CO
C09
CORb
COMb
CV

DCM
dl
dm
ECG
EDTA
EKG
 PA
H
HCN
He
hg
Hg
HgO
hv
Angstrom
Alveolar-artery pressure difference in Op

Aerometric and Emissions Reporting System
Air to fuel ratio
Amthauer's Intelligence Structure Test
Air Quality Control Regions
Argon
Arteriosclerotic heart disease
Bal1i stocardiogram
Degrees Centigrade (Celsius)
Continuous Air Monitoring Program
Cerebral blood flow; also coronary blood flow
Critical flicker fusion frequency
Methane
Coronary heart disease
Centimeter
Cubic centimeters
Central nervous system
Contingent negative variation
Carbon monoxide
Carbon dioxide
Carboxyhemoglobi n
Carboxymyoglobin
Coefficient of variation; standard deviation divided
 by the mean
Dichloromethane; Methylene chloride;
Deciliter
Decimeter
Echocardiogram
Ethylene-diaminetetraacetic acid, often used as
 the disodium salt.
Electrocardi ogram
Environmental Protection Agency
Degrees Fahrenheit
Gram
Molecular hydrogen
Hemoglobin
Hydrocyanic acid
Helium
Hectogram (100 g)
Mercury
Mercuric oxide
The product of Planck's constant times the frequency
 of radiated energy (v) = quantum of energy (E).
 The amount of energy  contained  in a unitary particle
 of light of frequency v.
CH2C1£
                                    xvm

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H0
kg
kJ/mol
km
Kr
LDH
M
m
Mb
MetHb
mg/m
ml

N&AQS
NADB
NBS
NDIR
nm
N09
N90

°
09Hb
P
  °2
ppb
ppm
psi
REM
SAROAD
SF
Sll
SRM
VER
VMT
*V
  0
2 max

A'
*(V/Q)
                    Water
                    Iodine pentoxide
                    Chemical  reaction rate constant
                    Ki 1 ogram
                    Kilo joules per mole
                    Ki 1 ometer
                    Krypton
                    Lactate dehydrogenase
                    Haldane constant (in relation to carboxyhemoglobin);
                     or, in atmospheric chemistry,  an inert molecule  or
                     particle which participates in a chemical  reaction
                    Meter
                    Myoglobin
                    Methemoglobin
                    Microgram
                    Milligrams per cubic meter
                    Mill iHter
                    Molecular nitrogen
                    National  Ambient Air Quality Standards
                    National  Aerometric Data Bank
                    National  Bureau of Standards
                    Non-dispersive infrared photometry
                    Nanometer
                    Nitrogen  dioxide
                    Nitrous oxide; "laughing gas"
                    Molecular oxygen
                    Ozone
                    Hydroxyl  radical
                    Oxyhemoglobin
                    Carbon monoxide partial pressure
                    Oxygen partial pressure

                    Parts per billion
                    Parts per million
                    Pounds per square inch
                    Rapid eye movement
                    Storage and Retrieval of Aerometric Data
                    Sulfur hexafluoride
                    State Implementation Plans
                    Standard  Reference Materials
                    Visual evoked response
                    Vehicle miles travelled
                    Maximal aerobic capacity
                    Ventilation perfusion ratio
2,3-DPG             2,3 - Diphosphoglycerate

"appears in text as:  8, A-aDQ2, PQ2, VQ2 max, and VA/Q
                                      xix

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                          CONTRIBUTORS AND REVIEWERS
The following persons were contributing authors to the document.


 Dr. David J. McKee, Environmental Criteria and Assessment Office,
     Environmental Research Center, U. S. Environmental Protection
     Agency, Research Triangle Park, North Carolina 27711.

 Mr. Ronald E. Bales, Consultant, Informatics, Inc., Rockvllle, Maryland
     20852.

 Dr. Vernon A. Benlgnus, Clinical Studies Branch, U. S. Environmental
     Protection Agency, Building 224H, University of North Carolina,
     Chapel H111, North Carolina 27514.

 Dr. Jack Fishman, National Center for Atmospheric Research, Boulder,
     Colorado 80307, and Colorado State University.

 Dr. J. H. B. Garner, Environmental Criteria and Assessment Office,
     Environmental Research Center, U. S. Environmental Protection
     Agency, Research Triangle Park, North Carolina 27711.

 Dr. Steven M. Horvath, Institute of Environmental Stress, University of
     California at Santa Barbara, California 93106.

 Dr. Terry L. Miller, Enviro-Measure, Inc., Knoxville, Tennessee 37917.

 Dr. Robert W. Rogers, Informatics, Inc., Rockvllle, Maryland 20852.

 Dr. Martha Sager, Department of Environmental Systems Management,
     The American University, Washington, D. C. 20016.

 Dr. Alfred Weissler, Consultant, Informatics, Inc., Rockvllle, Maryland
     20852.
The following persons served on the EPA task force and/or were responsible
for the review and preparation of this document.


 Dr. David J. McKee, Task Force Chairman, Environmental Criteria and
     Assessment Office, Environmental Research Center, U. S.
     Environmental Protection Agency, Research Triangle Park,
     North Carolina 27711.
                                      xx

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Mr. Michael A. Berry, Environmental Criteria and Assessment Office,
    Environmental Research Center, U. S. Environmental Protection
    Agency, Research Triangle Park, North Carolina 27711.

Dr. Robert M. Bruce, Environmental Criteria and Assessment Office,
    Environmental Research Center, U. S. Environmental Protection
    Agency, Research Triangle Park, North Carolina 27711.

Mr. Michael Claggett, Envlro-Measure, Inc., Knoxville, Tennessee 37917.

Ms. Josephine Cooper, Environmental Criteria and Assessment Office,
    U. S. Environmental Protection Agency, Research Triangle Park,
    North Carolina 27711.

Mr. Thomas C. Curran, Office of Air Quaility Planning and Standards,
    MDAD, Durham, North Carolina

Ms. Vandy Duffield, Environmental Criteria and Assessment Office,
    Environmental Research Center, U. $. Environmental Protection
    Agency, Research Triangle Park, North Carolina 27711.

Mr. Warren P. Freas, Office of Air Quaility Planning and Standards,
    AMTB, Durham, North Carolina

Mr. Garry Evans, Environmental Monitoring and Support Laboratory,
    U. S. Environmental Protection Agency, Research Triangle Park,
    North Carolina 27711.

Dr. Lester D. Grant, Environmental Criteria and Assessment Office,
    Environmental Research Center, U. S. Environmental Protection
    Agency, Research Triangle Park, North Carolina 27711.

Dr. Robert Norton, Health Effects Research Laboratory,
    U. S. Environmental Protection Agency, Research Triangle Park,
    North Carolina 27711.

Mr. Alan Hoyt, Environmental Criteria and Assessment Office,
    Environmental Research Center, U. S. Environmental Protection
    Agency, Research Triangle Park, North Carolina 27711.

Mr. Charles Mann, Office of A1r Quality Planning and Standards,
    MDAD, Durham, North Carolina

Mr. Justice Manning, Office of Air Quality Planning and Standards,
    SASD, U. S. Environmental Protection Agency, Durham, North Carolina.

Mr. Thomas McMullen, Environmental Criteria and Assessment Office,
    U. S. Environmental Protection Agency, Research Triangle Park,
    North Carolina 27711.
                                     xx i

-------
 Mr.  Edwin L.  Meyer,  Jr.,  Office of Air Quality Planning and Standards,
     AMTB, Durham,  North Carolina.

 Mr.  John O'Connor, Office of Air Quality Planning and Standards,
     U.  S. Environmental Protection Agency, Durham, North Carolina.

 Mr.  Kenneth Rehme, Environmental Monitoring and Support Laboratory, U.
     S.  Environmental Protection Agency, Research Triangle Park, North
     Carolina 27711.

 Mr.  Harvey Richmond, Office of Air Quality Planning and Standards,
     SASD, Durham,  North Carolina.

 Mr.  Jerry Romanovsky, Environmental Sciences Research Laboratory,
     Environmental  Research Center, U.  S. Environmental Protection
     Agency, Research Triangle Park, North Carolina 27711.

 Mr.  S.  Z. Shariq,  Health Effects Research Laboratory, U.  S.  Environmental
     Protection Agency, Research Triangle Park, North Carolina 27711.

 Mr.  Jacob G.  Summers, Office of Air Quality Planning and Standards,
     NADB, Durham,  North Carolina.

 Ms.  Beverly Tilton,  Environmental  Criteria and Assessment Office,
     Environmental  Research Center, U.  S. Environmental Protection
     Agency, Research Triangle Park, North Carolina 27711.
The following persons served as consulting contributors and reviewers
in the preparation of this document.
 Dr. Wilbert S. Aronow, Chief, Cardiovascular Section, Veterans Adminis-
     tration Hospital, Long Beach, California 90822.

 Mr. Lucian Chaney, University of Michigan, Ann Arbor, Michigan 48109.

 Dr. C.  C. Delwiche, LAWR, Hoagland Hall, University of California at
     Davis, California 95616.

 Dr. Laurence Fechter, Department of Environmental Health Sciences,
     Johns Hopkins University School of Hygiene, Baltimore, Maryland 21205.

 Dr. Patrick A. Gorman, George Washington University Medical School,
     Washington, D. C. 20037.

 Dr. Harvey Jeffries, Department of Environmental Science and Engineering,
     School of Public Health,  University of North Carolina, Chapel Hill,
     North Carolina 27514.
                                      xxii

-------
 Dr.  James Kaweckl,  University of Maryland, College Park, Maryland 20740.

 Dr.  Thomas L.  Kurt, B-130, Division of Cardiology, University of
     Colorado Medical Center, Denver, Colorado 80262.

 Dr.  Kenneth Noll, Department of Environmental Engineering, Illinois
     Institute of Technology, Chicago, Illinois 60616.

 Dr.  Auguste T.  Rossano, Air Resources Program, University of Washington,
     Seattle, Washington 98195.

 Dr.  Wolfgang Seller, National Center for Atmospheric Research, Boulder,
     Colorado 80307.

 Ms.  Kathy Seiple, Department of Environmental Science and Engineering,
     School of Public Health, University of North Carolina, Chapel Hill,
     North Carolina 27514.

 Dr.  R.  P. Stewart,  Department of Environmental Medicine, Medical College
     of Wisconsin A-B Laboratory, Milwaukee, Wisconsin 53005.
 Dr.  Leonard Weinsteln, Boyce Thompson Institute, Ithaca, New York.
The following persons from Informatics Inc., Rockville, Maryland, 20852,

provided consulting, word-processing and technical assistance under
contract with the Environmental Criteria and Assessment Office, EPA.
Ms. Ruth H. Ness, Chairman

Dr. W. B. Dockstader

Ms. Joanna CHchton

Mr. Lewis Johnson

Ms. Marge Herridge
                                    xxi 11

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The following persons from the Environmental Criteria and Assessment
Office provided word-processing and technical assistance in the development
of this document.
Ms. Diane Chappell

Mr. Douglas Fennel 1

Ms. Mavis Pope

Ms. Evelynne  Rash

Ms. Donna Wicker
                                      xx iv

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                         1.  SUMMARY AND CONCLUSIONS

1.1  INTRODUCTION
     Section 109(d) of the Clean Air Act, as amended, requires a thorough
review of the air quality criteria for carbon monoxide (CO) by December 31,
1980, and at five-year intervals thereafter.  The Administrator of the
Environmental Protection Agency (EPA) is required to make such revisions
of the criteria as may be appropriate.  In addition, the Administrator
may from time to time review, and where appropriate, modify the criteria
under the authority of Section 108(c).
     This document is designed to evaluate the scientific information
which will form the basis for the National Ambient Air Quality Standard
(NAAQS) for CO.  Major questions addressed in this document, which
covers new research published since the original CO criteria document
was issued, include the following:
     (1)  At what level of CO exposure do adverse health effects occur?
     (2)  What are the major health effects from exposure to CO?
     (3)  What are the special groups at risk to CO exposure?
     (4)  What are the major sources of CO exposure?
     (5)  Are there additive effects from CO exposure in combination
with other pollutants and drugs, or at high altitudes?
                                      1-1

-------
     (6)  Do present monitoring methods adequately reflect human exposure to



CO?



     (7)  What are the global effects of increased emissions of CO to the



atmosphere?



1.2  PROPERTIES AND PRINCIPLES OF FORMATION OF CARBON MONOXIDE



     Natural processes such as forest fires, methane oxidation, and biological

                                                                  o

activity maintain a CO background concentration of about 0.05 mg/m  (0.044 ppm)



Global atmospheric mixing of urban and industrial sources of CO creates levels


                 3                                                          3
of about 0.2 mg/m  (0.18 ppm) in the northern hemisphere and about 0.06 mg/m



(0.05 ppm) in the southern hemisphere.   Much higher levels exist in cities as



a result of local combustion of fossil  fuels.



     On the average, nearly 85 percent of the CO in urban atmospheres is due



to mobile sources.  Carbon monoxide emissions from internal combustion engines



can be reduced by improving the efficiency of combustion through changes in



design and operating conditions, or by the use of catalytic reactors in the



exhaust gas stream to oxidize CO to carbon dioxide (CO^).   The measurement of



CO in effluent gas is used to indicate the proper and efficient operation of



any combustion process.  The reactions of CO with oxygen (0^), ozone (0~), and



nitrogen dioxide (NOp are relatively slow, but the rapid oxidation of CO by



OH radicals is an important factor affecting its abundance in the atmosphere.



1.3  ESTIMATION OF CARBON MONOXIDE EMISSIONS FROM TECHNOLOGICAL SOURCES



     Nationwide, the estimated annual emission from man-made sources of CO in



the U.S. rose from 102 million metric tons in 1970 to 104 in 1972.
                                      1-2

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These emissions declined to 97 million metric tons in 1975 and increased to
103 million metric tons in 1977.  As of 1977, highway vehicles contributed
75.2 percent of the emission total, nonhighway transportation 8.2 percent, and
industrial processes 8.1 percent.  Miscellaneous combustion (agricultural
burning, forest fires, structural fires, etc.) accounted for 4.8 percent,
solid waste combustion 2.5 percent, and heat and electric power generation 1.2
percent.
     Future emissions will depend on trends in vehicle use, the effectiveness
of pollution control devices on automobiles, and the efficiency of vehicle
operation.  By estimating the growth rate of vehicle use and the increased
control of pollution, total CO emissions from automobiles in the U.S. are
expected to decline after 1979.  However, this forecast depends on trends
which may change due to increased fuel prices, traffic flow improvements,
conversion to alternate fuels, and maintenance of pollution control equipment.
1.4  ANALYTICAL METHODS
     The EPA-approved method for measuring CO levels in ambient air utilizes
non-dispersive infrared photometry (NDIR).  NDIR is based on the characteristic
absorption of infrared radiation by CO.  The NDIR continuous-monitoring systems
are  sensitive over a wide range of concentrations and have short response
times.  Because the systems are adversely affected by vibration or shock, they
are  unsuitable for mobile use.
     The operating range of NDIR systems is up to 50 ppm CO.  Very low background
levels  of atmospheric CO can be measured using highly sensitive instruments
                                       1-3

-------
such as a gas chromatograph fitted with a flame ionization detector.
Relatively high levels, as found in parking garages, can be measured by
the catalytic oxidation of CO measured by an electrochemical or a
temperature-rise sensor depending on need for accuracy of results.
     Blood carboxyhemoglobin (COHb) levels, a good index of CO exposure,
can be measured using several techniques.   These include spectrophoto-
metry, gas chromatography or NDIR.  Exhaled air also reflects CO
content of the blood if the air sample is collected under special
conditions.
1.5  CARBON MONOXIDE CONCENTRATIONS IN AMBIENT AIR
     The selection of monitoring sites is critical for the accurate
assessment of CO exposure.  Site selection depends on the monitoring
program:  microscale, mesoscale, or macroscale air pollution regimes.
For instance, the microscale regime should include monitoring sites
along urban roadways, an area with high CO concentrations.
     Continuous Air Monitoring Program (CAMP) stations have been operated
by the Federal government at downtown sites in some major cities since
1962.   Current measurements of CO levels are reported quarterly to EPA
by state, local, and Federal agencies.  California has been the major
contributor to the national CO data base, with 59 sites.  Measurements
of CO levels disclose that the NAAQS are often exceeded, especially near
major streets in urban areas.  In 1977, 211 out of 456 monitors showed
at least one 8-hour NAAQS violation, but only 11 showed 1-hour NAAQS
violations.
                                      1-4

-------
     Concentrations of CO vary with time, season, and geographical
location.  These variations often follow predictable trends.  In most
cities, CO levels peak at 7 to 9 a.m., 4 to 7 p.m., and 10 p.m. to
midnight.  The first two peaks arise from automobile traffic coupled
with meteorological conditions.  The midnight peak can be primarily
attributed to calm wind conditions which result in a reduced dispersion
of CO emissions.  The highest CO levels tend to occur in the fall and
winter.
     The dispersion of CO emissions is affected by wind speed, wind
direction, atmospheric stability, vertical mixing height, and ambient
temperature.  In addition, this dispersion is affected by topographic
features such as mountains and buildings.
     Mathematical models have been proposed to describe CO transport,
dispersion, and chemical transformations in the atmosphere.  These
models can be used to predict air quality CO levels on the basis of the
characteristics of the emission sources plus meteorologic and topographic
factors.
     Exposure to unusually high ambient levels of CO may result from the
following scenarios:  (1)  On a big city freeway where traffic has come
                                                  3
to a halt, the ambient CO level may exceed 50 mg/m  (44 ppm).
(2)  Inside a closed auto where cigarettes are being smoked, CO concen-
                            3
trations may exceed 100 mg/m  (87 ppm).  (3)  In enclosed, unventilated
                                        3
garages, CO levels in excess of 115 mg/m  (100 ppm) have been found.
(4)  In a heavily-travelled vehicular tunnel, a 1-hour maximum of 250
mg/m  (218 ppm) CO was recorded.  And (5), for certain occupational
                                      1-5

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exposures, such as those encountered by fire fighters and some foundry



workers and miners, high CO levels have been reported.



1.6  THE GLOBAL CYCLE OF CARBON MONOXIDE



     Much of the discussion about the global cycle of CO in the atmos-



phere currently centers on the relative importance of the role of anthro-



pogenic activity in the formulation of the global budget of this gas.



Prior to 1970, nearly all CO emissions were thought to originate from



combustion processes.  However, in the early 1970's speculation evolved



that a significant natural source of CO existed from the oxidation of



methane in the unpolluted troposphere.  The early estimates of the



source strength of CO from methane oxidation indicated that this source



was approximately ten times greater than man's input of CO into the



atmosphere.  With the advent of more sophisticated models, a better



understanding of the geographical distribution of CO, and new chemical



kinetics data being made available, more recent calculations in the late



1970's have suggested that methane oxidation is not the dominant source



of CO in the atmosphere and that man's activities are responsible for



the presence of much and possibly most of the CO observed in the



atmosphere, especially in the Northern Hemisphere.  If, indeed, anthro-



pogenic sources of CO have perturbed the natural distribution of this



gas in the troposphere, it then seems likely that the abundance, distri-



bution and the global cycles of many other trace constituents in the



atmosphere have also been altered.  Some of these studies even imply



that increased CO amounts may have a significant indirect influence on



the chemistry which maintains the stratospheric ozone layer.
                                      1-6

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1.7  EFFECTS OF CARBON MONOXIDE ON VEGETATION AND CERTAIN MICROORGANISMS
     Carbon monoxide is a normal constituent of the plant environment.
Plants can both metabolize and produce CO.  This may explain the rela-
tively high levels of CO necessary to produce detrimental effects.
     There are few studies from which thresholds for detrimental or
other effects might be inferred, although defoliation or inhibition of
leaf and flower formation are demonstrable at high CO (above 100 ppm)
concentrations.  These studies are of little value in determining effects
at ambient CO levels since the concentrations used were 1000 or more
times greater than the usual atmospheric concentrations.
     Microorganisms show a wide range of response to CO, including its
autotrophic oxidation.  Thus, any change in global atmospheric concen-
tration might be expected to reflect a corresponding alteration of soil
microbial population distribution.  Soil microflora have the capability
of responding to changing environmental conditions.  Soil microflora may
be considered to be a buffering system and an eventual sink for CO.
     Comparatively low levels of CO in the soil inhibit nitrogen fixation.
                          3
Concentrations of 113 mg/m  (98 ppm) have been shown to reduce nitrogen
fixation, while 572 to 1145 mg/m3 (500 to 1000 ppm) result in nearly
complete inhibition.  An estimated consumption rate of 5 x 10   g/yr
indicates that soil microorganisms are a major sink for CO.
     High concentrations of CO can induce the formation of adventitious
roots in higher plants as well as stimulate the growth of latent root
primordia.  Plants exposed to 11,450 mg/m3 (10,000 ppm) CO exhibit
growth abnormalities including epinasty and hyponasty in leaves, retarded
                                       1-7

-------
stem elongation, smaller and/or deformed leaves, and premature abscission


                                                           3
of leaves.   Concentrations of CO in the 1145 to 11,450 mg/m  (1,000 to



10,000 ppm) range can induce female expression in genetically male



plants of Cannabis sativa.  Many species of plants are capable of ab-



sorbing and metabolizing CO photosynthetically.  Although it has been



demonstrated that plants absorb CO, they function as net producers,



emitting more CO than they absorb.



1.8  METABOLISM OF CARBON MONOXIDE IN MAMMALS



     Carbon monoxide exists in mammals primarily from the inhalation of



ambient air and from the normal catabolism of pyrrole rings.  Endogenous



sources of CO result in COHb levels of approximately 0.5 percent.   Any



increment above this level is assumed to have resulted from an exogenous



source.  Factors which control and determine the final level of COHb are



the concentration of inspired CO, alveolar ventilation, red cell volume,



barometric pressure, and the diffusive capability of the lungs.



     The apparent toxicity of CO is related to the strength of the



coordination bond formed with the iron atom in protoheme (C~ J-L«N.04Fe).



Hemoglobin (Hb), a ferrous iron complex of a protoporphyrin combined



with globin, is contained within the erythrocyte (red blood cell).



One of its primary functions is to transport 0^ and C0?.  Hb combines



readily with either 0£ (to form 02Hb) or CO (to form COHb).   The affinity



of Hb for CO is about 240 times greater than its affinity for 02.   The



presence of COHb in blood not only reduces the availability of 0^ to



the body but also inhibits the dissociation of the remaining 0?.  Carbon



monoxide also combines reversibly with heme compounds in the body cells.
                                      1-8

-------
     A number of conclusions may be derived from Chapter 9.  The reduc-
tion in Og-carrying capacity of the blood is proportional to the amount
of COHb present.  However, the amount of available 0^ is still further
            *
reduced by the inhibitory influence of COHb on the dissociation of any
02Hb still available.  Carbon monoxide diffuses more rapidly through
blood and pulmonary and placental tissues than would be predicted from
comparative solubilities of 02 and CO in water.  The small reductions in
Q£ content at 5 to 10 percent COHb may be quite critical for patients
suffering from cardiovascular diseases or chronic obstructive lung
disease.  It has been suggested that the principle mechanism of CO
toxicity is not hypoxemia, but rather a blocking of the energy flow
on the cellular level through the cytochrome system.  The administration
of CO results in chemoreceptor stimulation.  The response appears to be
almost linear with the COHb concentration (at least definitely above 8
percent).  Available evidence suggests the presence of a biphasic decline
in arterial blood COHb (percent) levels.  The distribution phase, which
persists for the first 20 to 30 minutes, is followed by a slower linear
decline (elimination phase).  And, although no final judgment has been
made regarding the effects of CO on oxidative transport, experimental
evidence suggests that the cytochromes are affected during CO poisoning.
1.9  EFFECTS OF CARBON MONOXIDE ON EXPERIMENTAL ANIMALS
     Animal studies provide information that may be of importance to
human reactions under similar circumstances.  Animal data may permit
predictions concerning sensitive human populations, such as those with
existing CNS and cardiovascular defects.
                                      1-9

-------
                                         o

     Carbon monoxide exposures of 58 mg/m  (50 ppm; 4 to 7 percent COHb)



have produced cardiovascular effects.   The minimal concentration of CO



affecting behavior and CNS appears to be 115 mg/m  (100 ppm; 12 to 20



percent COHb).



1.10  EFFECTS OF LOW-LEVEL CARBON MONOXIDE EXPOSURE ON HUMANS



     As seen in the animal studies, human exposures to low levels of CO



have also resulted in deleterious effects on the CNS and cardiovascular


                                              3
systems.  While an 8-hr exposure to 17-21 mg/m  (15-18 ppm; 2.5-3



percent COHb) CO affected cardiovascular systems, concentrations of CO



as low as 29-34 mg/m  (25-30 ppm; 4-6 percent COHb) affected behavior



and the CNS.



     Fetuses, persons with cardiovascular or central nervous system



defects, sickle cell anemics, young children, older persons, persons



living at high altitudes, and those taking drugs comprise groups at



special risk to CO exposure.  The current literature offers little



information regarding the high risk groups; however, it is apparent that



exposure for 8 hrs to CO concentrations as low as 15-18 ppm may be



detrimental to the health of persons suffering cardiac impairment.
                                      1-10

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                               2.  INTRODUCTION

     This document has been prepared pursuant to Sections 108(c) and
109(d)(l) of the Clean Air Act, as amended.  Section 108(c) requires
that the Administrator of the EPA from time to time review and, as
appropriate, modify and reissue criteria published pursuant to Section 108(a)
Section 109(d)(l) requires both that the Administrator complete a thorough
review, and as may be appropriate, make revisions in the criteria by
December 31, 1980, and at five-year intervals thereafter.  Air quality
criteria are required by Section 108(a) to identify effects on public
health and welfare caused by varying amounts of pollutants in the air.
These criteria must be supported by the latest available accurate
scientific information.
     The original criteria document for carbon monoxide (CO), The
National Air Pollution Control Administration publication No. AP-62, was
issued in 1970.  Since that time, new information has been published.
This document summarizes the pertinent information which will be used in
considering whether the present CO standards are adequate or revisions
are advisable or required.
     The purpose of these criteria is to identify air pollution effects
and serve as the basis for national ambient air quality standards
                                     2-1

-------
promulgated by the Administrator under Section 109 of the Clean A1r Act,
as amended.  This document therefore is concerned with CO as a pollutant
and will present the air quality criteria descriptive of the presently
available scientific data.  Specifically, air quality criteria for CO as
a pollutant are intended to reflect accurately the latest scientific
knowledge useful in indicating the kind and extent of all identifiable
effects on public health and welfare which may be expected from its
presence in the ambient air in varying quantities.  There are many
factors and interactions which must be considered in developing such a
criteria document.
     This document does not cite extensively the literature reporting
excessively high levels of CO, but focuses on this pollutant as it is
found in ambient environments.  The intent is to present an updated
comprehensive review of the available scientific information and data on
CO as an air pollutant.
     It is essential for understanding the basis of air pollution effects
that the basic chemistry and sources of CO be considered.  Furthermore,
it is necessary to consider analytical techniques and methods so proper
assessment can be made of concentration and potential exposure patterns.
The foregoing information precedes the detailed discussion of the effects
of CO on certain plants and microorganisms.
     Ambient and experimental levels of CO are expressed in milligrams
                     3
per cubic meter (mg/m ) followed by a parenthetical expression in parts
per million (ppm).  Gas density varies with pressure and temperature so
that accurate expression of concentrations requires cognizance of these
                                     2-2

-------
parameters.  The conversion factor, for example, at a constant standard

pressure of 760 mm Hg, at 0°C 1 mg/m  equals 0.800 ppm and 1 ppm equals
          O       _         ^J                                             A
1.250 mg/m ; at 25 C, 1 mg/m  equals 0.874 ppm and 1 ppm equals 1.145 mg/m .

     There is some indication that the production of CO and its concomi-

tant release into the atmosphere may have significant effects on some

aspects of the global atmosphere.  Some attention is directed toward

this as it may eventually affect human health and welfare.

     The last three chapters deal with the metabolism of CO by animals

and most importantly the effects it has on animals and man.  Much of the

effort and scientific information contained in this document is directed

toward the health and welfare of humans.  Carbon monoxide is a pollutant

that has at least one specific reaction product, carboxyhemoglobin

(COHb), in the human system which appears to be equated to exposure and

detrimental effects.  Other physiological responses and reactions have

been postulated recently and are expected to aid in the elucidation of

CO toxicity.  Much of the physiological information involves the concen-

tration of COHb in the blood resulting from exposure to ambient or

experimental levels of CO.

     In the preparation of this document, much use was made of previous

EPA documentation efforts on the subject as well as the monograph prepared

by the National Academy of Sciences which was published late in 1977.
                                      2-3

-------
        3.   PROPERTIES AND PRINCIPLES OF FORMATION OF CARBON MONOXIDE
     Even far from human habitation, carbon monoxide (CO) occurs in air



at an average background concentration of 0.05 mg/m , primarily as a



result of natural processes such as forest fires and the oxidation of



methane.  Much higher concentrations occur in cities due to technological



sources such as automobiles and the production of heat and power.
                                                    <


Carbon monoxide emissions are increased when the fuel  is burned in an



incomplete or inefficient way.  The physical and chemical properties of



CO suggest that atmospheric removal of CO occurs primarily by reaction



with hydroxyl (OH) radicals.



3.1  INTRODUCTION



     Carbon monoxide was first discovered to be a minor constituent of


                                  21
the earth's atmosphere by Migeotte   in 1948.  While taking measurements



of the solar spectrum, he observed a strong absorption band in the

                                                    1 Q

infrared region at 4.7 urn which he attributed to CO.    On the bases of



the belief that the solar contribution to that band was negligible and



of his observation of a strong day-to-day variability in absorption,



Migeotte concluded that an appreciable amount of CO was present in the



terrestrial atmosphere of Columbus, Ohio.  In the 1950's many more


            9 10 19 99 33 37
observations >''*'   of CO were made, with measured concentrations
                                      3-1

-------
ranging from 0.08 to 100 ppm (parts per million).   On the basis of these



and other measurements available in 1963, Junge   stated that CO appeared



to be the most abundant trace gas, other than carbon dioxide, in the


                                37
atmosphere.  The studies of Shaw   indicated higher mixing ratios near the



ground than in the upper atmosphere, implying a source in the biosphere,



but Junge emphasized that knowledge of the sources and sinks of atmospheric



CO was extremely poor.  It was not until the late 1960's that concerted



efforts were made to determine the various production and destruction



mechanisms for CO in the atmosphere.



     The remainder of this chapter will focus on the physical properties



and formation principles of CO which contribute to its release into the



atmosphere.  In Chapter 4, a review of the various factors which deter-



mine the technological emission source strength will be discussed; a



description of other source strength estimates as well as the global



cycle of CO will be presented in Chapter 7.



3.2  PHYSICAL PROPERTIES

                         «

     Carbon monoxide is a tasteless, odorless, colorless diatomic



molecule which exists as a gas in the earth's atmosphere.  Radiation in



the visible and near ultraviolet regions of the electromagnetic spectrum



is not absorbed by CO, although the molecule does have weak absorption



bands between 125 and 155 nm.  It absorbs radiation in the infrared



region corresponding to the vibrational excitation of its electronic



ground state.  Carbon monoxide has a low electric dipole moment (0.10



debye), short interatomic distance (1.23 8), and a high heat of formation



from atoms, or bond strength (2072 kJ/mol), suggesting that the molecule
                                      3-2

-------
                                          Ol

is a resonance hybrid of three structures,   which all contribute



nearly equally to the normal ground state.  General physical properties



of CO are given in Table 3-1.



3.3  GASEOUS CHEMICAL REACTIONS OF CARBON MONOXIDE



     In its review of the gaseous chemical reactions of CO in 1970,



the National Air Pollution Control Administration (later to become



part of the U. S. Environmental Protection Agency) concluded that no



gaseous reactions have been  shown to be important scavengers of CO in



the atmosphere.  No data since that time  indicate that the processes



they considered, which included reactions of CO with 02, H«0, NOp,



and 0-, are of any importance to atmospheric chemistry.  However, the



report did speculate that CO reactions with radicals in the atmosphere



could provide an important sink for CO.   Subsequent research has



shown that the CO reaction of most importance  in the atmosphere is OH



radical attack.  Other radicals react with CO  much more slowly


                     15
(Hampson and Garvin):



     CO + H0£  T    C02 + OH, k = 10"19 cm3/(molecule x sec),


                                        -17    3
and  CO + CH30 T    products, k = 4 x 10    cm /(molecule x sec).


                                               39                4
Carbon monoxide also reacts  with ground state,   and metastable,



atomic oxygen.  The relative importance of these reactions to the



overall chemistry occurring  in the atmosphere  is very slight.  In the

                                o

troposphere and stratosphere, 0( P) is much more likely to react with



molecular oxygen, 0?, in a three-body reaction to form ozone, or with



nitrogen dioxide, N02, to produce NO and  02.   Since 0( D) is a highly



reactive species, it is more likely to react with water vapor, methane,



or any other molecule which  is more abundant than CO in the atmosphere.
                                      3-3

-------
             TABLE 3-1.  PHYSICAL PROPERTIES OF CARBON MONOXIDE
                                                               24
Molecular weight
Critical point
Melting point
Boiling point
Density
  at 0 C, 1 atm
  at 25 C,l atm
Specific gravity relative to air
Solubility 1n water
  at 0°C
  at 20°C

  at 25°C
Explosive limits in air
Fundamental vibration transition
  CO(X'I  ,v' = lEv"0)
Conversion factors
  at 0 c, 1 atm

  at 25°C, 1 atm
28.01
-140°C at 34.5 atm
-199°C
-191.5°C

1.250g/liter
1.145g/liter
0.967

3.54ml/100mjl
(44.3 ppmm)
2.32ml/100ml
(29.0 ppmm)
2.14ml/100ml
(26.8 ppmm)
12.5-74.
2143.3cm
(4-67 urn)

1 mg/m  = 0.800 ppia(
1 ppm * 1.250 mg/m
1 mg/m  = 0.873 ppm
1 ppm = 1.145 mq/m
aVolume of carbon monoxide is at 0 C, 1 atm (atmospheric pressure at sea
.   level = 760 torr).
 Parts per million by mass (ppmm = mg 1)
 Parts per million by volume.
                                      3-4

-------
Collision of 0( D) with N2 or 0£ is quite likely to bring this excited



atom down to ground state.  Thus, with the exception of the OH reaction,



there is no evidence that any reactions involving CO are of any



consequence in the atmosphere.



     Many studies of the measurement of the reaction rate governing the



reaction



               CO + OH   T    C0£ + H



have appeared in the literature since the late 1960's (see Table 3-2).



Until 1976, all of the measurements agreed fairly well, ranging between


        -13   3                              -13   3
1.3 x 10    cm /(molecule x sec) and 1.9 x 10    cm /(molecule x sec);



the National Bureau of Standards review   recommended a value of 1.4 x


  -13   3
10    cm /(molecule x sec) and did not find any reason to believe that



either a substantial temperature or pressure dependence existed for this



reaction.


                        6                                     -13   3
     However, Cox et al.  reported a rate constant of 2.7 x 10    cm /



(molecule x sec) for this reaction at 760 torr (1 atm) using a mixture


                                            38
of Np and 0« as the diluent gas.  Sie et al.   likewise showed that the



CO + OH reaction rate increased as the pressure in their reaction chamber



increased when they used molecular hydrogen as a carrier gas.  They also



noted that the type of diluent employed for their experiments had an



effect on the rate of reaction.  Subsequent research efforts have


                                    38
supported the findings of Sie et al.    In general, it appears that



there is no pressure effect if noble gases (e.g., He or Ar) are used as



the carrier gas, but when other gases, which may be more representative



of the real atmosphere, are utilized in these studies the CO + OH reaction
                                       3-5

-------
                      TABLE 3-2.   REPORTED ROOM TEMPERATURE RATE CONSTANTS
                             FOR THE REACTION OF OH RADICALS WITH CO
    fiate~constant
(10   cnr/mol  x sec)
Pressure, torr/
diluent gas
Reference
No observed pressure
1.91 ± 0.08
1.48 ± 0.15
1.49 ± 0.05
1.42
1.66 ± 0.50
1.35 ± 0.20
1.33
1.44
1.56 ±0.2
1.59
1.58
1.51 ± 0.08
1.54 ± 0.16
Pressure dependence
1.00 ± 0.14
1.47 ± 0.19
2.98 ± 0.19
3.45 ± 0.22
3.18 ± 0.29
1.19
2.29
3.41
dependence
-v 1 (He or Ar)
100 (Ar)
not reported
100 (He)
0.2-1.0 (Ar or He)
20 (He)
1-3 (He or Ar)
10-20 (He or N90 + H9)
0.3-6 (He, Ar 5r N9r
20 (He) *
20 (N-)
730 (mostly Ar)
25-654 (Ar)
observed
19.9 (H.)
83.4 (H;)
296 (H9r
702 (H;)
774 (754 H9 + 20 H90)
627 (He) * *
569 (SFfi)
627 (SFg)

9
Dixon-Lewis et^al., 1966
Greiner, 1967^ 47
Wilson and O'Donovan, 1967
Greiner, 1969" 23
Mulcahy and Smith, 1921
Stun! and Niki, 1972** 4fi
Westenberg and de Haas,41973
Smith and Zellner, 1973™
Howard and Evenson* 1974
Davis et al., 1974^
Davis et al., 1974° --
Gordon and Mulac, 1975
Atkinson et al. , 1976

Sie et al., 197638







    1.37 ± 0.20
    2.97 ± 0.16

    2.04
    3.24

    1.50 ± 0.15
    1.52 ± 0.15
    1.52 ± 0.16
    1.62 ± 0.19
    1.62 ± 0.24

    1.53 ± 0.16
    1.93 ± 0.20
    2.40 ± 0.24
    3.09 ± 0.31
    3.43 ± 0.35
100 (air)
700 (air)

 59 (He)
200-359 (SFC)
           D
 25 (Ar)
 75 (Ar)
225 (Ar)
406 (Ar)
643 (Ar)

 25 (SF,)
 76 (SF°)
208 (SF°)
404
Chan et al., 1977'
Overand and Paraskevopoulos, 1977
                                 29
Perry et al.,  1977
                  32
Perry et al., 1977
                  32
604 (SFH
       D
                                        3-6

-------
rate exhibits an important pressure dependence.  Table 3-2 summarizes


most of the reported studies of the CO + OH reaction.  Most noteworthy

about the recent efforts is the suggestion that the rate of reaction is

at least twice as fast at pressures representative of lower tropospheric

conditions than was previously indicated.  This fact has led to important

changes in our understanding of the global CO cycle as well as the

budgets of several other trace gases.  These points will be discussed in

more detail in Chapter 7.

3.4  PRINCIPLES OF FORMATION

     In all cases, the burning of any carbonaceous fuel produces, among

other lesser products, two primary products -- carbon dioxide (CO^) and

CO.  The production of C0« predominates when the air or oxygen supply is

in excess of the stoichiometric needs for complete combustion.  If

burning occurs under fuel-rich conditions, with less air or oxygen than

is needed, CO will be produced in abundance.  Most of the CO and C0«

formed in past years was simply emitted into the atmosphere.

     In recent years, concerted efforts have been directed to reducing

concentrations of potentially harmful materials in ambient air.   The CO
                                       ?

found in urban air today originates almost entirely from local combustion

processes.  The background concentration of CO contributes less than
         Q
0.23 mg/m  (0.20 ppm) to the ambient air concentration at any given

urban location.  As a result of natural processes such as forest fires,

oxidation of methane and biological activity, the background level of CO
                                  o            35
is estimated to be about 0.05 mg/m  (0.04 ppm).    Global atmospheric

mixing of urban and industrial pollutants probably accounts for a measured
                                      3-7

-------
                                3
CO background of about 0.20 mg/m  (0.18 ppm) in the northern hemisphere

                   o                                       oc
and about 0.06 mg/m  (0.05 ppm) in the southern hemisphere.    The

                                            3
global average appears to be about 0.12 mg/m  (0.10 ppm) and does not

                                                             34
appear to have been increasing substantially in recent years.


     Considerable effort has been made to reduce emissions of CO and


other pollutants to the atmosphere.   Generally the approach has been


technological:  reduction of CO emissions to the atmosphere either by


improving the efficiency of the combustion processes, thereby increasing


the yield of C0« and decreasing the yield of CO; or by applying secondary


catalytic combustion reactors in the waste gas stream to convert CO to


co2.


     The development and application of control technology to reduce


emissions of CO from combustion processes has generally been successful


and is continuing to receive deserved attention.  However, the 1977

                               5
amendments to the Clean Air Act  postpone meeting the desired automobile


emission control schedules, reflecting in part the apparent difficulty


encountered by the automobile industry in developing and supplying the


required control technology.  Since the automobile engine  is recognized


to be the major source of CO in most urban areas, special  attention is


given to the control of automotive emissions.


     Table 3-3 shows the automobile emission control schedules that have


resulted from the 1970 Clean Air Act and later amendments.
                                      3-8

-------
              Table 3-3.   AUTOMOBILE EMISSION CONTROL SCHEDULES7

                                (in grams/mile)

1970




Clean Air Act
HC
CO
NO
1976

1.5
15.0
3.1
1977

0.41
3.4
2.0
1978 1979

—
—
0.4
1980 1981 1982

— — — _ T
T
T
As of jfily 1, 1977



1977




HC
CO
NO
Amendments
HC
CO
NOV
X
1.5
15
3.1

1.5
15
3.1



2.0

—
—
2.0

TO. 41 —
T3.4
0.4

_»
--


T
T


TO. 41
T7.0 3.4 T
1.0 T

     The problems encountered in mass-producing and marketing effective



control technology for automobile engines are complex, since a number of



simultaneous requirements are involved, i.e., control of multiple air



pollutants, fuel economy and efficiency, durability and quality control


                                                45
of components, and maintenance.  Current testing   of automobiles having



fuel injection and catalytic emission control systems has indicated that



durability of the controls will be a problem in meeting the 1981 require-



ment of <3.4 g of CO per mile after 50,000 miles.  (Emissions will be



less than 3.4 g of CO per mile on new automobiles.)



     The following sub-sections present a brief discussion of the general



principles and mechanisms of formation of CO and control of emissions



associated with the many combustion processes.  The processes are commonly



classified in two broad types, mobile sources and stationary sources,



since this division does generally separate distinct  types of major



combustion devices.  Control techniques for CO emissions from mobile and



stationary sources are detailed in references 27 and  28.
                                      3-9

-------
3.4.1  General Combustion Processes



     Incomplete combustion of carbon or carbon-containing compounds



creates varying amounts of CO.  The chemical and physical processes that



occur during combustion are complex, because they depend not only on the



type of carbon compound reacting with oxygen, but also on the conditions


                                   20 30
existing in the combustion chamber.  '    Despite the complexity of the



combustion process, certain general principles regarding the formation



of CO from the combustion of hydrocarbon fuels are widely accepted.



     Gaseous or liquid hydrocarbon fuel reacts with molecular oxygen in



a chain of reactions that result in CO.  Carbon monoxide then reacts



with hydroxyl radicals to form carbon dioxide (COp).  This second



reaction is approximately 10 times slower than the first.  In coal



combustion, the reaction of carbon and oxygen to form CO is also one of



the primary reactions, and a large fraction of carbon atoms go through



the monoxide form.  Again, the reaction of monoxide to dioxide is much



slower.



     Thus, four basic variables control the concentration of CO in all



combustion of hydrocarbon gases.  These are:  (1) oxygen concentration,



(2) flame temperature, (3) gas residence time at high temperatures, and



(4) combustion chamber turbulence.  Oxygen concentration affects the



formation of both CO and COp because oxygen is required  in the initial



reactions with the fuel molecule and in the formation of the hydroxyl



radical.  As the availability of oxygen increases, more  complete



conversion of monoxide to dioxide results.  Flame and gas temperature



affects both the formation of monoxide and the conversion of monoxide to
                                      3-10

-------
dioxide because both reaction rates increase exponentially with increasing



temperature.  Also, the hydroxyl radical concentration in the combustion



chamber is very temperature-dependent.  The conversion of CO to C0? is



also enhanced by longer residence time, because this  is a relatively



slow reaction in comparison to CO formation.   Increased gas turbulence



in the combustion zones increases the actual reaction rates by increasing



the mixing of the reactants and assisting the  relatively slower gaseous



diffusion process, thereby resulting in more complete combustion.



3.4.2   Combustion Engines



3.4.2.1  Mobile Combustion Engines—Most mobile sources of CO are



internal combustion engines of two types:  (1) carbureted, spark-



ignition, gasoline-fueled, reciprocating engines, and (2) diesel-fueled



reciprocating engines.  The CO emitted from any given engine is the



product of the following  factors:  (1) concentration of CO in the exhaust



gases, (2) the flow rate  of exhaust gases, and (3) the duration of



operation.



3.4.2.2  Internal Combustion Engines (Gasoline-Fueled, Spark-



Ignition Engines)— Exhaust concentrations of  CO  increase with lower



(richer) air to fuel  (A/F) ratios, decrease with  higher (leaner) A/F



ratios, but remain relatively constant with ratios above the stoichio-



metric ratio of about  15  to 1.    The behavior of gasoline automobile



engines before and after  the installation of pollutant control devices



differs considerably.  Depending on the mode of driving, the average



uncontrolled engine operates at A/F ratios ranging from about 11 to 1



to a point slightly above the stoichiometric ratio.   During the idling
                                       3-11

-------
mode, at low speeds with light load (such as low speed cruise), during
the full-open throttle mode until speed picks up, and during deceleration,
the A/F ratio is low in uncontrolled cars and CO emissions are high.  At
higher-speed cruise and during moderate acceleration, the reverse is
true.  Cars with exhaust controls generally remain much closer to
stoichiometric A/F ratios in all modes, and thus the CO emissions are
kept lower.  The relationship between CO concentrations in engine exhaust
and A/F ratios is shown in Figure 3-1.  The exhaust flow rate increases
with increasing engine power output.
     Correlations between total emissions of CO in grams per vehicle
mile and average route speed show a decrease in emissions with increasing
              38 41 43
average speed.  *  '    During low-speed conditions (below 32 km/hour or
20 miles/hour average route speed), the greater emissions per unit of
distance traveled are attributable to an increase in the frequency of
acceleration, deceleration, and idling in the driving cycle encountered
by the vehicle in heavy traffic; and the consequent increase in the
operating  time per mile driven.
     The CO and the unburned hydrocarbon exhaust emissions from an
uncontrolled engine result from incomplete combustion of the fuel-air
mixture.   Emission control on new vehicles is being achieved by engine
modifications, improvements in engine design, and changes in engine
operating  conditions.  Substantial reductions in CO and other pollutant
emissions  result from consideration of design and operating factors such
as leaner, uniform mixing of fuel and air during carburetion, controlled
heating of intake air, increased idle speed, retarded spark timing,
                                      3-12

-------
           10
co
 i
H*
CO
                                                                        AIR-FUEL RATIO
         Figure 3-1.  Effect of air-fuel ratio on exhaust gas carbon monoxide concentrations from three test engines.^ (Used with permission of Society of

         Automotive Engineers, Inc. Copyright 1964.)

-------
improved cylinder head design, exhaust thermal reactors, oxidizing and
reducing catalysts, secondary air systems, exhaust recycle systems,
electronic fuel injection, A/F ratio feedback controls, and modified
                 25
ignition systems.
3.4.2.3  Internal Combustion Engines (Diesel Engines)—Diesel engines in
use are primarily the heavy-duty type which power trucks and buses.
Diesel engines allow more complete combustion and use less volatile
fuels than do spark ignition engines.  The operating principles are
significantly different from those of the gasoline engine.  In diesel
combustion, CO concentrations in the exhaust are relatively low since
high temperature and large excesses of oxygen are involved in normal
operation.  The exhaust emissions from diesel engines have the same
general composition as gasoline engine emissions, though the concentra-
tions of different pollutants vary considerably.  For example, the
diesel emits larger quantities of NO  and polycylic organic particulates
                                    f^.
than gasoline engines; it emits lesser quantities of CO.
3.4.2.4  Stationary Combustion Sources (Steam BoilersV^This section
refers to fuel-burning installations such as coal-, gas-, or oil-fired
heating or power generating plants (external combustion boilers).
     In these combustion systems, the formation of CO is lowest at a
ratio near or slightly above the stoichiometric ratio of air to fuel.
At lower than stoichiometric A/F ratios, high CO concentrations reflect
the relatively low oxygen concentration and the possibility of poor
reactant mixing from low turbulence.  These two factors can increase
emissions even though flame temperatures and residence time are high.
                                      3-14

-------
At higher than stoichiometric A/F ratios, increased CO emissions result
from decreased flame temperatures and shorter residence times.  These
two factors remain predominant even when oxygen concentrations and
turbulence increase.  Minimal CO emissions and maximum thermal efficiency
therefore require combustor designs that provide high turbulence,
sufficient residence time, high temperatures, and near stoichiometric
A/F ratios.  Combustor design dictates the actual approach to that
minimum.  The measurement of CO in effluent gas is therefore used as an
indication of improper and inefficient operating practice for any given
combustor, or of inefficient combustion.
3.5  NON-COMBUSTION INDUSTRIAL SOURCES
     There are numerous  industrial activities which result in the
                                                    44
emission of CO at one or more stages of the process.    Manufacturing
pig iron can produce as  much as 700 to 1050 kg CO/metric ton of pig iron.
Other methods of producing iron and steel can produce CO at a rate of
9  to 118.5 kg/metric ton.  However, most of the CO generated is normally
recovered and used as fuel.  Conditions such as "slips" can cause
instantaneous emissions  of CO.  Slips have been greatly reduced with
modern  equipment.  Grey-iron foundries can produce 72.5 kg CO/metric ton
of product but an efficient afterburner can reduce the CO emission to
4.5 kg/metric ton.
     Charcoal production results in CO emissions of 160 kg/metric ton
with or without the installation of chemical recovery equipment.
Emissions from carbon black manufacture can range from 5 to 3200 kg
CO/metric ton depending  on the efficiency and quality of the emission
control systems.
                                       3-15

-------
     Some chemical processes such as phthalic anhydride production give
off as little as 6 kg CO/metric ton with proper controls or as much as
200 kg CO/metric ton if there are no controls installed.  There are
numerous other chemical processes which produce relatively small CO
emissions per metric ton of product, such as sulfate pulping for paper
at 1 to 30 kg CO/metric ton; lime manufacturing normally runs 1 to 4 kg
CO/metric ton; and CO from adipic acid production is zero or slight with
proper controls.  Other industrial chemical processes which cause CO
emissions are the manufacture of terephthalic acid and the synthesis of
methanol and higher alcohols.  As a rule most industries find it economi-
cally desirable to install suitable controls to reduce CO emissions.
     Even though some of these CO emission rates seem excessively high,
they are in fact only a small part of the total pollutant load.   Mention
of these industries is made to emphasize the concern for localized
pollution problems when accidents occur or proper controls are not used.
     While the estimated CO emission resulting from forest wildfires in
the United States for 1971 was 4 x 10  metric tons, the estimated total
industrial process CO emission of the U. S. for 1971 was 10.3 x 10
metric tons.
                                      3-16

-------
                                  BIBLIOGRAPHY

1.    Atkinson, R., R. A.  Perry,  and J.  N.  Pitts,  Jr.   Kinetics of the reactions
     of OH radicals with  CO  and  N20.   Chem.  Phys.  Lett.  44:204-208, 1976.

2.    Benesh, W.,  M. Migeotte,  and L.  Neven.   Investigation of atmospheric CO
     at the Jungfraujoch.  J.  Opt.  Soc.  Am.  43:1119-1123,  1953.

3.    Chan, W. H., W. M. Uselman,  J.  G.  Calvert,  and J.  H.  Shaw.   The pressure
     dependence  of the  rate  constant for the reaction:   OH + CO •> H + C00.
     Chem. Phys.  Lett.  45:240-244,  1977.                                 ^

4.    Clerc, M.,  and F.  Barat.  Kinetics of CO formation studies by far-uv
     flash photolysis of  C02  J.  Chem.  Phys.  46:107-110, 1967.

5.    Clean Air Act. §109(c), as  amended by Pub.  L.  95-95,  91 Stat.  691,  42
     U.S.C. §7409, 1977.

6.    Cox, R. A.,  R, G.  Derwent,  and P.  M.  Holt.   Relative  rate constants for
     the reactions of OH  radicals with H«, CHA,  CO, NO  and HONO at atmospheric
     pressure and 296°K.   J. Chem.  Soc.  Faraday  Trans.  I 72:2031-2043,  1976.

7.    Council on  Environmental  Quality.   Environmental Quality - 1977.   The
     Eighth Annual Report of the Council  on Environmental  Quality.   U.S.
     Government  Printing  Office,  Washington,  DC,  December  1978.

8.    Davis, D. D., S. Fisher,  and R.  Schiff.   Flash photolysis-resonance
     fluorescence kinetics study:   Temperature dependence  of the reactions  OH
     + CO -» CO,  + H and OH + CHA ->  H90 + CH7.  J.  Chem.  Phys.  61:2213-2219,
     1974.    *                4    ^      d

9.    Dixon-Lewis, G., W.  E.  Wilson, and A. A.  Westenberg.   Studies of hydroxyl
     radical kinetics by  quantitative ESR.  J. Chem.  Phys.  44:2877-2884,  1966.

10.  Faith, W. L., N. A.  Renzetti,  and L.  H.  Rogers.   Fifth Technical  Progress
     Report.  Report No.  27, Air Pollution Foundation,  San Marino,  CA,  March
     1959.
                                                    o
11.  Gordon, S.,  and W. A. Mulac.   Reaction of OH(X II)  radical  produced by
     the pulse analysis radiolysis  of water vapor.   Iji:   Proceedings of the
     Symposium on Chemical Kinetics Data for the Upper  and Lower Atmosphere,
     Stanford Research  Institute and National  Bureau of Standards,  Warrenton,
     Virginia, September  15-18,  1974.   Int.  J. Chem.  Kinet.  Symp.  (1):  289-299,
     1975.

12.  Greiner, N.  R.  Hydroxyl  radical  kinetics by kinetic  spectroscopy.
     I.  Reactions with H«,  CO,  and CH. at 300°K.   J.  Chem.  Phys.  46:2795-2799,
     1967.                *

13.  Greiner, N.  R.  Hydroxyl  radical  kinetics by kinetic  spectroscopy.
     V.  Reactions with H« and CO in the range 300-500  K.   J.  Chem. Phys.
     51:5049-5051, 1969.  *
                                     3-17

-------
14.   Hagen, D. F. , and G. W. Holiday.  The effects of engine operating  and
     design variables on exhaust emissions.  In:  Vehicle Emissions.  (Selected
     SAE Papers).  Technical Progress Series Volume 6, Society of Automotive
     Engineers, Inc., New York, 1964. pp. 206-223.

15.   Hampson, R. F., Jr., and D. Garvin.  Chemical Kinetic and Photochemical
     Data for Modeling Atmospheric Chemistry.  NBS Technical Note 866,  U.S.
     Department of Commerce, National Bureau of Standards, June, 1975.

16.   Howard, C. J., and K. M. Evenson.   Laser magnetic resonance study  of the
     gas phase reactions of OH with CO,  NO, and N0?.  J. Chem. Phys.  61:1943-1952,
     1974.                                        *

17.   Junge, C. E.  Air Chemistry and Radioactivity.  Academic Press,  New York,
     1963.

18.   Lagemann, R. T. , A. H. Nielsen,..and F. E>  Dickey.  The infra-red spectrum
     and molecular constants of C^0lt? and C1J0   .  Phys. Rev. 72:284-289,
     1947.

19.   Locke, J. L., and L. Herzberg.  The absorption due to carbon monoxide  in
     the infrared  solar spectrum.  Can.  J. Phys.  31:504-516, 1953.

20.   Mellor, A. M.  Current kinetic modeling techniques for continuous  flow
     combustors.   In:  Emissions from Continuous  Combustion Systems,  Proceedings
     of the Symposium on Emissions from  Continuous Combustion Systems,  General
     Motors Research Laboratories, Warren, Michigan, September, 27-28,  1971.
     Plenum Press, New York, 1972. pp. 23-53.

21.   Migeotte, M.  V.  The fundamental band of carbon monoxide at 4-7  mm in  the
     solar spectrum.  Phys. Rev. 75:1108-1109, 1949.

22.   Migeotte, M.  V., and L. Neven.  Recent progress in observing the infrared
     solar spectrum at the  scientific station at  Jungfraujoch, Switzerland.
     Mem. Soc. R.  Sci. Liege 12:165-178, 1952.

23.   Mulcahy, M.  F. R., and R.  H.  Smith.  Reactions of OH radicals  in the
     H-NO£ and H-N02-CO systems.   J. Chem. Phys.  54:5215-5221, 1971.

24.   Committee on  Medical Biologic Effects of Environmental Pollutants. Carbon
     Monoxide.   National Academy Sciences, Washington, DC, 1977.

25.   Committee on  Motor Vehicle Emissions.  Automotive Spark  Ignition Engine
     Emmission Control Systems  to  meet the Requirements of the 1970 Clean Air
     Act Amendments.  National  Academy of Sciences, Washington, DC, May 1973.

26.   Committee on  Challenges of Modern Society.   Air Quality  Criteria for
     Carbon Monoxide.  Report No.  10, North Atlantic Treaty Organization,
     Brussels, June 1972.

27.   National Air  Pollution Control Administration.  Control  Techniques for
     Carbon Monoxide Emissions  from Stationary Sources.  National Air Pollution
     Control Administration Publication  No. AP-65, U.S. Department  of Health,
     Education,  and Welfare, Washington, DC, March 1970.


                                    3-18

-------
28.  National Air Pollution  Control  Administration.   Control  Techniques for
     Carbon Monoxide, Nitrogen  Oxide,  and Hydrocarbon Emissions from Mobile
     Sources.  National Air  Pollution  Control  Administration  Publication No.
     AP-66, U.S. Department  of  Health,  Education,  and Welfare,  Washington,  DC,
     March 1970.

29.  Overand, R., and G.  Paraskevopoulos.   The question of a  pressure effect
     in the reaction OH + CO at room temperature.   Chem.  Phys.  Lett.  49:109-111,
     1977.                                                            —

30.  Palmer, H.  B.  Equilibria  and  chemical  kinetics  in flames.   Combustion
     Technology:  Some Modern Developments.   H.  B.  Palmer and J.  M.  Beer,
     Academic Press, 1974. pp.  1-33.

31.  Pauling, L.  The Nature of the Chemical  Bond  and the Structure  of Molecules
     and Crystals:  An Introduction to Modern Structural  Chemistry.   Third
     Edition.  Cornell University Press,  Ithaca, NY,  1960 pp. 194-195.

32.  Perry, R. A.,  R. Atkinson,  and J.  N.  Pitts, Jr.   Kinetics  of the reactions
     of OH radicals with  C2H£ and CO.   J.  Chem.  Phys.  67:5577-5584,  1977.

33.  Renzetti, N. A., (ed.).  An Aerometric Survey of the Los Angeles Basin
     August-November, 1954.   Report No.  9,  Air Pollution  Foundation,  Los
     Angeles, CA.,  1955.

34.  Robbins, R. C., K. M. Borg, and E.  Robinson.   Carbon monoxide in the
     atmosphere.  J. Air  Pollut. Control  Assoc.  18:106-110, 1968.

35.  Seiler, W.  The cycle of atmospheric CO.   Tellus 26:116-135,  1974.

36.  Seiler, W., and C. Junge.   Carbon monoxide in the atmosphere.   J.  Geophys.
     Res. 75:2217-2226, 1970.

37.  Shaw, J. H.  A determination of the  abundance of nitrous oxide,  carbon
     monoxide and methane in ground level  air at several  locations near Columbus,
     OH.  Scientific Rpt.  No. 1, Contract No.  AF19 (604)-2259,  Air Force
     Cambridge Research Center,  38  pp.,  1959.   PB  143359.

38.  Sie, B. K.  T., R. Simonaitis,  and J.  Heicklen.   The  reaction of OH with
     CO.  Int. J. Chem. Kin.  8:85-98,  1976.

39.  Simonaitis, R., and  J.  Heicklen.   Kinetics and mechanism of the reaction
     of 0(3P) with  carbon monoxide.  J.  Chem.  Phys. 56:2004-2011,  1972.

40.  Smith, I. W. M., and R.  Zellner.   Rate measurements  of reactions of OH by
     resonance absorption.   Part 2.  -  Reactions of OH with CO,  C«H.  and C?H«.
     J. Chem. Soc.  Faraday Trans. 2. 69:1617-1627, 1973.

41.  Starkman, E. S.  Fundamental Process in Nitric Oxide and Carbon Monoxide
~~~   Production  from Combustion Engines.   XII Congress International  des
     Techniques  del1 Automobile - FISITA  Bericht,  1968.
                                     3-19

-------
42.  Stuhl, F., and H. Niki.  Pulsed vacuum-uv photochemical study of reactions
     of OH with H9, D9, and CO using a resonance-fluorescent detection method.
     J. Chem. PhyS. 57:3671-3677, 1972.

43.  National Air Pollution Control Administration.  Air Quality Criteria  for
     Carbon Monoxide.  National Air Pollution Control Administration Publication
     No. AP-62, U.S. Department of Health, Education, and Welfare, Washington,
     DC, March 1970.

44.  Office of Air Quality Planning and Standards.  Compilation of Air Pollutant
     Emission Factors.  Parts A and B.  Third Edition.  AP-42, U.S. Environmental
     Protection Agency, Research Triangle Park, NC, August 1977.

45.  Walsh, M. P., and B. D. Nussbaum.  Who's responsible for emissions after
     50,000 miles? - Automot. Eng. 86:32-35, 1978.

46.  Westenberg, A. A., and N. deHaas.  Rates of CO+OH and H2+OH over an
     extended temperature range.   J. Chem. Phys.  58:4061-4065, 1973.

47.  Wilson, W. E., Jr., and J. T. O'Donovan.  Mass-spectrometric study of the
     reaction rate of OH with itself and CO.  J.  Chem. Phys. 47:5455-5457,
     1967.                                                   ~~
                                    3-20

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    4.   ESTIMATION OF CARBON MONOXIDE EMISSIONS FROM TECHNOLOGICAL SOURCES

     The estimated total annual emissions from all man-made, sources in
the U.  S. rose from 102 million metric tons in 1970 to 104 in 1972, but
then declined to 97 in 1975 and subsequently increased to 103 million
metric tons in 1977.  About 75 percent of the total comes from highway
vehicles, 8.5 percent from railroads, aircraft, and other non-highway
transportation, 8 percent from industrial processes, 5 percent from
miscellaneous combustion (forest fires, agricultural burning, structural
fires, etc.), 2.5 percent from solid waste combustion, and 1 percent
                                                          o
from combustion for heating and electric power generation.
     Total emission trends and emission rates for specific sources or
source groups derived from calculated emission estimates provide a basis
for assessing the magnitude and pattern of air pollution resulting from
the various sources and allow the development of methods of estimating
future air quality conditions.
     The magnitude of future CO emissions will depend primarily upon
increased vehicle use trends, the effectiveness of pollution control
devices on automobiles, and the efficiency of vehicle operation.  The
concentrations of CO will generally be highest along congested major
                                      4-1

-------
highways, because of vehicle exhausts.  The interplay between the normal
growth rate of vehicle use and the near-term increase in effectiveness
of pollution control devices will probably cause total CO emissions from
highway vehicles in the U. S. to decline after 1979.
4.1  NATIONAL EMISSION LEVELS
     Estimates of the annual emissions of CO and other major air
pollutants from all sources in the U. S. are summarized in Table 4-1
for the years 1970 through 1977.   It may be noted that 102.2 million
metric tons of CO were discharged to the atmosphere in 1970.  An increase
is shown for 1971 and 1972 to 103.8 million metric tons and a subsequent
decrease is shown for each of the years 1973, 1974, and 1975 to a level
of 96.9 million metric tons.  In 1976 the emission of CO rose to
102.9 million metric tons and in 1977 to 102.7 million metric tons.
     Total nationwide emissions are shown according to the source
                        Q
categories in Table 4-2.   The percentage contributed to the total
national emission of CO by each of the designated source categories is
shown in the last column.
     The calculated nationwide annual emissions of CO from various
source categories are compared for the years 1970 through 1977 in Table
    o
4-3.   The estimations cited in Tables 4-1, 4-2, and 4-3 are the result
of current methodology and refined emission factors and should not be
compared with data reported earlier.  These data show that from 1970
through 1977 the CO emissions increased by 0.5 percent.  Since these
data are only calculated estimates of total nationwide emissions,
                                      4-2

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          TABLE  4-1.   SUMMARY OF NATIONAL EMISSION ESTIMATES,  1970-1977


                                 (10  metric tons/yr)
                                                                        8
Year
1970
1971
1972
1973
1974
1975
1976
1977
TSPa
22.2
20.9
19.6
19.2
17.0
13.7
13.2
12.4
S0x
29.8
28.3
29.6
30.2
28.4
26.1
27.2
27.4
N0x
19.6
20.2
21.6
22.3
21.7
21.0
22.8
23.1
VOC
29.5
29.1
29.6
29.7
28.6
26.9
28.7
28.3
CO
102.2
102.5
103.8
103.5
99.7
96.9
102.9
102.7
a)  TSP = total suspended particulates



    SO  = sulfur oxides
      /\


    NO  = nitrogen oxides
      /\


    VOC = volatile organic compounds



    CO  = carbon monoxide
                                          4-3

-------
                         TABLE 4-2.   NATIONWIDE EMISSION ESTIMATES, 1977



                                    (10  metric tons/year)
                                                                        8
Source Category
Transportation
Highway vehicles
Non- highway vehicles
Stationary fuel combustion
Electric Utilities
Industrial
Residential, commercial,
and institutional
Industrial processes
Chemicals
Petroleum refining
Metals
Mineral products
Oil & gas production & marketing
Industrial organic solvent use
Other processes
Solid waste
Miscellaneous
Forest wildfires
Agricultural burning
Coal refuse burning
Structural fires
Miscellaneous organic solvent use
TSP
1.1
0.8
0.3
4.8
3.4
1.2
0.2
5.4
0.2
0.1
1.3
2.7
0
0
1.1
0.4
0.7
0.5
0.1
0
0.1
0
S0x
0.8
0.4
0.4
22.4
17.6
3.2
1.6
4.2
0.2
0.8
2.4
0.6
0.1
0
0.1
0
0
0
0
0
0
0
N0x
9.1
6.7
2.5
13.0
7.1
5.0
0.9
0.7
0.2
0.4
0
0.1
0
0
0
0.1
0.1
0.1
0
0
0
0
VOC
11.5
9.9
1.6
1.5
0.1
1.3
0.1
10.1
2.7
1.1
0.1
0.1
3.1
2.7
0.3
0.7
4.5
0.7
0.1
0
0
3.7
CO
85.7
77.2
8.5
1.2
0.3
0.6
0.3
8.3
2.8
2.4
2.0
0
0
0
1.1
2.6
4.9
4.3
0.5
0
0.1
0
Percentage of
Total CO
83.4
75.2
8.2
1.2
0.3
0.6
0.3
8.1
2.7
2.3
2.0
0
0
0
1.1
2.5
4.8
4.2
0.5
0
0.1
0

TOTAL
12.4
27.4
23.1
28.3
102.7
100 100
NOTE:   A zero indicates emissions of less than 50,000 metric tons.
                                               4-4

-------
cn
                                     TABLE 4-3.   NATIONWIDE CARBON MONOXIDE EMISSION ESTIMATES, 1970-1977



                                                         (10  metric tons/year)
                                                                                                         8
Source Category
Transportation
Highway vehicles
Non-highway vehicles
Stationary fuel combustion
Electric utilities
Industrial
Residential, commercial &
institutional
Industrial processes
Chemicals
Petroleum refining
Metals
Mineral products
Oil & gas production & marketing
Industrial organic solvent use
Other processes
Solid waste
Miscellaneous
Forest wildfires
Agricultural burning
Coal refuse burning
Structural fires
Miscellaneous organic solvent use
1970
80.5
70.9
9.6
1.3
0.2
0.6
0.5
8.0
2.9
2.1
1.1
0
0
0
0.9
6.2
6.2
4.3
1.5
0.3
0.1
0
1971
81.1
71.7
9.4
1.4
0.2
0.6
0.6
7.9
2.7
2.1
2.2
0
0
0
0.9
4.7
7.4
5.9
1.2
0.2
0.1
0
1972
85.4
76.1
9.3
1.3
0.2
0.6
0.5
7.9
2.5
2.2
2.3
0
0
0
1.0
4.0
5.2
4.2
0.8
0.1
0.1
0
1973
85.9
76.5
9.4
1.4
0.3
0.6
0.5
8.2
2.7
2.2
2.3
0
0
0
1.0
3.6
4.4
3.5
0.7
0.1
0.1
0
1974
81.7
73.3
8.4
1.3
0.3
0.6
0.4
8.2
2.5
2.3
2.4
0
0
0
1.0
3.2
5.3
4.5
0.6
0.1
0.1
0
1975
82.0
73.8
8.2
1.1
0.3
0.5
0.3
7.3
2.2
2.4
1.8
0
0
0
0.9
2.9
3.6
3.0
0.5
0
0.1
0
1976
85.1
75.6
8.5
1.2
0.3
0.6
0.3
7.8
2.4
2.4
1.9
0
0
0
1.1
2.9
5.9
5.3
0.5
0
0.1
0
1977
85.7
77.2
8.5
1.2
0.3
0.6
0.3
8.3
2.8
2.4
2.0
0
0
0
1.1
2.6
4.9
4.3
0.5
0
0.1
0

TOTAL
102.2
102.5
103.8
103.5
99.7
96.9
102.9
102.7
     NOTE:  A zero indicates emissions of less than 50,000 metric tons per year.

-------
trends in emissions for local areas may be much different.  Nevertheless*
national emission estimates should be indicative of the overall general
trend in the quantities of air pollutants released to the atmosphere.
     Overall, carbon monoxide emissions have not changed significantly
during the period 1970-1977.  Emissions have been reduced as a result of
less burning of solid waste and agricultural materials.  However,
despite controls implemented on highway motor vehicles, total emissions
                                                            8
from this source category have increased by about 9 percent,  due to
the increase in vehicle miles traveled.
4.2  EMISSIONS AND EMISSION FACTORS BY SOURCE TYPE
4.2.1  Mobile Combustion Sources
     Table 4-3 shows the nationwide annual emission estimates for the
"transportation" category which includes emissions from all mobile
sources.  Highway vehicles include passenger cars, trucks, and buses.
Non- highway vehicles include aircraft, railroads, vessels, and
miscellaneous mobile engines such as farm equipment, industrial ano!
construction machinery, lawnmowers, and snowmobiles.  The estimated
emissions of CO by highway vehicles in 1977 was 77.2 million metric tons
and by non-highway vehicles, 8.5 million metric tons, representing
75.2 percent and 8.2 percent, respectively, of the total national
emissions of CO.
     For localized pollutants such as CO, the ability of test procedures
to predict changes in emissions depends on the similarity of the localized
driving pattern and associated operating conditions to those in the test
procedure.  The EPA therefore has developed a series of correction
factors to expand upon the light duty vehicle (LDV) and heavy duty
                                      4-6

-------
vehicle (HDV) test procedures and to predict emissions from a large
number of user-specific scenarios.  Data required to develop these
correction factors have been generated using carefully designed statis-
tical studies which test consumer-owned vehicles.  Composite average
emission factors determined for a number of combinations of operating
conditions and vehicle mixes are available in the literature.
     The data collected in the EPA exhaust emission surveillance programs
are analyzed to provide mean emissions by model-year vehicle in each
calendar year, change in emissions with the accumulation of mileage,
change in emissions with the accumulation of age, percentage of vehicles
complying with standards, and effect on emissions of vehicle parameters
(engine displacement, vehicle weight, etc.).  These surveillance data,
along with prototype vehicle test data, assembly line test data, and
technical judgment, form the basis for existing and projected mobile
                          '
 source  emission  factors.
 4.2.2   Combustion  for  Power  and  Heat
     Table  4-3 shows the  nationwide annual  emission estimates for the
 "stationary fuel combustion"  category, which  includes all stationary
 combustion  equipment such as  boilers  and  stationary internal combustion
 engines.
     The  specific  emission factors for stationary  fuel combustors vary
 according to the type  and size of the installation and the fuel used as
 well as the mode of operation.   The EPA compilation of air pollutant
 emission  factors6  provides emission data  obtained  from source tests,
 material  balance studies, engineering estimates, etc., for the various
 common  emission  categories.
                                       4-7

-------
4.2.3  Technological Processes Producing CO


     Table 4-3 shows the nationwide annual emission estimates for the


"industrial processes" category, which includes the emissions resulting


from the operation of process equipment by industries manufacturing


chemicals, refining petroleum, producing metals and metal products, and
                                                                 i

by other processing industries (combining the emissions from pulp and


paper, wood products, agricultural, rubber and plastics, and textile


industries).


     The specific emission factors for the various applicable processes


used in these manufacturing industries are detailed in the EPA compilation


of air pollution emission factors.   Some specific information on the CO


emissions  from industries was included in Chapter 3.


4.2.4  Solid Waste Combustion


     Table 4-3 shows the nationwide annual emission estimates for the


"solid waste" category, which includes the emissions resulting from the


combustion of wastes in municipal and other incinerators, and from the


open burning of domestic and municipal refuse.


     Specific emission factors for the various waste combustion procedures


in use are detailed in the EPA compilation of air pollution emission


factors.


4.2.5  Miscellaneous Combustion


     Table 4-3 shows the nationwide annual emission estimates for a


"miscellaneous" category, which includes emissions from combustion of


forest, agricultural, and coal refuse materials and from structural


fires.
                                      4-8

-------
     Emission factors specific to the materials combusted and the


methods used are detailed in the EPA compilation of air pollution


emission factors.



4.3  ESTIMATION OF FUTURE EMISSION  LEVELS



     Future exposure to ambient CO  concentrations will clearly depend


upon future amounts of CO emitted into the atmosphere and future CO


emission patterns.  Since highest concentrations of CO generally result
               >

from auto emissions, substantial research effort has been expended to


characterize those emissions accurately.  Recently, the EPA  has adminis-


tered a series of exhaust emission  surveillance programs in order to


characterize how well vehicles perform in actual.use.  Based on these


surveillance data, the EPA  has published a method for calculating


existing and projected mobile source emission factors and has tabulated


average highway vehicle emission factors for 21 different combinations


of operating conditions and vehicle mixes,


     Table 4-4 presents the estimated vehicle emission factors in units


of grams of CO per vehicle mile and per vehicle kilometer for the years


1970 through 1999 and for two selected highway scenarios.  These data


are plotted in Figure 4-1, which illustrates the projected future


decrease in CO emissions per vehicle-kilometer of travel due to the


gradual replacement of vehicles without emission control equipment by


vehicles with control equipment.  The rate of yearly decrease in CO


emission factors (i.e., the slope of the curve) is also affected by the


gradual deterioration of emission control equipment with accumulated age



and mileage.
                                      4-9

-------
            TABLE 4-4.  AVERAGE VEHICLE EMISSION FACTORS
                 FOR TWO SELECTED HIGHWAY SCENARIOS

                               AVERAGE EMISSION FACTORS
Condi ti
Grams/mile
86.9
83.9
81.6
80.0
79.0
77.0
74.3
71.4
68.3
65.2
60.6
55.5
50.6
45.7
40.9
36.7
33.0
30.0
27.6
25.6
24.2
23.1
22.2
21.5
21.1
20.7
20.7
20.7
20.7
20.7
on A
Grams/km
54.0
52.1
50.7
49.7
49.1
47.8
46.1
44.3
42.4
40.5
37.6
34.5
31.4
28.4
25.4
22.8
20.5
18,6
17.1
15.9
15.0
14.3
13.8
13.4
13.1
12.9
12.9
12.9
12.9
12.9
Condi ti
Grams/mile
85.6
82.4
80.0
78.2
77.1
75.1
72.5
69.9
67.1
64.3
60.2
55.8
51.6
47.2
42.9
38.9
35.2
32.2
29.5
27.3
25.6
24.1
23.0
22.1
21.4
20.8
20.8
20.8
20.8
20.8
on B
Grams/km
53.2
51.2
49.7
48.6
47.9
46.6
45.0
43.4
41.7
39.9
37.4
34.7
32.0
29.3
26.6
24.2
21.9
20.0
18.3
17.0
15.9
15.0
14.3
13.7
13.3
12.9
12.9
12.9
12.9
12.9
    Year

    1970
    1971
    1972
    1973
    1974
    1975
    1976
    1977
    1978
    1979
    1980
    1981
    1982
    1983
    1984
    1985
    1986
    1987
    1988
    1989
    1990
    1991
    1992
    1993
    1994
    1995
    1996
    1997
    1998
    1999

Speed:  19.6 mph (31.6 kph); Temperature:  75° F, % cold start: 20.6%
                                          and % hot start:   27.3%.

Condition A:  vehicle miles traveled = 8.3% automobiles,
    5.8% for each of the two light truck classes, 4.5% heavy gas trucks,
    3.5% heavy duty diesels, and 0.5% motorcycles, approximating national
    vehicle miles traveled mix.

Condition B:  vehicle miles traveled = 63% automobiles,
    16% for each of the two light truck classes, 2.5% heavy gas trucks,
    and 2.5% heavy duty diesel vehicles, approximating a mix of vehicle
    miles traveled that might be found in a central city area.
                                      4-10

-------






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33

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27
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18

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.
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*' 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
        72 74 7678  80828486 88  9092 9496  98   2000 2002

                          TIME, year

Figure 4-1.  Average composite emission factors for carbon
monoxide.
                              4-11

-------
     Total CO emission rates are also reflected by vehicle-use trends.  Over
the past 20 years, there has been an increase in vehicle miles of travel
averaging 4.6 percent a year. '  *   Vehicle miles of travel (VMT) increased
4.6 percent in 1971 and 1972; 2.4 percent in 1973 and 1974; 3.4 percent in
1975; and 5.9 percent in 1976.  Federal Highway Administration projections
indicate that VMT will continue to increase at an annual average rate of 2.2
                     2                                           7
percent through 1999.   The latest published EPA emission factors  suggest
that CO emissions from mobile sources will peak between 1973 and 1979, then
decrease until 1994.  After 1994, total CO emissions from automobiles may rise
again with increases in VMT.  There are a number of other factors which may
influence future CO emission trends:  delay of the clean car performance
standards, inspection and maintenance of pollution control equipment, possible
retrofit of less well-controlled vehicles, conversion to alternate fuels,
traffic flow improvements, motor vehicle use restraints, use of car pools,
increased fuel prices, etc., which cannot be predicted with certainty.
     Ambient levels of CO generally improved from 1972 to 1977.  There was a
20 percent increase in the number of sites with sufficient data for trends
analysis due to the expansion of State and local monitoring programs.  Data
for CO trend analysis were obtained from EPA's National Aerometric Data Bank.
All sites having at least 4,000 annual values during both 1972-1974 and 1975-1977
were designated as trend sites.   For carbon monoxide, 243 sites met this
selection criterion, and more than 80 percent of these sites had at least 4
years of data.
     During the 1972-77 period, 80 percent of the selected CO sites showed
long-term improvement and this trend was fairly consistent for all 10 EPA
Regions.  The median rate of improvement for the 90th percent!le of 8-hour
                                      4-12

-------
values was approximately 6 percent per year.  From 1976 to 1977, 70 percent of
the 243 sites improved.  Consistent with this downward trend, almost one-third
of these sites reported their lowest values in 1977.
     In discussing the relationship between ambient CO levels and CO emissions,
it is important to clarify certain components involved in estimating CO emissions,
Two key factors are the vehicle miles travelled (VMT) and the emissions per
VMT.  In its simplest form, total CO emissions may be viewed as merely the
product of emissions per mile multiplied by the number of miles travelled.
Total CO emissions in 1976-77 were higher than in 1974-75.  During this time,
the emissions per VMT actually decreased due to emission controls, but this
was more than offset by an even greater increase in VMT.  The net effect was
an overall increase in total CO emissions.  Translating these emission components
in terms of ambient CO levels, it would be reasonable to expect improvement at
downtown locations that are saturated with traffic because the emissions per
mile reductions would outweight any increase in VMT.  On the other hand,
growth areas could record increases in ambient CO levels because increases in
                                              Q
VMT offset the reduction in emissions per VMT.
                                       4-13

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           TABLE 4-1.   SUMMARY OF NATIONAL EMISSION ESTIMATES,  1970-19778



                                 (10  metric tons/yr)
Year
1970
1971
1972
1973
1974
1975
1976
1977
TSPa
22.2
20.9
19.6
19.2
17.0
13.7
13.2
12.4
S0x
29.8
28.3
29.6
30.2
28.4
26.1
27.2
27.4
NOX
19.6
20.2
21.6
22.3
21.7
21.0
22.8
23.1
VOC
29.5
29.1
29.6
29.7
28.6
26.9
28.7
28.3
CO
102.2
102.5
103.8
103.5
99.7
96.9
102.9
102.7
a)  TSP = total suspended participates



    SO  = sulfur oxides
      ^


    NO  = nitrogen oxides
      s\


    VOC = volatile organic compounds



    CO  = carbon monoxide
                                          4-14

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                                 BIBLIOGRAPHY

1.    Berens, A. P., and M. Hill.  Automobile Exhaust  Emission  Surveillance
     Analysis of the FY 1974 Program.   EPA 460/3-76-019, U.S.  Environmental
     Protection Agency, Ann Arbor, ML,  September  1976.

2.    Beaton, J. L., E. C. Shirley, and  J. B. Skog.  Air Quality Manual. Volume
     III. Traffic  Information  Requirements of  Highway Impact on Air Quality.
     U.S. Department of Transportation,  Washington, DC, April  1972.

3.    Office of Air Quality Planning  and Standards.  Complication of Air Pollution
     Emission Factors.  Parts  A  and  B.   Third  Edition.  AP-42, U.S. Environmental
     Protection Agency, Research Triangle Park,  NC, August  1977.

4.    Highway Research Board.   Highway Capacity Manual  1965.  Special Report
     87, Publication 1328, National  Academy of Sciences, Washington, DC, 1966.

5.    Office of Transporation and Land Use Policy.  Mobile Source Emission
     Factors.  Final document.   EPA-400/9-78-005,  U.S. Environmental  Protection
     Agency, Washington,  DC,   March  1978.

6.    Office of Air Quality Planning  and Standards.  National Air Quality and
     Emissions Trends Report,  1977.  EPA-450/2-78-052, U.S. Environmental
     Protection Agency, Research Triangle Park,  NC, December 1978.

7.    Thayer, S. D., and J. D.  Cook.  Vehicle Behavior in and Around Complex
     Sources and  Related  Complex Source Characteristics.  Volume VI-Major
     Highways.  EPA-450/3-74-003-f,  U.S. Environmental Protection Agency,
     Research Triangle Park, NC, November 1973.

8.   Federal Highway Administration.  Highway  Travel  Forecasts.  U.S.  Department
     of  Transporation, Washington, DC,  November  1974.
                                     4-15

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           5.   ANALYTICAL METHODS FOR MEASUREMENT OF CARBON MONOXIDE







     It 1s Impossible to monitor and maintain air quality (or even to



study^the health effects of pollutants) without reliable methods for



measuring the amount of carbon monoxide (CO) present.  This chapter



contains surveys of the analytical methods for CO in air and in blood,



as well as some comments on sampling techniques.



5.1  INTRODUCTION



     To promote uniform enforcement of the air quality standards set



forth under the Clean Air Act as amended, EPA has established provisions



under which analytical methods can be designated as "reference" or


                     175
"equivalent" methods.     A reference method or equivalent method for air



quality measurements is required for acceptance of measurement data by EPA.



     At present the reference methods for monitoring CO in the atmosphere



must be based on non-dispersive infrared photometry (NDIR).  However,



before a particular NDIR instrument can be used in a reference method,



it must be so designated by EPA in terms of manufacturer, model number,



components, operating range, etc.  Several NDIR instruments have been so



designated.  No equivalent methods using a measurement principle other



than NDIR have been designated thus far for CO in ambient air.
                                      5-1

-------
                                        o
     An operating range of up to 58 mg/m  (0 to 50 ppm) CO in air is typical
for the NDIR instruments designated for reference method use.  Analytical
                                                                            i
capability is needed not only for this range but also for a narrower range up
         o
to 1 mg/m  (0 to 1 ppm) for measuring background levels in unpolluted atmospheres
                                 o
and a wider range up to 1150 mg/m  (up to 1000 ppm) for measuring high concen-
trations, such as in vehicular tunnels and parking garages.
     There is a recognized need to relate results by other methods (including
those used in health effects and field studies) to those obtained by the NDIR
reference method, but this is difficult because reported information on the
other methods is inadequate as to variations in operator competence and the
effects of experimental conditions.
5.1.1  Overview of Techniques for Measurement of CO in Air
     In the past decade, there have been several excellent reviews on the
measurement of CO in the atn)ospnere.43,54,74>87>97,136)145,164>169)170)184
For monitoring, the best technique at present is nondispersive infrared
photometry,49'81'111'112'125'128'148'149'157'158 usually with a Luft-type
         102
detector.     A more sensitive method, suitable for measuring background
levels, is gas chromatography.19'22'46'130'160'167'168  For high levels, a
useful technique is catalytic oxidation of the CO, using Hopcalite or other
catalysts    either with temperature-rise sensors   »l"»i4o or ^^ eiectro-
chemical sensors.12'13'19'50'136'144
     Other analytical schemes used for CO in air include:  infrared gas-
filter correlation, a refinement of HDIR;1'11'24'25'65'68'69'75'187 dual
isotope infrared fluorescence, another technique derived from NpiR;101)107}108
the reaction with hot mercuric oxide to give elemental mercury
                                      5-2

-------
vapor.I*.110,115,123,138 the react1on w1th heated ioc|ine pentoxide to

give elemental iodine;2'113'118*179'186 and color reactions as with
palladium salts or the silver  salt of p_-sulfamoylbenzoate.4'15'60'88'92'
GO TOR 1^4. 1 fil
  *   *   '     A classical procedure for many decades was to use
gasometric apparatus such as the Orsat or Haldane44 1n which the CO
present in a gas sample  Is  absorbed  by cuprous chloride solution, and
the decrease 1n volume or pressure 1s measured, but this 1s not sensi-
tive enough for trace amounts.  Many of these methods are described 1n
Section 5.3.
     For the future, microwave rotational spectroscopy offers promise of
an analytical  technique  of  high specificity.   '     Other possible ways
                                                                   180
to determine CO include:  the  chemiluminescent reaction with ozone,
                                   fifi                 QE
X-ray excited  optical fluorescence,   radiorelease of   Kr from the
kryptonates of mercuric  oxide  or  iodine pentoxide,   '    and utilization
                                      8 64
of narrow-band infrared  laser  sources.  *
5.1.2  Calibration  Requirements
     Whichever method or instrument  is used,  it is essential that the
results be validated by  frequent  calibration with samples of known
composition  similar to the  unknowns.42'    '     Chemical analyses can be
relied on only after the analyst  has achieved  acceptable accuracy in the
analysis of  such  standard samples through an  audit program.
5.2  PREPARATION  OF CARBON  MONOXIDE  GAS STANDARDS
5.2.1  Gravimetric  Method
     A set of  reliable gas  standards for CO  in air certified at  levels
of approximately  12, 23,  and 46 mg/cm3  (10,  20, and  40 ppm) is
                                       5-3

-------
obtainable from the National Bureau of Standards (NBS), Washington, D.C.
      17ft
20234.     These NBS Standard Reference Materials (SRMs) are supplied as
compressed gas (at about 1700 psi) in high-strength aluminum cylinders
                o
containing 31 ft  of gas at standard temperature and pressure, dry (STP)
and are accurate to better than 1 percent of the stated values.  Because
of the time and effort required in their preparation, SRMs are not
intended for use as daily working standards, but rather as primary
standards against which transfer standards can be calibrated.
     The gravimetric method used by NBS for preparing primary standards
     83 84
of CO  '   is as follows.  An empty gas cylinder is tared on an analytical
balance; then 2 g of pure CO, weighed accurately to ±2 mg, is added from
a high-pressure tank.  Next, 100 g of pure air (accurately weighed) is
added  from a pressure tank, and the concentration of CO is calculated
from the respective weights added and the molecular weights of the two
gases.  Not only the average "molecular weight" of the air, but also the
requisite careful check of purity, is obtained by mass spectrometry and
gas chromatography analyses of the air and the CO.  Lower-concentration
primary standards are prepared by serial dilutions (not more than a
factor of 100 for each step) using the same technique.
     The commercial suppliers of compressed gases are another source of
                                        3
samples of air containing CO in the mg/m  or ppm range.  However, the
nominal values for CO concentration supplied by the vendor should be
verified by intercomparison with an SRM or other validated standard
sample.  A three-way intercomparison has been made among the NBS SRMs
and commercial gas blends and an extensive set of standard gas mixtures
                                      5-4

-------
prepared by gravimetric blending at the Environmental Protection Agency.124



The results showed that commercial gas blends are within ±2 percent of



the true value represented by  a primary standard.  Another study on


                 59
commercial blends   found poorer accuracy.  To achieve compatible results



1n sample analyses, different  laboratories  should interchange and compare



their respective working standards at frequent intervals.


                                                                83
     In making and using standards, many  precautions are needed;   one



deserves special mention.  Large but unpredictable decreases in CO



concentration occur in mixtures prepared  in ordinary mild steel gas



cylinders, within a few months, as shown  in Figure 5-1.  This may be due



to carbonyl formation or oxidation to carbon dioxide.  The difficulty



can be avoided by the use of gas cylinders  made  of stainless steel or



aluminum.  A  special treatment for aluminum, which includes enhancement


                                                          188
of the aluminum  oxide surface  layer, has  been recommended.



     In addition to the set of Standard Reference Materials for CO in



air, another  set of SRMs is available from  NBS for CO in nitrogen, which



covers concentrations from 10  to 957 ppm.



5.2.2  Volumetric Gas Dilution Methods



     Standard samples of CO  in air can also be prepared by volumetric

                                                                          pc

gas dilution  techniques.   In a versatile  system  designed for this purpose,



air at a pressure of 10 to 100 psi is first purified and dried by



passage through  cartridges of  charcoal and  silica gel, then passed



through a  sintered metal filter into a flow control and flowmeter system.



The CO (or a  mixture of CO  in  air which  is  to be diluted further), also



under pressure,  is passed  through a  similar flow control and flowmeter



system.
                                       5-5

-------
                                                                    400
Figure 5-1.  Loss of carbon monoxide with time in mild steel cylinders.83
(Used with permission of ISA Transactions, Vol. 14, No. 4 Copyright Instrument
Society of America, 1975.)
                                     5-6

-------
     Both gas streams are led into a mixing chamber, which is designed
to mix the gas streams rapidly and completely before passage into the
sampling manifold from which the standard samples may be withdrawn.
From the air flow rate, F., and the CO flow rate, F  , the concentration
                         ft                         CO
of CO in the sample, CCQ, is readily calculated by the expression

                    C               co
                                 Fco+FA
For samples prepared by dilution of a more concentrated bulk mixture,
the concentration  is given by
                                  F  +F         >
where Fb and C. are the values of flow rate and concentration of CO,
respectively,  for the bulk mixture.
5.2.3  Other Methods
     Permeation tubes have been  used for preparing standard mixtures of
                                                                  119 143
other pollutant gases such as sulfur dioxide and nitrogen dioxide.   *
In this technique, a sample of the pure gas under pressure is allowed to
diffuse through a calibrated partition at a defined rate into a diluent
gas stream, to give a standard sample of known composition.  Although
permeation tubes for making CO standards are not routinely used at
present in the United States, such tubes are believed to be in use in
Europe.
     Another possible way to liberate known amounts of CO into a diluent
gas is by thermal decomposition  of nickel tetracarbonyl .  However, an
attempt to use this as a gravimetric calibration source showed that the
relation between CO output and weight loss of the Ni(CO)4 is norr
stoichiometric.
                                       5-7

-------
     Chemical assay methods such as those noted in Section 5.1.1



can be used to verify the CO concentration in a standard mixture, but



they do not provide greater accuracy or reliability than is attained by



careful preparation of the standard sample, as for example 1n prepara-



tion of an NBS SRM.



5.3  MEASURING CARBON MONOXIDE IN AIR



     Ambient CO monitoring is an expensive and time consuming task,



requiring skilled personnel and sophisticated analytical equipment.



This section discusses several important aspects of the continuous and



intermittent measurement of CO in the atmosphere, including sampling



techniques, sampling schedules, and recommended analytical methods for



CO measurement.



5.3.1  Sampling Techniques



     Carbon monoxide monitoring requires a sample introduction system,



an analyzer system, and a data recording system, as illustrated in


           174
Figure 5-2.     While the "heart" of any air pollution monitoring



system is the air pollution analyzer, Figure 5-2 shows that there is



a considerable amount of supportive equipment that is necessary in



order to perform continuous air monitoring.



     A sample introduction system consists of a sampling probe, an



intake manifold, tubing, and air movers.  This system is needed to



collect the air sample from the atmosphere and to transport it to the



analyzer without altering the original concentration.  It may also be



used to introduce known gas concentrations in order to check periodically



the reliability of analyzer output.  Construction materials for the
                                      5-8

-------
                 SAMPLE INTRODUCTION SYSTEM
OS
vo
           BLOWER
                       SAMPLE INTAKE PORT
                MFOLD^S.
                + +. JL. ^.\JU ^  &
                                              ANALYZER SYSTEM
            FIRST STAGE
            PRESSURE v^
            GAUGE    T?)
           CYLINDER
           PRESSURE
           VALVE
    SECOND STAGE
    PRESSURE GAUGE
SECOND STAGE
PRESSURE VALVE
                                              CARBON MONOXIDE ANALYZER
                                                         MOISTURE
                                                          CONTROL
                                               ROTAMETER I-1


PARTICULATE
FILTER
                ZERO GAS
                  SPAN GAS
 DATA RECORDING
     AND
 DISPLAY SYSTEM
                                                                                  AMPLIFIER
                                                                                     	I
ANALYZER
INDICATOR
                                                                                      STRIP CHART
                                                                                       RECORDER
                                                                                                              DATA
                                                                                                          -(ACQUISITION
                                                                                                             SYSTEM
                                            Figure 5-2. Carbon monoxide monitoring system.

-------
sampling probe, intake manifold, and tubing should be tested to demon-
strate that the test atmosphere composition or concentration is not
significantly altered.  It is recommended that the sample introduction
                                                          37
system be fabricated from borosilicate glass or FEP Teflon   when
monitoring for all pollutants.  However, when sampling for only CO, it
                 191
has been reported    that no measurable pollutant losses were observed
when sampling systems were constructed of tygon, polypropylene,
polyvinylchloride piping, aluminum, or stainless steel.   The sample
introduction system should be constructed such that it presents no
pressure drop to the analyzer.
     The analyzer system consists of the analyzer itself and any sample
preconditioning components that may be necessary.  Sample preconditioning or
optical filters require a moisture control system to help minimize the false
positive response of the analyzer (e.g., the NDIR analyzer) to water
vapor, and a particulate filter to help protect the analyzer from clogging
and possible chemical interference due to particulate buildup in the
sample lines or analyzer inlet.  The sample preconditioning system may
also include a flow metering and flow control device in order to control
the sampling rate to the analyzer.  As for the analyzer, there are
several analytical methods for the continuous measurement of CO as fully
discussed in Section 5.3.4.
     A data recording system is needed to record the output of the
analyzer.  Data recording systems range from simple strip chart recorders
to digital magnetic tape recorders to computerized telemetry systems
which transfer data from remote stations to a central location via
telephone lines or radio waves.
                                      5-10

-------
     In order to ensure the accuracy and validity of data collected from
the CO monitoring system, a quality assurance program  1s required.
Such a program consists of procedures  for  calibration, operational and
preventive maintenance, data  handling,  and auditing, and are fully
documented 1n a quality assurance  program  manual.
     Calibration procedures consist of periodic  multipoint primary
calibration and secondary calibration  which are  prescribed to minimize
systematic error.   Primary calibration involves  the introduction of test
atmospheres of known  concentration to  an instrument in its normal mode
of operation for the  purpose  of producing  a calibration curve.
     A calibration  curve  is derived from the analyzer  response obtained
by introducing several  successive  test atmospheres of  different known
concentrations.  One  recommended method for generating CO test atmos-
pheres is by using  zero air (containing no CO) and several known concen-
trations of CO 1n air or  nitrogen  contained in high pressure gas cylinders
                                                       175
and  verified using  NBS-cert1fied SRM wherever possible.     The number
of standard gas mixtures  (cylinders) necessary to establish a calibration
curve  depends  on  the  nature of the analyzer output.  A multipoint cali-
bration  at  five or  six different CO concentrations covering the operating
range  of the analyzer is  recommended by the EPA.1   '     Alternatively,
the  multipoint calibration  is accomplished by diluting a known high-
concentration  CO  standard gas with zero gas using a calibrated flow
dilution system.
                                       5-11

-------
     Primary calibrations should be performed when the analyzer is first
                                       174
purchased and every 30 days thereafter.     Primary calibration is also
recommended after the analyzer has had maintenance which could affect
its response characteristics or when results from the auditing program
                                                              174
show that the desired performance standards are not being met.
     Secondary calibration consists of a zero and upscale span of the
                                                    177
analyzer which is recommended to be performed daily.      If the analyzer
response differs (say by greater than ±2 percent) from the certified
concentrations, then the analyzer is adjusted accordingly.   Complete
records of secondary calibrations should be kept to aid in data reduction
and for use in the auditing program.
     Operational and preventive maintenance procedures consist of
operational checks which are made to insure the proper operation of the
analyzer and a preventive maintenance schedule which is necessary to
prevent unexpected analyzer failure and the associated loss of data.
Operational checks include checks of zero and span control  settings,
sample flow rate, gas cylinder pressures, sample cell pressure, shelter
temperature, water vapor control, the particulate filter, the sample
introduction system, the recording system, and the strip chart record.
These checks may indicate the need for corrective/remedial  action.  They
are usually performed in conjunction with secondary calibrations.   In
addition to operational checks, a routine schedule of preventive mainte-
nance should be developed.  Maintenance requirements of the analyzer are
usually specified in the manufacturer's instrument manual.   Routine
maintenance of supportive equipment (i.e., the sample introduction
                                      5-12

-------
system and the data recording system)  is also  required.  This may include
sample line filter changes, water vapor control changes, sample line cleaning,
leak checks, and chart paper supply changes.
     Data handling procedures consist  of data  generation, data reduction, data
validation, data recording, and data analysis  and interpretation.  Data generation
is the process of generating raw, unprocessed  and unvalidated observations as
recorded on a strip chart  record.  Data reduction is the conversion of recorder
output as percent of full  scale to concentration units with the use of calibration
records.  This is usually  a manual operation which requires an individual to
scan a stripchart record and visually  average  the trace over a given time
period (usually one hour).  This is a  difficult procedure and care should be
taken.  Data validation involves final screening of data before it is recorded.
Questionable data "flagged" by the monitoring  technician are reviewed at this
point with the aid of daily calibration and operation records to assess their
validity.  Specific criteria for data  selection and several instrument checks
are outlined in reference  174.  Data recording involves the recording of data
in a standard format for data storage, interchange of data with other agencies,
and/or data analysis.  The EPA has adopted a standard recording format known
                                                     173
as SAROAD (Storage and Retrieval of Aerometric Data).     An example of an
hourly SAROAD data form is given in Figure 5-3.  Data analysis and interpretation
usually includes a mathematical or statistical analysis of air quality data
and a subsequent effort to interpret results in terms of exposure patterns,
meteorological conditions, characteristics of  emission sources, and geographic
and topographic conditions.
                                       5-13

-------
             Hourly Data Form
OS
 I
          0-
                            Country
                           City Name
ENVIRONMENTAL PROTECTION AGENCY
     National Aerometric Data Bank
           P.O. Box 12055
        Research Trianqle Park
        North Carolina 27711
                          Site Address
                                                            Paiamrter obsrived
                                                                                            Method
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                                                                                                                                           Monih
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                                                                                                                              Method    Units
                                                                                                                                              DP
                                                                                                                     LJ.J
                                                           Time interval of obs.
                                                                                           Units of obs.
                                                                                                              23 ;4  .'S 26 27    28 29    30 31   32
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-------
     Auditing procedures consist of several quality control checks and
subsequent error analyses in order to determine an estimate of the
accuracy and precision of air quality measurements made.  The quality
control checks for CO include a data processing check, a control sample
check, and a water vapor interference check, which should be performed
by a qualified individual independent of the regular operator.  The
error analysis is a statistical evaluation of the accuracy and precision
of air quality data.  Guidelines have been published by EPA174 for
calculating an overall bias and standard deviation of errors associated
with data processing, measurement of control samples, and water vapor
interference from which the accuracy and precision of CO measurements
can be determined.  More recently, EPA    has recommended a method for
determining the accuracy and precision of CO measurements based on
primary and secondary calibration records.  Accuracy is the agreement of
an observed measurement with an accepted reference or true value and can
be estimated based on multipoint calibration records.  Precision is a
measure of repeatability and can be estimated based on secondary
calibration records.
     In summary, the data provided by the quality control checks and
subsequent error analyses are sufficient to provide an overall estimate
of data quality and an indication that data quality may be inadequate.
If the data quality is not adequate, the causes of large deviations
should be determined and appropriate action taken to correct the
deficiencies.  These actions may include an increased auditing program,
increased frequency of primary calibrations, increased frequency of
preventive maintenance, changes in monitoring procedures, replacement of
analyzer, and/or personnel changes.
                                       5-15

-------
5.3.2  Sampling Schedules


     Carbon monoxide concentrations in the atmosphere exhibit large


temporal variations due to changes in the time and rate that CO is


emitted by different sources and due to changes in meteorological conditions


which govern the amount of transport and dilution which take place.


During a 1-year period an urban CO station may monitor hourly concentrations

                                          3
of CO ranging from 0 to as high as 50 mg/m  (45 ppm).   Violations of the


NAAQS are based on the second highest 1-hr and 8-hr average concentration,


which represents an isolated and "rare" event when compared to the 8760


hours which constitute one year.  In order to measure this "rare" event,


the "best" sampling schedule to employ is continuous monitoring 24 hours


per day, 365 days per year.  Even so, continuous stations rarely operate


for significant periods without data losses due to malfunctions, upsets,


and routine maintenance.   Data losses of 5 to 10 percent are not uncommon,


which represents 438 to 876 hours.  As a result, the data must be inter-


preted in terms of the "likelihood" that the NAAQS were attained or


violated.  Statistical methods can be employed to interpret the results.  '


     While continuous monitoring is the "best" sampling schedule,


statistically valid sampling can be performed using random or systematic


schedules.  Most investigations of various sampling schedules have been

                                            8fi 1?T T ?7
performed on particulate air pollution data,  *   '    but the same


sampling schedules could also be used for CO monitoring.  However, NDIR

                                                                     o
instruments do not perform reliably in intermittent sampling.  Akland


evaluated six years of particulate data and showed that sampling one day


every two weeks could be used to obtain annual mean suspended particulate
                                      5-16

-------
concentrations within an accuracy of 2.9 percent  to  5.8 percent compared



to sampling every day, for systematic and  random  sampling, respectively.



By collecting samples every three days, the precision was improved to



0.2 percent and 3.9 percent for the systematic and random methods,



respectively.  The systematic method uses  a regular  sampling interval of



any number of days except 7 or multiples of 7.  This ensures that all



days of the week are sampled equally.  Random selection is more likely



to result in a less precise yearly estimate than  systematic sampling due



to the highly heterogeneous nature of the  units (daily fluctuations)

                             o

within the sampling interval.   Systematic sampling  tends to be more



representative.



     For any number of air samples, the expected  deviation of the sample



mean from the true population mean can be  determined using statistical


                                               142
techniques such as those described by Saltzman.      These methods can be



used a priori to determine the desired number of  samples to be collected


                    121
during a study.  Ott    has shown that annual mean CO concentrations can

                                           3

be measured with an accuracy of ±2.16 mg/m (±1.94 ppm), at 0.99 confi-



dence level, with as few as nine random 1-hr average samples during the



year (based on San Jose data).  With 144 random 1-hr samples, the accuracy

                          3

was improved to ±0.54 mg/m  (±0.49 ppm).   The annual mean concentration



at this site was 3.93 mg/m3 (3.54 ppm).  Using random sampling techniques



and using automatic bag samplers filling one bag  each hour, CO measure-



ments can be made at many more locations and at less cost than continuous



monitoring.  Ott121 estimates the cost of  random  sampling at nine sites

                                                                 ^         f

to be 70 percent less expensive than continuous monitoring at the same



sites.
                                       5-17

-------
     Short-term studies designed to sample during "worst case" seasons
and/or times of day can provide data needed on maximum 1-hr and 8-hr CO
concentrations for comparison to NAAQS.   In other cases, where concentra-
tion trends are not known and where CO concentrations are expected to be
high, a full year of data may be necessary.
5.3.3  Recommended Analytical Methods for CO Measurements
     Different analytical methods for CO measurement are required for
different purposes, depending on the concentrations to be measured
and the physical environment to which the analyzer will be exposed
(i.e., temperature, vibration, etc.).  When very low global background
concentrations are being monitored, only the most sensitive analytical
methods can be used.  However, for monitoring CO in urban atmospheres
for the purpose of determining compliance with National Ambient Air
Quality Standards (NAAQS) an EPA "reference" or "equivalent" method
should be used.  Specifications for automated analytical methods for
the measurement of CO have been issued by EPA (see Table 5-1).  The
EPA    has specified NDIR as the measurement principle for reference
methods for determining compliance with the NAAQS for CO.  An "equivalent
method" can be so designated when an analytical method is shown to
produce results that are equivalent to an approved NDIR method.
     Presently, several reference methods using the NDIR principle have
been approved for monitoring for NAAQS achievement.  No gas chromato-
graphic/flame ionization (GC) methods have been designated as equivalent
methods but some appear to be suitable for such designation.
The I«0c coulometric method is considered to be "unacceptable" due to
                                      5-18

-------
         TABLE 5-1.  PERFORMANCE SPECIFICATIONS FOR AUTOMATED
               ANALYTICAL METHODS FOR CARBON MONOXIDE175
Range
Noise
Lower detectable limit
Interference equivalent
 Each interfering substance
 Total interfering substances
Zero drift
 12 hour
 24 hour
Span drift, 24 hour
 20 percent of upper range limit
 80 percent of upper range limit
Lag time
Rise time
Fall time
Precision
 20 percent of upper range limit
 80 percent of upper range limit
0 to 57 mg/m^ (0 to 50 ppm)
    0.6 mg/m:: (0.50 ppm)
    1.2 mg/m  (1.0 ppm)
            3
   ±1.2 mg/m3 (±1.0 ppm)
    1.7 mg/m  (1.5 ppm)

   ±1.2 mg/m? (±1.0 ppm)
   ±1.2 mg/m  (±1.0 ppm)

     ±10.0 percent
     ±2.5 percent
     10 min.
      5 min.
      5 min.

    0.6 mg/rru (0.5 ppm)
    0.6 mg/m  (0.5 ppm)
Definitions:
  Range:  Nominal minimum and maximum concentrations that a method is
capable of measuring.
  Noise:  The standard deviation about the mean of short duration
deviations in output that are not caused by input concentration changes.
  Lower Detectable Limit:  The minimum pollutant concentration that
produces a signal of twice the noise level.
  Interference Equivalent:  Positive or negative response caused by a
substance other than the one being measured.
  Zero Drift:  The change in response to zero pollutant concentration
during continuous unadjusted operation.
  Span Drift:  The percent change in response to an up-scale pollutant
concentration during continuous unadjusted operation.
  Lag Time:  The time interval between a step change in input concentration
and the first observable corresponding change in response.
  Rise Time:  The time interval between initial response and 95 percent of
final response.
  Fall Time:  The time interval between initial response to a step decrease
in concentration and 95 percent of final response.
  Precision:  Variation about the mean of repeated measurements of the
same pollutant concentration expressed as one standard deviation about
the mean.
                                      5-19

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its slow response, sensitivity to temperature, and interferences by


                                                                   172
mercaptans, hydrogen sulfide, olefins, acetylenes, and water vapor.



All other methods not specifically designated automatically fall under



the "unapproved" category.  Current lists of designated reference and



equivalent methods of analysis for air pollutants can be obtained from



EPA regional offices.



     Monitoring of CO for purposes other than NAAQS compliance, such as



atmospheric research, industrial hygiene, or stack sampling may employ



other methods which may be more sensitive to low CO concentrations, or



more suitable to the rigors of field studies.  Instruments employing the



NDIR method are very sensitive to vibration, which makes them unsuitable



for mobile or even portable use.  The physical size and usual construc-



tion of both NDIR and GC  instruments limit their application primarily



to laboratory environments.



     Portable instruments are commercially available for making CO



measurements in the field using different analytical techniques.



Instruments based on controlled-potential electrochemical analysis have


                                    3           13 20
detection  limits of less  than 1 mg/m  (0.9 ppm).  *    These instruments



can be employed for portable measurements in mines and hostile working


                                                                 45
environments, as well as  research for commuter "in-car" exposure,


                       45
indoor worker exposure,   or CO measurements taken from aircraft.



Another common technique  for obtaining intermittent CO concentration



data is to employ portable pumps and air sampling bags to collect an air



sample which can be later analyzed for CO concentration using an NDIR or


             38 120
other method.   '     Bags of 2- to 90-liters are typical.  Construction
                                      5-20

-------
materials Include Mylar, Tedlar, aluminlzed Scotch-pak, Scotch-pak,
Saran, and Teflon.  >     The  inert properties of CO make  it ideal for
bag sampling, since the rate  of decay of the sample while in the bag is
slow.  However, investigators using the bag sampling technique should
perform their own tests of decay rate as part of their quality assurance
program.
     Grab samples from stacks or automobile exhaust pipes where CO
                                      3
concentrations may  range from 500 mg/m  (450 ppm) to several percent CO
                                                          fi OQ
may be analyzed using colored silver sols  detection tubes '   or by
Orsat analysis.  Bag samples  of these exhaust gases can also be taken,
                                                               Oft
quantitatively diluted, then  analyzed using an  NDIR instrument.
5.3.4  Continuous Measurement Methods
5.3.4.1  Nondispersive Infrared Photometry—Carbon monoxide has a
characteristic infrared absorption near 4.6 urn  so that the absorption
of infrared  radiation by the  CO molecule can be used to measure CO
concentration  in the presence of other gases.   The NDIR method is based
on this principle.
     Although  the size, shape, sensitivity, and range of  NDIR instruments
vary with manufacturer, their basic components  and configurations are
similar.  Most commercially available instruments include a hot filament
source of infrared  radiation, a rotating sector (chopper), a sample
cell, a reference cell, and a detector (see Figure 5-4).
     The reference  cell contains a non-infrared-absorbing gas while the
sample cell  is continuously flushed with the sample atmosphere.  The
detector consists of a two-compartment gas cell (both filled with CO
                                       5-21

-------
                                      INFRARED
                                       SOURCE
              REFERENCE
                 CELL
SAMPLE
 CELL
RECORDER
                                                                   SAMPLE IN
                                                          O  
-------
under pressure) separated by a diaphragm whose movement causes a change

of electrical capacitance in an external circuit and ultimately an

amplified electrical signal which  is suitable for  input to a servo-type

recorder.

     During analyzer operation an  optical chopper  intermittently exposes

the reference and sample cells to  the  infrared sources.  At the frequency

imposed by the chopper, a constant amount of infrared energy passes

through the reference cell to one  compartment of the detector cell while

a varying amount of infrared energy, approximately inversely proportional

to the CO concentration in the sample  cell, reaches the other detector

cell compartment.  These unequal amounts of residual infrared energy

reaching the two compartments of the detector cell  cause unequal expan-

sion of the detector gas, resulting in variation in the detector cell

diaphragm movement, which in turn  produces the electrical signal

previously discussed.
                                                              •Cx
     Because water vapor is the principal interfering substance in

determining CO by NDIR techniques, a moisture control system is particu-

larly important.  To reduce water  vapor, which gives an erroneously high

value, water can be removed by drying  agents or cooling, or its effect

can be reduced by optical filters.

     Nondispersive infrared systems have several advantages.  They are

not sensitive to flow rate, they require no wet chemicals, they are

reasonably independent of ambient  air  temperature  changes, they are

sensitive over wide concentration  ranges, and they have short response

times.  Further, NDIR systems may  be operated by nontechnical personnel.
                                       5-23

-------
Such systems also have some disadvantages, such as zero drift, span



drift, nonlinearity, and high cost.  Some newer instruments have minimum



drift because good-quality thermostats and solid-state electronics are



used in their manufacture.  Such instruments also have automatic zeroing,



spanning, and recalibrating capability; they may also be obtained with



essentially linear outputs.



5.3.4.2  Gas Chromatography - Flame Ionization--A gas sampling valve, a



back flush valve, a precolumn, a molecular sieve column, a catalytic



reactor, and a flame ionization detector comprise the gas chromatography-



flame ionization system.  In operation, measured volumes of air are



delivered 4 to 12 times per hour to a hydrogen flame ionization detector



that measures the total hydrocarbon content (THC).  A portion of the



same air sample, injected into a hydrogen carrier gas stream, is passed



through a column where it is stripped of water, carbon dioxide, and



hydrocarbons other than methane.  Methane is then separated from CO by a



gas chromatographic column.  The methane, which is eluted first, is



unchanged after passing through a catalytic reduction tube into the



flame ionization detector.  The CO eluted into the catalytic reduction



tube is reduced to methane before passing through the flame ionization
         130
detector.     Between analyses the stripping column is flushed out.



Nonmethane hydrocarbon concentrations are determined by subtracting the



methane value from the total hydrocarbon value.



     There are two possible modes of operation.  One of these is a



complete chromatographic analysis showing the continuous output from the



detector for each sample injection.  In the other, the system is programmed
                                      5-24

-------
for both automatic zero and  span  settings  to  display  selected  elution peaks as
bar graphs.  The peak height is then  the measure  of the  concentration.  The
first operation is referred  to as the chromatographic or "spectro" mode and
the second as the barographic or  "normal"  mode.
     Since measuring CO entails only  a small  increase in cost,  instrument
                                         ->
complexity, and analysis time, these  instruments  are  customarily used to
measure three pollutants:  methane, total  hydrocarbons,  and CO.
     The instrumental sensitivity for each of these three components is
          3
0.023 mg/m  (0.02 ppm).  The lowest full-scale  range  available  is usually up
           3                            3
to 2.3 mg/m  (0 to 2 ppm)  up to 5.7 mg/m   (up to  5 ppm),  although at least one
                              o
instrument has up to 1.2 mg/m (up to 1 ppm)  range.   Because of the complexity
of these instruments, continuous  maintenance  by skilled  technicians is required
to minimize excessive downtime which  may be considered a possible disadvantage
of the system.
5.3.4.3  Electrochemical Analyzers
5.3.4.3.1  Control!ed-potential electrochemical analysis.  Carbon monoxide is
measured by means of the current  produced  in  aqueous  solution by its electro-
oxidation at a catalytically active electrode.  The concentration of CO
reaching the electrode is  controlled  by its rate  of diffusion through a membrane.
                                                                 12 13
This is dependent on its concentration in  the sampled atmosphere.  '    Proper
selection of both the membrane and such cell  characteristics as the nature of
the electrodes and solutions make the technique selective for various pollutants,
                                                          194
A similar technique has been reported by Yamate and Inoue.
                                      5-25

-------
     The generated current is linearly proportional to the CO concen-
                          o                                           3
tration from 0 to 115 mg/m  (0 to 100 ppm).  A sensitivity of 1.2 mg/m

(1 ppm) and a 10-second response time (90 percent) are claimed for a

currently available commercial instrument.

     Acetylene and ethylene are the chief interfering substances:

1 part acetylene responds as 11 parts CO and 1 part ethylene as

0.25 part CO.  For hydrogen, ammonia, hydrogen sulfide, nitric oxide,

nitrogen dioxide, sulfur dioxide, natural gas, and gasoline vapor,

interference is less than 0.03 part CO per 1 part interfering substance.

5.3.4.3.2  Galvanic analyzer.  Galvanic cells employed in the manner

described by Hersch  '   can be used to measure atmospheric CO

continuously.  When an air stream containing CO is passed into a

chamber packed with IpO,- and heated to 150°C^ the following reaction

takes place:

                         . T n      (150or,         ^ T
The liberated iodine is absorbed by an electrolyte and transferred to

the cathode of a galvanic cell.  At the cathode, the iodine is reduced

and the resulting current is measured by a galvanometer.  Instruments

using this detection system have been used successfully to measure CO

levels in traffic along freeways.

     Mercaptans, hydrogen sulfide, hydrogen, olefins, acetylenes, and

water vapor interfere.  Water may be removed by sampling through a

drying column; hydrogen, hydrogen sulfide, acetylene, and olefin inter-

ferences can be minimized by sampling through an absorption tube con-

taining mercuric sulfate on silica gel.
                                      5-26

-------
5.3.4.3.3  Coulometric analyzer.  A coulometric method employing a



modified Hersch-type cell has been used to measure CO In ambient air on


                   57
a continuous basis.    The  reaction of I205 with CO  liberates iodine,



which is then passed into a Ditte cell, and the current generated is



measured by an electrometer-recorder  combination.  Interferences are the



same as those discussed  above for the galvanic analyzer.



     This technique may  be  used for a minimum detectable concentration

           o
of 1.2 mg/m   (1  ppm) with good  reproducibility and accuracy  if flow



rates and temperatures are  well  controlled.  This method requires careful



column preparation and use  of filters to  remove interferences.  Its



relatively slow  response time may be  an added disadvantage in some work.



5.3.4.4  Mercury Replacement—Mercury vapor formed by the reduction of



mercuric oxide by CO  is  detected photometrically by  its absorption of



ultraviolet  light at  253.7  nm.   The  reaction  involved is:



                     CO + HgO     (21Q°C)      CQ2 + Hg



It  is potentially a  much more  sensitive method than  infrared absorption



because  the  oscillator  strength of  mercury at 253.7  nm  is 2,000 times



greater  than that of CO  at  4.6  urn.   Hydrogen  and  hydrocarbons also



reduce mercuric  oxide to mercury and there is some thermal decomposition



of  the oxide.   Operation of the detector  at constant temperature  results



in  a regular background  concentration of  mercury  from thermal decomposition.



The instrument is portable  and has  a capability  for  analyzing CO  concen-

                                                                          o

trations  of  0.025 to 12  mg/m3 (0.020 to 10.0  ppm).   Changes  of  0.002  mg/m



 (0.002 ppm)  are  detectable.  For this reason,  this  instrument has been



used to  determine global CO levels.
                                       5-27

-------
     McCullough et al.   *    recommended a temperature of 175°C to
minimize hydrogen interference.  A commercial instrument employing these
                                                      115
principles was made and used during the middle 1950's.      The technique
has been recently used for measuring background CO concentrations.
              138
Robbins et al.    have described an instrument in which the mercuric
oxide chamber is operated at 210°C, and the amount of hydrogen inter-
ference is assessed by periodically introducing a tube of silver oxide
into the intake air stream.  At room temperature silver oxide quantita-
tively oxidizes CO but not hydrogen.  Thus, the baseline hydrogen
concentration can be determined,  Additional minor improvements are
discussed by Seiler and Junge,    who gave the detection limit for CO as
0.003 mg/m3 (0.003 ppm).
                           123
     More recently, Palanos    described a less sensitive model of this
instrument intended for use in urban monitoring.  It has a range of 0 to
       3                                           3
23 mg/m   (20 ppm), a sensitivity of about 0.58 mg/m  (0.5 ppm) and a
span and zero drift of less than 2 percent per day.  As in other similar
instruments, specificity is achieved by removal of the potentially
interfering substances other than hydrogen (which is less than 10 percent)
     All of these instruments assume a constant hydrogen concentration.
In unpolluted atmospheres, the hydrogen concentration is roughly
         3
46.5 ug/m  (0.56 ppm).  However, the automobile is not only a source of
CO but also of hydrogen.  Therefore, if this technique is used in
polluted areas, it will be necessary to measure the hydrogen
concentration frequently.
                                      5-28

-------
5.3.4.5  Dual Isotope Fluorescence—This instrumental method utilizes



the slight difference in the infrared spectra of isotopes.  The sample



is alternately illuminated with the characteristic infrared wavelengths



of carbon monoxide-16 (CO  ) and carbon monoxide-18 (CO18).  The CO in



the sample that has the normal isotope ratio, nearly 100 percent CO  ,



absorbs only the CO   wavelengths.  Therefore, there is a cyclic varia-



tion in the  intensity of the fluorescent light that is dependent on the



CO16 content of the sample.101'107'108

                                      3
     Full-scale ranges of 0 to 23 mg/m  (0-20 ppm) and up to 0 to

        3                                                    3
230 mg/m  (0-200 ppm) with a claimed sensitivity of 0.23 mg/m  (0.2 ppm)


are available  in this instrument.  The response time (90 percent) is



25 seconds,  but a  1-second response time is  also available.  An advan-


tage of this technique is that it minimizes  the effects of interfering



substances.                                                       '


5.3.4.6  Catalytic Combustion-Thermal Detection--Determination of CO by



this method  is based  on measuring the temperature rise resulting from



catalytic oxidation of the CO  in the sample  air.


     The sample air is first pumped into a furnace that brings it to a



pre-set, regulated temperature and then over the catalyst bed in the



furnace.  A  thermopile assembly measures the temperature difference



between the  air leaving the catalyst bed and the air entering the



catalyst bed.  The output of the thermopile, which is calibrated with



known  concentrations  of CO in  air,  is read on a strip-chart recorder as

                                                                        3

parts  of CO  per million parts  of air.  The sensitivity is  about 1.2 mg/m



(1 ppm).  Most hydrocarbons are oxidized by  the same catalyst, and will
                                       5-29

-------
interfere unless removed.   These systems are widely used in enclosed



spaces; their applicability for ambient air monitoring is limited



because they function best at high ambient concentrations.



5.3.4.7  Second-Derivative Spectrometry—A second-derivative spectrometer



processes the transmission versus wavelength function of an ordinary



spectrometer to produce an output signal proportional to the second



derivative of this function.   Ultraviolet light of continuous wavelength



1s collected and focused onto an oscillating entrance slit of a grating



spectrometer.  By slowly changing the grating orientation,  the existing



light  has a slowly scanning center wavelength with sinusoidal wavelength



modulation Created by the oscillating entrance slit.   This  radiation



passes through a gas sample and is detected with a photomultiplier tube.


The signal is then electronically processed to produce a second-


                    96
derivative spectrum.    This method has the advantage that it can be



used to measure other pollutants as well as CO.  Commercial instruments



are being developed.


5.3.4.8  Fourier Transform Spectroscopy—Fourier transform spectroscopy



is an  extremely powerful infrared spectroscopic technique   which has


developed in the past 20 years and has been applied in the last 10 years

                                      7? 9fi
to air pollution measurement problems.  '    The advantages of this



technique over a standard grating or prism spectrometer are that it has



a higher through-put, which means that the available energy is used more



effectively and a much higher resolving power is obtainable.  In air



pollution measurements individual absorption lines can be resolved.
                                      5-30

-------
     A special advantage for air pollution measurements is that all the



data required to reconstruct the entire absorption spectrum are acquired



at the same time.  The spectrum as a function of wavelength is generated



by a built-in computer.  This means that several gases can be measured



simultaneously.  Several commercial instruments are now available with



resolutions of 0.06/cm or better.  These instruments are capable of



clearly defining the spectra of any gaseous pollutant, including carbon



monoxide, and are currently being used for special air pollution studies.



5.3.4.9  Gas Filter Correlation Spectroscopy—A gas filter correlation


             25
(GFC) monitor    is in essence a modern NDIR monitor, but has not been



defined as such  by EPA.  It has all the advantages of an NDIR instrument



and the additional advantage of smaller size, no interference from COp,



and very small interference from water vapor.  It is not sensitive to



flow rate, requires no wet chemicals, has a very fast response, and is



independent of reasonable ambient temperature changes.  There is a



problem with zero drift, but not with span drift.  Furthermore, the



instrument has recently  been packaged as a portable monitor.



     In this instrument, the infrared beam is collimated by a lens



before passing through the gas filter, the interference filter, and the



sample cell.  The signal arises from the difference in the amplitude of



the signal which alternately passes through one-half of the filter cell



containing CO and the other half containing a neutral gas such as N2



and a neutral filter.  The signal is balanced when no CO remains in the



sample cell.  An increase in CO in the sample cell will increase the



difference signal since  the portion of the beam which has already passed
                                       5-31

-------
through the CO in the gas filter will be unchanged by the CO in the


sample cell, whereas the beam passing through the neutral half will be


attenuated by the CO in the sample.  A prototype version of this monitor

                                                  27
had a minimum sensitivity of 50 parts per billion.


5.3.5  Intermittent Analysis


     Intermittent samples may be collected in the field and later


analyzed in the laboratory by continuous analyzing techniques described


above.  Sample containers may be rigid (glass cylinders or stainless


steel tanks) or they may be non-rigid (plastic bags).  Because of


location or cost, intermittent sampling at times may be the only practical


method for air monitoring.  Samples can be taken over a few minutes or


accumulated intermittently to obtain, after analysis, either "spot" or


"integrated" results.  Additional techniques for analyzing intermittent


samples are described below.


5.3.5.1  Colorimetric Analysis


5.3.5.1.1  Colored silver sol method.  Carbon monoxide reacts in an


alkaline solution with the silver salt of p_-sulfamoylbenzoate to form a

                                                        3
colored silver sol.  Concentrations of 12 to 23,000 mg/m  (10 to 20,000 ppm)

                                  28-32 98
CO may be measured by this method.     '    The method has been modified


to determine CO concentrations in incinerator effluents.  Samples are


collected in an evacuated flask and reacted.  The absorbance of the


resulting colloidal solution is measured spectrophotometrically.  Acetylene


and formaldehyde interfere, but can be removed by passing the sample


through mercuric sulfate on silica gel.  Carbon monoxide concentrations

                     3
of 5.8 to 20,700 mg/m  (5 to 18,000 ppm) may be measured with an accuracy


of 90 to 100 percent of the true value.
                                      5-32

-------
5.3.5.1.2  National Bureau of Standards colorlmetric Indicating gel,


A National Bureau of Standards  (NBS) colorimetric indicating gel


(incorporating palladium and molybdenum salts)  has been devised to


                                              151 152
measure CO in the laboratory and  in the field.    '     The  laboratory

          ,r?                                                          i

method involves  colorimetric comparison with  freshly-prepared indicating

                         V

gels exposed to  known  concentrations of CO.   The methooT has an accuracy


range of  5 to 10 percent of the amount of  CO  involved, and  the minimum

                                    o
detectable concentration is 1.2 mg/m   (1 ppm).  This technique requires


relatively simple  and  inexpensive equipment;  but oxidizing  and reducing


gases  interfere, and the preparation of the  indicator tube  is a tedious


and time-consuming task.


5.3.5.1.3  Length-of-stain indicator tube.   An  indicator  tube method

                                                                153
using  potassium palladosulfite is a commonly used manual  method.


Carbon monoxide reacts with the contents  of  the tube and .produces a



discoloration.
                                                           /

     The length of discoloration is an exponential  function of the CO


 concentration.   This method and other  indicator tube manual methods  are


 estimated to be accurate to within ±25 percent of the  amount  present,

                                                    3
 particularly at CO concentrations of about 115 mg/m  (100 ppm).   Such


 indicator tube manual  methods have been used frequently in air pollution


 studies.  Ramsey132 used the technique to measure CO  at traffic


 intersections, and Brice and Roesler21 used color-shade detector tubes


 to estimate CO concentrations with an accuracy of ±15 percent.


      Colorimetric techniques and length-of-stain discoloration  methods


 are recommended for use only when the other physicochemical monitoring
                                       5-33

-------
systems are not available.  They may be used in the field for gross



mapping where accuracy is not required and might be of great value



during emergencies.



5.3.5.2  Frontal Analysis—Air is passed over an adsorbent until



equilibrium is established between the concentration of CO in the air



and the concentration of CO on the adsorbent.  The CO is then eluted



with hydrogen, reduced to methane on a nickel catalyst at 250 C, and



determined by flame ionization as methane.

                                             3

     Concentrations of CO as low as 0.12 mg/m  (0.10 ppm) can be measured.



This method does not give instantaneous concentrations but does give


                                                   55 56
averages over a 6-minute or longer sampling period.  '



5.4  MEASURING CARBON MONOXIDE IN BLOOD



     The best index of CO exposure is the carboxyhemoglobin (COHb)

                         \

percent saturation.  Carboxyhemoglobin can be determined satisfactorily



on venous blood since insignificant differences have been found between



venous and arterial concentrations.  Venous blood should be collected in



a closed container (vacutainer tubes are adequate) with an anticoagulant



such as dry sodium heparin or sodium ethylene-diaminetetraacetic acid



(EDTA).  There must be no air trapped in the syringe or container.



Blood  samples may be preserved for several days prior to analysis if



kept in the cold (4°C) and in the dark.  Complete mixing of blood must



be performed if CO, as a  gas, and hemoglobin (Hb) are measured separately.



This mixing must assure that the normal hematocrit of the sample is



present prior to analysis.  Total Hb determination is most conveniently


                                                     53
performed by the reaction to form cyanomethemoglobin.    A satisfactory
                                      5-34

-------
procedure is to use the reagent of Van  Kampen and Zijlstra181 with
precautions to prevent gradual loss  of  hydrogen cyanide  (HCN) from the
acid reagent and to allow  sufficient time  for total conversion of COHb.
Measurements of CO by elaboration of the gas or by nondestructive
spectrophotometric procedures  have been developed (Table 5-2).
     Carbon monoxide combines  rapidly with Hb to form COHb, which is
much more stable than 02Hb.  This decreases the 0« transport capability
of blood, causing 02 deprivation  in  tissues and, thus, impaired physio-
logic  status.  Therefore,  the  chemical  analysis of blood for its COHb
content  is an  important measure of toxic effect, as well as recent
exposure, for  CO.
     The analytical results  are usually expressed as the ratio of the
concentrations of COHb to  total Hb.   In humans there is  a baseline level
of about 0.5 percent of COHb in blood,  due to endogenous production of
small  amounts  of CO by catabolic  processes. This basal  level can be
higher at certain times  in females,  individuals with hemolytic disease,
etc.   Urban  nonsmokers show about 1  percent COHb  in blood, while moderate
                              1 fifi
smokers  show about  5 percent.      Parking  garage  employees have shown
                                                  133
levels above 10 percent  at the end  of the  workday.
     There are several  reviews on analytical procedures  for CO in
blood;40'52'61'104  these  can be grouped into nondestructive, destructive,
and  equilibrium methods.
5.4.1   Other Methods
     If the  COHb concentration is measured as  such  in  solution, the
method is nondestructive;  if the  complex  is destroyed  in order to
liberate the CO gas for  measurement, the  method  is  destructive.
                                       5-35

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                 TABLE 5-2.   COMPARISON OF REPRESENTATIVE TECHNIQUES
                             FOR ANALYSIS OF CO IN BLOODa
Reference
GASOMETRIC
Horvath andQ
Roughton
Sc ho lander, and
Roughton1^
OPTICAL
Coburn, Forster
and Kane
Small et al.156
Maas, Hamelink-.Q3
and De Leeuw
CHROMATOGRAPHIC
McCredJeqand
Joseluy
Col lison, Rodkey
and O'Neal^
9
Ayers et al.
47
Dahms & Horvath

Method

Van Slyke
Syringe-
capi llary

Infrared
Spectro-
photometric
CO-Oxi meter

Thermal
conductivity
Flame
ionization
Thermal
conductivity
Thermal
conductivity
Sample
vol ,
ml

1.0
0.5

2.0
0.1
0.4

1.0
0.1
1.0
0.25

Resolution,
ml/dl

0.03
0.02

0.006
0.08
0.10

0.005
0.002
0.001
0.006

Sample
analysis
time,
min

15
30

30
10
3

20d
20
30
6.5

5T

6
2-4

1.8



1.8
1.8
2.0
1.7

a                                47
.From Dahms and Horvath modified.
 Smallest detectable difference between duplicate
       determinations.
Calculated based on samples containing less than
       2.0 ml CO per deciliter.
 Best estimate.
                                      5-36

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     The intense color of Hb and its complexes suggests the use of
spectrophotometry as a nondestructive analytical tool.  Very strong
Soret absorption peaks in the 410 to 435 nm region, as well as moder-
ately strong peaks in the 520 to 600 nm region, are shown by reduced
Hb, COHb, 02Hb, MetHb, and other Hb derivatives.53»90»131»156  Even
though the spectrophotometric curves are distinctive for each compound,
they overlap so much that it is not possible to quantitate one component
(such as COHb) in a mixture by a simple measurement of absorbance at
a wavelength where it absorbs light and other Hb derivatives do not.
     A systematic procedure in such situations is to (1) determine
the absorptivity of each pure compound at each of several carefully
selected wavelengths; (2) measure the absorbance of the unknown
mixture at each of the wavelengths; and (3) separate the contribution
of each pure compound by solving a set of simultaneous equations
which contain coefficients for the individual absorptivities at each
wavelength.  A high precision spectrophotometer with excellent
wavelength stability and resolution is needed.
                                                   1 'Sfi
     An example of this approach is Small's method.     After dilution
of blood 1:70 with 0.04 percent ammonia solution, the absorbance is
measured at four wavelengths in the Soret region.  From a set of
simultaneous equations containing these measured values, calculations
give the percent COHb, percent MetHb, and percent 02Hb.  The stated
error is ±0.6 percent COHb at concentrations of 25 percent COHb or
lower, which provides ample accuracy at high levels, but makes this
method less useful at low levels of around 1 percent COHb or less.
                                       5-37

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                   105
A related technique    is the basis for a commercial instrument, the



CO-Oximeter model 282 (Instrumentation Laboratory, Inc. , Lexington,



Mass.), which uses four wavelengths outside the Soret region and



includes a small computer for performing the calculations, yielding



percentages of total Hb as well as of COHb, 02Hb, and MetHb.  CO-


                          103 122
Oxi meters are used widely,   '    but require careful calibration at



COHb concentrations below 5 percent.  This comparison was made against



a CO-X model 182 and the discrepancy at low COHb is correct, but it


                                               140
is not known how this related to the Model 282.

                                5

     An earlier method by Amenta  is similar in principle and also



uses wavelengths outside the Soret region: 498 nm (an isosbestic



point), 560 nm, and 575 nm.  The percent COHb results obtained in the



low concentration range have a precision of only 10 percent.


                                                                       73 90
     Other spectrophotometric methods include some chemical treatments.  '



In Klendshoj's procedure, oxalated blood is first diluted 1:100 with



0.4 percent ammonia; then sodium dithionite ("hydrosulfite") is added



and the absorbance is measured at 480 nm and 555 nm.  After dithionite



treatment, the only Hb species present are reduced Hb and COHb.  These



two have the same absorptivity at 555 nm, but different absorptivities



at 480 nm; the ratio ACr-r-/A/,on decreases with increased COHb concentration.
                      ODD
A calibration curve  is prepared from known standards; certain precautions


                                       193
are needed in making up such standards.     Klendshoj's method is simple,



rapid, and accurate  enough to measure a 2 percent change in COHb



concentration, but at low levels is less useful.
                                      5-38

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     Another spectrophotometric method makes use of the fact that 02Hb



is much more readily precipitated than COHb when heated eight minutes



at 57 C.     After the solution is filtered and cooled, the change in



absorbance at 555 nm is measured and the COHb content of the blood is



measured by calibrating the method with standard solutions of known



concentration.  The procedure  is simple but not very sensitive or accurate.



     In the differential spectrophotometric technique of Commins and


        41
Lawther,   an aqueous solution of the blood sample is divided equally



and oxygen is bubbled through  one half of the solution for 15 minutes to



convert any COHb into 02Hb.  The spectra of the two halves are then



compared and the difference between them (together with a measurement of



Hb in the oxygenated portion)  is used to find the COHb content of the



blood.  This method is stated  as able to detect 0.2 percent COHb in



blood, and has shown good agreement with two different destructive


                          23
methods for COHb analysis.



     Double wavelength spectrophotometry is used in a recently developed


                      131
rapid method for COHb.     Two monochromators in the same instrument



send  light beams of different  wavelengths alternately through a single



cuvette; the difference in absorbance is measured by the photometer.



The carefully chosen wavelengths are 530.6 nm and 583.0 nm, at which



0?Hb has equal absorptivities, and also at which reduced Hb has equal



absorptivities.  Any difference in absorbance found is due to the



presence of COHb, which has unequal absorptivities at the two wavelengths.



As with all such methods, careful calibration with known samples is



required.  The procedure has acceptable accuracy at levels of a few



percent of COHb, but MetHb causes interference.
                                       5-39

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     Infrared spectrophotometry of CO bound to Hb can be performed
directly on blood and other tissues, and holds future promise as a
specific method for COHb analyses.  An exploratory study used measure-
ments at 1951 cm   in CaF« cells having 0.05 mm optical pathlength.
     Other possible spectrometric techniques for COHb analysis include
Mossbauer (which would require a solid sample, such as frozen blood),
carbon-13 nuclear magnetic resonance, and electron spin resonance.
These offer some promise of specificity, but are far from being developed
into usable methods.
     A different approach to COHb analysis is to decompose the complex
and measure the amount of CO gas released.  Such liberation of CO has
been carried out by addition of various acids (hydrochloric, sulfuric,
phosphoric, acetic, citric, lactic) and/or oxidizing agents such as
potassium ferricyanide or potassium hydrogen iodate.   These methods
tend to have the disadvantage of requiring (1) larger samples of
blood than for spectrophotometry, and (2) a separate analysis for
total concentration of Hb, if the percent COHb is needed.
     Of the many analytical methods available for gaseous CO, several
are noted briefly below.
                                                               80 182 183
5.4.1.1  Gasometric—The Van Slyke method and its modifications  '     *
                                                         159
measure the volume or the pressure of the CO gas present.      Historically
they were macro methods and not of high sensitivity, but successful
                                     141 146
micro procedures have been developed.   '     They require considerable
skill and are time-consuming.
                                      5-40

-------
5.4.1.2  Infrared Spectrometry—Carbon monoxide has a characteristic
infrared absorption near 4.6 urn.  This is widely used for analysis,
especially with nondispersive  instruments as in the EPA reference
method for atmospheric monitoring.   In this method, the absorption
due to any CO present is measured by its differential heating effect
and resulting displacement of  a flexible diaphragm which is one
element of a capacitance detector.   Methods using NDIR for COHb
analysis in blood are available.35>63>189  Water vapor interferes
unless its concentration is carefully controlled.
5.4.1.3  Catalytic Oxidation—Like NDIR, this method has enough sensi-
tivity and accuracy to detect  small  changes in COHb concentration.
The liberated CO can be oxidized by  a catalyst such as Hopcalite and
the temperature rise caused by this  exothermic reaction measured with a
thermopile or quartz crystal.100'117'129'163
5.4.1.4  Electrochemical Sensors—Another analytical technique based
on oxidation of CO is electrochemical.  In a special electrode, the
gas sample is allowed to diffuse through a Teflon membrane bearing a
thin  film of catalytically active metal (such as platinum) on the far
side, in contact with the electrolyte.  At a controlled applied
potential, the current flow is determined by the CO concentration in
the gas.13»17»18»20>34»50  A different electrical procedure for analysis
of CO is to measure the change in conductivity it causes when adsorbed
by a  semiconductor such as metal oxides.   '
5.4.1.5  Gas chromatography—The chromatographic separation of CO from
other blood gases is readily accomplished by a molecular sieve. »   »   »  »
                                       5-41

-------
In order to achieve greater sensitivity than given by a thermal conduc-
tivity detector, a flame ionization detector can be used in the gas
chromatograph if the CO is first catalytically reduced to methane, in-
                                                 39 130 139 192
line after its separation by the molecular sieve.   '    '   5
5.4.1.6  Colorimetric palladium chloride reaction—In a Conway micro-
               93
diffusion cell,   CO released from blood diffuses into a solution of
palladium (II) chloride, which is reduced to metallic palladium.
The excess PdCl« is determined colorimetrically, by conversion to the
                      4
pinkish iodide complex  or by formation of a violet complex with
          OQ
promazine.    Another col ori metric reagent for CO is  a mixture of
                                   92 99
palladium and molybdenum compounds.  *
5.4.2  Equilibrium Methods
     If equilibrium can be established between blood  gases and lung
gases, then analysis of exhaled air will give a measure of COHb blood
levels 26,60,126,134,155,185  Jhe relationship is
                    [COHb] = M [0£Hb]  GP
                                      P02
where ^0^  is the partial pressure of 0« in the pulmonary blood, pCQ is
the measured partial pressure of CO in the exhaled air, the bracketed
quantities are the blood concentrations of COHb and O^Hb, respectively,
and M is the ratio of the stability constant of COHb to that of 0«Hb.
The Haldane constant, M,   has a numerical value of about 220 to 250 for
humans at physiological pH and body temperature.  '
                                      5-42

-------
     The alveolar air method should be used  in epidemiological studies
only with extreme care.  Hoover and Albrecht,79 in their study of driving
in New York City traffic, reported that CO concentrations in alveolar
air did not correlate acceptably with measurements of COHb.  The equi-
librium method cannot be used  in people with chronic lung disease,
because their alveolar gas composition can be quite variable.  Even
healthy subjects need special  training in the method in order to achieve
valid results.
     In this method, the main  problem is to  approach equilibrium condi-
tions even though the composition of lung gas is changing continually
during normal respiration.  One solution is  breath-holding.  When a
subject holds his breath, the  alveolar concentration of CO increases
initially as CO diffuses out of the blood toward equilibration.7'19'36'48'89'137
However, as the alveolar 0« content decreases, some of the CO is re-
absorbed Into the blood.  The  optimum time period for breath-hoi ding was
found to be 20 seconds.
     The standard technique is for the subject to expel air from his
lungs maximally, then breathe  in as far as possible, hold his breath for
20  seconds, and then exhale as far as possible.  The first 500 ml of
expired air is discarded, and  the remainder  is collected in a gas-tight
bag for CO analysis by a reliable method.  A rugged instrument for field
use, as for measuring COHb  in  firefighters,  is the Ecolyzer, which
measures CO by electrochemical oxidation at  a Teflon-bonded diffusion
anode.165
                                       5-43

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                                      5-46

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169.  National Air Pollution Control Administration.  Air Quality  Criteria for
     Carbon Monoxide.  National Air Pollution  Control Administration No.
     AP-62, U.S. Department of Health, Education, and Welfare, Washington, DC,
     March 1970.
                                      5-56

-------
170. National Institute  for Occupational  Safety and Health.   Criteria for a
     Recommended Standard...Occupational  Exposure  to Carbon  Monoxide.
     NIOSH-TR-007-72, U.S. Department of  Health, Education,  and Welfare,
     Washington, DC, 1972.

171. U.S. Environmental  Protection  Agency.   National  primary and secondary
     ambient air quality standards.   40CFR50:3-33,  July  1, 1977.

172. Office of Air Quality Planning and Standards.   Designation of  Unacceptable
     Analytical Methods  of Measurement for  Criteria Pollutants.   EPA-450/4-74-005,
     U.S. Environmental  Protection  Agency,  Research Triangle Park,  NC, September
     1974.

173. Office of Air Quality Planning and Standards.  AEROS Manual  Series Volume
     II:  AEROS User's Manual.   EPA-450/2-76-029,  U.S. Environmental  Protection
     Agency, Research Triangle  Park,  NC,  December  1976.

174. U.S. Environmental  Protection  Agency.   Guidelines for development of  a
     quality assurance program.  Washington,  DC, EPA-RA-73-028a,  119  pp.,  June
     1973.

175. U.S. Environmental  Protection  Agency.   Ambient air  monitoring  refererence
     and  equivalent methods.  40CFR53:812-839,  July 1, 1977.

176. U.S. Environmental  Protection  Agency,  letter  from Dr. George M.  Goldstein
     to Mr. Jack Thompson dated 9/23/77 on  carboxyhemoglobin measurements,

177. U.S. Environmental  Protection  Agency.   Air quality  surveillance  and data
     report.  Proposed regulatory revisions.   Fed.  Regist 43:34892-34934,
     August 7, 1978.

178. National Bureau of  Standards.   Catalog of NBS  Standard  Reference Materials,
     1975-76 Edition.  NBS Special  Publication 260,  U.S. Department of Commerce,
     Washington, DC, June 1975.

178a.     National Bureau of  Standards.   NBS Standard Reference Materials  1977
     Price List.  NBS Special Publication 260 Supplement, U.S.  Department  of
     Commerce, Washington, DC,  1977

178b.     National Bureau of  Standards.   NBS Standard Reference Materials  1978
     Interim SRM Price List.  U.S.  Department of Commerce, Washington, DC,
     1978

179. van  Dijk, J. F. M.,  and  R.  A.  Falkenburg.   A  high sensitivity  carbon
     monoxide monitor for ambient air.    In:  International Conference on
     Environmental Sensing and  Assessment.   Volume  2, a  Joint Conference
     comprising the International Symposium on Environmental  Monitoring and
     Third Joint Conference on  Sensing of Environmental  Pollutants, Las Vegas,
     Nevada, September 14-19, 1975.   Institute of  Electrical  &  Electronics
     Engineers, Inc., New York,  1976.  paper no. 35-5.

180. van  Heusden, S., and L.  P.  J.  Hoogeveen.   Chemiluminescent determination
     of reactive hydrocarbons.   Z.  Anal.  Chem.  282:307-313,  1976.
                                      5-57

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181.  van Kampen, E. J. , and W. G. Zijlstra.  Standardization of  hemoglobinometry.
     II. The hemoglobincyanide method.  Clin. Chim. Acta 6:538-544,  1961.

182.  Van Slyke, D. D., and J. M. Neill.  The determination of gases  in  blood
     and other solutions by vacuum extraction and manometric measurement.   I.
     J. Biol. Chem. 61:523-573, 1974.

183.  Van Slyke, D. D., A. Miller, J.  R. Weisiger, and W. 0. Cruz.  Determination
     of carbon monoxide in blood and  of total and active hemoglobin  by  carbon
     monoxide capacity.  Inactive hemoglobin and methemoglobin contents of
     normal human blood.  J. Biol. Chem. 166:121-148, 1946.

184.  Verdin, A.  Gas Analysis Instrumentation.  John Wiley & Sons, Inc.,  New
     York, 1973.

185.  Vogt, T. M., S. Selvin, G. Widdowson, and S. B. Hulley.  Expired air
     carbon monoxide and serum thiocyanate as objective measures of  cigarette
     exposure.  Am. J. Public Health  67:545-549, 1977.

186.  Vol'berg, N. Sh., I. I. Pochina.  Continuous determination  of the  concentration
     of carbon monoxide in the atmosphere by a coulometric method.   Tr.  Gl.
     Geofiz. Obs. (314):114-122, 1974.

187.  Ward, T. V., and H. H. Zwick.  Gas cell correlation spectrometer:   GASPEC.
     Appl. Opt. 14:2896-2904, 1975.

188.  Wechter, S. G.   Preparation of stable pollution gas standards using
     treated aluminum cylinders.  In:  Calibration  in Air Monitoring, a Symposium,
     American Society for Testing and Materials, Boulder, Colorado,  August
     5-7,  1975.  ASTM Special Technical Publication 598, American Society for
     Testing and Materials, Philadelphia, PA, 1976. pp. 40-54.

189.  Werner, A. B.   A sensitive, rapid infrared method for analyzing carbon
     monoxide in blood.  Scand. J. Clin. Lab. Invest.  36:203-205, 1976.

190.  Whitehead, T. P., and S. Worthington.  The determination of carboxyhaemoglobin.
     Clin. Chim. Acta 6:356-359, 1961.

191.  Wohlers, H. C., H. Newstein, and D. Daunis.  Carbon monoxide and sulfur
     dioxide adsorption on- and desorption from glass, plastic,  and  metal
     tubings.  J. Air Pollut. Control Assoc. 17:753-756, 1967.

192.  Wu, A., and C.  L. Hake.  Improved carbon monoxide measurements  in  blood
     by gas chromatography.  Clin. Toxicol. 9:31, 1976.

193.  Yamamoto, K.  Spectrophotometric two-wavelength method for  carboxyhemoglobin
     determination—with special reference to van Kampen1s method.   Nippon
     Hoigaku Zasshi 30:299-305, 1976.

194.  Yamate, N. and A. Inoue.  Continuous analyzer  for carbon monoxide  in
     ambient air by electrochemical technique.  Kogai to Taisaku 9:292-296,
     1973.
                                     5-58

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                 6.  OBSERVED CARBON MONOXIDE CONCENTRATIONS

     Ambient concentrations of carbon monoxide (CO) in urban communities
exhibit wide temporal and spatial variations.  Exposure patterns of CO
are complex, but they can be discerned from ambient air measurements and
the estimates of computer models.  This chapter presents some typical
results of continuous air monitoring of CO in order to provide a better
understanding of the CO problem.  In addition to a discussion of observed
diurnal, seasonal, and annual patterns of ambient CO levels in urban
areas, this chapter discusses the importance of air monitoring site
selection, of meteorological and geographical effects on CO exposures,
techniques of CO trend analyses, special CO exposure situations, and an
overview of meteorological diffusion models.  The CO problem exists
primarily in the urban areas.
6..1  SITE SELECTION
     Because of the many variables which must be considered, site
selection is one of the most complex and critical elements in the design
of CO air monitoring programs.  If the wrong sites are chosen, or if a
critical site is missed, no amount of accurate data collection will
allow the objective of the monitoring program to be fully realized.
It has been generally recognized that the choice of monitoring sites
                                                                    cc
depends on the objective of the monitoring to be performed.  The EPA
recognizes the following as general objectives for monitoring:
                                      6-1

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     1.    To judge compliance with and/or progress made toward meeting
          ambient air quality standards.

     2.    To activate emergency control procedures to prevent air
          pollution episodes.

     3.    To observe pollution trends throughout the region including
          the nonurban areas.  (Information on the nonurban areas is
          needed to evaluate whether air quality in the cleaner portions
          of a region is deteriorating significantly and to gain knowledge
          about background levels.)

     4.    To provide a data base for application in evaluation of effects;
          urban, land use, and transportation planning, development and
          evaluation of abatement strategies; and development and validation
          of diffusion models.
     Ground level concentrations of CO within an urban area vary widely

due to the large number and close proximity of the principal source of

CO, automobiles.  Each car in a city contributes to the CO problem, but

it is large numbers of cars contributing collectively which produce high

CO levels in urban areas.  The concentration of CO measured at a

monitoring site will depend on the site's location relative to CO sources,

The scale of representativeness of the data will also be dependent on

the proximity of the monitor to CO sources.   Monitoring sites located

well-removed from highways can be representative of a fairly large-scale

air mass.  Sites located at the edge of a highway measure CO concen-

trations which are representative of a fairly small spatial area.  The

   80a
EPA    has defined six scales of spatial representativeness for CO

monitoring sites:  microscale, middle scale, neighborhood scale, urban

scale, regional scale, and national and global scales.

     The choice of monitoring site location depends on the monitoring

objective and the scale of -representativeness which meets the objective

requirements.   Most CO monitoring conducted in the United States is for

the purpose of determining attainment or nonattainment of air quality

                                      6-2

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standards.  Since monitoring resources have been and continue to be



severely limited, sites chosen for monitoring are usually where maximum



CO concentrations are expected to occur.  As a result, many CO sites are



located within the close proximity of major highways, arterials, and



downtown street canyons.  These locations are where maximum CO levels



occur, but the scale of representativeness is small.  Also, the results



relate primarily to pedestrian exposure near the monitoring station.



Monitoring sites located outside the influence of major roadways, but



within highly populated neighborhoods with a high traffic density, may



be more representative of the maximum CO concentrations to which a large



portion of the population of a city may be exposed.


        48
     Ott   has stated the need for standardization  in site selection and



has  recommended certain siting criteria depending on station type.



Ott's criteria are presented in Table 6-1.



     The  EPA80a has also published guidelines for CO monitor siting



which deviate somewhat from Ott's criteria primarily in site type



definition and recommended separation distance between the station and



the  nearest major highway.  In EPA's criteria, the  minimum separation



distance  is dependent on traffic volume measured in vehicles per day (VPD)



These guidelines are given in Table 6-2.


                                                                 80
      In regard to which sites should be monitored,  EPA guidelines   give



the  highest priority to microscale sites within street canyons and



neighborhood  sites where maximum concentrations are expected.  Table 6-3



lists EPA80 priorities for various station types.
                                       6-3

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           TABLE 6-1.  CRITERIA FOR SITING MONITORING STATIONS48
Station                           Description
  Type
TYPE A   Downtown Pedestrian Exposure Station.  Locate station in the central
         business district (CBD) of the urban area on a congested, downtown street
         surrounded by buildings--a "canyon" type street—and having many pedestrians
         Average daily travel (ADT) on the street must exceed 10,000 vehicles/day,
         with average speeds less than 15 miles/hour.  Monitoring probe is to be
         located 1/2 meter from the curb at a height of 3 ±1/2 meters.

TYPE B   Downtown Background Exposure Station.  Locate station in the central
         business district (CBD) of the urban area but not close to any major
         streets.  Specifically, no street with average daily travel (ADT)
         exceeding 500 vehicles/day can be less than 100 meters from the monitoring
         station.  Typical locations are parks, malls, or landscaped areas having
         no traffic.  Probe height is to be 3 ±1/2 meters above the ground surface.

TYPE C   Residential Population Exposure Station.   Locate station in the midst of
         a residential or suburban area but not in the central business district
         (CBD).  Station must not be less than 100 meters from any street having a
         traffic volume in excess of 500 vehicles/day.  Station probe height must
         be 3 ±1/2 meters.

TYPE D   Mesoscale Meteorological Station.  Locate station in the urban area at
         appropriate height to gather meteorological data and air quality data at
         upper elevations.  The purpose of this station is not to monitor human
         exposure but to gather trend data and meteorological data at various
         heights.  Typical locations are tall buildings and broadcasting towers.
         The height of the probe, along with the nature of the station location,
         must be carefully specified along with the data.

TYPE E   Nonurban Background Station.  Locate station in a remote nonurban area
         having no traffic and no industrial activity.  The purpose of this station
         is to monitor for trend analyses, for nondegradation assessments, and for
         large-scale geographical surveys.  The location or height must not be
         changed during the period over which the trend is examined.  The height of
         the probe must be specified along with the data.  A suitable height is
         3 ±1/2 meters.

TYPE F   Specialized Source Survey Station.  Locate station very near a particular
         air pollution source under scrutiny.  The purpose of the station is to
         determine the impact on air quality, at specified locations, of a particular
         emission source of interest.  Station probe height should be 3 ±1/2
         meters unless special considerations of the survey require a nonuniform
         height.
                                     6-4

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                                            TABLE 6-2.  SPECIFIC PROBE EXPOSURE CRITERIA
                                                                                        80
         Site Type
Height
Above
Ground
Expected
Concentration    Separation of
Gradient with    Monitor from
Height           Influencing
(1-hr. Average) Sources	
                              General Remarks
        Street  Canyon

          Peak  Cone.
          Average Cone,
cn
          Corridor
3 + 1/2 m   Z.5 ppm/m
3 + 1/2 m   Z.3 ppm/m
                 Mid-sidewalk or 2 m
                 from side of building.
                 On leeward side of
                 street.

                 Mid-sidewalk or 2 m
                 from side of building.
                         Central  Business District.
                         High density, slow-moving traffic.
                         Dense multiple-story buildings
                         lining both sides of street.
                         J10 m from intersection.
Neighborhood
Peak Cone.
Average Cone.
3 * 1/2 m 5%/m
3 + 1/2 m 5%/m
Setback
3.5 km
1.5 km
200 m
100 m
35 m
25 m
VPD
100,000
50,000
10,000
5,000
1,000
any
Commercial or residential neighbor
This separation criteria limits th
effect of these streets to II ppm.
3 + 1/2 m
F.3 ppm/m

J5%/m
Dependent on traffic     Stop  and go  or  limited  access
volume, road configura-   traffic  J50,000 VPD  or  greatest
tion and setback         in  area.
distance of commercial
or residential  activity.	

-------
                                                        TABLE 6-2 (Continued)
        Site Type
Height
Above
Ground
Expected
Concentration    Separation of
Gradient with    Monitor from
Height           Influencing
(1-hr. Average) Sources	
                              General Remarks
      Background
3 to 10 m
 2%/m
5 to 6 km;
03,000 VPH max.
400 m; J100 VPD,
35 km downwind in least frequent
wind direction from city,
limit effects to .2 ppm.	
cr>
      New Source Review
        Preconstruction   3 + 1/2 m   5%/m
        Post-
        Construction
3 + 1/2 m  J5%/m to
            F.5 ppm
                 Usually the same as
                 neighborhood.

                 Usually the same as
                 corridor or street
                 canyon.	
                         Area of lowest concentration in
                         proposed indirect source location
                         for background.

                         Area of maximum concentration in
                         area of complete area source.

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    TABLE 6-3.  SUGGESTED PRIORITIES OF CARBON MONOXIDE MONITORING SITES80
                    Site Types                    Priority
               Peak Street Canyon                   #1
               Peak Neighborhood                    #1
               Average Street Canyon                #2
               Corridor                             #3
               Background                           #4
               Average Neighborhood                 #5
     The variability of CO concentration with height in the vicinity of
a highway is also sufficiently large that the representativeness of
measurements will be strongly affected by variability of the inlet probe
height.  It is, therefore, necessary to standardize the height of the
inlet probe so that data collected at one air monitoring station is
comparable to data collected at others.  In an effort to characterize
typical human exposure, the sample inlet probe height should ideally be
set at breathing level.  However, as a compromise between representation
of breathing height and practical considerations, such as prevention of
vandalism, it is recommended that inlets for most kinds of sampling be
                        1 5
at a height of 3 ±0.5 m. '   A 1-m minimum separation of the probe from
adjacent structures to avoid the frictional effects of surfaces on the
                                    75
movement of air is also recommended.
     The number of monitoring sites required depends on the objectives
of the monitoring effort and on the complexity of the problem under
study.  At present, the only guidelines are from the EPA   which requires
one site for cities with 100,000 or less population, 1+0.15 sites per
100,000 population up to 5,000,000 people, and 6+0.05 sites per 100,000
population for populations greater than 5,000,000.
                                      6-7

-------
     Site selection for special purpose studies may not follow the



specific criteria which apply to continuous monitoring sites used for



trends analysis and compliance with air quality standards.  In fact,



special purpose studies, where CO concentrations are measured at many



locations, provide the Information about the spatial variations of



ambient CO that form the basis for setting siting criteria.  Among the



principal types of special purpose monitoring are research studies for



diffusion model development and improvement, and source surveillance



studies.  Source surveillance studies may be conducted for highways or



point sources of CO.  Diffusion model development studies may be for


                                 71            81
line source models (such as HIWAY   or CALINE-2  ) or area source



models (such as APRAC-2  ).  For special purpose studies, the criteria



for site selection is a decision for the investigator.



6.2  UNITED STATES DATA BASE



     In accordance with requirements of the Clean Air Act and EPA


                                                   15
regulations for State Implementation Plans (SIP's),   ambient CO data



from state, local, and Federal networks must be reported each calendar


                                                                       73
quarter to the EPA's Aerometric and Emissions Reporting System (AEROS).



As a result, continuous measurements of ambient CO concentrations from



numerous cities throughout the United States are available from the



U.S. Environmental Protection Agency's National Aerometric Data Bank



(NADB) in standard Storage and Retrieval of Aerometric Data (SAROAD)

                 73
reporting format.



     The nationwide status of CO monitoring activities reporting to the



AEROS in 1977 1s summarized 1n Table 6-4.  This table lists, by state,



the number of CO monitors that reported any CO data.
                                      6-8

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TABLE 6-4.   STATUS OF CO MONITORING IN 197780b
     State

 01  Alabama
 02  Alaska
 03  Arizona
 04  Arkansas
 05  California
 06  Colorado
 07  Connecticut'
 08  Delaware
 09  District of Columbia
 10  Florida
 11  Georgia
 12  Hawaii
 13  Idaho
 14  Illinois
 15  Indiana
 16  Iowa
 17  Kansas
 18  Kentucky
 19  Louisiana
 20  Maine
 21  Maryland
 22  Massachusetts
 23  Michigan
 24  Minnesota
 25  Mississippi
 26  Missouri
 27  Montana
 28  Nebraska
 29  Nevada
 30  New Hampshire
 31  New Jersey
 32  New Mexico
 33  New York
 34  North Carolina
 35  North Dakota
 36  Ohio
 37  Oklahoma
 38  Oregon
 39  Pennsylvania
 40  Puerto  Rico
 41  Rhode  Island
 42  South Carolina
 43  South Dakota
 44  Tennessee
 45  Texas
 46  Utah
 47  Vermont
 48  Virginia
 49  Washington
 50  West Virginia
 51  Wisconsin
 52  Wyomi ng
 53  Guam
 54  Virgin Islands
Total Number of Monitors
   Reporting any Data

             4
             6
            16
             0
            84
            10
             9
             3
             9
            12
             4
             1
             1
            20
             7
             5
             7
            15
             0
             4
            15
             9
            11
             8
             0
            14
             4
             3
             3
             3
            22
            10
            29
             1
             0
            16
             4
             5
            13
             0
             1
             3
             0
             5
            19
             6
             2
            15
             7
             2
             9
             0
             0
             0
                          TOTAL
           456
                            6-9

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     The nationwide historical data base for CO is very limited compared



to total suspended participate or sulfur dioxide air pollutant data, but



it continues to expand.  In 1973, 212 sites reported CO data to the EPA.



During 1975, 453 sites submitted CO data though much of it was incomplete.



Total numbers of CO monitors reporting during 1976 and 1977 were 448 and



456, respectively.     In 1975, 102 sites had three or more years of



data, while in 1976 there were 202 sites with at least three years of


     79
data.    The State of California with its well-established monitoring



program is the major contributor to the national CO data base with 84



sites.



     Among the oldest CO monitoring sites are the Continuous Air



Monitoring Program stations which have been operated by the Federal



government since 1962.    Continuous Air Monitoring Program (CAMP) data



have been collected at nine sites, one each in the cities of Los Angeles,



San  Francisco, Denver, Chicago, New Orleans, St. Louis, Cincinnati,



Philadelphia, and Washington, D. C.  The stations in Chicago, Cincinnati,



Philadelphia, and Washington, D. C. have been part of the program since



its  inception.  The Washington, D. C. station was moved to a new location



in 1969, interrupting the continuous data record for that site.  The



stations in every case are located in the downtown, central business



district of the city-  Since a CAMP station constitutes only one sampling



site per city, its data do not necessarily represent air pollution



levels prevailing beyond the immediate vicinity of the station.



     An additional problem with CAMP station data is that continuity is



often lacking due to changes in site location or CO monitoring procedures
                                      6-10

-------
which have occurred since the  beginning  of  the program.  Specifically,


1n 1970 the original CO  instruments  (mono-beam NDIR) were  replaced with


dual-beam NDIR detectors with  integrating chambers  added,  and  in 1971


calibration gases were changed from  CO 1n nitrogen  to CO in air.  These


changes tended to eliminate water  vapor  interference, smooth out the


concentration plots, and eliminate C02 interference.67  Similar changes


in CO monitoring procedures were first implemented  by the  Los  Angeles

                                          CO
County Pollution Control District  in 1968.    Figure 6-1 shows the


annual mean CO concentrations  measured at three  Los Angeles basin sites

before and after the changes were  made.  A  significant decrease in CO
                                              co
levels measured  in  1968  and  later  is apparent.


     Computer retrievals of  raw data submitted to the AEROS and published


data summaries such as the National  Air  Quality  and Emission Trends

Report67'68'70'74'75*79*8013  or Air Quality  Data  - 1976 Annual  Statistics


are available.

     However, state and  local  air  pollution control agencies are not


required  to  submit  all CO  data collected from their monitoring network.


These agencies may  also  conduct special  studies  for certain "in-house"

purposes.  State departments  of transportation and  local metropolitan


planning  commissions  are sources of  CO data for  the preparation of


environmental  impact  statements for  proposed transportation projects

and/or  in the preparation  of SIP revisions.  Air quality  impact research


sponsored by the  EPA,  the  Federal  Highway Administration,  universities,


and private  industries also  provide  sources of  CO data.
                                       6-11

-------
                D1961-67 O1968-72
    20
 E
 a
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z"
O
p
<
cc
I-
z
o
o
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o
          I   I   I   I
          (a) LENNOX
                      I   I   I   I   I   I   I

                      D
                         D
             D
            62
  66

YEAR
                                    70
 a
 a
 *
z
o
K
<
CC
\-
z
LU
O
z
o
u
     20
     15
o
          I   I   I   I   I   I   I
          (b) DOWNTOWN L.A.
                     D
                              0 °
            62
  66


YEAR
                                    70
     20
 E
 a
 a
H-
<
CC
I-
z
LU
O
z
o
o
o
         T  III
          (c) AZUSA
         D D
               D
                                          t
            62
                        66
              70
                       YEAR



Figure 6-1. Annual average CO levels In Los Angeles.

(Used with permission of Journal of Air Pollution Control Association,

2500:1129-1136, 1975.)
                      6-12

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6.3  TECHNIQUES OF DATA ANALYSIS


6.3.1  Introduction


     Air quality surveys inherently involve the taking of a limited


number of samples from a highly variable and uncontrolled population


(i.e., the environment).  For this reason, air quality data should be


analyzed using statistical methods, which can be used to describe the


behavior of the total population based on a finite number of samples.
                                                             ,3

In particular, statistical parameters can be calculated to describe the


typical values observed, the maximum or peak values observed, and the


range of values observed.


     Although intermittent sampling is an important research tool for


conducting special studies, the majority of CO monitoring instruments in


use today are intended to operate continuously and yield successive


hourly averages.  These data are applied to two principal uses:


(1) characterizing environmental conditions by describing short-term


(hourly, daily, seasonal) and long-term (year-to-year) urban CO concen-


tration patterns, and (2) evaluating, for statutory purposes, an area's


status wfth respect  to the 1-hour and 8-hour average NAAQS for CO.


     At a minimum, an analysis of CO air quality data should include a


comparison of the highest (or second highest) observed pollution concen-


tration to established air quality standards.  In addition, an analysis


of CO data may include calculation of population statistics, frequency


analyses, averaging  time analyses, trend analyses, and case analysis.
                                       6-13

-------
6.3.2  Calculation of Population Statistics

     Statistical parameters can be calculated to describe the typical CO

values observed, the maximum or peak CO values observed, and the range

of CO values observed.  Indicators of typical CO values are the arith-

metic mean, the median, and the geometric mean.   When the term "average"

is used, the arithmetic mean is usually implied.  The median is the

middle value of the CO data, that is, the value that has half the data

above it and half below it.  The median is a convenient statistic that

is not influenced by changes in extremely high or low CO values of the

distribution, as would be the arithmetic mean.  The geometric mean* is

probably the least intuitive of the statistics presented.   If a distri-

bution is symmetric, such as the normal distribution, the expected value

of the arithmetic mean and median are identical.  However, for a lognor-

mally distributed variable (and CO data often have a distribution that

is approximately lognormal), it is the geometric mean that approximates

the median.

     The histogram of Figure 6-2 illustrates the relative frequency of

occurrence of 1-hour average CO concentrations.   The shape of the

histogram, which is "skewed to the right" is typical for lognormally

distributed data.  A more illustrative method of plotting the data is

shown in Figure 6-3.  This curve illustrates the cumulative frequency

distribution of the data when plotted on logarithmic versus probability

(log-probability) graph paper.  When the cumulative frequency distribution
*-The geometric mean is calculated by taking the logarithm of each
  sampled concentration, adding all of them together, dividing by the
  number of samples, and taking the antilog.
                                      6-14

-------
    40
    30
09

 *
>
o

UJ

O
UJ
DC
    20
    10
       __  I
           2.3
  6.9        11.5        16.1



CO CONCENTRATIONS, mg/m3
                                                       20.7
Figure 6-2.  Histogram of 1-hr average CO concentrations,

Washington, DC (CAMP).46
                   6-15

-------
CO



 ~0>




 Z*

 O



 g
Z

UJ
O
u

o
o
   100.0
    50.0
    20.0
    10.0
     5.0
     2.0
     1.0
             I I  I  I  I  I   I   I    I  II I  I  I   I   II   I   I  I  I  I

           99.9   99.5 98    90    70   50   30    10     2  0.5 0.05 0.01




                           FREQUENCY, percent
Figure 6-3. Cumulative frequency distribution of 1-hour average CO

concentrations.
                                  6-16

-------
of the data 1s plotted, each point represents the cumulative frequency
of equaling or exceeding the specific CO concentration.
     The cumulative frequency distribution  leads to some useful statis-
tical applications which allow CO monitoring data to be analyzed to
determine the maximum CO concentration which probably occurred during a
monitoring period, even though the maximum  value itself may not have
been recorded.  This is especially applicable to sampling programs
designed to collect CO data Intermittently  (i.e., every other day, every
third day, or randomly selected  days, etc.), which allows for consider-
able chance for maximum CO concentrations not to be sampled.  It also
applies to continuous CO monitoring where data are missed due to
calibrations, maintenance, or instrument failure.  The assumption of
lognormality of the data allows  these "missed" values to be estimated.
The actual days which maximum CO concentrations occurred cannot be
determined, but the frequency of occurrence of high CO concentrations
can.
     Maximum CO values may be indicated by  listing the maximum and/or
the second highest value.  The second highest value is important because
compliance with the short-term air quality  standards for CO is determined
by this value.  Since the second highest value does not allow for
differences in sample sizes, difficulty would arise if continuous CO
monitoring data were missed due  to calibrations, maintenance, or instru-
ment failure; or  if CO were sampled  intermittently.  To allow for
dependence on sample size, various percent!les are sometimes used to
indicate maxima.  By using a percentile value rather than an absolute
                                       6-17

-------
count of samples, allowance is made for sampling schedules that differ



from site to site and year to year.



     The customary statistics used to indicate the variability of CO



data are the arithmetic standard deviation and the geometric standard



deviation.  Ranges or percentiles can also be used as indicators of



spread.  These statistics indicate how variable the data collected are



(i.e., a measure of the uniformity of the data).



6.3.3  Frequency Analysis



     A number of investigators,1»32'33'34'50'88 primarily Larsen and


       34
Zimmer,   have shown that short time averaged air pollution concentrations



(from 5-minute to 24-hour averages) sampled over a much longer period of



time (i.e., weeks, months, or years) tend to be lognormally distributed



within the longer sampling interval.  Described simply, a lognormal



frequency distribution means that CO data collected frequently exhibit



many low concentrations, a significant number of moderate concentrations,



and a relatively small number of extreme, peak, or maximum concentrations.



     While the standard lognormal model is commonly used in evaluating



air pollution data, other investigators continue to search for improved



methods of statistically describing concentration distribution.  Examples



of these are the three-parameter lognormal distribution, proposed by



Mage and Ott,   and the Wei bull and Gamma distributions studied by Pollack.



6.3.4  Comparing CO Data to National Ambient Air Quality Standards



     The NAAQS for CO are currently based on a 1-hour and an 8-hour



averaging time.  Carbon monoxide data are most frequently collected



using time averages of one hour.  Evaluating compliance with the 1-hour
                                      6-18

-------
standard simply requires rank-ordering 1-hour values for a year and

comparing the second-highest value with the 1-hour standard, which 1s

currently 40 mg/m3 (35 ppm).  If the second-highest 1-hour value 1s less
            o
than 40 mg/m , the standard has been met.

     Evaluating compliance with the 8-hour standard Involves the calcula-

tion of moving 8-hour averages from the 1-hour data set.  These 8-hour

averages are also rank-ordered to obtain the second-highest non-overlap-

ping" value for comparison with the 8-hour standard, which 1s currently
       3
10 mg/m  (9 ppm).  For enforcement purposes, only non-overlapping 8-hour

Intervals are counted as violations, as discussed 1n the Guidelines for
                                            qn
the Interpretation of A1r Quality Standards.    It has been shown,

however, that the full set of moving 8-hour averages should be examined

for excessive values.  Proposed simplifications such as calculating only

three consecutive non-overlapping 8-hour averages per day can easily

result in missing peak 8-hour intervals and may not afford equitable

comparisons among stations with differing diurnal patterns.

     For partial data sets, if continuous CO monitoring data were missed

due to calibrations, maintenance, or instrument failure, or if CO were

sampled intermittently, comparing CO data to standards using lognormal

cumulative frequency distribution plots may become a useful guide.

Once the CO data has been plotted on log-probability graph paper, the

frequency of equaling or exceeding any specified CO concentration can

easily be determined.  For example, in Figure 6-3 observe that the CO
                                       o
concentration equals or exceeds 10 mg/m  7 percent of the time and

20 mg/m3 for 0.05 percent of the time.  The NAAQS for a 1-hour average
                                      6-19

-------
                                3

concentration of CO is 40.0 mg/m , not to be exceeded more than once



per year.  The frequency of occurrence of the second highest concentra-



tion can be expressed as a percentage by dividing two hours by the



number of hours in a year (i.e., 2 r 8,760 = 0.02284 percent).



6.3.5  Averaging Time Analysis



     A method which can be used to determine a maximum 8-hour average CO



concentration when only 1-hour average data is available is a mathemati-


                             33
cal model developed by Larsen   known as "Larsen's Transform".  Data



fitting  this model can be graphed as shown in Figure 6-4 which includes



the maximum, minimum, and frequency of equaling or exceeding specified



CO concentrations for averaging times ranging from one second to one



year.  The most useful and important part of the graph, however, is the



annual maximum line which can be used to determine the annual maximum 8-



hour average CO concentration from 1-hour average values.



6.3.6  Trend Analyses



     Carbon monoxide concentrations vary considerably from hour to hour,



day to day, season to season, and year to year.  These variations are



usually  not random but follow fairly predictable temporal  patterns



according to season of the year, day of the week, and hour of the day.



Predicted, long-term, statistical variations in CO concentrations are



referred to as trends.



     Carbon monoxide trends are best illustrated using graphs which can



show diurnal, daily, seasonal, or yearly CO concentration comparisons.



Examples of the different ways trends can be shown are illustrated later



in this  section.
                                      6-20

-------
                1.000
                 100 k-
o>
 I
           .
           «
          o
cc
I-
          o
          u
                  10
                  0.1
                                second

                                  1
                                                             AVERAGING TIME

                                                       minute,              hour                'day

                                                         5   1015  30   1   2   4   8 12   1    247
                                                               14
                                                              month

                                                         23   6  12
                                170.90
                                149.19
                                    mg/m-*
                                     ppm
                                                                    I    I  I  I"T
            56.3Q
            49.15
            34.73
            30.32
  M    II    f   I
23.31   18.93
20.35   16.53
        EXPECTED ANNUAL MAXIMUM CONG
10.02
 8.75
7.02
6.13
                             0.01
                                         1
                                                           I
                                                                                           GEO. MEAN FOR 1-hr. = 6.36 mg/m3 = 5.552 ppm
                                                                                           STANDARD GEOMETRIC DEVIATION = 1.56
                                                                                           87 percent OF HOURS HAVE DATA AVAILABLE
                                                                     I
                                                                                                                                           10,000
                                                                                                                                           1,000
                                                                                                                                          100
                                                                                                                                          10
                                                                                                                                        a
                                                                                                                                        a
                                                                                                                                                  O
                                                                                                                                       111
                                                                                                                                       u
                                                                                                                                       z
                                                                                                                                       o
                                                                                                                                       o
                                                                                                                                          0.1
                                                                      0.01
                          0.0001
                              0.001
0.01
0.1            1            10

    AVERAGING TIME, hours
                100
 1,000
                                                                                                                                      10,000
                    Figure 6-4. Concentration vs. averaging time and frequency for carbon monoxide from 12/1/63 to 12/1/68 at site 662, St. Louis.

-------
     Carbon monoxide concentrations also follow fairly predictable

spatial patterns.   Spatial distributions of CO concentrations can be

illustrated by the use of isopleth maps.  Isopleth CO concentration maps

can be prepared illustrating the spatial distribution of average CO

concentrations, maximum CO concentrations, typical CO values during a

particular time of day or season of year, or the CO concentration distri-

bution that typically occurs under specific meteorological conditions

(wind speed, wind direction, atmospheric stability).   Isopleth maps are

especially useful  for illustrating the size of the geographical area

affected by CO levels.  Examples of isopleth maps are illustrated in

Figures 6-5 and 6-6.

6.3.7  Special Analyses

     A useful analysis technique not previously presented is the

"pollution rose" as illustrated in Figure 6-7.   The pollution rose

presents the joint frequency distribution of wind direction versus

ambient CO concentration.  The pollution rose is very helpful in deter-
                                   i
mining the wind direction associated with the highest ambient CO concen-

trations and intuitively the location of sources of high CO emissions.

     Another analysis technique is the case analysis  which can be used

to characterize the meteorological and/or emission conditions associated

with observed CO concentrations.  For example,  in order to characterize

the meteorological conditions associated with the occurrence of high CO

levels, meteorological records can be evaluated for the days when highest

CO concentrations were observed concurrently at several monitoring sites

throughout an urban area.  The results of the analysis can then be used
                                      6-22

-------
24
         15
                                                                                  12
                                                                                                        12
                                            12
                 12
      Figure 6-5. Predicted 1-hour average ambient CO concentrations (mg/m3) in vicinity of I-85 in Atlanta, GA,for 1976.18

-------
MISSISSIPPI RIVER
            E-H.CRUMPBLVD
      Figure 6-6. Measured 8-hour average background CO concentrations in Memphis, TN.62
                                         6-24

-------
               NORTH
                                               10%
                 LEGEND
             CO CONC, mg/m:
     0-6.8
Figure 6-7. Pollution rose for St. Louis, MO.
                    6-25

-------
to develop a meteorological scenario for input to a mathematical model


for the purpose of modeling "worst case" CO concentrations.


6.4  URBAN LEVELS OF CARBON MONOXIDE


6.4.1  Comparison to NAAQS


     Measurements of CO in U. S. urban areas show that the NAAQS* for CO


is frequently violated.  In 1973, 153 of 212 CO monitoring stations


operated in the U. S. (i.e., 72 percent) reported violations of the 8-


hour NAAQS with 24 stations (i.e., 11 percent) exceeding the 1-hour


NAAQS.70  Of the 30 Air Quality Control Regions (AQCR's) which were


Priority I for CO in 1973, 26 reported at least 1 quarter's data and 25


exceeded the 8-hour standard.  Also, 34 AQCR's, classified Priority III


in 1973 which were not required to monitor CO, established monitors and


28 reported at least one site where the 8-hour NAAQS was exceeded.


Figure 6-8 shows a map prepared by the EPA   of the location of AQCR's


which observed violations of the NAAQS for CO in 1973.


     Since 1973, NAAQS violations have continued to occur, although the


percentage of total monitors reporting NAAQS violations have decreased.


In 1974, 211 out of 377 stations (i.e., 56 percent) reported violations


of the 8-hour NAAQS.    In 1975, 234 out of 434 monitors (i.e., 54 percent)

                               76
showed 8-hour NAAQS violations.    Of these, 111 sites measured CO


concentrations at least 50 percent greater than the NAAQS.  in 1977,


211 out of 456 monitors (i.e., 46 percent) showed 8-hour NAAQS violations.


Carbon monoxide concentrations exceeding the 1-hour NAAQS were observed
   *-The NAAQS (National Ambient Air Quality Standard) for CO is 10 mg/m3
                3
     and 40 mg/m  for 8-hour and 1-hour averagin
     not to be exceeded more than once per year.
           3
and 40 mg/m  for 8-hour and 1-hour averaging times, respectively,
                                      6-26

-------
 i
ro
                                                                                8-hour STANDARD EXCEEDED


                                                                                ALL REPORTED DATA BELOW THE 8-hour STANDARD


                                                                                NO DATA
                                             Figure 6-8. Status of carbon monoxide levels, 1973.70

-------
at only 27 locations (i.e., 6 percent) in 1975   and at only 11 locations



(i.e. , 2 percent) in 1977.80b



     Part of the reason so many NAAQS violations are observed is due to



the fact that most CO monitoring sites are located next to major streets



in urban areas.  While the measured concentrations are probably accurate,



the scale of representativeness of these sites is small such that the



number of people exposed to these CO levels may be relatively small.



6.4.2  Hourly Patterns



     Ambient CO concentrations may follow regular hourly patterns of



variation which result from nearby vehicular traffic activity and mete-



orological factors affecting the dispersion of the CO.  Three examples



are shown in Figures 6-9, 6-10, and 6-11 which Illustrate the annual



average and "worst case day" hourly CO curves based on 1977 data from CO


                                        42                  10
monitoring sites in Baltimore, Maryland,   Denver, Colorado,   and

                        CO

Los Angeles, California,   respectively.  (The "worst case day" 1s



defined herein as that day on which the annual maximum 8-hour average CO



concentration was observed.)  While the exact shape and magnitude of the



hourly CO curve for these communities is dependent to a large extent on



meteorological factors, two peaks corresponding with the morning and



evening "rush hour" traffic are evident 1n the figures.  For comparison,



an example of typical hourly variations in traffic volume 1s given 1n



Figure 6-12.  A third peak in CO concentration during the late evening/



early morning hours can also be noted in several of the figures.  This



peak is influenced by late night calm meteorological conditions.
                                      6-28

-------
E
I
to"
<
oc
o
o
u
o
u
36

34

32

30  -

28  -

26

24

22

20

18

16

14

12

10

 8

 6

 4

 2
          BALTIMORE
                   /
                                       I     I
                   I    I     I    I
                                                /,
                                                M

                     \
J
                                                    T
               T
  I     T
                                                                                        	 ANNUAL AVERAGE
                                                                                        	WORST CASE DAY
                                                                                                     \
      12   1
                               6
                              AM
9   10  11
                      12    1
                     NOON
 6
PM
10  11    12
                                                     TIME OF DAY
                       Figure 6-9. Hourly variations of ambient CO concentrations for Baltimore, MD.

-------
 i
w
o
                   34

                   32


                   30


                   28


                   26


                   24


                   22
«   20


 *  «

 O
 t  16
                Ul
                O
                   14
                8  12
                O
                o
                   10


                    8


                    6
        DENVER     I     I    I    I


            —"•— ANNUAL AVERAGE
       _   — — - WORST CASE DAY
                                                                                    A
                                                                                  /     \

                                                                                                               \
                                                                                                                I
                                                                                                               I
                                                                                                               I
                                                                                                              lU
                                                                                                             I    I    I     I
                     12
                                 6
                                AM
9  10   11   12    1
           NOON


    TIME OF DAY
                                                                                                    6
                                                                                                    PM
9  10   11  12
                                     Figure 6-10. Hourly variations of ambient CO concentrations for Denver, CO.

-------
                   36
                           LOS ANGELES  I    I     I    I     1    I     I     I    I     I    T
 I

CO
               O
               01
               o

               O
               o

               o
               o
34



32




30



28




26




24



22




20




18




16



 14




 12



 10




  8|



66



  4



  2
                            •       ANNUAL AVERAGE

                            	WORST CASE DAY
                                                    A
                                       X^x
                            I    II	I
                       12
                                   I     I    I     I    I     I    I     I    I    I     I    I
                              6

                             AM
10
 11   12   1

    NOON


TIME OF DAY
 6

PM
9   10   11  12
                                    Figure 6-11. Hourly variations of ambient CO concentrations for Los Angeles, CA.

-------
               1—I—I—I—I—I—[
cr>
 i
u>
ro
                   i    i     r
                                                  i—i—i—i    r~






                                                          •CBD


                                                    	CENTRAL CITY


                                                    	SUBURBS
                                                         I     I     i    I     I     I    I
                                                        I    I     I     1    I     I
           0
6
8
10  11   12
13
14  15   16   17   18   19   20   21  22   23   24
                                                              TIME, hours
                                                                                        oo
                                             Figure 6-12.  Hourly variations of traffic volume.

-------
     Carbon monoxide levels 1n most of the cities generally reach their
Initial dally maximum between 7-9 a.m., coincident with heavy morning
automobile traffic and prior to Inversion layer breakup.  The second
peak 1s usually reached 1n the late afternoon between 4-7 p.m.  The late
evening peak generally occurs between 10 p.m. and 12 midnight.  Although
the morning peak 1n CO concentrations 1s generally the highest, Figure 6-
10 Illustrates that the opposite cart occur.
6.4.3  Seasonal Patterns
     Ambient CO levels also follow seasonal patterns, which result
primarily from changes 1n meteorological factors.  Figures 6-13, 6-14,
and 6-15 show the seasonal arithmetic mean, maximum 8-hour and maximum
1-hour CO concentrations based on 1977 data for Baltimore,   Denver,
                co
and Los Angeles,   respectively.  These figures show the highest ambient
CO concentrations during the winter.
     In the winter, the tendency toward colder ambient temperatures
results 1n Increased production of CO emissions from cars, 1n addition
to CO emitted from other fuel burning sources.  Also, the more stable
atmospheric conditions and low wind speeds which occur during winter
result 1n decreased dispersion of CO emissions and contribute a substan-
tial part to the occurrence of high ground level CO concentrations.
6.4.4  Annual Patterns
     Annual trends of CO concentrations are presented 1n Figures 6-16
through 6-23 for Baltimore,41 Denver,10>64>n LOS Angeles,57'58'64
Chicago,70 Cincinnati,70 Philadelphia,70 St. Louis,70 and Washington, DC.70
Plotted are the highest 1-hour average, the highest 8-hour average, and
the annual arithmetic mean CO concentration observed each year.
                                      6-33

-------
CO
 cc
 H
 LU
 O
 O
 O
 O
 O
34
32
30
28
26
24
22
20
18
16
14
12
10
 8
 6
 4
          BALTIMORE
1-hr MAX
        •M
8-hr MAX __
SEASONAL,
  AVG
         WINTER SPRING SUMMER  FALL
Figure 6-13.  Seasonal variations of ambient CO
concentrations for Baltimore, MD.
                              42
                     6-34

-------
  o>
  E
 DC
 h-
 ui
 O
 o
 u
 o
 o
40
38
36
34
32
30
28
26
24
22
20
18
16
14
12
10
 8
 6
 4
 2
            1
DENVER

1-hrMAX
8-hr MAX
SEASONAL
AVERAGE
         WINTER SPRING SUMMER FALL
Figure 6-14. Seasonal variations of ambient CO
concentrations for Denver, CO.
                           10
                    6-35

-------
CO
 ^
  TO

 CO*
 z
 O
 <
 cc
 H
 LU
 O
 O
 O
 O
 O
40
38
36
34
32
30
28
26
24
22
20
18
16
14
12
10
 8
 6
 4
 2
                  LOS ANGELES
                  1-hr. MAX
                  8-hr. MAX
                  SEASONAL AVERAGE
        WINTER SPRING SUMMER  FALL
Figure 6-15. Seasonal variations of ambient CO
concentrations for Los Angeles, CA.
                               58
                     6-36

-------
.E

I
 *,
Z
O
I-

cc
I-
z
LU
O
z
O
O
O
O
    56



    48




    40



    32



    24




    16



     8
                               1     I      I     T
—   8 hr MAX
            68
                70
                                  72

                                 YEAR
                                            74
                                                76
Figure 6-16. Annual variations of ambient CO concentrations for
Baltimore, MD.
                                  6-37

-------
 at
 E
 cc
 I-
 z
 UJ
 o
 z
 o
 o
 o
 o
    100
     90
     80
     70
     60
     50
40
30
     20
     10
                                                    1     T
      MAX. 1-hr.
MAX. 8-hr.
         ARITH.MEAN
                I	I
                                               I	I
          62     64    66     68     70    72    74    76     78



                                YEAR




Figure 6-17.  Annual variations of ambient CO concentrations for

Denver, CO.
                              6-38

-------
 z
    80
    70
    60
    50
    40
z
uu
O
z

o   30

O
o
    20
    10
      - MAX. 1-
         MAX. 8-hr
      — ARITH.MEAN
              68
                      70
                                I
 72



YEAR
74
76
78
Figure 6-18. Annual variations of ambient CO concentrations for Los

Angeles, CA, SAROAD Site No. 053900001.
                             6-39

-------
 I
cc
I-

LU
O
z
o
o
o
o
    70
     60
    50
    40
    30
    20
         62
             ARITH.MEAN


                I      I
              64
66
68
70
                              YEAR
72
74
76
78
Figure 6-19. Annual variations of ambient CO concentration for

Chicago, IL, SAROAD Site No. 141220002 (former CAMP station).
                               6-40

-------
 z
 o
    40
 f  30
    20
 1-
 Z
 LU
 O


 8  10

 O
 o
         MAX. 1-
-MAX. 1-
       ARITH. MEAN

          I	I
         62
          64
66
68
70
72
74
                              YEAR
Figure 6-20. Annual variations of ambient CO concentrations for
Cincinnati, OH, SAROAD Site No. 361220003 (former CAMP station
discontinued in 1973).
                            6-41

-------
CO
oc
h-
Z
UJ
o
z

8
O
O
    70
    60
    50
 2  40
    30
    20
    10
        MAX. 1-hr.
         MAX. 8-hr.
        ARITH.MEAN
        62
              64
66    68
 70    72


YEAR
74
76
78
Figure 6-21.  Annual variations of ambient CO concentrations for
Philadelphia, PA, SAROAD Site No. 397140002 (former CAMP

station).
                              6-42

-------
CO



 £
 LU
 O

 o
 0

 o
 o
    40
    30
 tt  20
 H-
    10
          MAX. 1-hr.
          MAX. 8-hr.
       ARITH.MEAN'
          62
                  64
66
68
70
72
74
                               YEAR
Figure 6-22.  Annual variations of ambient CO concentrations for

St. Louis, MO, SAROAD Site No. 264280002 (former CAMP station

discontinued in 1973).
                               6-43

-------
 O)

 E
cc
h-
z
UJ
o
2
O
O

o
o
     70
    60
    50
 1  40
    30
    20
    10
MAX. 1-hr.
MAX. 8-hr.



ARITH. MEAN
                                i     i      i      i      r
                                SITE MOVED TO NEW LOCATION
         62
     64
                   66
68
70
72
74
76
78
                              YEAR
Figure 6-23. Annual variations of ambient CO concentrations for

Washington, DC, SAROAD Site No. 090020002 moved in 1969 and

redesignated No. 090020003 (former CAMP station).
                             6-44

-------
     For Baltimore County, monitoring data from 1976 shows a factor of
3.4 decrease in annual maximum 1-hour average CO concentrations and a
similar decrease (i.e., a factor of 3.1) in annual maximum 8-hour average
CO concentrations compared with 1967 levels.
     For Denver, a 53 percent and 32 percent decrease in annual maximum
1-hour and 8-hour average CO concentrations, respectively, has been
observed from 1968 to 1977.  The annual arithmetic mean CO concentration
has decreased 44 percent from 1968 to 1977.  The number of observed
NAAQS violations has also decreased in Denver over a 10-year period.
Eighty-three violations of the 8-hour standard were observed in 1968
with a peak of 153 violations observed in 1972, then decreased to 48
observed violations in 1977.  The number of violations of the 1-hour
standard has decreased from six observations in 1968 to one observation
in 1977.
     For Los Angeles, a 50 percent and 24 percent decrease in annual
maximum 1-hour and 8-hour average CO concentrations, respectively, has
been observed from 1968 to 1978.  A 45 percent decrease in the annual
arithmetic mean CO concentration has been observed from 1968 to 1978.
Although a significant reduction in ambient CO concentrations has been
observed in Los Angeles, the number of observed NAAQS violations still
remains relatively high.  Sixty-four violations of the 8-hour standard
were observed in 1977 compared with 172 observed violations in 1968.
     A general trend  of decreasing ambient  CO levels is evident in most
of the curves presented.  This trend toward lower ambient CO concentra-
tions is presumably due to the lower CO emissions of later model
automobiles which incorporate air pollution controls.  The CO emissions,
although being maintained at a relatively  constant level, are decreasing
in urban areas.
                                      6-45

-------
     A1r monitoring results have been presented only from selected sites



1n several major U. S.  cities.  These sites are generally those located



close to major highways and thus measure some of the highest CO



concentrations; however, measurements at the sites are not necessarily



representative of CO concentrations 1n these cities.  Monitoring sites



in the same cities located 100-200 meters from any highway would be



expected to record much lower concentrations.  More information on CO



levels measured In, U. S. cities 1s published annually in EPA's Air



Quality Trends Reports.67'68'70'74'76'79'80"



6.5  SPECIAL CARBON MONOXIDE EXPOSURE SITUATIONS



     There are a number of circumstances where people may be exposed to



unusually high concentrations of CO.  Some of these result from the



operation of automobiles 1n areas which are poorly ventilated.  These



exposure situations include highway tunnels, urban street canyons, and



underground parking garages.  Other high CO exposure situations may



occur where auto emissions are unusually high (due to large traffic



volumes and congested conditions) such as near large arterial inter-



sections, freeway  toll booths, shopping centers, sports stadiums, and



roadway repair and construction sites.  The commuter may also be exposed



to high CO concentrations either within his car (especially 1f smoking)



or from the ambient air.  Exposure to CO emitted by cars on city streets



is a special concern of bicyclists.



     Some occupations require working on or very close to automobile



traffic for long periods of time during the work day which may result 1n



unusually high exposures to CO.  These occupations include street repair
                                      6-46

-------
crews, street cleaners, street vendors, delivery men, toll collectors,

garage attendants, police, and taxi and bus drivers.  There are other

occupations where exposure to CO is due to sources other than automobiles.

Those include fire fighters, certain airport workers, and some miners

and foundry workers.

6.5.1  Variations with Type of Vehicle Traffic

     Ambient CO concentrations near city streets were reported as high
          3                                         3
as 57 mg/m  (49.6 ppm), 1-hour average and 41.4 mg/m  (36.0 ppm), 8-hour

average for the "worst case" New York City site in 1975.  Similar
                                                               3
measurements in Los Angeles showed CO concentrations of 60 mg/m
                                         3                            43
(52.2 ppm), 1-hour average, and 49.7 mg/m  (42.6 ppm), 8-hour average.

These measurements represent some of the highest ambient concentrations

of CO reported in the United States near open city streets.

     Concentrations of CO in highway tunnels have been reported by
                                    4
several investigators.  Ayres et al.  have reported 30-day average CO
                           3
concentrations of 72.5 mg/m  (63 ppm) measured at the Queens Midtown
                                                   3
Tunnel  in New York and a 1-hour maximum of 250 mg/m  (217 ppm).

Measurements at the Sumner Tunnel in Boston, Massachusetts show 1-hour
                                               3
average CO concentrations as high as 145.2 mg/m  (126.3 ppm) with a 24-
                         3                            45
hour maximum of 58.4 mg/m  (50.8 ppm).  Miranda et al.   reported that
                                           3
many tunnels usually operate below 115 mg/m  (100 ppm) CO, employing
                                                               3
emergency ventilating fans whenever CO levels exceed 287.5 mg/m  (250 ppm)
                  oc
     Wright et al.   measured CO concentrations in underground parking
                                                    3
garages.  They found CO levels in excess of 115 mg/m  (100 ppm) in

enclosed, unventilated garages.  Similar measurements taken in a
                                       6-47

-------
well-ventilated underground parking facility showed maximum CO

                           3
concentrations of 49.5 mg/m  (43 ppm).

                                             49
     In a study conducted by Patterson et al.   CO measurements were


made in the vicinity of Liberty Tree Mall, a regional shopping center in


the Boston area.  The study was conducted for two weeks prior to


Christmas of 1973.  The maximum 1-hour average concentration measured

             3                                                     3
was 35.2 mg/m  (30.6 ppm); the maximum 8-hour average was 16.3 mg/m


(14.2 ppm).

                                                 5
     A  similar study was conducted by Bach et al.  at two sports stadia:


Three Rivers Stadium 1n Pittsburgh, Pennsylvania and Atlanta Stadium


in  Atlanta, Georgia.  Measurements were made during both day and night


baseball games 1n June and July, 1973.  The maximum 1-hour average CO

                                    3
concentration measured was 28.8 mg/m  (25 ppm); the 8-hour maximum was

        3
9.4 mg/m   (8.2 ppm).


     In order to determine the CO exposure of bicyclists, Kleiner and

        30
Spengler   conducted a study in Boston during the summer of 1974.


As  expected, CO exposures of bicyclists on city streets were a function


of  traffic volume,  street configuration, proximity of traffic, and

                                                                      3
ventilation.  Typical Summer exposures were between 12.7 and 17.3 mg/m


(11 and 15 ppm) for trips ranging from 10 to 45 minutes.  In no case did

                                             3
the trip-averaged exposure approach 40.3 mg/m  (35 ppm).


6.5.2   Car Passenger Exposure to Carbon Monoxide


     Carbon monoxide concentrations have also been measured Inside

                    o
automobiles.  Chaney  measured CO concentrations within an automobile
                                       6-48

-------
traveling on the Dan Ryan Expressway (1-94) 1n Chicago, and on the


San Diego Freeway (1-405) 1n Los Angeles and found that CO levels varied


with traffic speed.  According to Chaney "when the traffic slowed to

                                                               3
10 mph (16 kph) the CO concentration usually exceeded 17.3 mg/m  (15 ppm);

                                                                   o
when 1t halted completely, the CO concentration was about 51.8 mg/m


(45 ppm)".  Chaney also observed variations 1n pollution concentration


Inside his automobile depending on the type and age of vehicle he was


following.  Heavily-loaded vehicles produced the highest results.  While


following a truck over the Sierra Nevada mountains, Chaney recorded CO

                                      3
concentrations which reached 57.5 mg/m  (50 ppm) on the steepest grade

                           O                                        QC
and remained over 28.8 mg/m  (25 ppm) for 30 minutes.  Wright et al.

                                           3
have reported CO concentrations of 104 mg/m  (90 ppm) inside an automobile


due primarily to CO from passengers' cigarette smoke.


6.5.3  Occupational Exposure
       I
                                                                     ftfi
     Certain occupations necessitate exposure to CO.  Xlntaras et al.


have reported CO exposures of six toll collectors working at 1-65 in


Louisville, Kentucky.  The maximum 8-hour average concentration measured

             3
was 65.6 mg/m  (57 ppm).  Over the 12 days of the study, the average 8-

                           3
hour exposure was 26.2 mg/m  (22.8 ppm).
                                                  •}

     Measurements of CO concentrations in foundry air have been made by

                        83
Virtamo and Tossavalnen.    They found that iron cupola exhaust gases


may contain 20 to 30 percent CO.  Forty-six measurements of CO concen-

                                                                    3
tration 1n the vicinity of the cupolas showed an average of 276 mg/m

                                                  3
(240 ppm).  They also measured an average 127 mg/m  (110 ppm) CO in the

                                                     3
casting area of foundries (909 samples) and 97.8 mg/m  (85 ppm) in the
                                       6-49

-------
breathing zone (61 samples) of foundry workers.  Similar measurements in

                                        3

steel foundries showed less than 23 mg/m  (20 ppm) of CO in areas



around electric furnaces.  Measurements in the melting and casting areas

                                          3
of copper alloy foundries averaged 23 mg/m  (20 ppm) of CO.


            54
     Rodgers   measured CO concentrations in phosphate and copper mine



environments resulting from the use of explosives.  Carbon monoxide


                                3
concentrations exceeded 173 mg/m  (150 ppm) for 45 minutes and exceeded


       3
58 mg/m  (50 ppm) for 110 minutes during shot firing of nitroglycerin



explosives within the mine.  Ammonium-nltrate-oil and water gel type



explosives tended to produce less CO than equal weights of nitroglycerin



explosives.



     Fire fighters can be exposed to very high concentrations of CO due


                                 35                       51
to smoke inhalation.  Loke et al.   and Radford and Levine   both report



maximum carboxyhemoglobin (COHb) levels of 10 percent to 14 percent in



the  bloodstream of fire fighters after a fire.  Carbon monoxide concen-



trations were  not reported.



6.5.4  Indoor  Carbon Monoxide Exposure



     Indoor levels of CO have been studied by the General Electric



Company   for  two buildings in New York City-  One was a high-rise



apartment building straddling the Trans Manhattan Expressway; the other,



a high-rise office building located adjacent to a midtown Manhattan



street canyon.  The study showed that indoor CO levels were directly



related to nearby outdoor CO levels.  While indoor concentrations



"lagged behind" (in time) outdoor levels there was "no significant



difference in  CO levels along the outside walls and inside the two
                                      6-50

-------
structures".  The G. E. study typically reported Indoor and outdoor CO


concentrations of from 4.6 to 11.5 ra,g/m3 (4 to 10 ppm).

                      55
     Shaplowsky et al.   have reported the results of CO levels Inside


1,820 houses throughout the United States.  Their results showed that


16.8 percent had levels above 11.5 mg/m  (10 ppm).  In a similar study

                             CO
conducted by Rench and Savage   in 80 households 1n Fort Collins,


Colorado, concentrations 1n homes were recorded 1n the kitchen and


family room around the dinner hour.  Their measurements showed over

                                                                        3
6 percent of the households had CO concentrations greater than 11.5 mg/m

                                                     3
(10 ppm).  The mean CO levels measured were 3.55 mg/m  (3.09 ppm) 1n

                      3
kitchens and 2.01 mg/m  (1.75 ppm) in family rooms.

                                  87
     In a study conducted by Yocum   CO measurements were made inside


domestic buildings.  Yocum found that indoor CO levels increased more


slowly than outdoor levels, but, once built up, indoor levels remained


higher for a longer period of time.  Thus, domestic premises have a


tendency to entrap gaseous pollutants.  Yocum measured typical CO

                                   3
concentrations of 0.87 to 6.92 mg/m  (0.76 to 6.02 ppm).


     The effect of smoking cigarettes on indoor CO levels has been

                               c.
investigated by Bridge and Corn  who measured CO during two experimental

                        3          3
"parties".  In one 145 m  (5120 ft. ) room containing 50 people, 25


people smoked 50 cigarettes and seven cigars in 1 1/2 hours.  With a

                                                                  3
room air exchange rate of seven times per hour, CO averaged 8 mg/m

                                               3          3
(7 ppm).  During a second experiment in a 106 m  (3750 ft. ) room


containing 73 people, 36 people smoked 63 cigarettes and 10 cigars in

                                                      3
1 1/2 hours producing an average CO content of 10 mg/m  (9 ppm).
                                      6-51

-------
          28                                       ^
     Hoegg   conducted experiments in a closed 25 m  chamber.  He found


that CO levels increased with the number of cigarettes smoked.

                                    3
Concentrations ranged from 11.5 mg/m  (10 ppm) for four cigarettes to

       3
80 mg/m  (69.8 ppm) for 24 cigarettes.

                         2
     Anderson and Dalhamn  measured CO concentrations due to smoking in

                    3
a medium sized (80 m ) meeting room.  Fifty cigarettes were smoked in

                                                                       3
two hours.  With six air changes per hour, initial levels were 2.3 mg/m

                                                      3
(2 ppm) and average peaks during smoking were 6.9 mg/m  (6 ppm).

               22
     In Harke's   experiments, 21 persons smoked two cigarettes each in

                                                            3
enclosed office rooms and within 16 to 18 minutes, in a 57 m  room, they

                  3
produced 56.4 mg/m  (49 ppm) of CO.  Ventilating the room decreased


these concentrations by 80 percent.  In the case of one person smoking

                                     3
11 cigarettes in five hours in a 30 m  room, the CO concentration was

                   3
less than 11.5 mg/m  (10 ppm).


     Smoking in automobiles can produce significant CO concentrations.

            23~27
Harke et al.      conducted experiments where smoking was done in a car


within a wind tunnel.  During the experiment, time spent smoking was


varied, as was wind speed and ventilation.  At 0 km/hr, with full

                                         3
ventilation, CO averaged 9.2 to 11.5 mg/m  (8 to 10 ppm); when six


cigarettes were smoked intermittently, CO reached a maximum concentration

            3
of 34.5 mg/m  (30 ppm).  When cigarettes were smoked continuously, one

                                                           3
after the other, final CO levels were registered at 92 mg/m  (80 ppm)


with no wind or ventilation factor.  With wind and ventilation, however,

                              3
CO remained at 5.8 to 6.9 mg/m  (5 to 6 ppm), with no increases observed.
                                      6-52

-------
In all cases CO levels returned to base levels, even with no ventilation,


within a few minutes after smoking stopped.


     Srch   measured CO concentrations produced by cigarettes in a


closed automobile with no ventilation.  The test car was parked in an


unventilated garage while two people smoked five cigarettes each in one

                                              3
hour.  Carbon monoxide levels reached 104 mg/m  (90 ppm) in that time.


Carboxyhemoglobin in smokers rose from 5 to 10 percent and from 2 to


5 percent  in the two nonsmokers present.


     The U. S. Department of Transportation in 1973 conducted a study of


cigarette-caused pollution on intercity buses.  Inside a stationary


Greyhound  bus with the engine off, vents open, and blower on, cigarettes


were allowed to burn in the ashtrays.  Tests conducted ranged from the


"worst" case, where it was assumed that all 43 passengers smoked half


the  time,  to the "realistic" case, where only the last 20 percent of the


seats were allotted to smokers.  After 30 minutes in the worst case,

                          3
CO stabilized at 38.0 mg/m  (33 ppm), and in the realistic case, CO

                       3
stabilized at 20.7 mg/m  (18 ppm), after 43 minutes, with the outside

               3
level 15.1 mg/m  (13 ppm).


     Many  other studies have been performed to determine indoor exposure


levels of  pollutants.  A summary of  results of many experiments has been


prepared by Sterling and Kobayashi   and by the EPA.


6.6   EFFECTS OF METEOROLOGY AND TOPOGRAPHY


     Meteorology governs the transport and dispersion of CO emissions in


the  atmosphere and thus has a strong influence on the ground level CO


concentrations detected at receptor  points downwind of the emission
                                       6-53

-------
sources.   Meteorological variables that determine CO transport xand



dispersion patterns include wind speed, wind direction, atmospheric



stability, vertical mixing height, and ambient temperature.



     Wind speed and direction influence the horizontal dispersion of CO



emissions.  Low wind speeds provide little dilution air, allowing CO



emissions to build up, resulting in higher CO concentrations.  Conversely,



high wind speeds aid in the dispersion of CO emissions by increasing the



amount of dilution which takes place, thus decreasing CO concentrations.



Wind direction determines the direction of horizontal transport of CO



emissions and consequently the impact that CO emissions from one area



will have on air quality in another area.   For wind directions crossing



an urban area, an accumulation of CO emissions will occur in the downwind



direction, such that mesoscale (1-10 km) CO concentrations will be



highest at the downwind edge of the urban area.   In the microscale



regime (1-100 m), for a highway line source, wind directions nearly



parallel to the highway will allow for an accumulation of CO emissions



in the downwind direction, resulting in CO concentrations higher than



would be expected for perpendicular winds under the same conditions.



     In addition to transporting pollutants, winds produce turbulence in



the atmosphere which enhances the mixing and dispersion of pollutants in



the air.  Turbulence is the result of both mechanical forces and thermal



forces in the atmosphere.



     The effect of surface roughness (i.e., mountains, buildings, etc.)



on the wind speed profile over several types of topographic features is



illustrated in Figure 6-24.  With increased surface roughness, either
                                      6-54

-------

                       600
                        500
                        400
                        300
                        200
en

01
01
                        100
                                                URBAN AREA



                                              GRADIENT WIND
SUBURBS
LEVEL COUNTRY
                                                                                   0         5         10



                                                                                       WIND SPEED, m/sec
                                                      10
                                                       Figure 6-24. Effect of terrain roughness on the wind speed profile,

-------
natural or man-made, the wind speed profile is decreased and the depth


of the affected layer is increased.  The net effect of increased surface


roughness over an urban area is to induce mechanical turbulence which


aids in the dispersion of CO emissions.
                                                 y

     Radiation and thermal properties of topographic features influence


the heating and cooling of the atmosphere near the ground surface.   The


most notable of these effects is the urban "heat island" effect.  Heat


sources, including the asphalt and concrete associated with an urban


area, tend to radiate heat, causing a "heat island" compared to the


cooler surrounding terrain.  The buoyant effect of warmer air over the


city tends to induce thermal turbulence (i.e., more unstable atmospheric


conditions) which tend to aid in the dispersion of CO emissions, thus


lowering ambient CO concentrations.


     Drainage winds, such as sea-land breezes, lake-land breezes, or


mountain-valley winds are caused by the differential heating of


topographic forms.  Drainage winds which affect the net transport of CO


emissions may deviate from the prevailing wind direction.  These winds


generally flow in one direction during the day, then in the opposite


direction at night.  As a result, an urban area can experience "blow-


back" of CO emissions emitted during the day resulting in higher CO


concentrations at night.  Also, the boundary region of the drainage


winds sometimes causes the air mass to remain nearly stationary, or


oscillate back and forth for periods up to several  hours, and can be the


site of nearly calm conditions or varying winds.  This results in the


slow net transport of CO emissions, allowing them to accumulate, and


thus resulting in higher ambient CO concentrations.
                                      6-56

-------
     Vertical mixing height affects the total ventilation capacity of
the atmosphere.  When the temperature-altitude relationship 1s reversed
from normal, the resulting Increase 1n temperature with Increase 1n
height produces an Inversion or Inversion I1d which limits vertical
mixing, and thus limits the dilution capacity of the atmosphere.
     An Important form of Inversion for CO dispersion 1s the surface or
radiation Inversion.  It usually occurs at night with light winds and
clear skies, when the loss of heat by long-wave radiation from the
ground surface cools the surface and subsequently the air adjacent to
It.  The surface inversion usually persists for hours and because 1t
typifies stable atmospheric conditions, 1t tends to result 1n high
mlcroscale and mesoscale CO concentrations.  With the proper relative
humidity, these same conditions will lead to the formation of radiation
fog.  The presence of early morning fog 1s often associated with a
surface-based  temperature Inversion.
     Another type of Inversion 1s the subsidence Inversion.  It Is
caused by a gradual descent of air aloft, accompanied by an Increase 1n
pressure which results 1n an adlabatlc warming of the descending layer.
The  resulting  subsidence Inversion 1s Illustrated 1n Figure 6-25 where
the  temperature decreases with height, and then 1s capped by a subsidence
inversion layer, above which there 1s a normal decrease of temperature
with height.   The subsidence inversion usually persists on the order of
days and tends to contribute to high urban background CO concentrations.
The  subsidence inversion is usually more persistent during the summer
and  fall months.
                                      6-57

-------
   1000
 *

I
CD
    500
rn    IY~I   i    i    i    i    r
                                              in   r
                         2nd MIXING LAYER
                                     INVERSION "LID'
                                     1st MIXING LAYER   —
            II    11    1    1   I   \   I
       0                  10                 20

                         TEMPERATURE, °C


  Figure 6-25. Schematic representation of an elevated inversion.
                            6-58

-------
     The shape of typical plots of hourly CO concentrations (See Figures
6-9, 6-10, and 6-11) can be attributed 1n large part to the effect of
changing wind speeds, atmospheric stability and inversion height during
the course of a day.  Figure 6-26 shows the average hourly wind speed
                                                            63
and Inversion height occurring in Los Angeles during Summer.    The
higher wind speeds and inversion height during early afternoon are
typical throughout the continental United States and play a significant
role 1n lowering urban CO concentrations at midday.  Figure 6-26 shows
that traffic volumes, and subsequently CO emissions from cars, would
still be expected to be high at this time of day.  Around midnight, when
traffic volumes are relatively low, the effect of low wind speeds and
low Inversion heights tend to cause CO concentrations to increase.  Many
monitoring stations 1n the United States observe these relatively high
CO concentrations late at night.
     In addition to transport and dispersion effects, ambient surface
temperature also has a unique effect on the production rate of CO
emissions from automobiles.  Using a variety of automobiles tested at
artificially-controlled ambient temperatures of 20°, 50°, 75°, and
110°F, the EPA   found that lowest CO emissions were produced at 75°F.
However, colder temperatures seem to Increase the emission rate of CO
from automobiles resulting in higher ambient CO concentrations.  Warmer
temperatures tend to minimize the emission rate of CO from automobiles
resulting in lower ambient CO concentrations.
                                      6-59

-------
    10
            WIND SPEED
                           INVERSION HEIGHT
a
E

Q
ui
UJ
a.
CO
O
                                                                                                                     20
                                                                                                                         CM
                                                                                                                          O
                                             I
                                             iu
                                             X
                                                                                                                     15
                                                     12
18
24
                                                          TIME, hours
                   Figure 6-26.  Hourly variations in inversions height and wind speed for Los Angeles in summer.

-------
6.7  CARBON MONOXIDE DISPERSION MODELS

     A dispersion model relates pollutant emissions to ambient air

quality by providing a mathematical description of the transport,

dispersion, and chemical transformations that occur in the atmosphere.

This ability to relate source emissions to receptor air quality is very

important to air quality maintenance planning and environmental impact

assessment.

     Dispersion models vary in complexity from the simple empirical or

statistical relationships to sophisticated multi-source models that

describe the transport and dispersion of CO throughout an urban area.

For estimates of ambient CO concentrations, a line source model is needed
   t,
to estimate the CO levels near a single source or group of sources and

an area source model is needed to estimate the background CO levels due to

other  sources.  The types of models used, therefore, will depend mainly

on the source configuration to be modeled (i.e., area, line, or point

sources).

     Model input data consist of parameters such as traffic volume,

vehicle speed, truck mix, and vehicle age (needed to estimate emissions),
    ?
and wind speed and direction, atmospheric stability class, source charac-

teristics  such as road location, road width, number of lanes, median

width, and receptor location, etc.  Typically, model output consists of

tabulated  results of input data and predicted CO concentrations.  Some

models can provide computer plots of results and isopleth maps showing

the calculated spatial variation in CO levels.
                                      6-61

-------
                       CQ
     The rollback model   1s a simple modeling technique which assumes a


linear relationship between ambient air quality and area pollutant


emissions.   The use of rollback requires air monitoring data and emission


Inventories.  Its main use has been to calculate the percent reduction


of pollutant emissions needed to achieve the ambient air quality standard.


It has also been used to predict future ambient pollutant concentrations


by factoring air monitoring data by a ratio of projected future pollutant


emissions to base year pollutant emissions.  Rollback is widely used


because it  is simple and easily understood.  In order to use the rollback


method, ambient air monitoring is required to establish existing CO


levels.  For those areas without available monitoring data, an alternate


modeling scheme would be necessary.  Also, the rollback method incor-


porates the assumption that an overall proportional reduction of emissions


in the area is required to meet the ambient air quality standard when,


in some cases, a reduction in emissions at a few specific sources may be


sufficient  to meet the standards.  Finally, the model provides little or


no spatial  resolution of ambient pollutant concentrations.


     More sophisticated techniques for modeling background CO concen-

                                         90 91             37
trations include the Hanna-Gifford model,  '   and APRAC-2.    In the


Hanna-Gifford model, area source emissions are assigned to grid squares


where it is assumed that the area source strength is uniform across each


square.  Gifford's "reciprocal plume" concept is employed in order to


estimate the surface concentrations due to area sources upwind of the


receptor grid.  The vertical distribution of the pollutant is assumed to
                                      6-62

-------
be Gaussian.  The spatial resolution of the model 1s on the order of



kilometers.  The authors of the model feel that 1t performs nearly as



well as much more complex models that require the use of digital computers.



Depending on the model application, correlations between predicted and


                                                           19
measured pollutant concentrations ranging from 0.60 to 0.95   have been



found.


                                 37
     The APRAC-2 dispersion model   uses a number of area segments



spaced at logarithmic upwind intervals from a receptor point as shown in



Figure 6-27.  This area segment scheme overlaps the coded traffic network



from which  traffic links and portions of links falling within each area



segment are identified.  The emissions from each individual link are



then calculated and accumulated to determine the average emission rate



for each of the nine area segments.  Background CO concentrations are



calculated  from two basically different formulations.  For sources near



the receptor, a-Gaussian model is used.  A simple "box" model is used



under limited vertical mixing conditions, at the point of restricted



vertical dispersion.  The spatial resolution of the model is on the



order of tenths of kilometers.



     The APRAC-2 model also provides a choice of two special models for



calculating CO concentrations from nearby highway sources:  the street



canyon model and the intersection model.  The street canyon model is

                        -in                             o/r

based on work by Georgli   and the San Jose experiment.    These studies



showed that because of lower wind speeds and a general helical circulation,



higher CO concentrations on the leeward side of the street result due to



the reverse flow component at ground level.  The intersection model
                                      6-63

-------
                    16km
 i
en
                                                                                                       RECEPTOR
                                                                                                       POINT
                                                 EXPANDED VIEW OF
                                                 ANNULAR SEGMENTS
                                                 WITHIN 1 km OF
                                                 RECEPTOR
62
    RECEPTOR
    POINT
                          Figure 6-27. Area segment scheme for spatial portioning of emissions.

-------
predicts CO concentrations In the vicinity of an Intersection by
combining a traffic model, a modal emissions model*, and a  line source
dispersion model.  The line source model 1s based on an Integrated point
source technique.
     Field experiments were performed 1n downtown St.  Louis  1n 1971 to
                                               89
evaluate the performance of the APRAC-1A model.    Carbon monoxide
concentrations were calculated at four locations within street canyons,
and two at roof  level.  These calculations were compared to  about 600
hour-average observations for each location.  The observed concentrations
                                                                    3
of CO were simulated with root-mean-square errors of 3.5 to  4.6 mg/m
(3 to 4 ppm).  Median and 90-percentile concentrations were  specified
                      3              89
within 2:3 to 3.5 mg/m  (2 to 3 ppm).
     The most widely used line source dispersion models are  based on the
                                      89
Gaussian plume equations, namely HIWAY  --developed and distributed by
                                                 ~29 84
the Environmental Protection Agency—and CALINE-2  *   —developed by the
California Department of Transportation and distributed by the Federal
Highway Administration.  The HIWAY model uses an Integrated  Gaussian
point source equation to calculate CO concentrations near a  highway line
source.  The model approximates a Vine source by a finite number of
point sources of emission strength equal to the total  line  source
emission strength divided by the number of sources used to  simulate the
Hne.  CALINE-2  uses an Integrated Gaussian point source equation for
the "pure" parallel wind case (I.e., 0° with respect to the  highway) and
                      97
    *-Kunselman  et  al.    have  developed  a model which  can  be  used  to
      describe air  pollution emissions from  automobiles  as a  function  of
      operating  mode  (I.e., steady-state, acceleration,  and deceleration).
                                       6-65

-------
a Gaussian line source equation for the "pure" crosswlnd case (I.e., 90°


with respect to the highway).  For those wind directions which are


neither 0  nor 90  with respect to the highway, the model uses a


trigonometric function to weight the parallel and crosswind terms.


These line source models provide detailed spatial resolution between


0 and 300 meters from the highway.


     In addition to the mathematical differences between the two models,


HIWAY uses a virtual source correction providing an initial dispersion


height of 1.5 meters while CALINE-2 assumes initial dispersion from a


theoretical mechanical "mixing cell" at a height of 4 meters.  The HIWAY


model also uses dispersion coefficients that differ from the coefficients


used by the CALINE-2 model.


     A comparison of HIWAY and CALINE-2 model predictions is presented


in Figures 6-28 and 6-29 for crosswind and parallel wind predictions,

             47
respectively.    Based on these model predictions, ambient concentrations


near highways tend to be greatest at the roadside edge, decreasing with


distance from the highway:  typically, concentrations 300 meters from


the highway may be only 20 percent of roadside edge concentrations.

           47
Noll et al.  ^flnd, from a comparison of predicted and measured concen-


trations, that HIWAY and CALINE-2 overestimate concentrations for


parallel wind conditions and underestimate concentrations for oblique

                                      47
and crosswind conditions.  Noll et al.   report typical correlation


coefficients for the models ranging from 0.5 to 0.85.  Higher correla-


tions have been reported but for small sample sizes (i.e., less than 20).
                                      6-66

-------
 O  0.2
 LLI
 O
 O
 O

 I
 2!
 O
 01
 N L
 cc ;
 O',
 O
                                            EPA HI WAY
                                            CALINE 2
     0.02 -
     0.01
                       100
150
200
250
300
               X, NORMAL DISTANCE FROM ROAD EDGE, meters

Figure 6-28.  Normalized concentrations versus normal distance from the
road edge for perpendicular wind conditions for B and E atmospheric
stability category.
                               6-67

-------
      4.0
      3.0


      2.0
                                    EPA HIWAY
g
*t
DNCENTR>
U
1-
z

D
i
•wJ
_J
O
O.
O
UJ :
N ;
	 1 i
NORMAI
O '
3
U






1.0 '^
0.8
0.6
0.5
0.4
A
R*
0.3 h\- \\
P\ E\\
0.2



0.1
0.08

0.06
0.05
0.04

0.03

0.02


0/*1
H v
M V
\\ \\
\\ \

"V \

:\\
XNk\
x\A
Xjs\
>\
\ ^..
\ v\
i i \ i\
0 50 100 150
r
                                      200      250
                                      	|r

        X, NORMAL DISTANCE FROM ROAD EDGE, meters

Figure 6-29.  Normalized concentration versus normal
distance to the road edge for parallel wind conditions
for B and E atmospheric stability category.
                           6-68

-------
     Other line source modeling techniques Include the numerical modeling



approach and turbulent wake theory approach.   Numerical models include


                          52        12         56               40
those proposed by Ragland,   Danard,   Sklarew,   and Maldonado.


                                                           14
Turbulent wake theory models Include those proposed by Fay.    Some



other Gaussian and pseudo-Gaussian models have been developed and tested

                                     9
for use on highways by General Motors  and by the Virginia Highway and



Transportation Research Council.
                                      6-69

-------
                                 BIBLIOGRAPHY

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-------
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                                   6-71

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                                   6-72

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43.  McMullen, T. B.  Interpreting  the  eight-hour National  Ambient Air Quality
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     36:569-573, 1974.
                                    6-73

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56.   Sklarew, R. C., A. J. Fabrick, and J. E. Prager.  A Particle-In-Cell
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                                                                           ^
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64.   Office of Air Quality Planning and Standards.  Air Quality Data - 1968
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64b. Office Air Quality Planning and Standards.  Air Quality Data - 1970
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64c. Office of Air Quality Planning and Standards.  Air Quality Data - 1971
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64d. Office of Air Quality Planning and Standards.  Air Data - 1972 Annual
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                                   6-74

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64f. Office of Air Quality Planning and Standards.  Air Quality Data  -  1974
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                                    6-75

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76.   Office of Air Quality Planning and Standards.  National Air Quality and
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                                   6-76

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88.
89.
                    .  I. Larsen.  Calculating air quality and its control
                    ol Assoc. 15:565-572, 1965.
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Agency, Research Triangle Park, NC, February 1977.
                                    6-77

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                   7.   THE GLOBAL CYCLE OF CARBON MONOXIDE
     Although many studies in the last decade have been devoted to the



identification and quantification of the various sources and sinks of



carbon monoxide (CO) in the global atmospheric equation, a wide range of



uncertainty still exists about the magnitude of many of the terms which



compose the global CO budget.  The fundamental question centers around



the natural vs. anthropogenic origins of CO in the atmosphere.   Research



efforts in the late 1970's suggest that human activities have signifi-
                                              i


cantly altered the background concentration of CO, especially in the



Northern Hemisphere.  The effects of such an alteration are complex, but


                    6 12
most recent theories '   speculate that the increase in CO background



concentrations will have an important impact on the tropospheric and



stratospheric ozone distributions, as well as having an influence on the



global budgets of several other trace gases.



7.1  INTRODUCTION



     Prior to 1970, the general picture of the sources of CO was quite



simple and the sources were thought to be well understood.  For the most



part, CO was thought to be produced by incomplete combustion of



carbonaceous matter; any other source was thought to be small compared



to production through combustion.    However, a new era of speculation
                                     7-1

-------
                 23
evolved when Levy   proposed that the hydroxyl (OH) radical was present



in the unpolluted troposphere in concentrations greater than 10

            3

molecules/cm .   With this OH number density, the observed clean air



concentration of methane, and the measured rate constant governing the



(CH4 + OH) reaction,14 it could be shown that a substantial quantity of



CO is generated in the clean atmosphere if the methane oxidized by OH is



converted to CO.  According to this scheme, the initial estimates of the



methane oxidation source of CO were 10 to 25 times larger than the



estimated combustion source.  *    Thus, a new philosophy of atmospheric



chemistry that  included photochemical processes in the unpolluted



troposphere  (OH can be generated only through a photochemical sequence)



developed in the 1970's.



     More recent photochemical calculations indicate that methane oxida-



tion probably is not as large a source of CO as indicated by those first



studies.  Because of the uncertainties inherent in numerical models of



photochemical processes and because relatively few measurements must be



extrapolated to derive other global source terms for CO, no definite



conclusion  can  be drawn as to the dominant source of CO in the atmosphere.



A more  detailed discussion of CO sources in the following sections will



review  many of  the previous studies.



7.2  GLOBAL SOURCES



7.2.1   Technological Sources


                          17 32
     The  early  inventories   '   of CO emissions focused on combustion



sources since no significant natural source of any other type had been



positively  identified.  Estimates of global emissions  of CO  from fossil
                                      7-2

-------
                                                    32 34
fuel combustion differ by more than a factor of two.   '    To derive the



values, emissions from technological sources were computed by assessing



the amount of coal and petroleum fuels produced in a given year and then


                                                                    18
multiplying that figure by previously determined conversion factors.



The emission rates calculated by this method were 2.6 x 10   g/yr by


                     32
Robinson and Robbins,   who used fossil fuel usage data from 1966, and



3.6 x 1014 g/yr by Jaffe,18 who utilized 1970 data.  In general, these



investigators concluded that the automobile was the largest technological



source of CO and that emissions increased  substantially between the

                                             3
onset of widespread use of the auto and 1970.   The study of Robinson



and Robbins showed that mobile sources were responsible for 68 percent



of the CO emissions; Jaffe's estimate was  70 percent.


           34
     Seiler   has presented the most detailed study to date on the



global cycle of atmospheric CO.  He contends in his analysis that the



previously estimated CO emission rates are lower limits.  He cites the



fact that the home heating source  of CO in West Germany was shown to be



30 percent of the automobile source, whereas Jaffe1s calculations used a



relative home heating contribution of  less than 1 percent.  Furthermore,



Seiler contends that several industrial sources, such  as ammonia and



methanol reforming facilities, synthetic gas and organic chemical manu-



facturing plants, and other possible emitters of CO were not considered


                                        34
in previous inventories.  Thus, Seiler1s   calculation of technological

                        "i /i

CO emissions is 6.4 x 10   g/yr, about two times greater than Jaffe's



estimate.  Subsequently,  aircraft  data obtained over Munich and extrapo-



lated  for the globe suggest a total technological  source ranging from



6 x 1014 to 10 x  1014 g/yr.44
                                      7-3

-------
     In addition to direct emission of CO, the oxidation of nonmethane
hydrocarbons given off by automobiles may be considered an indirect
technological source of CO.   Although no quantitative estimates of this
potential source have been published, it is possible that if most of the
                                                                 52 53
carbon contained within the hydrocarbons emitted in an urban area  '
were converted to CO, it would account for a source strength equal to
nearly half of the direct CO emissions.   The mole-to-mole conversion
rate of certain hydrocarbons found in automobile exhaust to CO has been
observed to exceed 0.4  in smog chamber studies.  Although the magnitude
                                                 \
of this source has never been computed in detail, it may be equivalent to a
sizable fraction of the amount of CO released directly to the atmosphere
in automobile exhaust.
7.2.2  Natural Sources
7.2.2.1  Forest Fires and Agricultural Burning—Because combustion
processes then appeared to be the only mechanism by which CO was produced,
                                                            32
the early emission inventory studies of Robinson and Robbins   and
     18
Jaffe   assumed that natural releases of CO, if they occurred, likewise
originated  from combustion of carbonaceous matter.  To date, however,
forest fires and agricultural burning have not been shown to be signifi-
cant sources of atmospheric CO.  The estimated CO emissions from these
natural sources range from 0.1 x 10   g/yr   to 1.5 x 10   g/yr.
7.2.2.2  Carbon Monoxide Production  from Oceans—Analyses of ocean  ,
     ?ft 41  4? 4.8 4Q  Rfi
water  '^•i»'^°>H'   often indicate supersaturated quantities
of CO.  The highest  supersaturation  factors were found in nutrient-
rich waters and are  believed to be a result of microbiological
                                     7-4

-------
activity.  Thus, the ocean acts as a source of atmospheric CO; its
                                                   14
strength has been estimated to lie between 0.2 x 10   g/yr and 2.0 x
1014 g/yr.27'42'50
7.2.2.3  Oxidation of Natural Hydrocarbons—Carbon monoxide is produced
by photochemical oxidation of naturally occurring hydrocarbons and
chlorophyll.  Went   pointed out that the apparent lifetime of terpene-
like hydrocarbons in the atmosphere does not appear to be very long.
Concentrations of these compounds range between 2 and 20 ppb (parts per
         31                57
billion),   from which Went   estimated a global emission rate of 10 x
  14                                                                32
10   g/yr for such volatile organic compounds.  Robinson and Robbins
                                       14
estimated from these data that 0.6 x 10   g/yr of CO could be produced.
Their calculation is based on the assumptions that one molecule of CO is
                                               21
produced from three molecules of organic matter   and that the average
organic  molecular weight is 150.
     More recent studies, however, suggest that oxidation of naturally
emitted  hydrocarbons from vegetation results  in a global CO source
ranging  from 4 x 1014 to 13 x 1014 g/yr.36'62  Derivation of the CO
source strength from this process requires the inclusion of many
assumptions, and, therefore, it  is fair to say that the amount of CO
produced from naturally emitted  hydrocarbons  is not definitely known.
Many more laboratory and field studies are still required to reduce the
uncertainty about the strength of this source.
                                  59
7.2.2.4  Emission by P1ants--Wi1ks   reported that green plants grown
in  a clean  illuminated environment liberate  small quantities of CO  as
                                                  45
well as  certain aldehydes.  Although Siegel  et al.    showed that CO
                                      7-5

-------
was given off by plant material in the dark, it could not be ascertained



whether the CO was emitted directly or was formed as a result of



photolysis of the aldehydes.  Further investigation of these phenomena



by Seiler et al.   showed that plants contribute 0.7 x 10   g/yr  to



global CO concentrations.  This estimate  is obtained from ij} situ meas-



urements observed from four different C~-type plants and was found to



increase as the radiation intensity increased.
                                     23
7.2.2.5  Methane Oxidation- -When  Levy   proposed that  sufficient  concen-



tration  of  the OH  radical could exist  in the troposphere  to produce



quantities  of formaldehyde (CHLO) on the order of  2  ppb (v/v)  from



methane  oxidation,  it was easy to show that significant quantities of  CO



could  be formed through  CHJ3  degradation.  Every known important  homo-



geneous  process that removed  CH«0 from the troposphere results in direct



formation  of CO:



                     CH20 + hv -»   CO +  H2,



           or        CH20 + hv -»   H + HCO,



           and        CH20 + OH -»   H20 + HCO,



rapidly  followed  by HCO + 02 -»   CO +  H02.


                                                                          5 61
The oxidation of  methane (CH-)  in the  troposphere  may  proceed  as  follows:  '
                         + OH       ->



                         + 02 + M   ->  CH302 + M,



                        02 + NO     -»  CH30 + N02,



                and  CH30 + 02      ->  CH£0 + H02.



 Once OH attacks a methane molecule, the subsequent reactions proceed



 very fast,  and thus the limiting factor in the production of CO is the
                                      7-6

-------
initial rate of the (CH4 + OH) reaction.  The net result of the above
demands that the amount of methane oxidized in the troposphere is the
same molar quantity as the CO produced from this process.
     Table 7-1 summarizes many of the studies which have been conducted
to determine the various source strengths of atmospheric CO.  Of primary
importance is the fact that the first estimates of CO production from
                 24 29 52 61
methane oxidation  '  >  '   showed that this source was five to 20 times
                                                                        32
larger than the anthropogenic sources estimated by Robinson and Robbins,
whose  study was the only comprehensive CO source inventory available at
the time of the initial methane oxidation calculations.  In all the
photochemical studies cited above, globally and diurnally averaged OH
                                              go           go
radical number densities ranged between 1 x 10 /cm  and 3 x 10 /cm .
Similar calculations were made later by Weinstock and Chang   and Wofsy.
However, those studies employed several key reaction rate constants
which  were subsequently shown to be quite inaccurate.  In particular,
the reaction rate governing the OH radical's attack on CO (which was
                                                                 4
discussed in detail in Section 3.3) was reported in later studies  to be
pressure dependent and to be more than  twice as fast at tropospheric
pressures as the rates measured prior to 1976.  Since this reaction
dominates all others  in determining the destruction frequency of OH in
the troposphere, a factor-of-two increase in its rate results (to a
first  approximation)  in a factor-of-two decrease in the average amount
of OH  calculated by earlier numerical models.
                        6                        11
     Crutzen and Fishman  and Fishman and Crutzen   have presented
numerical analyses which  incorporate the more  recent chemical  kinetic
                                      7-7

-------
         TABLE 7-1.   GLOBAL CARBON MONOXIDE SOURCE STRENGTH ESTIMATES

                    Fossil     Forest     Methane    Oxidation of
  Reference          Fuel      Fires     Oxidation   Hydrocarbons  Oceans   Plants


Seller, 197434       6.4       0.6a                    0.6         1.0
Robinson & Robbins,
  1969^   1p        2.5       0.1                     0.6
Jaffe, 1973i^(.       3.2       0.4
Seiler, 1976                                  4                    0.4     0.2-2.0
SeilerA Zankl,
  1976^            6-10
McConnell et al.,
       .y                                     27
Weinstpck & Niki ,
      54                                     50
Wofsy et al., 1972                           15
Levy, 1973^                                 33
Weinstpck & Chang,                             .
      DD                                     38
Wofsy, 1976""                                14
Crutzep & Fishman,                             .
  1977b                                 0.6-4.0°
Fishman,& Crutzen,                             ,
  197831-1                               2.9-7.4°
Zimmerman et al. ,
  1978                                                 4-13
Stevensfiet al.  ,
  19724b  n                                            2.0-5.0C
NAS, 1977*™                                            0.5
Swinnerton et al. ,
1970"
Linnenbom et al . ,
1973
Liss &9Slater,
1974^
Seiler.& Schmidt,
1974
Seiler^ Giehl,
1977 J/
Seiler,.gt al . ,
1978
Range of
Estimates 2.5-10 0.1-0.6 0.6-50 0.5-13
0.2

2.0

0.4

0.7





0.2-2.0








0.5

0.5-1.0

0.2-2.0
Units are 10   g/yr
^Includes agricultural burning
 Global values derived by doubling Northern Hemisphere values reported in
   these studies.
cNorthern Hemisphere estimate.
                                     7-8

-------
data.   In their reports some of the uncertainties inherent in the deter-



mination of the rates of photochemical production and destruction of CO



and other trace gases are discussed.  In the 1977 paper, Crutzen and



Fishman point out that the methane oxidation reaction sequence may be



broken and no CO produced from it if peroxides are formed and then



removed from the atmosphere by a rapid heterogeneous process.  Under


                                         14            14
such an assumption, as little as 0.6 x 10   to 4-0 x 10   g/yr of CO


                                                                      35
would be produced as a result of methane oxidation.   Similarly, Seiler


                            14
calculated a value of 4 x 10   g/yr for methane oxidation.   Anthropogenic

                                        O /I O C. O C.

CO source strengths calculated by Seiler  '  '   are 2 to 5 times


                                          18                          32
higher than previous calculations by Jaffe   and Robinson and Robbins.



Thus it now appears that methane oxidation is no longer believed the



dominant source of atmospheric CO as was the case in the early '70's.


                                                 47
7.2.2.6  Other Natural Sources—Swinnerton et al.   report that very



high supersaturation values of CO have been found in both rainwater and



cloud droplets.  Furthermore, rainwater samples in both unpolluted



(Hawaii) and polluted (Washington, D.C.) regions showed excessive amounts



of CO.  The mechanism for this phenomenon is not well understood, but



two possible explanations are the dissociation of carbon dioxide by



electrical discharges and the photolysis of aldehydes dissolved in the



droplets.  Quantification of this source on a global scale has been


                    34
attempted by Seiler,   but too many uncertainties exist to produce a



number which is accurate to more than several orders of magnitude.  This



is probably not a significant source of CO in the atmosphere.
                                     7-9

-------
     Other natural CO sources have been found, but to date none of them
is believed to contribute significantly to the global budget.  Green
      13
et al.   showed that CO could be produced by charged-particle deposition
mechanisms and atmospheric discharge phenomena, including cloud corona
discharges, background radioactivity, natural electrostatic discharges,
photoelectrons in the ionosphere, auroral electrons and protons, cosmic
'rays, and solar wind.  The decomposition of hemoglobin in animals also
                         34
results  in CO production.    A small amount of CO production by volcanoes
has  been noted.  Above 70 km, photodissociation of carbon dioxide (C02)
is a source of CO.
7.3   BACKGROUND LEVELS AND FATE OF CARBON MONOXIDE
7.3.1 Measured Background Levels of Carbon Monoxide
7.3.1.1  Geographic  Distribution--A distinct latitudinal variation in
                                                                    CO
background concentrations has been observed by both Wilkness et al.-,
                                                   34
in measurements over the Pacific Ocean, and Seiler,   in measurements
over the Atlantic Ocean.  Seiler1s values are shown in Figure 7-1 and
are  averages based on- the integrated concentrations during 1969 obtained
between  the surface  and the  tropopause.  Integration of these data over
each hemisphere shows that more than twice as much CO is present in the
Northern Hemisphere  than in  the Southern Hemisphere.  Robinson and
       33
Robbins   report average mixing ratios of 140 ppb for the Northern
Hemisphere and 60 ppb for the Southern Hemisphere, which have since been
reconfirmed by Seiler's later and more extensive work.
           34
      Seiler   points out that the background mixing ratios in the
Southern Hemisphere  remain very constant.  The standard deviation of CO
                                      7-10

-------
    200
    150
.o
a
a.


Z
o
g   100
z
o
o
     50
                                 ATLANTIC OCEAN (SEILER, 1974)
                    	PACIFIC OCEAN (ROBINSON & BOBBINS, 1970)
                               \
                                     \
        90     80     70     60     50     40     30     20     10     E     10


                                   SOUTH                         LATITUDE
20    30
40     50


   NORTH
60     70      80     90
                             Figure 7-1.  Latitude distribution of carbon monoxide. (Used with permission of Tellus 26:116-135.)

-------
concentrations in a region between 50 and 65° S and 30 and 80° W over a



three-month period was less than 3 percent, approximately equal to the



accuracy of the instrument being used.  Carbon monoxide variations are



largest in the North Atlantic and are attributed to the passage of



continental plumes from North America.  A relatively sharp difference in



mixing ratios was quite often observed within the Trade Wind inversion



layers on either side of the intertropical convergence zone in both the



Atlantic and the Pacific.34'58



     The considerably higher average CO concentration in the Northern



Hemisphere, where 90 percent of the anthropogenic emission sources are



located, does not support the hypothesis that CH. oxidation is the


                                                                          30
dominant source of CO as was proposed by the National Academy of Sciences.


                                                     18
Since CH. is evenly distributed throughout the world,   the magnitude of



the CH. oxidation source of CO should be nearly equal in both hemispheres.



Furthermore, if the anthropogenic CO source is only 10 percent of the


               30
natural source,   such a small difference in the overall source strengths



in the two hemispheres should result in a much smaller interhemispheric



gradient.  Although the inclusion of CH. oxidation as a source of CO is



necessary to develop a clear picture of the global CO budget, its



magnitude relative to other sources, on the basis of the current distri-



bution of CO, remains to be assessed.


                                                40
7.3.1.2  Variation with Height—Seiler and Junge   and Seiler and


       43
Warneck   showed that CO mixing ratios decreased sharply above the



tropopause.  In their reports, mixing ratios of less than 40 ppb were



measured at an altitude less than 1 km above the tropopause, in contrast
                                     7-12

-------
to values between 130 and 160 ppb measured just below the stratospheric



boundary in the northern midlatitudes.  Thus,  it appears that  there  is a



strong atmospheric sink for CO in the stratosphere; the nature of this



sink most likely is the reaction of CO with OH radicals.  This belief is



supported by theoretical calculations,  which  show that OH concentra-



tions increase above the tropopause because of the much larger ozone



concentrations in the stratosphere.  The  larger ozone concentrations are



significant because OH radical production is initiated by ozone photolysis



               03 + hv        ->    0( D)  + 02, A.O20 nm,



followed by    O^D) + H20    -»    2 OH,



               O^D) + CH4    -»    OH + CH3,



or             OC^-D) + H£     -»    OH + H.



     Within the troposphere, background-level  CO profiles vary at dif-



ferent  latitudes.  Tropospheric profiles  at low and middle latitudes of



both hemispheres are depicted in Figure 7-2.   The CO concentrations  in



the lower troposphere (below 3 km) reflect the strong latitude gradient
      jf


depicted  in Figure 7-1.  The midlatitude  profiles (45° N and 45° S)



fall off  to typical stratospheric  values  at 12 km, since this  height is



in  the  stratosphere at these latitudes.   The vertical gradient in the



upper troposphere  is much  stronger in the Northern Hemisphere. The



average CO concentrations  in the tropics  at an altitude of 12  km are



higher  than the midlatitude concentrations at  a corresponding  altitude



since the average  height of the tropopause is  greater than 12  km in  the



tropics.
                                      7-13

-------
I
o
HI
Q
D
12


11


10


 9


 8


 7


 6


 5


 4
     2


     1
           i    r
          i     i     i    r
               40
                    80
120
160
                                                  45° N
                                                     \
200
240
                            CO MIXING RATIO, ppb
             Figure 7-2. Latitudinal profiles of carbon monoxide.
                                 7-14

-------
7.3.1.3  Diurnal and Seasonal Variation—During an ocean cruise to



measure background concentrations of trace constituents in the Pacific


                               20
in June 1970, Lamontagne et al.    reported a consistent diurnal pattern



of CO concentrations both in sea water and in air samples taken just



above the ocean surface.  Both sets of data show a maximum concentration



in the afternoon, when concentrations were typically 20-40 ppb higher



than the average concentration of 130 ppb.  However, this finding is



inconsistent with our present knowledge of CO fluxes from the ocean into



the atmosphere.   Thus, the diurnal amplitudes reported by Lamontagne et


   20
al.   would imply a global oceanic source strength considerably larger



than that given in Table 7-1.  In agreement with the latter hypothesis,



failure to detect a significant diurnal cycle of CO concentration over



ocean surfaces  has been reported.  *



     Using an  instrument that monitored CO continuously over a nine-



month period in Hawaii  (at Mauna Loa Observatory, elevation 3400 m),


             39
Seller et al.   detected an average diurnal cycle.  A slightly higher



(less than 10  percent)  average concentration was observed in the afternoon.



From these data,  it appears that this diurnal cycle may be caused by



local sources  in  combination with local meteorological phenomena, such



as Upslope and downslope winds.



     Data which show seasonal variation of CO concentrations are quite



scarce.  Although Stevens et al.   showed that the isotopic composition



of CO measured in rural Illinois exhibited a seasonal dependence, a



conclusive seasonal variation in the background CO concentrations could



not be established.
                                      7-15

-------
     Analysis of data collected by continuous monitoring during 1975 and
    *3 f\
1976   at Mauna Loa Observatory in Hawaii (19.5° N) indicates that the

highest seasonal background CO concentrations exist in the spring (March

and April).  The highest average values (120-130 ppb) are considerably

greater than those measured in late summer (70-80 ppb).  A good explana-

tion of these observations is not readily available, although the

seasonal variation of tropospheric OH concentrations suggests that more

CO scavenging may take place in the summer.  However, such an explanation

is speculative and other factors, including seasonal variation of large-

and small-scale meteorological parameters, must be examined to see how

they could influence the Hawaiian measurements.

     In the Northern Hemisphere temperate mid-latitude belt, Dianov-
             o
Klokov et  al.  have reported a similar seasonal variation in the total

amount of  CO in the U. S. S. R.  They also find maximum values in March

and April  and minimum values between July and September.

7.3.2  Residence Time and Removal Mechanisms of Atmospheric CO

7.3.2.1  Carbon Monoxide Residence Time--To derive a budget of a trace

gas  in the atmosphere, all possible sources and sinks of that species

are examined.   If no increasing or decreasing trend is detected for the

concentrations of the gas, then it is assumed that the sum of the sources

equals the sum of the sinks.  Under such conditions, a residence time

can be computed by dividing the measured quantity of the gas in the

atmosphere by either the total emission rate or the total destruction

rate.
                                     7-16

-------
     An estimate of the atmospheric residence time of CO by Robinson and


       32
Robbins   was computed by assuming an average atmospheric mixing ratio


                                                                14
of 0.1 ppm, which yields a CO mass in the atmosphere of 5.6 x 10   g.



Division of the calculated mass by their estimated source strength at


        14                                                            35
3.2 x 10   g/year results in a CO residence time of 1.8 years.  Seiler



estimated a residence time of 0.3 year.  By using the wide range of



published source strengths summarized in Table 7-1, a CO residence time



ranging from 0.07 to 1.38 years can be computed.



7.3.2.2  Removal Processes for Carbon Monoxide—The mechanisms by which


                                                          34
CO is removed from the atmosphere are summarized by Seiler   and the


                             30
National Academy of Sciences;   these studies concluded, after con-



sidering the possible CO sinks, that the major destruction term in the



CO budget  is oxidation by the OH radical.  More recent reaction rates



measured for the (CO + OH) reaction discussed in Section 3.3 indicate



that the magnitude of this sink is probably twice as large as the values



indicated  in these two previous reviews  if the globally averaged



concentration of OH is the same.



7.3.2.2.1  The  Stratosphere as a Sink for Tropospheric CO.  As previously


                                                                  41 43
mentioned, CO mixing ratios decrease sharply above the tropopause.   '



From the average concentrations measured on either side of the tropopause,



a theoretical calculation of the CO flux into the stratosphere can be



made if the atmospheric diffusion coefficients  in the region are known.


                              34
Using this methodology, Seiler   derived a tropospheric CO loss rate of


        14
1.1 x 10   g/year by migration into the  stratosphere.  Because of the



large difference in the average CO concentrations above and below the
                                      7-17

-------
                                                                14
tropopause in the Northern Hemisphere (see Figure 7-2), 0.9 x 10


                                                                      14
g/year enter the stratosphere north of the equator while only 0.2 x 10



g/year migrate to the upper atmosphere in the Southern Hemisphere.


                                22
7.3.2.2.2  Soil as a Sink.  Levy   showed that nonsterile soil rapidly



depleted CO from test atmospheres containing initial concentrations of



100 ppm.  The effect of this removal process was enhanced by increasing



the soil temperature but eliminated by sterilizing the soil.  The latter



finding suggests that the biological activity of microorganisms in the



soil  is responsible for CO removal.


                     15
      Ingersoll et al.   likewise found that soil was potentially a major



sink  of CO, but their studies showed that the soil uptake rate reached a



maximum at 30°C and decreased at higher and lower temperatures.  At 0°C


                      '                       o
the uptake rate was negligible, whereas at 50 C the uptake rate was less



than  10 percent of that at 30°C.  Seiler   indicated that at 50°C, CO



was given off  from the soil rather than taken up by it.


                        22                     15
      The studies of Levy   and  Ingersoll et al.   concluded that the



magnitude of the soil sink was  considerably larger than the anthropo-


                                    34
genie source of CO.  However, Seiler   points out that the soil uptake



rate  is linearly dependent on the concentrations of CO in the atmosphere



directly above the surface, and thus both estimates are too high because



unrealistically high initial CO concentrations were used in the experiments,



Using an initial atmospheric concentration of 0.2 ppm over the continent,


                                             14
Seiler estimated a global CO sink of 4.5 x 10   g/yr due to soil uptake.


             26 37
Later studies   '   over different types of soil supported the sink


                             34
strength estimated by Seiler.
                                      7-18

-------
                                                  34
     Such an estimate, however, is extremely crude   because of vari-



ations observed in the CO equilibrium concentrations above the soil, in



the different types of soil, and in soil temperatures.  For example,



Inman et al.   point out that soils from different locations exhibit an



eight-fold variability in their ability to remove CO under the same


                              34
laboratory conditions.  Seiler   even speculates that some soils may act



as sources rather than sinks of CO.  It is clear that more research is



needed to quantify the role of soil on the global CO cycle better.



7.3.2.2.3  Vegetation.  The role of vegetation in the global CO cycle is



currently not well understood.  Some researchers have suggested that


                                      37 45 59
plants are a source of atmospheric CO;  '  '   but others have indicated


                                                                  19
that  CO  is absorbed by vegetation.  For example, Krall and Tolbert



exposed  barley leaves to an artificial atmosphere containing CO and



determined that some of it was converted to serine and other compounds.

                             2
Similarly, Bidwell and Fraser  investigated the incorporation of carbon-



14 from  an artificial CO atmosphere into plant carbon compounds.  Seven



of nine  plant species were observed to take up CO.  Extrapolation of



these data  indicates that plants are a significant sink for atmospheric


                               14           14
CO, absorbing as much as 7 x 10    to 70 x 10   g/yr.


                                    37                  38
      More  recently, Seiler and Giehl   and Seiler et al.   concluded


                                    2
that  the study of Bidwell and Fraser  is not a true measure of the net



CO exchange  rate between plants and the atmosphere.  They point to the



fact  that  the Bidwell and Fraser experiment is useful only to detect the



amount of  CO going into the plant  and note that the large artificial CO



concentrations used in the laboratory environment precluded accurate
                                      7-19

-------
measurement of any CO coming back into the atmosphere.  On the other
hand, the method of Seiler and Giehl enables them to detect only the net
influence of plants on atmospheric CO; they cannot distinguish the
production from the uptake rates of the plants.  Their findings indicate
                                                 14
that vegetation is a net source of about 0.5 x 10   gCO/yr when both
production and uptake processes are taken into account.
7.3.2.2.4  Reaction with Hydroxyl.  Estimates of the amount of CO removed
from the atmosphere by reaction with OH indicate that this mechanism is
the primary removal process for atmospheric CO. »  »  »    if the amount
of CO  in the atmosphere is known, the global destruction rate as a
function of the OH distribution can easily be computed.  Similarly, if
the distribution of CH. in the atmosphere is known, the amount of CO
produced by methane oxidation can be calculated as a dependent variable
of the average amount of OH present in the atmosphere.
     Figure 7-3 shows graphically the results of such a simple calculation,
in which the following parameters are assumed:  CH. and CO mixing ratios
           9
of 1.4 ppm and 0.1 ppm, respectively;
                                -13  3
               ^CO+OH = 2.5 x 10   cm /(molecule* sec); and
               kru +OH = 4'8 x 10~15cm3/(molecule*sec).
 When the above  values  are  used,  the  ratio of the rate of photochemical
 destruction  of  CO,  D(CO),  to  the rate of photochemical production of CO,
 P(CO),  is 3.7.   This ratio is a  lower limit, since it depends on the
 assumption that every  CH.  molecule oxidized results  in the production of
 a  CO molecule.   Such a ratio  demands that no more than 27 percent of the
 CO produced  in  the  atmosphere comes  from CH. oxidation.  Furthermore,
 such a  ratio is totally independent  of  the amount of OH  in the  atmosphere
                                      7-20

-------
I
Ol
I-
U
co
Ul
O
z
g

o

Q
o
cc
Q.
o
o
                                     CO DESTRUCTION FROM

                                     REACTION WITH OH
CO PRODUCTION FROM METHANE

OXIDATION (UPPER LIMIT)
                                                                                                             14
                                             15
                                                      OH CONCENTRATION, 105/cm3
        Figure 7-3. Carbon monoxide photochemical production and destruction rates as a function of average OH concentration.

-------
     Although the D(CO)/P(CO) ratio is not affected by the average OH



concentration, the magnitude of each of these terms clearly is affected



(see Figure 7-3).  Since about 90 percent of these terms is derived from



tropospheric photochemical activity,   the average OH number density on



the abscissa refers to a tropospheric value.  Although previous studies



derived information about the CO budget from calculated OH distributions,  '



the simple analysis depicted by Figure 7-3 can provide some useful


                                                                   35
insights into the global distribution of OH.  For example, Seiler's


                                            14
inventory of CO  sources shows that 13.2 x 10   g/yr of CO are emitted to



the atmosphere.  If it is assumed that the only CO sink is reaction with

                                                5

OH, then an average OH concentration of 3.6 x 10 /cm will destroy CO at


                   14
a  rate of 13.2 x 10   g/yr more than it can produce from methane oxidation.



7.3.2.2.5  Other Removal Processes.  Carbon monoxide adsorption onto


                                                            25
atmospheric particulate matter has been reported by Liberti.    His



analyses indicate that adsorption by dust which is subsequently deposited



on the earth's surface could be an important removal mechanism for



ambient CO.  The magnitude of this possible sink is not known.  Further



studies are necessary to determine the adsorption efficiency of different



aerosol materials for the varying concentrations of CO found in the



atmosphere.



7.4  SUMMARY



     Although many studies in the last decade have been devoted to the



identification and quantification of the various sources and sinks of CO



in the atmosphere, it is clear from this review that a wide range of



uncertainty exists about the magnitude of many of the terms which compose
                                     7-22

-------
the global CO budget.  The fundamental question about the global cycle



of CO raised in the 1970' s centers around the natural vs. anthropogenic



origins of CO in the atmosphere.  Resolving this issue is very important



if society is to determine whether or not emission controls are necessary



to decrease CO input into the atmosphere.  If the CO production from the



natural oxidation of CH. greatly dominates all anthropogenic input


                                                       24 29 54
terms, as was suggested  by studies in the early 1970' s,J>   suppres-



sion of CO emissions should have little effect on the amount of CO in



the atmosphere.  However, the reformulation of the CO budget, which



includes photochemical calculations utilizing more recent chemical



kinetic information, shows that ChL oxidation may not be the dominant
                    fi
 source  term  for  CO.  '    The verification of these theoretical discus-



 sions on photochemical  production and destruction rates of CO awaits



 more measurement of OH,  NO, and  N0«  in the atmosphere.  Until such data



 are available, no authoritative  conclusion can be drawn.



     If, on  the  other  hand, CO is produced primarily  by processes which



 are directly or  indirectly controlled by man, it is important to consider



 the consequences.   The simple answer is to say that anthropogenic emis-



 sions will raise the background  concentrations of CO  and  that no sub-



 stantial harm will  come until these  levels approach a concentration



 which is dangerous to  man's environment.  However, there  may be other



 consequences of  increased CO concentrations which are not so obvious.



 For example, since CO  is the predominant scavenger of OH  in the



 troposphere, increased global concentrations of CO will decrease the



 tropospheric quantities of OH.   In turn, lesser OH concentrations  in the
                                      7-23

-------
                                                                   51
troposphere may allow greater quantities of trace gases such as CH-



and methyl chloroform  to enter the stratosphere, since the primary



tropospheric removal mechanism for these gases is reaction with OH.



Thus, it is not impossible that increased CO emissions may have an



important impact on stratospheric photochemistry and the ozone layer.



     The fate of CO in the atmosphere may also provide some insight into


                                                        12
the budget and distribution of ozone in the troposphere.    Along with



CO, a considerable amount of tropospheric ozone may likewise be produced


                   5 10
from CH. oxidation. '    In addition, photochemical degradation of CO



may produce  large quantities of ozone in the troposphere through the



sequence:



               CO + OH        -»  C02 + H,



               H + 02 + M     ->  H02 + M



               H02 + NO       ->  N02 + OH



               N02 + hv       -»  NO + 0



               0+02+M     +03+M
                CO  +  202       •*  C02 + 03   (net).


                   12
 Fishman  and Crutzen    speculate, on the basis of the present knowledge



 of tropospheric photochemistry, that the above mechanism may be the



 largest  source  of  ozone  in  the troposphere.



      The importance  of obtaining a better  understanding of the global



 cycle of CO should not be underestimated.  A clearer picture of the



 distribution of OH in  the troposphere as well as a  better understanding
                                      7-24

-------
of the global budgets of methane, tropospheric ozone and other trace



gases will result from a more accurate description of the role of CO.



One hopes that this goal will be realized as more measurements of



ambient atmospheric trace constituents and better laboratory data



are made available.
                                      7-25

-------
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                                      7-30

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     8.   EFFECTS OF CARBON MONOXIDE ON VEGETATION AND SOIL MICROORGANISMS





8.1  INTRODUCTION


     Because of the potential toxicity of CO to living organisms, there


has been much concern over the large quantities (103 million metric tons


in 1977) of carbon monoxide (CO) released into the atmosphere from


anthropogenic sources.  While much work has been done on the effects of


CO on man and animals, relatively little research has been done regarding


the influence of CO on plants.  Man's health and well-being, however,


are fundamentally and inextricably bound to the success of the plants,


those organisms which transform the sun's radiant energy into the food


and oxygen necessary for habitation of the planet.


     There are no known detrimental effects on green plants due to


carbon monoxide at the natural global background concentrations of CO,

                 3
0.01 to 0.23 mg/m  (0.01 to 0.20 ppm).  In urban areas, however, CO


concentrations may be much higher and are closely related to motor


traffic density.  Carbon monoxide concentrations, therefore, exhibit


variation along well-marked diurnal patterns with peaks corresponding to


morning and evening "rush hours."  High traffic density, when combined


with prolonged periods of air stagnation, has resulted in ambient CO

                      3
levels of over 34 mg/m  (30 ppm) for an 8-hour period in Los Angeles and
                                     8-1

-------
             3                     15
over 412 mg/m  (360 ppm) in London.    Even discovery of these relatively



high concentrations, however, has not motivated significant levels of



new research into the effects of CO on plants.



     Early investigations into plant growth and development as affected


                                                           3                42 43
by CO were carried out at high concentrations (>11,450 mg/m  or 10,000 ppm),   '



and were directed at determining the manifestation of external symptoms



by treated plants.  More current research to determine the effects of



CO, at both ambient and higher concentrations, on vegetation and soils



has been conducted in the following areas:



          Effects of CO on plants



               1.  Visible symptom expression



               2.  Growth, yield, reproduction



               3.  Biochemical or physiological response



                      a.  Photosynthesis



                      b.  N«-Fixation



                      c.  Other metabolic effects



               4.   Removal of CO  from the environment



                      a.  By plants



                      b.  By soils



                      c.  By soil micro-organisms



               5.   Production of  CO by photosynthesis



8.2   EFFECTS OF  CO ON PLANTS



8.2.1 Visible Symptoms



      One of the  earliest  studies on the effect of CO on plants was


                                          20
carried out by Knight and Crocker  in 1913.    Pea epicotyls were exposed
                                      8-2

-------
to CO derived from potassium ferrocyanide, from oxalic acid, and from

                                                        o
sodium formate in concentrations of 6,000 to 24,000 mg/m  (5,200 to


20,900 ppm).  Reactions exhibited by the pea seedlings included a


pronounced swelling of the epicotyl accompanied by stem declination, as


much as 90  in some cases.  Reactions were similar throughout the range


of concentration levels and no correlation between degree of effect and


CO origin was noted.

                             43
     Zimmerman et al. in  1933   performed a series of experiments in


which they observed the reactions of plants exposed to CO.  At CO concen-

                               3
trations of 572 to 572,000 mg/m  (500 to 500,000 ppm), stem tissues of


several plant species exhibited initiation and profuse growth of adven-


titious roots; stimulated development of latent root primordia also

                                 42
occurred.   In a subsequent study,   the same authors found that the

                                 3
exposure of plants to 11,000 mg/m  (9,600 ppm) CO for up to 23 days


also:   (1)  induced epinasty and hyponasty of leaves; (2) retarded stem


elongation; (3) produced  smaller and/or deformed leaves; (4) induced


premature abscission of leaves, flowers, and fruits; and (5) produced


foliar  lesions that were  characterized by a yellowing of older leaves.

                                                                26
Premature leaf abscission was also reported by McMillan and Cope   when


they exposed seedlings of several geographic variants of Acacia farnesiana

              3
to 23,000 mg/m  (20,000 ppm) CO for 24 hr.  Varying degrees of leaf


abscission  including complete defoliation occurred in the species


mentioned,  while two other species of Acacia were not as severely

                                                                  3
affected.   Garden pea (Pisum sativum) seedlings exposed to 27 mg/m

                                                                c
(24 ppm) CO also exhibited increased abscission of older leaves.
                                      8-3

-------
                  41
     Wolf and Kidd   found that the greening response of etiolated wheat



seedlings upon exposure to light was almost completely inhibited by



exposure to CO at levels that are described only as "high concentrations".



     Carbon monoxide has found a commercial application in the produce



industry.  Carbon monoxide, in combination with other gases, has been



used to prolong post-harvest storage and increase the appearance and


                                                          36
consumer acceptability of head lettuce.   Stewart and Uota,   working in



the Market Quality and Transportation Laboratory, USDA, held head lettuce


                               3                                 3
in an atmosphere of 34,000 mg/m  (30,000 ppm) Op plus 17,000 mg/m



(15,000 ppm) CO for 7 days at 3.3°C.  Each head was evaluated for



appearance disorders endemic to lettuce such as butt discoloration, pink



rib and rusty brown discoloration.   In general, lettuce held in the



experimental atmosphere had a better overall appearance than lettuce



exposed to other gas mixtures.  Butt discoloration and pink rib were



inhibited by exposure to the C0/0« combination, while rusty brown



discoloration was not affected in any way.



     As  stated previously, no visible effects have been identified in

                                                 3
plants exposed to CO at ambient 0.01 to 0.23 mg/m  (0.01 to 0.20 ppm)



concentrations.



8.2.2  Growth, Yield, and Reproduction



     Concentrations of CO at levels much higher than those found in the



ambient  air  have been shown to inhibit stem elongation in many species


                            42
of plants.   Zimmerman et al.   exposed a variety of plant species to CO


                             3               3
at concentrations of 115 mg/m  to 11,500 mg/m  (100 to 10,000 ppm) for



from 4 to 23 days.  While practically no growth retardation was noted in



plants exposed at the lower level, stem growth was inhibited at the
                                     8-4

-------
higher concentration by as much as 100 percent when compared with



controls.  The effects varied considerably among the different species



of plants, tobacco being only slightly retarded while others were



affected greatly.  Exposure to the higher concentration of CO also had a



significant effect on the formation and development of new leaves.  In



many species, new leaves failed to grow as large as normal and had a



tendency to curl down at the edge.



     Pea and bean seedlings also  exhibited abnormal leaf formation after

                         3
exposure to CO at 27 mg/m  (24 ppm) for several days.  Pea seedlings



showed a decrease in the rate of  development of new leaves while leaf



formation  in bean seedlings was completely inhibited by the 18th day.



There was  no effect noted on the  relative rates of germination of peas



and beans  exposed to the experimental atmosphere as compared with



controls;  likewise there was no observable difference in the growth



rates of exposed plants as determined by  increased stem length.



     Several studies have demonstrated the influence of CO on sex


                                               27
differentiation  in plants.  Minina and Tylkina   exposed different


                                                          3                '
varieties  of cucumber to CO at concentrations  of 1145 mg/m  to 11,450 mg/m*



(1000 to 10,000  ppm) for 50 to 200 hours.  The  results showed that



sexual differentiation was shifted markedly to  the expression of female



characteristics  under the  influence of the gas.  Thus, at the highest

                            ;

level and  with prolonged exposure, plants formed exclusively female

                                                                 3

flowers.   With exposure to CO concentrations of 3400 to 5700 mg/m



(3000 to 5000 ppni), female flowers developed first with the appearance



of a very  few male flowers a week later.  Plants treated at the  lowest
                                      8-5

-------
                   3
CO level (1145 mg/m ; 1000 ppm) proceeded with the development of male


flowers, as is normal for the species studied, and then shifted to


female expression at the sixth day.  Controls developed males first, and


this continued throughout the course of the experiment.


     Similar results were reported by Heslop-Harrison,   who studied the


modification of sexual expression in Cannabis sativa by CO.  Young

                                           3
plants exposed briefly to CO at 11,450 mg/m  (10,000 ppm) modified the


subsequent sexual expression of the dioecious male plants, inducing the


formation of intersexual or even functionally female flowers.  The


effect was registered in flower primordia of a particular age; sex of


the  older ones was already determined, and younger ones apparently


recover  from treatment to develop normally.  Basically, the effect of CO


in modifying sexual expression is similar to that induced by auxin


administration, and it is possible that at effective concentrations the


gas  upsets auxin metabolism in treated tissues, perhaps by inhibiting


enzyme  systems normally responsible for regulating endogenous auxin


levels.  The gross effects of CO on plants are summarized in Table 8-1.


8.2.3   Biochemical and Physiological Processes


     Biochemical and physiological responses in plants exposed to CO at


above ambient concentrations have been investigated in various species


and  on  different metabolic systems with conflicting results, especially


with respect to plant uptake and production of CO.  The effects of CO


on photosynthesis and nitrogen fixation are discussed  below.
                                      8-6

-------
                      TABLE 8-1.  EFFECTS OF CO ON PLANTS
Cone.
Duration
Effects
Author
 5000
10,000 ppm
             No evidence of swelling in
             pea epicotyls.

             Swelling of epicotyls
             1-2 cm long; declination of
             70-90°.
                                  Knight & Crocker
                                                                            20
20,000 ppm
0.05-50%
by volume
0.01-50%
by volume
 0.3-1.0%
 by volume


 1.0%
 by volume

 1.5%
 by volume
 24  ppm
2-15 days
2-30 days
50-200 hrs,
24-48 hrs.
 24  hours
 unreported
             Swelling of epicotyls
             1-1.5 cm long; declination
             of 80-90°.
Stimulated development of
root and subsequent root
generation.  Some alteration
of normal geotropic growth pattern.
Zimmerman et al.
                                                                            43
Epinasty, hyponasty,
retarded skin elongation,
abnormally small new leaf size,
general loss of sensitivity to
external stimuli, leaf abscission.

Sex differentiation was
shifted markedly towards
females.

Generation of female
flowers from male plants.

Leaf abscission, with
severity of effects being
dependent upon geographical
variant used.

Exposure of seeds to CO
had essentially no effect on
germination. Some reduction of
leaf formation when seedlings
were exposed was noted.
Zimmerman et al.
                                                                            42
                                  «^
 a-PPM  CO  can  be  converted to  mg/m  CO  by multiplying
   the  above concentrations by 1.145 (@STP).
                                                                            27
Minina & Tylkina
Heslop-Harrison.,&
Heslop-Harrison
McMillan & Cope
                                                              26
Chakrabarti
                                                                       .6
                                      8-7

-------
8.2.3.1  Photosynthesis--There is evidence that CO can be assimilated by

                           4                      3
plants.  Bidwell and Fraser  and Bidwell and Beebe  found that many species


of plants can absorb and metabolize CO photosynthetically.


     Bennett and Hill,  however, in 1950, found that CO concentrations as

               3
high as 91 mg/m  (80 ppm) had essentially no effect on C02 uptake in


plants.  Kortschak and Nickel! found that sugar cane leaves removed CO from

                                     2    19
the atmosphere at a rate of 0.01 mg/m /hr.


8.2.3.2  Nitrogen Fixation—Carbon monoxide has been shown to affect

                                   23
nitrogen fixation.  Lind and Wilson   demonstrated as early as 1941 that CO


inhibition of nitrogen fixation in red clover could usually be observed

                                    3
when plants were exposed to 115 mg/m  (100 ppm) CO and that complete

                                       3
inhibition occurred at 573 to 1145 mg/m   (500 to 1000 ppm).  The authors


suggested  that the inhibition might be due to carbon monoxide and molecular


nitrogen having the same molecular weight, the same number of valence


electrons  and possessing many physical properties which are remarkably


similar.   Due to these similarities, inhibition of the uptake of atmospheric


nitrogen by CO might  be the result of the competitition of these two gases


for adsorption on the surface of the enzyme responsible for fixation.  The


effect appeared to be readily reversible.  The same authors also showed

                  3
that CO at 23 mg/m  (20 ppm)  inhibited  nitrogen fixation  by Azobacter


vinelandii, a free-living, nitrogen-fixing bacterium in culture.  Table 8-2


summarizes the  CO effects  on  nitrogen fixation.

                           2
     Bergersen  and Turner,  in  1968, demonstrated that CO inhibition of


nitrogen fixation is  both  specific and  competitive with respect to


nitrogenase activity.  Also,  there is an  obligatory relationship between
                                      8-8

-------
  TABLE 8-2.   CARBON MONOXIDE EFFECTS ON NITROGEN FIXATION BY MICRO-ORGANISMS


Cone.         Duration     Effects                           Author

                                                                         23
.005-0.3%    3-34 days    Inhibition of nitrogen fixation   Lind & Wilson
                          beginning at 0.01% and almost
                          complete inhibition at 0.05-0.1%.

                                                                         24
0.05-0.6%    35-45 hrs.   Inhibition of nitrogen fixation   Lind & Wilson
                          observed at 0.1-0.2% with almost
                          complete suppression at 0.5%-0.6%.

PCO of       30 min.      50% inhibition of CphU-reducing   Pankhugst &
5+10  Pa                  activity in nitrogen fixing       Sprent
                          nodules.
                                 4*
 a-PPM CO can be converted to mg/m  CO by multiplying
  the above concentrations by 1.145  (@STP).
                                      8-9

-------
the occurrence of leghemoglobin, an oxygen binding hemeprotein occurring in



the nitrogen fixing root nodules of legumes, and the ability of the nodule



to fix nitrogen.  Various workers have demonstrated the great affinity of


                     29 40                      29
leghemoglobin for CO.  *    Pankhurst and Sprent   have shown that this



affinity interferes with oxygen binding, thus limiting the amount of oxygen



that is available to the bacteroids (bacteria) in the interior of the



nodule and consequently limiting the nitrogen-fixing ability of the bacteria.



As further evidence, acetylene-reducing activity, which is used to estimate



the rate of nitrogen fixation, was found to be inhibited by CO in soy bean



nodules.



8.3  REMOVAL OF CO FROM THE ENVIRONMENT



     There has been concern over the large amounts of CO that are being



released into the atmosphere by both anthropogenic and natural sources,



with many fearing that ambient global CO concentrations may someday increase



to levels detrimental to plants and animals.  Large amounts of CO are



emitted annually to the atmosphere due to man's activities; however, as of



1973, ambient concentrations did not appear to have changed appreciably



over the previous 20 years.    It is apparent, then, that something is



happening to CO soon after its liberation.  The chemical and photochemical



reactions known to transform CO in the atmosphere were regarded as being



too slow to account for the disappearance of the quantity of CO in question.



Consequently, attention was turned to components of the biosphere as possible



utilizers of CO.  The utilization of CO by plant life and soil microorganisms



is considered in the following sections.
                                     8-10

-------
8.3.1  Plants
     As previously mentioned, it has been demonstrated that CO can be
assimilated by plants.  '   Bidwell and Fraser  supplied   CO to bean
                                              3
leaves in light or darkness at 174 to 314 mg/m   (150 to 270 ppm)  in air.
In the presence of light, CO was absorbed and converted mainly to sucrose
                            14
and proteins.  In darkness,   CO was absorbed nearly as fast as in light
but was almost completely converted to C0«  and released.
     Carbon monoxide  fixation by a number of species of plants, while
                                                 3
illuminated, was measured using 0.87 to 8.7 mg/m  (0.75 to 7.5 ppm) in
                                               2
air, with rates varying from 0 to 0.25 umole/dm  /hr.  Rates were  roughly
proportional to CO concentration but were unrelated to rates of photosynthesis,
                  4
Bidwell and Fraser  ,  using the bean leaf as an intermediate CO
                      3                                                  2
absorber, at 1.7 mg/m  (1.5 ppm) CO with an uptake rate of 0.06 |jmole/dm /hr,
and  assuming a leaf area index (area of leaf per unit area of ground)
between 3 and 30, calculated that the rate  of CO uptake would be  0.5 to
       2                                          2
5 mg/m ground per hour, or about 12 to 120 kg/km  per day.
                          19
      Kortschak and Nickel!   found that the leaves of the sugar cane
plant  can absorb and  metabolize CO, with sucrose as an end product.
These  authors, however, found the rates of  CO uptake to be in the order
      -4      2
of 10   mg/dm /hr, which would be too low to be  significant in removing
CO from the atmosphere.   Hill,12  in 1971, and Hill and Chamberlain13 in
1976,  found that under  carefully  controlled laboratory conditions,
alfalfa canopies did  not significantly  remove CO from the atmosphere.
The  production and  utilization of CO by plant life is summarized  in
Table  8-3.
                                      8-11

-------
   TABLE 8-3.   PRODUCTION AND UTILIZATION OF CO BY PLANTS AND MICRO-ORGANISMS
Cone.
Duration
Effects
                                  Author
Wide variation in data
for different plants
and experimental
conditions.
0-10 ppm
100-120
ppm


200-360
ppm
80% CO
in air.

6 ppm
Not
reported
<0.1-0.6
ppm
1-2 hr.
3 hrs.
15-25 min,
30 days


15-45 min.
Not
reported
24 hrs.
Data suggests significant role
for plants in reducing
atmospheric CO concentrations;
production of CO may exceed
uptake, however.

The amount of CO uptake by
alfalfa was below limits
of detection.

Indigenous soil fungi reduced
atmospheric CO concentration
from 100-120 ppm to 0 in 3 hours.
                                               Delwiche'
                                  Hill
                                                                12
                                  Inman & Ingersoll
                                                                             17
Test plants absorbed CO,          Bidwell & Fraser
converting it to organic material
by day and C0« by night.
                                               o
It is indicated that algae are    Crespi & Katz
responsible for significant
natural CO emissions.
                                  Nozhevnikgva &
                                  Zavarzin

                                  Bidwell & Beebe*
                                  Shaedle & Oliver32
Decrease in CO content.
Exposed plants absorbed CO
at an average rate of
0.19/|jl/hg fresh weight.

CO incorporation rates varied
from 0.32 n moles/dm -hr to
28.48 n moles/dm -hr. Grasses
tended to have the lowest rate
of fixation.

Air CO within closed box.
Diurnal variation, temperature-
dependent. Glass box over
natural soil  surface.
                          Several micro-organisms produce   Radler et al.
                          trace amounts of CO in the range
                          of 0.4-2.6 ppm. Media containing
                          glucose was found to stimulate
                          CO production.
                                  Seiler
                                                                  33
                                                                         31
a-PPM CO can be converted to mg/m  CO by multiplying
  the above concentrations by 1.145 (@STP).

                                     8-12

-------
8.3.2  Soil Microorganisms


     Inman and Ingersoll   tested non-sterile potting  soil  in plastic

                                                                            o
atmospheric chambers and found that CO concentrations  dropped from 105 mg/m


(90 ppm) to 0 within a 3-hour period.  No change  occurred  in CO concentra-


tions occurred over the controls using sterile  soil  controls.  This  indicated


that potting soil, at least, had a distinct  capacity for CO uptake.  Samples


of natural soils when tested comparatively all  varied  in their ability to


take up CO.  Carbon monoxide uptake appeared to be correlated with high


organic matter and low pH.


     From  the various tests which were conducted, it appeared that the


capacity for CO  uptake was mediated either by a biological  mechanism, or by


some physical absorptive process which,  on the  basis of the inactivity of


sterile soil, was  labile to steam heat.  A series of tests  were conducted


to characterize  the phenomenon  further.  The authors found  that when 2.8 kg


of autoclaved potting soil was  inoculated with  1  g of  non-sterile potting


soil,  uptake activity increased  as a  function of  time  following the


inoculations.  Uptake of CO was  inhibited by the  addition  of 50 ml of 10


percent NaCl to  200 g potting  soil.   Incubation under  anaerobic conditions


for  5  days prior to testing also inhibited CO uptake,  as did drenching the


soil with  50 ml  of an antibiotic solution containing streptomycin,


erythromycin and cyclohexamide.


     These results strongly indicated that the  uptake  of CO was mediated by


a biological rather than physical mechanism. It  was suspected  that  certain


elements of the  soil microflora were  responsible  for CO  fixation.   Inman


and  Ingersoll    then attempted to estimate the  total capacity of  the soil
                                      8-13

-------
to remove CO from the atmosphere.  The average activity of the soils tested


                      2
was 8.44 mg of CO/hr/m  of soil, equivalent to 191.1 metric tons per year



per square mile.  If it is assumed that this value is representative of the



average capacity of soils in the temperate zone, the capacity of the total



soil surface of the Continental United States to take up CO [2,977,128


     2              2
miles  (7,792,533 km )] is estimated to be 569 million metric tons per
year.
                     22
      Liebl and Seiler   found soil uptake of CO to be not as great as that
 reported by  Inman and Ingersoll   but concurred that the soil must be



 recognized as a major natural sink for CO released into the atmosphere.



 Microorganisms other than the soil microflora may have a role in atmospheric


                  39
 CO  removal.  Uffen   described a species of Rhodopseudomonas, a species of



 photosynthetic bacteria that requires CO as the sole source of carbon and


                                                                    28
 uses  it under anaerobic conditions.  Also, Nozhevnikova and Zavarzin   have



 stated that  there exist bacteria which have the capability of oxidizing CO



 and are capable of  growing and developing on a substrate in which CO serves



 as  the sole  source  of carbon and energy.  These bacteria represent a



 potentially  powerful factor in eliminating CO from the atmosphere.  The



 bacteria which oxidize CO to C0« have not been well studied.  Table 8-4



 summarizes data showing soils as CO sinks.



 8.4  PRODUCTION OF  CO BY PLANTS



      Carbon  monoxide evolution by fresh water algae has been shown by


               o

 Crespi and Katz  to be associated with biosynthesis and degradation of



 photosynthetic pigments.  Their results indicated that plants may be the


             O

 source of 10 tons  or more of CO per year.  Production and utilization of
                                      8-14

-------
                TABLE 8-4.  SOILS AS A SINK FOR CARBON MONOXIDE
Cone.
Duration
Effects
Author
80-130 ppm
in air
2-19 hrs,
5-100 ppm
in air
2 hrs.-
45 days
 0-40 ppm
 in  gas
Not
reported
 100 ppm
 2-3  hrs.
Results indicated that the        Ingersoll
phenomenon of CO uptake by soil
was due to a biological rather
than physical mechanism and that
CO uptake was due primarily to
indigenous soil microflora. Rate of
uptake was also temperature dependent.

The uptake of CO by soils  i_n      Ingersoll
situ is variable with soils
rangingpfrom 7.5 to 104.0  mg
CO/hr/m . Tropical soils were
most active; desert soils  were
least active. CO uptake by soils
was greatest at a concentration of
100 ppm and decreased as the
concentration decreased.
                                                                     15
                                                                     14
Removal of CO by the forest       Heichel
soil exceeded that of the field
soil at all moisture contents when
the two were compared at the same
CO concentration. Maximum rates of
removal approached 0.20 mg CO/dm  hour.
                                                                    10
Soils  of major  vegetative
regions of  North  American were
tested as well  as roadside
soils  and soils under  cultivation.
CO  uptake ranged  from  7.6-115 mg
CO/h/m with  tropical  soils  showing
greatest activity and  desert soils
the least.  Roadside  soils were
consistently  higher  in CO uptake
capacity. Natural soils were more
active in CO  uptake  than sterile soil.
IngersolJR Inman
  &r* * i   -LO
  Fisher
 a-PPM CO can be converted to mg/m  CO by multiplying
   the above concentrations by 1.145 (@STP).
                                      8-15

-------
CO by algae and two higher plants (Zostera man*na and Medicago sativa) have


                                     25
been reported by Loewus and Delwiche.    The assimilation and utilization



of CO by a variety of plants proceeds at a significant rate, exceeding



maximum observed rates of production in some cases.   Based on laboratory



studies it can be calculated that a field of 100 hectares of alfalfa could



produce approximately 2000 liters of CO in a ten-hr period.  The effect of



temperature on the evolution of CO by the soil also still remains to be



learned, although there are data on temperature effects of CO uptake by



soil.    Carbon monoxide production rates were found, however, to be light


                                       -13     2
dependent with an average value of 3x10    g/cm /sec of leaf area for a


                           4        2
radiation intensity of 5x10  ergs/cm sec.  The total CO production by


                                         14        34
plants is estimated to be 0.5 to 1.0 x 10   g/year.     This estimate



indicates that plants may contribute significantly to the atmospheric CO



cycle with production rates comparable to the total  CO production rate in



the  oceans.



8.5  SUMMARY



     Of the literature dealing with effects of CO on microorganisms and



plants or with the production and utilization of CO by them, most earlier



work was directed toward physiological studies without reference to



atmospheric concentrations.  There are few studies from which thresholds of



detrimental (or other) effects might be inferred.  Thus, although neither



defoliation nor the inhibition of leaf formation is demonstrable at


                             3

concentrations of 11,000 mg/m  (10,000 ppm) CO or higher, this study



provides little information regarding possible threshold effects since the



concentration used was more than 10,000 times greater than normal



atmospheric levels.
                                     8-16

-------
     The few reports of effects at lower concentrations suggest that



influences in the normal atmospheric concentration range for CO are not



great and that a "threshold" as such does not exist.   Since plants can both



metabolize (apparently photosynthetically) CO and produce CO, it is



considered a normal constituent of the plant environment.



     Microorganisms have a wide range of responses to CO including its



autotrophic oxidation.  Thus, any change in atmospheric concentration could



be expected to result in a corresponding alteration of soil microbial



population distribution; however, no studies seem to have been made.  This



flexibility in the response of the soil microflora to changing environmental



conditions is a generalized one and the soil can be viewed as a buffering



system  and eventual sink for CO.
                                      8-17

-------
                                 BIBLIOGRAPHY

1.    Bennett, J. H., and A. C. H111.  Inhibition of apparent photosynthesis by
     air pollutants.  J. Environ. Qua!. 2:526-530, 1973.

2.    Bergersen, F. J., and G. L. Turner.  Comparative studies of  nitrogen
     fixation by soybean foot nodules, bacteroid suspensions and  cell-free
     extracts.  J. Gen. Microbiol. 53:205-220, 1968.

3.    Bldwell, R. G. S., and G. P. Bebee.  Carbon monoxide  fixation  by  plants.
     Can. J. Bot. 52:1841-1848, 1974.

4.    Bldwell, R. G. S., and D. E. Fraser.  Carbon monoxide uptake and  metabolism
     by  leaves.  Can. J. Bot. 50:1435-1439, 1972.

5.    Bortner, M. H., R. H. Kummler, and L. S. Jaffe.  A review of carbon
     monoxide sources, sinks, and concentrations in the earth's atmosphere.
     NASA CR-2081, National Aeronautics and Space Administration, Washington,
     DC, June 1972.

6.    Chakrabarti, A. G.  Effects of carbon monoxide and nitrogen  dioxide on
     garden pea and string bean.  Bull. Environ. Contam. Toxlcol. 15:214-222,
     1976.

7.    Chapanis, A.  The relevance of laboratory studies to  practical  situations.
     Ergonomics 10:557-577, 1967.

8.    Crespi, H. L., D. Huff, H. F. DaBoll, and J. J. Katz.  Carbon  monoxide in
     the Biosphere:  CO Emission by Fresh-Water Algae.  Argonne National
     Laboratory, Argonne,  IL, October 1972.

9.    Delwlche, C. C.  Carbon monoxide production and utilization  by higher
     plants.  Iji:  Biological Effects of  Carbon Monoxide,  Proceedings  of a
     Conference, New York  Academy of Sciences, New York, January  12-14, 1970.

10.  Heichel, G. H.  Removal of carbon monoxide by field and forest soils.   J.
     Environ. Qual. 2:419-423, 1973.

11.  Heslop-Harrison, J.,  and Y. Heslop-Harrison.  Studies on flowering-plant
     growth and organogenesis.  II. The modification of sex expression in
     Cannabis satlva by carbon monoxide.  Proc. R. Soc. Edinburgh Sect. B
     66:424-434, 1957.

12.  Hill, A. C.  Vegetation:  a sink for atmospheric pollutants.   J.  Air
     Pollut. Control Assoc. 21:341-346, 1971.

13.  Hill, A. C., and E. M. Chamberlain,  Jr.  The removal  of water  soluble
     gases from the atmosphere by vegetation.  In:  Atmosphere-Surface Exchange
     of  Particulate and Gaseous Pollutants (1974),  Proceedings of  a Symposium,
     Battelle Memorial Institute and U.S. Atomic Energy Commission, Richland,
     Washington, September 4-6, 1974.  ERDA Symosium Series 38, U.S. Energy
     Research and Development Administration, Washington,  DC, January  1976.
     pp. 153-170.
                                      8-18

-------
14.  Ingersoll, R. B.  The Capacity  of  the  Soil  as a Natural  Sink for Carbon
     Monoxide.  Final Report  to  Coordinating Research Council  and Environmental
     Protection Agency.  Stanford  Research  Institute, Menlo Park, CA, December
     1972.

15.  Ingersoll, R. B.  Soil as a Sink for Atmospheric Carbon  Monoxide.   Final
     Report to Coordinating Research Council  and Environmental  Protection
     Agency.  Stanford Research  Institute,  Menlo Park,  CA,  October 1971.

16.  Ingersoll, R. B., R. E.  Inman,  and W.  R.  Fisher.  Soil's  potential  as a
     sink for atmospheric carbon monoxide.   Tell us 26:151-159,  1974.

17.  Inman, R. E. , andJJ. B.  Ingersoll.   Note on the uptake of carbon monoxide
     by soil fungi.   J. Air Pollut.  Control  Assoc.  21:646-647,  1971.

18.  Inman, R. E., R. B. Ingersoll,  and E.  A.  Levy.   Soil:   a  natural sink for
     carbon monoxide.  Science 172:1229-1231,  1971.

19.  Kortschak, H. P., and L. G. Nickel!.   Photosynthetic carbon monoxide
     metabolism by sugarcane  leaves.  Plant Sci. Lett.  1:213-216, 1973.

20.  Knight, L. I.,  and W. Crocker.   Toxicity of smoke.   Bot.  Gaz.  (Chicago)
     55:337-371,  1913.

21.  Krall, A. R., and N. E.  Tolbert.   A comparison of the light dependent
     metabolism of carbon monoxide by barley leaves with that  of formaldehyde,
     formate and  carbon dioxide.   Plant Physio!. 32:321-326,  1957.

22.  Liebl, K. H., and W. Seller.  CO and hL destruction at the soil  surface.
     In:  Proceedings of the  Symposium  on MTcrobial, Production and Utilization
     of Gases (I-L, CH-, CO),  Akademie der Wlssenschaften, Goettlnger, Germany,
     September 1-5,  1975.  H. G. Schlegel,  G.  Gottschalk, and  N.  Pfennig,
     eds., E. Goltze KG, Goettinger,  Germany,  1976.   pp.  215-229.

23.  L1nd, C. J., and P. W. Wilson.   Mechanism of biological  nitrogen fixation.
     VIII. Carbon monoxide as an inhibitor-for nitrogen fixation by red  clover.
     J. Am. Chem. Soc. 63:3511-3514,  1941.

24.  Lind, C. J., and P. W. Wilson.   Carbon monoxide inhibition of nitrogen
     fixation by  Azotobacter.  Arch.  Biochem.  1:59-72,  1942.

25.  Loewus, M. W.,  and C. C. Delwiche.   Carbon monoxide production by algae.
     Plant Physio!.  38:371-374,  1963.

26.  McMillan, C., and J. M.  Cope.   Response to carbon monoxide by geographic
     variants in  Acacia farnesiana.   Am.  J.  Bot. 56:600-602,  1969.

27.  Minina, E. G.,  and L. G. Tylkina.   Physiological study of the effect of
     gases upon sex  differentiation  in  plants.   Dokl. Akad.  Nauk SSSR 55:165-168,
     1947.

28.  Nozhevnikova, A. N., and G. A.  Zavarzln.   Symbiotic oxidation of carbon
     monoxide by  bacteria.  Mikrobiologiya  42:158-159,  1973.
                                       8-19

-------
29.   Pankhurst, C. E., and J. I. Sprent.  Effects of water  stress  on the
     respiratory and nitrogen fixing activity of soybean  root  nodules.
     J. Exp. Bot. 91:287-304, 1975.

30.   Quayle, J. R.  The metabolism of one-carbon compounds  by  micro-organisms.
     Adv. Mlcrob. Physio!. 7:119-203, 1972.

31.   Radler, F., K. D. Greese, R. Bock, and W. Seller.  The formation of
     traces of carbon monoxide by Saccharomyces cerevlslae  and other
     microorganisms.  Arch. Mlcrobiol. 100:243-252, 1974.

32.   Schaedle, M., and D. Oliver.  Carbon monoxide fixation by three plant
     communities.  Plant Physlol. Suppl.:33, 1974.

33.   Seller, W.  The cycle of atmospheric CO.  Tellus 26:116-133,  1974.

34.   Seller, W., H. G1ehl, and G. Bunse.  The influence of  plants  on atmospheric
     carbon monoxide and dinitrogen oxide.  Pure Appl. Geophys.  116:439-451,
     1978.

35.   Smith, L., Jr., and E. H. C. Sie.  Response of luminescent bacteria to
     common atmospheric pollutants.  Proc. Annu. Tech. Meet. Inst.  Environ.
     Sci. 15:154-157, 1969.

36.   Stewart, J. K., and M. Uota.  Market quality of head lettuce  as Influenced
     by added CO and C0« and by  low 0~ during simulated transit. Hort Science
     9:274, 1974.      *             *

37.   Stewart, J. K., and M. Uota.  Postharvest effect of modified  levels of
     carbon monoxide, carbon dioxide, and oxygen on disorders  and  appearance
     of head lettuce.  J. Am. Soc. Hortic. Sc1. 101:382-384, 1976.

38.   Thompson, C. R., 0. C. Taylor, M. D. Thomas, and J. 0.  Iv1e.   Effects of
     air pollutants on apparent  photosynthesis and water use by citrus  trees.
     Environ. Sci. Technol. 1:644-650, 1967.

39.   Uffen, R. L.  Anaerobic growth of a Rhodopseudomonas species  in the dark
     with carbon monoxide as sole carbon and energy substrate.  Proc.  Natl.
     Acad. Sci. U.S.A. 73:3298-3302, 1976.

40.   Wittenberg, J. B., C. A. Appleby, and B. A. Wittenberg.   The  kinetics of
     the reactions of leghemoglobln with oxygen and carbon  monoxide.   J.  B1ol.
     Chem. 247:527-531, 1972.

41.   Wolf, F. T., and G. H. Kidd.  Effect of various gas atmospheres upon the
     greening of etiolated seedlings.  2. Pflanzenphysiol.  70:115-118,  1973.

42.   Zimmerman, P. W., W. Crocker, and A. E. Hitchcock.  The effect of carbon
     monoxide on plants.  Contrib. Boyce Thompson Inst. 5:195-211,  1933.

43.   Zimmerman, P. W., W. Crocker, and A. E. Hitchcock.   Initiation and
     stimulation of roots from exposure of plants to carbon monoxide gas.
     Contrib. Boyce Thompson Inst. 5:1-17, 1933.
                                      8-20

-------
                 9.   METABOLISM OF CARBON MONOXIDE IN MAMMALS







     Adverse health effects of carbon monoxide (CO) are due primarily to



diminished oxygen (Op) transport by the blood and to interference with



biochemical utilization of 02 in tissues.  The chemical binding of CO to



hemoglobin (Hb) and other heme compounds in tissues is so much stronger



than the binding of Op to these compounds that Op is excluded in part



from its normal physiological role.  The apparent toxicity of CO is



related to the strength of the coordination bond formed with the iron



atom in protoheme (C-.H-pN.O-Fe).  Hemoglobin, a ferrous iron complex of



a protoporphyrin combined with globin, is contained within the erythrocyte



(red cell).  A small amount of CO is produced within the body by normal



breakdown processes, which result in carboxyhemoglobin (COHb) levels of



about 0.5 percent in blood.  Any increase above this level is assumed to



result from outside sources.  The excretion of CO in exhaled air appears



to occur in two stages, rapidly at first and then more slowly.



9.1  INTRODUCTION



     Mammals obtain CO from two sources:  (a) the endogenous one,



normally from the breakdown of Hb, and (b) by inhaling exogenous CO from



the ambient air.  The quantity of endogenous CO is small although greater



quantities can be produced in various disease states and by ingestion or
                                     9-1

-------
inhalation of certain drugs and chemicals.   Exogenous CO, from inhalation,



increases the concentration of CO in the alveoli of the lung, which



increases its diffusion through the pulmonary and capillary membranes



into the blood.  The final, and most important, factor is the great



avidity with which the Hb in the red cell (erythrocyte) combines with



the CO.  The changes in the concentration of this combined Hb and CO



(COHb) is finally determined by many factors:  the endogenous CO produced,



the concentration of CO inhaled, the volume of inhaled air (which is



related to the degree of physical activity of the individual), body



size, barometric pressure, and the functional capacity of the lung


                                                             35
itself.  These factors have been briefly summarized by Klocke   and



Coburn.



     An Op supply adequate to maintain tissue metabolism is provided by



the integrated functioning of the respiratory and cardiovascular systems



to transport Op from the ambient air to the various tissues of the body.



Nearly all of the 0«, except that dissolved in plasma, is bound reversi-



bly to the Hb contained within the erythrocytes.  The most significant



chemical characteristic of the air pollutant, CO, is that it is also



reversibly bound by Hb.  Therefore, it is a competitor with 0« for the



four binding sites on the Hb molecule.  The reduction in the Op-carrying



capacity of the blood is proportional to the amount of COHb present.



A simplistic example is provided by comparing an anemic individual



having 7.5 g percent of Hb with another individual having 15 g percent



but with half of this Hb as COHb, i.e., 50 percent COHb.  The Op-carrying



capacity is equivalent in both.  However, the amount of available Op is



still further reduced by the inhibitory influence of COHb on the dissocia-



tion of any oxyhemoglobin (OpHb) still available.
                                     9-2

-------
9.2  THEORETICAL CONSIDERATIONS



     The equilibrium constant, M (Haldane's constant), expresses the



relative affinity of Hb for CO and 0« under conditions in which the


                                               21
concentration of reduced Hb is minimal.  This M   is defined by the



following equation:



                    (COHb)
                            =  M
                    (0?Hb)     "   Pn

                      *              2



where P«Q and PQp represent the equilibrium gas partial pressures:



each pressure being the same in the erythrocytes or Hb solution as in



the equilibrated gas phase; (COHb) and  (OpHb)", on the left side of the



equation, are the concentrations of COHb and OJHb, respectively.



The value of M  is about 200 plus in most mammalian species (246 in man),



in spite of the fact that CO combines with Hb more slowly than does 0«.



Carboxyhemoglobin dissociates very slowly due to the tight binding of



CO to Hb.  Technically, it is not possible to measure the rate of



dissociation of CO from partly saturated Hb.  The dissociation velocity



constant has been measured only by a few investigators on sheep and



human Hb fully  saturated with CO.  The  most commonly used values for M

                                                               re

in the  recent literature have ranged from 210 to 230.  Roughton   has



presented the most comprehensive analysis of the interaction  of CO with



erythrocyte Hb.  He reviewed the extensive early literature and presented



new data on several portions of the dissociation curve.  Roughton1s data



clearly indicate that a mean value for  M is approximately 246, although



it is different for various portions of the dissociation curve.  The



attraction by the Hb molecule for CO, compared  to that for Op,  is thus
                                      9-3

-------
suggested to be some 246 times greater.  In fact, this value was the one


                                      21                                 34
originally suggested by Douglas et al.   and confirmed by Joels and Pugh.



     Solution of Haldane's equation would give an approximate level



of COHb; e.g., exposure to ambient environments containing 29, 57, or

        3

114 mg/m  (25, 50, or 99 ppm) CO would lead to COHb saturations of



approximately 4.8, 9.2, and 16.3 percent if arterial 0^ pressure were



80 torr.  The CO enters the lungs with each breath and diffuses across



the alveolar-capillary membrane in a manner similar to 0^.  If air with



a constant concentration of CO is breathed for hours, the rate of uptake



of CO decreases exponentially (roughly so) until an equilibrium state is



attained in which the partial pressure of CO in the pulmonary capillary



blood is equivalent to that in alveolar air.  The half-time for this



process is approximately two hours in a healthy individual engaged in



light physical activity.   This process is altered during heavier



physical exercise or in certain disease states.



     Transport of 0« in the blood is best described by the O^Hb dissocia-



tion curve (Figure 9-1).  This curve, in the presence of COHb, is no



longer  classically sigmoid but is shifted to the left so that a lower 0«



pressure is present for the same O^Hb saturation compared to blood with


    57                                        57
COHb    (see Figure 9-2).  Roughton and Darling   pointed out that only



the upper half of the steep portion of the 0« dissociation curve was



operative for Op unloading, with the  lower portion serving as a reserve.



When COHb is below 40 percent, 0« uptake is maintained by use of some or



even all of the reserve 0« from undissociated 0«Hb at low tensions.
                                     9-4

-------
i
Z
UJ
H
Z
O
o
 CM
O
                                         1     I        i   I   I
                 1= 0% COHb

                 2= 5% COHb

                 3= 10% COHb

                 4= 20% COHb
        10
20
30
40
60
80   100
                                  PO,
Figure 9-1. Oxygen dissociation curve with and without the presence of
varying concentrations of CO.
                                 9-5

-------
 0)
 o.
o

K

oc
D


CO
     100



      80





      60
      40
      30
      20
       10
         10
                        20
                                             pH7.4
                                   I	I
30     40
                                       PO,
60     80   100
Figure 9-2. Blood oxygen dissociation curves at various COHb values.
                                    9-6

-------
If COHb exceeds 40 percent, adequate amounts of 0? cannot be delivered



to the tissues.  Figure 9-2 illustrates the extent of the Haldane shift



to the left more clearly than the classical curves of Figure 9-1.


                42
Mulhausen et al.    illustrate this shift by observing that the P™



(half saturation) Op tension shifted from 26.7 to 23.2 torr in their



subjects, who were intermittently exposed to high concentration of


                    36            16
ambient CO.  Ledwith   and Collier   have presented methods for deter-



mining P,-0 in the presence of COHb and extended theoretical considera-



tions for the computation of PQ2 in the presence of CO.  Carbon monoxide



not only diminishes the total amount of Op available by direct replace-



ment of Op (Figure 9-1) but also alters the dissociation of the remaining



Op so that it  is held more tenaciously by Hb and released at lower Op



tensions.  The OpHb curve in the presence of COHb progressively resembles



the simple Op  dissociation curve of myoglobin.  Myoglobin is a heme



compound with  only one heme unit per molecule and does not exhibit heme-



heme  interactions.  It is possible that the combination of one or more



of the four  heme groups in Hb with CO decreases the heme-heme interac-



tions of the remaining heme units and results in a molecule approaching


                                           32
the behavior of myoglobin.  Hlastala et al.   have presented data indi-



cating that  heme-heme interaction is different for Op than for CO.  This


                                                                  44
decreased  heme-heme interaction has been confirmed by Okada et al.



      Carbon  monoxide poisoning is similar  to anemia wherein the Op



capacity of  the blood is  reduced due to a  reduction in the Hb concentration.



The Op dissociation curve of blood obtained from patients with anemia  is



shaped like  the normal curve but is vertically compressed.  However,
                                      9-7

-------
when curves from individuals with a 50 percent reduction in Hb content


are compared to dissociation curves determined in the presence of


50 percent COHb, there are striking differences.  Consequently, the


tendency to make such comparisons is likely to lead to erroneous deduc-

                                                                    5
tions as to effects occurring at the tissue level.  Brody and Coburn


have discussed these differences in relation to arterial and venous P
                                                                     CO
and PQ2 levels.
     The possibility that an adaptation to CO (such as in the case of


adaptation to  high altitudes) could alter the position of the 0«


dissociation curve as a consequence of extensive exposure to CO appears

                                        42
to  have been answered.  Mulhausen et al.   found no change in the


degree of  left shift in the blood of individuals exposed to CO for a


period of  8 days.  Unfortunately, the average COHb of 13 percent was


based on large individual variation in COHb and a periodic exposure to


relatively higher inhaled CO concentrations.


     Several investigators have  sought for evidence of a potential shift


of  the curve back to the right.  Red cell 2-3-diphosphoglycerate is


increased  in individuals with anemia and during residence at high altitude.


2,3-Diphosphoglycerate  (2,3-DPG) is a phosphorylated by-product of


glycolysis.  In erythrocytes of  man and most other mammals, the molar


concentration  of 2,3-DPG is roughly equal to that of Hb.  It and some


other organic  phosphates are bound rather strongly to deoxyhemoglobin


(de-02Hb)  but  have little affinity for 02Hb.  Increases in 2,3-DPG shift


the effective  0« affinity; i.e., a shift of the 0«Hb dissociation curve

                            3
to  the right occurs.  Astrup  found a small decrease in erythrocyte
                                      9-8

-------
2,3-DPG in human subjects maintained with 20 percent COHb for 24 hours.


             on
Dinman et al.    conversely found a small increase in 2,3-DPG in human



subjects after 3 hours at approximately 20 percent COHb and in rats



exposed to higher but variable concentrations of CO.  A shift of the



dissociation curve does not appear to indicate an important adaptation



to CO exposures of less than a few days.  Cameron et al.  have reported



that CO has a significantly greater effect upon the position of the 0?



dissociation curve in patients with sickle-cell anemia than in normal



subjects.   It is possible that in sickle-cell anemia there is an



increased Hb affinity for CO.



     Any consideration of the toxicity of CO must include not only the



decrease in the Op-carrying capacity of Hb but also the interference


                                                  4

with Op release at the tissue level.  Ayres et al.  raised the COHb



concentration to an  acute average of 9.0 percent saturation in 26 subjects,



some with and some without heart disease.  Mixed venous PQ2 decreased



from 39 to  31 torr,  suggesting a decrease in tissue Op pressure since



mixed  venous Op pressure must represent, at least roughly, the maximum



values  for  tissue oxygenation.  Arterial Op tension decreased 5 torr


                                           4
from the control level of 81.  Ayres et al.  also measured the alveolar-



arterial Op gradient.  The 9 torr increase in the gradient implies that



the pulmonary arterio-venous shunts became larger,  accounting for both



the increased alveolar-arterial Op  difference and the  decrease in


                            52
arterial Op tension.  Power,   however, found that  CO  diffuses more



rapidly through blood and pulmonary and placental tissues than would  be



predicted from comparative solubilities of Op and CO  in water.  Brody
                                      9-9

-------
          5
and Coburn  have indicated that if the 0« content of the mixed venous
blood is abnormally low, as in anemia or CO poisoning, the effect of the
shunted blood in lowering arterial PQ2 wil1 be greater than normal• and
a small increase in the alveolar-arterial pressure difference (A-aDQ2)
will result.  The change in the shape of the CLHb curve due to the
                                                                        5
presence of CO will also increase A-aDQ«.  Furthermore, Brody and Coburn
also showed that mild increases in COHb concentrations would have little
or no influence on the A-aDQ2 in normal subjects.  However, in patients
with large  intracardiac right-to-left shunts or with chronic lung disease
and regional variation in the ventilation perfusion ratio (V./Q), the
presence of CO in the blood will increase the A-aDQ?.
     The venous P0p values expected to result from various COHb levels can
              24 49
be calculated.  '    If blood flow and metabolic rate remain constant,
equilibration with an ambient CO of 200 ppm (25 percent COHb) will lower
venous  PQ2  from 40 to less than 30 torr.  A similar degree of venous
hypoxemia results from an ascent by a normal individual to an altitude
of 3658 m or a 35 percent reduction in 0« capacity in an anemic patient.
It can  also be calculated that at 5 percent COHb there will be only a
slight  drop in the mixed venous PQp.  Even more significant relationships
can be  obtained by plotting Op content against the partial pressure
      57
of Op.    The difference in Op content at various percentages of COHb
from zero to 20 reveal that only a small change occurs in the availability
of Op due to the Haldane effect (Figure 9-1).  It was this evaluation
                              57
which led Roughton and Darling   to conclude that COHb concentrations
less than 40 percent produce relatively easily compensated restrictions
                                     9-10

-------
in the amount of 0« available for tissue delivery.  This can only be



applied to subjects with normal respiratory and circulatory systems.



The small reductions in Op content at 5 to 10 percent COHb may be quite



critical for patients suffering from cardiovascular diseases or chronic


                                        12
obstructive lung disease.  Coburn et al.   published a detailed theoreti-



cal analysis of the physiology and variables that determine blood COHb



levels  in man.  The details of the formulas used in these calculations


                                                49
are presented in section 9.3.  Permutt and Fahri   have calculated that



when COHb levels are approximately 5 percent, resting coronary blood



flow (CBF) must increase about 20 percent in order to prevent myocardial



ischemia.  This theoretical calculation has been confirmed experimentally


               1             33
by Adams et al .  and Horvath,   who demonstrated such approximate



increases in CBF despite having used very different methods to increase



blood  COHb levels.



     Cerebral function  is  said to be altered at low COHb levels and it



is of  some interest to  examine the available data on cerebral
                                                             CO

 tensions,  cerebral  blood flow, and cerebral metabolism.  Zorn   studied



 the effects  of  CO  inhalation  in vivo on brain  and  liver  Pno  using
                              - -                     \J£.


 platinum electrodes.  Tissue  PQ2  fell  in  both  organs,  even at COHb




 concentrations  of  2 percent,  and  the fall was  approximately  linear to




 increases  in COHb.   Oxygen  partial pressure decreased  0.2 to 1.8 torr




 for each I percent fall  in  0«Hb saturation.  These data  suggested that




 CO had influences  other  than  at the intracellular  level, since  if it was



 limited to this area, tissue  P««  would have been expected to increase.


                ep

 Weiss and Cohen   performed similar studies on rat brain and muscle.
                                      9-11

-------
They found a decrease in cerebral cortical PQ2 consequent to inhalation



of low levels of CO.  Unfortunately, they did not measure COHb levels in



these rats, although, in a group of sham-operated animals exposed to



similar levels of inhaled CO, COHb had increased to 3.3 percent.


                31
Haggendal et al.    reported that during progressive CO administration to



dogs, cerebral blood flow did not increase until COHb levels attained



20 percent.  Thereafter, cerebral blood flow increased progressively and



was double the control values when COHb reached 50 percent.  Paulson et


   48
al.   measured cerebral blood flow in five human subjects.  No changes



were observed at 8  percent COHb but a greater than 20 percent increase



occurred when COHb  was 20 percent.  Despite the increase in cerebral



blood flow, the PO« of jugular venous blood was reduced by 3.4 torr at



this high  level of  COHb.  Jugular venous PO« was reduced 1 mm when COHb



was 8 percent but no note was made as to whether this was a significant



decline.   Arterial  and jugular venous lactates were said to be unchanged.


                       39
     McGrath and Martin   have presented evidence that CO may have a



direct effect on the heart in addition to its well known Hb-mediated



effect.  Carbon monoxide caused a reduction in developed tension and an



increase in resting tension of cardiac muscle.  Recovery of muscle



function was also depressed.  Chen and McGrath  have also reported that



CO has a specific effect on the myocardial conducting system.  Carbon



monoxide may have specific effects independent of the reduction in 0?



availability.



     Total-body asanguineous, hypothermic perfusion was recently sug-


                                                2
gested as  a therapeutic measure in CO poisoning.   In an attempt to
                                      9-12

-------
                                              53
explain this beneficial effect, Ramirez et al .   compared the survival of



normal dogs given high levels of CO versus acutely anemic dogs transfused with



COHb blood.  All normal dogs with COHb levels of 54 to 100 percent died within



0.25 to 10 hours but the transfused animals, having a final mean COHb of



80 percent after transfusion, survived.  The authors suggested that hypoxic



anemia was not the principal mechanism of CO toxicity but that the blocking



out of the energy supply on the cellular level governed by the cytochrome



system was heavily involved.
                              — 9Q

     Goldbaum and co-workers      have suggested that in order for CO to



 affect mitochondrial respiration (particularly through combination with



 cytochromes) it must be dissolved first  in plasma.  They report that if



 0.001 ml  CO is physically dissolved  in the plasma, even though COHb levels



 were above 20 percent, this physically dissolved CO combines with the cyto-



 chromes,  and it is  this combination  rather than the reduction in 0^- transport



 capacity  of the blood that appears to be responsible for the toxic effects of



 CO.  Dogs injected  with CO intraperitoneally  survived indefinitely even though


                                                              45
 their COHb levels were as high as 75 percent.  Orellano et al .   presented



 experimental data which suggested that CO injected intraperitoneally into dogs



 is nontoxic.  The implication of these results suggests that the CO tension  in



 the blood after inhaling CO is high  because the combination of CO with Hb is



 not instantaneous.  They postulated  that blood leaving the lungs has a high  CO



 tension and this physically dissolved CO is more  likely to combine with the



 various heme compounds in tissue and so  produce a  local effect on mitochondrial



 metabolism.  There  may be some questions regarding these observations  since  the
                                      9-13

-------
kinetics of CO transport would not be completely supportive of the


                                 22
changes observed.  Drabkin et al.   had reported a similar effect in



1943 and explained the lack of toxicity as the Haldane effect.

                  o

     Chiodi et al».  indicated that the respiratory center or arterial



chemoreceptors were not stimulated to elevate the respiratory minute



volume even when COHb levels were as high as 40 percent.  Mills and


       41
Edwards   measured the frequency of electrical impulses in the afferent



nerves from the aortic and carotid chemoreceptors.  They showed that CO



administration does result in chemoreceptor stimulation.  The response



appeared to be approximately linear with the COHb concentration (at



least definitely above 8 percent).  These findings suggest that CO may



stimulate breathing.  The failure to observe an increased minute volume



might be explained by considering that, in the presence of CO, the



chemoreceptor stimulation was offset by hypoxic depression of brain



structures that are involved in  breathing.  There is some evidence that



this balancing between chemoreceptors and central nervous depression is

                    CO

operative  in anemia.    The difference in observed responses may be



related to varying sensitivities of the baro- and chemoreceptors to



carbon monoxide  and to PQ2.  Additional investigations are needed to



clarify this physiological effect of CO inhalation.



9.3  ABSORPTION,  EXCRETION, AND  EQUILIBRATION



     Carbon monoxide  in the body is produced endogenously from the



catabolism of the pyrrole rings  originating from  Hb, myoglobin,



cytochromes, and  other heme-containing pigments.  The adult's endogenous



production normally amounts to approximately 0.4  ml (STPD) per hour.   '
                                      9-14

-------
                                                    15
Increased production can occur in hemolytic anemias,   during the


                           18
menstrual cycle in females,   and in the induction of liver cytochromes



consequent to administration of drugs such as phenobarbital or


                  g
diphenylhydantoin.   The basal production of endogenous CO of approxi-



mately 0.31 ±0.07 umole/(hr/kg) can be increased in these conditions by



approximately threefold.    These increases are of minimum importance in



the elevation of COHb compared to the increases that occur when exogenous


                                      40
CO input is considered.  Mercke et al.   have found diurnal endogenous



production to be lowest in the morning.  Fasting for 24 hours resulted



in increased endogenous production.  It should be kept in mind that



there is considerable inter- and intra-individual variation in endogenous



CO production.  The primary factors determining the final level of COHb



are inspired CO, minute alveolar ventilation in rest and exercise,



endogenous CO production, blood volume, barometric pressure, and the



relative diffusion capability of the  lungs.  The rate of diffusion from



the alveoli and the combination of CO with the blood Hb is the step



limiting the rate of uptake into the blood.  A special case of CO exposure,



important to a large proportion of the population, is the intake from



tobacco  smoking.  This  is primarily direct exposure for the smoker and



indirect for the  nonsmoker, i.e.,  inhalation from a smoke-filled



environment.


                                                     23
     The classical absorption curves of Forbes et al.   have been



reevaluated for the resting person   and are presented in Figure 9-3.


                    50
Peterson and Stewart    exposed human volunteers to a variety of different



CO concentrations for periods ranging  from 0.5 to 24 hours.  Using
                                      9-15

-------
                  ABSORPTION OF CARBON MONOXIDE
 I
 2L
  %
O
o
O
-I
CO
z
00
o
o

LJLJ
X
>
X
o
CQ
OC
                                  I    !   II I  MM
VQQ= 0.007 ml/min
                                               1000 | 2000
                                                   24 hours
                                                   5000 min
Figure 9-3.  Exposure duration, ambient carbon monoxide concentrations
(resting individuals). (Reprinted from Annual Review of Pharmacology, with
the permission of the publisher.)
                                    9-16

-------
regression analysis, they derived the following empirical relationship



for blood COHb as a function of ambient CO concentration and exposure



time:



     Log1Q y = (0.85733 log1Q x + 0.62995 Iog10 t) - 2.29519;



          where y = % COHb,



                x = CO concentration in ppm, and



                t = time in minutes.



Although these new data come closer to presenting potential uptake in



individuals exposed to present-day ambient concentrations of CO, they do



not  address themselves to the uptake that would occur in an active


                         46
individual.  Ott and Mage   have objected to the Peterson and Stewart



presentation as representing a static model.  They indicate that the use



of averaging periods as long as 1 hour versus 10 to 15 minutes  introduces



an error  into recorded urban concentrations by obscuring short-term high



concentrations.


                                        23
     The  data presented by Forbes et al.   have been until recently the



only experimental information available which takes ventilation into



account and, even so, their information is inadequate since the full



range  of  inspired, ventilatory volumes possible in exercising man were


                                     50
not  considered.  Peterson and Stewart   reported excellent correlation



between the COHb values measured in their volunteer subjects with those


                                                                        12
predicted by the Coburn et al. equation (see Figure 9-3).  Coburn et al.



have developed an equation which permits the calculation of blood


     50
COHb  as  a function of time, considering appropriate physiological and



physical  factors.  This equation was used to calculate COHb concentrations
                                      9-17

-------
for exercising individuals, as represented in Figure 9-4.  In the equation,



0«Hb concentration depends upon COHb in a complex way and, therefore,



solution of the equation requires some special computer techniques



utilizing a second approximation.  These have been attempted, and general


                        12                      51
solutions are available.    Peterson and Stewart   have shown that this



equation appears to predict COHb levels as well for women as it does for



men, even though the female subjects absorbed CO more rapidly than most



male subjects.  Exercise sufficient to increase alveolar ventilation



approximately 2.5 times above resting levels was also predictive.  The



small number of subjects of each sex that were studied and the relatively



low exercise ventilatory rates limit the application of this prediction



formula and await further experimental verification.  Further development



of Coburn's concepts will undoubtedly improve the base on which theo-



retical uptakes can be calculated.  Calculations based on the Haldane



formula can be utilized for determining equilibrium COHb concentrations.



     There is no excretion of CO unless there is respiration.  When air



or 0« is breathed, CO dissociates from Hb, myoglobin, and heme pigments



and diffuses back into the plasma and into the expired air.  Carbon



monoxide can be almost completely recovered in the expired air.  Some



animal experiments suggest that  a small amount is oxidized i_n vivo to



carbon dioxide (C02).



     Adequate data are available on the rate of absorption of CO, but



there is considerably less information concerning the rates  of CO



egress from the lungs.  The same factors which determine how much CO is



taken up by the blood should apply in reverse when one considers clearance
                                      9-18

-------
                                                                            20 LPM 50 PPM CO


                                                                            10 LPM 50 PPM CO
                                                                            20 LPM 20 PPM CO
                                                                            10 LPM 20 PPM CO
                                                                            •First observable
                                                                             CO effects
                                                                            20 LPM  10 PPM CO
                                                                            10 LPM  10 PPM CO
Figure  9-4.  Exposure  duration,  ambient carbon  monoxide concentrations.
              (Exercising individuals)
                                    9-19

-------
of CO from blood.  The primary factors involved are the amounts of CO



and 09 present, the magnitude of ventilation, and the quality of the
     £-                                                    »


diffusion barrier.  Age influences the quality of the barrier and it



appears that with advancing age the barrier becomes more dense and there


                                               59
are fewer gas exchange membranes.  Sedov et al.   presented data on the



elimination of CO at various atmospheric pressures and ambient



temperatures.  Neither lower barometric pressures nor high temperatures


                                                          47
appreciably altered the rates of elimination.  Pace et al.   have implied



that a sex difference in elimination may also exist, i.e., females



appear to have a  faster rate than males, at least under their experi-


                                               30
mental conditions.  Similarly, Goldsmith et al.   indicated that men and



women have different COHb excretion rates — men having a half-life of



4  hours and women, 3 hours.  They explained these differences as being



related to physiologic differences in blood volume and pulmonary vital



capacity.



     Available evidence suggests the presence of a biphasic decline in

                                         OC CT

the percentage of COHb in arterial blood.   *    There is a rapid,



initial,  exponential decline (distribution phase), probably related to



distribution  of  CO from the circulating blood to splenic blood, myoglobin,



and cytochrome enzymes.  Elimination of CO via the lungs also occurs



during this phase.  The distribution phase, which persists for the first



20 to 30  minutes, is followed by a slower linear decline (elimination



phase).   This phase probably reflects the rates of release of CO from Hb



and myoglobin, pulmonary diffusion, and ventilation, as well as the fact


                                    43

that Prn  decreases with time.  Myrhe   found a similar biphasic excretion
                                      9-20

-------
pattern to occur at an altitude of 1630 meters.  However, he  noted that



the half-life of COHb was much longer — 5.5 hours.  Tiunov and Kustov



found that following continuous exposure to CO for 49 hours,  50 percent



was eliminated in 30 to 180 minutes and 90 percent within 180 to 420


                             12 40
minutes.  Other investigators  *   have reported exponential  COHb



elimination curves over many hours.  However, they were unable, because



of inadequate sampling in the early phase of elimination, to  observe the



more rapid initial decline.  The absolute level of COHb at the beginning



of elimination studies apparently modifies the rate of disappearance of



CO from the blood.  Utilizing the simpler linear relationship, it



appears that half-times for COHb levels of 5 to 16 percent and 20 to



43 percent are approximately 190 and 134 minutes,  respectively.  If the



more accurate exponential (semilogarithmic) relationship  is utilized,



the half-times for the above levels of COHb are 226 and 148 minutes,



respectively.  These rates must be considered as being approximations,



since  considerable individual variability has been observed.  In summary,



discharge of CO occurs first at a rapid rate and then becomes slower



with time; and the lower  the initial level of COHb, the slower the rate



of disappearance.  No  studies have apparently been made to determine the



disappearance rates at the low levels of COHb  (2 to 4 percent) that



might  be  present  following exposure to ambient concentrations of CO.
                                      9-21

-------
     Several procedures have been tried which could accelerate the



excretion of CO from the blood of individuals who have high levels of


                                     47
COHb (40 to 70 percent).  Pace et al.   reported that treatment of such



individuals in a recompression chamber with an 0« level equivalent to



2.5 atmospheres (partial pressure of 02 equal to 1900 torr or an alveolar



0« pressure of 1801) would facilitate removal of CO.  They indicated



that 1 hour in such a chamber would result in the reduction of COHb to



10 to 15 percent, whatever the initial level might have been.   Malorny


      38
et al.   have revived the Henderson and Haggard treatment concept.  They



evaluated the influence of breathing different gas mixtures on the



excretion of CO in animals having high COHb levels (60 to 74 percent).



It was determined that  in animals, 50 percent could be excreted in



19 minutes  if 5 percent C0? and 95 percent 0« were breathed, compared to



28 minutes  for 100 percent 02, and 41 minutes for ambient air.  Another

                                         2
approach was suggested  by Agostini et al.  who employed a total-body



asanguineous, hypothermic procedure.  The biological half-life of CO in



man under normal conditions is one and one-half hours.  This approach to



removal of  the body burden of excessive amounts of CO remains to be



fully evaluated in clinical trials.
                                      9-22

-------
     The following table (Table 9-1), based on the Haldane relationship



for resting individuals, indicates the equilibrium percentage saturation



of the Hb with CO at various alveolar pressures of CO (alveolar PO« is



assumed to be 98 torr):






                 Table 9-1.  PERCENT COHb VERSUS CO PRESSURE



                                        CO
%COHb
0.87
1.73
3.45
5.05
6.63
8.16
9.63
11.08
12.46
13.80
15.11
16.37
17.60
18.78
19.95
21.05
22.15
23.23
24.26
25.25
26.22
PPm
5
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
% Atmosphere
0.0005
0.001
0.002
0.003
0.004
0.005
0.006
0.007
0.008
0.009
0.010
0.011
0.012
0.013
0.014
0.015
0.016
0.017
0.018
0.019
0.020
Torr
0.0038
0.0076
0.0152
0.0248
0.0304
0.0380
0.0456
0.0532
0.0608
0.0684
0.0760
0.0836
0.0912
0.0988
0.1064
0.1140
0.1216
0.1291
0.1368
0.1442
0.1520
 9.4  DISTRIBUTION  IN BODY TISSUES



     When discussing the intracellular effects of CO, consideration must



 be given to the  interactions of all substances within the tissue cells



 which are involved with 0? delivery.  Since Hb and myoglobin are struc-



 turally related, they react with CO in a similar manner.  The function



 of myoglobin  (in vivo) may be to act as a reservoir for 0« within the



 muscle fiber.  There are approximately 132 g of myoglobin in the muscles



 of a 70-kg man.  The turnover rate  is on the order of 0.34 mg/day.  The
                                     9-23

-------
CO and 0^ equilibria of human myoglobin (in vitro) has been studied and
a hyperbolic 0« dissociation curve established.    This curve, unlike
the hemoglobin one, is not affected by the hydrogen ion concentration,
the ionic strength, or the concentration of myoglobin.  The relative
affinity constant, M, is approximately 40 but is still sufficient to
induce appreciable formation of carboxymyoglobin (COMb).  Coburn et
al.   '   as well as Luomanmaki   have studied the interrelationships
                                                14
between COHb and COMb.  Coburn1s work utilizing   CO has shown that
identical CO exposures can produce different degrees of saturation of
Hb, depending upon the partial pressures of 0« in blood and tissue.
                     13
Coburn and associates   determined that the ratio of CO content in
muscle to the content in blood is a function of arterial P02-  This
ratio, for skeletal muscle, was found to be approximately 1 but in
myocardial tissue  it was 3.  When arterial PQ« fell below 40 to 30 torr,
CO disappeared from the blood, presumably entering the muscle.  A sub-
stantial amount of extravascular CO stores are located in muscle.  The
higher ratio for cardiac tissue may be of considerable significance.
In an individual with a blood COHb level of 10 percent, some 30 percent
                                                                         13
of cardiac myoglobin may be saturated with CO.  Coburn and his associates
were  able to estimate the mean PQ2 of skeletal muscle and myocardium,
finding these to be 6 to 8 and 4 to 6 torr, respectively.
      Although no final judgment can be made regarding the next lower
step  involved in 0« transport, i.e., the role of cytochromes a3 and P-
450,  the fact that experimentally they react with CO  as do other heme-
containing substances suggests that they may play a role in CO poisoning.
                                      9-24

-------
The evidence available suggests that interactions between CO and cyto-



chrome oxidases are of minor significance at the concentrations of CO



found in community air pollution.  All of the data on the cytochromes



have been obtained from i_n vitro experiments.  Whether  similar events



occur i_n vivo remains uncertain.  The most  likely oxidase for inhibition



jj] vivo is P-450, but no convincing evidence for this effect is available.



Cooper et al.   have reported that the ratio of CO to 0« required for



50 percent inhibition is approximately 1 to 1, in contrast  to the similar


                                                     54
ratio for cytochrome a~ of between 2.2 and  2.8.  Root   believes that at



a  PpQ compatible with life, only insignificant blocking of  the 0«



consumption  system occurs.  In  terms of the total distribution throughout



the  body of  an  inhaled dose of  CO, the amounts bound to these hemoproteins



are  small compared with the amounts bound to Hb and Mb.  Coburn   has



presented a  diagrammatic representation of  the factors  influencing body



CO stores.   The possible significance of an important role  of these



hemoproteins lies  in the concept that under conditions  where tissue  P02



is decreased, the  affinity of  intracellular hemoproteins for CO may



increase.



9.5   SUMMARY



      One of  the primary functions of Hb is  to provide for the transport



of 02 and C0«.  Hemoglobin combines readily with either 0«  (to  form



02Hb) or CO  (to form COHb).  The affinity of Hb  for CO  is some  240 times



greater than its affinity  for  0«.  The presence  of COHb in  blood  not



only reduces the availability  of 0« to the  body, but  its presence



 inhibits the dissociation  of the remaining  0«.   Carbon  monoxide also



combines reversibly with heme  compounds in  the cell.
                                      9-25

-------
     Carbon monoxide is available primarily from two sources —



exogenously from the ambient air and endogenously from the catabolism of



pyrrole rings originating from heme-containing pigments.  Endogenous



sources of CO result in COHb levels of approximately 0.5 percent in



normal males.  Any increment above this level arises from exogenous



sources.  The primary factors determining the final level of COHb are



the concentration of inspired CO, alveolar ventilation, red cell volume,



barometric pressure, and the diffusive capability of the lungs.  The



uptake and final equilibrium level have been fairly well characterized,



but the excretion of CO requires further clarification.  The excretion



appears to be biphasic — a rapid exponential fall followed by a slower



rate  of decline.
                                      9-26

-------
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                                     9-28

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                                      9-30

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                                      9-31

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               10.   EFFECTS OF CO ON EXPERIMENTAL ANIMALS

10.1  INTRODUCTION
     Interpretation of comparative data from other species than man must
be carried out in recognition of the fact that there are species differ-
ences in the particular findings.  An attempt must be made to generalize
the principles rather than the particulars from other species to man.
For instance, it would not be surprising to learn that the threshold
level for CO effects on the cardiac system would differ in rat and man,
but it would be less likely that the effect in rats would be salutory
while in man deleterious.   The non-human data, although it must be
interpreted rather than simply transferred to man, serves the valuable
ends of (1) suggesting studies to be verified in man, (2) exploring the
properties and principles of an effect in a much more thorough and
extensive fashion than is possible in man, (3) protecting human subjects
from unwarranted exposure, (4) permitting a compression of exposure
duration in relation to aging due to the shorter life expectancies of
animals, and (5) obtaining body tissues, organs, and cellular material
more readily, allowing for studies to be carried out at the local tissue
level.
                                    10-1

-------
     Fortunately, the influence of CO on biological systems is not
limited to studies on non-human animals.  Many direct experiments have
been carried out on humans during the last century.  While many reports
describe inadvertent exposures to various levels of CO, there are a
considerable number of precise and delineated studies utilizing human
subjects.  Most of these have been conducted exposing young adult males
to concentrations of CO equivalent to those frequently or occasionally
detected during routine surveys conducted at various ambient monitoring
stations.
10.2  SELECTION OF ANIMAL MODELS
     Experimental animal studies have provided valuable insights to both
the potentially adverse effects of CO and the basic mechanisms by which
this substance influences physiological processes.   However, many studies
have utilized extraordinary levels of CO, i.e., levels rarely found in
ambient air.  These studies are not being considered in this chapter
except as parts of dose-response curves or to obtain insight into
processes, since the toxic effects of very high levels of CO have been
well documented for both animals and man.  Unfortunately, the oxygen (0«)
dissociation curves of the animals utilized in CO studies are not
equivalent.  There are also questions as to the relative affinities of
hemoglobin (Hb) in various animal species for CO.  Klemisch et al.
reported that the blood of hamsters has the greatest affinity for CO,
followed by rats, pigs, and rabbits, respectively.
     All of the effects reported later have been shown to occur to
some degree in most animals studied (mice, rats, rabbits, dogs, and
                                    10-2

-------
monkeys).  Some differences between species have been reported, but no



definitive studies towards elucidating special sensitivities have been
                                       V,

made.  Long-term exposures of animals to sufficiently high concentrations



of CO, producing levels of COHb in excess of 20 to 40 percent, can



induce pathological changes in the heart and brain.  As in acute high-



level intoxication in man, serious sequelae also develop in animals.



     Species differences in response are ideally illustrated in the


                        22 23 24
studies  by DeBias et al. *•»"»*•  on dogs and cynomolgus monkeys (Macaca



irus irus).  Chronic exposure (23 hours per day) over several months to

         o

115 mg/m (100 ppm) CO  resulted in COHb levels of 14 and 12.4 percent in



dogs and monkeys, respectively.  The dogs remained in clinically good


                                                                      23
health with no untoward signs that could be interpreted as CO-induced.



Serum enzymes, hematological parameters, and electrocardiograms did not



change significantly.   Carbon monoxide exposure of normal monkeys resulted



in myocardial effects.  Experimentally infarcted monkeys had greater P-



wave amplitudes and increased evidence of T-wave inversions than


                                               43
normal monkeys similarly exposed.  Jones et al.   exposed rats, guinea

                                               3

pigs, dogs, and monkeys to 58, 115, or 230 mg/m  (50, 100, or 200 ppm)



CO continuously for 90  days.  Hematocrit and Hb levels were unchanged at



the  lowest level of CO  exposure but were significantly elevated at the


                                                               94
two  higher levels in all animals but the dogs.  Theodore et al.   have



summarized the extensive data collected at the Aerospace Medical Research.



Laboratory.  Rhesus monkeys, baboons, dogs (beagles), rats, and mice

                                                         •2

were exposed for 71 days to CO concentrations of 460 mg/m  (400 ppm).



Pathological studies of these animals showed that large animals had no
                                     10-3

-------
changes in the central nervous system (CNS) or in the heart.  Cardiac
changes in the rat were the only positive findings.
     The above studies have been cited as examples of the particular
differences across species, to urge"caution in generalizing these
findings to man.  By such interpretation of the findings, the principles,
rather than the particulars, should be generalized.
10.3  NERVOUS SYSTEM AND BEHAVIOR
10.3.1  General Activity and Sleep
     Several authors report effects of CO on gross or overall behavior
such as general activity, sleep and motor performance.  Colmant   found
disturbances in the sleep patterns of rats when exposed to as little as
                                3
250 ppm for 96 hours or 345 mg/m  (300 ppm) for five hours.   Lower
levels of exposure did not affect sleep and higher levels produced
                                                                    3
progressively greater disturbances.  Female rats exposed to 174 mg/m
(150 ppm; 15 percent COHb) during the full term of their pregnancy by
                 33
Fechter and Annau   produced offspring which at first showed reduced
                                         33
activity levels and lowered body weights.    At 21 days postpartum,
however, no differences existed between offspring of CO-exposed mothers
and controls.  Apparently at much higher levels of exposure, neonatal
                                                                         19
and adult rats develop hyperactivity rather than reduced activity levels.
Levels of exposure of this extent produce brain damage from which
                                                     82
neonates but not adults recover.  Plevova and Frantik   have reported
decreased motor endurance in rats exposed by two different uptake rates
produced by using different CO concentrations for sufficient time to
reach the target and produce COHb concentration of 20 percent.  High
                                    10-4

-------
uptake rates, while producing equivalent COHb levels, had significantly
greater effects than low uptake rates.  Lewey and Drabkin50 demonstrated
alterations in gait in dogs exposed for 11 weeks to 115 mg/m3 (100 ppm)
CO (20 percent COHb).  Mussel man et al.66 showed no effect on rat
                                     o
activity level as a result of 58 mg/m  (50 ppm) exposure for three
months.
10.3.2  Learning and Performance
     Using a wide variety of behavioral paradigms, a number of investiga-
tors have shown effects of CO upon the acquisition of new behavior
and/or the performance of already learned tasks.  Zorn    exposed rats
           3
to 174 mg/m  (150 ppm; 10 percent COHb) for eight hours each night for
2, 4, and 10 weeks and showed that such exposures reduce efficiency of
                                                                        O£* 1%
shock-escape behavior at all exposure durations.  Goldberg and Chappell,
using a continuous food reinforcement schedule  in a lever-press task
with rats, showed reductions in response rate at exposure levels of 230
           3
to 288 mg/m  (200-250 ppm) CO for two hours.  They also showed adverse
effects of such exposures on the performance of a variable ratio task.
Xintaras   '    showed no effects on the performance of a fixed interval
                                                              3
lever press for food reinforcement in rats exposed to 115 mg/m  (100 ppm)
CO for two hours.
     Using more complicated schedules of reinforcement and/or more
complicated tasks, perhaps involving more "cognitive" behaviors, other
investigators have shown much higher thresholds for CO effects.  Merigan
             fil             6                   87
and Mclntire,   Ator et al.,  and Smith, et al.   used a small number of
rats in progressive ratio, differential-reinforcement-of-low-rates, and
                                    10-5

-------
fixed-consecutive-number schedules, respectively.  They showed no
                                                      3
statistically significant effects below about 690 mg/m  (600 ppm) CO but
with the small number of subjects it is possible that effects were
                                                                     94
hidden by high variability.  Using 12 rhesus monkeys, Theodore et al.
report no statistically significant effects on very complicated long-
term, multi-schedule, aversively-controlled performance tests with CO
                             3
exposures as high as 575 mg/m  (500 ppm) for 100 days, even though the
subjects "appeared to be ill."  It should be borne in mind that
aversively-controlled task performance is remarkably stable and insensi-
tive to environmental conditions.  These investigators also progressively
increased CO level rather than exposing subjects to the high level
initially and so could have induced behavioral adaptation, but no control
                                                             42
group was included to test this possibility.  Johnson et al.,   using
only three rhesus monkeys, found no effects from CO levels of up to
        3
575 mg/m  (500 ppm; 44 percent COHb) for 14 days on a food-reinforced
time discriminations task.  McMillan   found definite effects at CO
                           3
levels as high as 1150 mg/m  (1000 ppm) for 1.5 hours using a multiple
fixed-ratio/fixed-interval schedule with pigeons.  They showed, however,
                      3
that at about 575 mg/m  (500 ppm) CO for 1.5 hours, the response of
pigeons to d-amphetamine was altered with respect to controls.  Pigeons,
on such schedules of reinforcement, tend to be very stable responders in
the face of environmental alterations.
                  14a                                      3
     Carter et al.    report that rats exposed to 1150 mg/m  (1000 ppm)
CO for 1.5 hours had drastically reduced response rates on a food-
reinforced fixed-ratio schedule task.  If,  however, carbon dioxide (C0?)
                                    10-6

-------
was added at 2.5, 5.0, and 7.5 percent  levels to the CO-containing air,


performance was progressively and  substantially improved.  This was


apparently due to increased cerebral blood  flow initiated by the CO,,;


C02 levels by themselves produced  no behavioral effect.


10.3.3  Electrophysiological Effects


      It is not unlikely that CNS electrophysiological measures could

                                                            29
provide sensitive indices of pollutant  effects.  Dyer et al.   exposed

                         3
pregnant  rats to 174  mg/m   (150 ppm; 15 percent COHb) for their full


term.  Offspring were tested at 79 days of  age, and  it was shown that


some  components of  the cortical visual  evoked responses  increased in


amplitude in the females but not  in the males.  Using direct exposures

                                   3
of CO levels from 174 to 1150 mg/m (150 to 1000 ppm) in adult rats,

              28
Dyer  and  Annau   showed marginally increased amplitude in some superior

                                               3
colliculus visual-evoked potentials at  575  mg/m  (500 ppm) CO or greater.


Clearly  increased  latencies  in  all evoked potential  components were


shown only at a  level of 1150 mg/m (1000 ppm).  Xintaras et al.    '


reported  similar results in superior colliculus preparations in rats

                    3
exposed  to 115 mg/m  (100  ppm)  for two  hours, but  due to the lack of


 statistical  analysis, it is difficult  to evaluate  these  findings.


Xintaras  pointed out  that  increased evoked  potentials are similar to


those found  under  administration  of sodium  pentobarbitol and those  found

                                                   80
when  the  animal  is  going to sleep. Petajan et  al.    report that at  high


CO levels (2875  mg/m  ; 2500 ppm;  60 to  70 percent  COHb), cortical visual-


evoked responses are  attenuated.
                                     10-7

-------
          3
     Annau  reports that rats which have been trained to lever press for



the reward of an electrical stimulation to the hypothalamus show slightly

                                                            3

reduced response rates when exposed to as little as 174 mg/m  (150 ppm)



CO for 16 minutes while they were responding.  Higher concentrations



produced greater decrements.  These decrements represent early effects



of CO, before COHb equilibrium was reached.   It was also shown, in

                                                                  3

another part of the same study, that with an exposure to 1150 mg/m



(1000 ppm) CO the decline in response rates correlates highly with



increase in COHb.  They also reported data which indicated that CO had



more temporary and less severe effects than hypoxic hypoxia which reduced



venous PQ2 to equivalent levels.


                   75
     Pankow et al.,   using rats given subcutaneous injections of CO



sufficient to produce 19 percent and 60 percent COHb in two exposure



levels, showed that both levels decreased sciatic nerve conduction



velocity for a period of up to 28 days following exposure.  Grunnet and


        37                3
Petajan,   using 2875 mg/m  (2500 ppm) CO exposures until peroneal or



ventral caudal nerve conduction was lost, showed a deterioration of


                                                          86a
Schwann cells which regenerated by 14 to 21 days.  Shul'ga    showed



effects on motor chronaxie, CMS pathology, and porphyrin levels by CO


                        3

levels as low as 29 mg/m  (25 ppm) for eight hours per day for 10 weeks.



Pathological changes and porphyrin levels were not quantitatively



documented.



10.3.4  Cerebral Blood Supply


         114
     Zorn    measured various parameters of cerebral blood supply in



unanesthetized cats, rats,  and rabbits with exposure levels ranging from
                                    10-8

-------
               3
115 to 805 mg/m  (100 to 700 ppm) CO.  In all cases cerebral, subcortical,
and liver PQ2 measures declined as a linear function of COHb, with PQ2
                                                           62
recovery lagging behind COHb elimination.  Miller and Wood,   on the
other hand, using anesthetized and artifically respirated rats exposed
                    3
to 575 and 1150 mg/m  (500 and 1000 ppm), showed about twice the rate of
    decline in the liver as in the brain.  Their findings in the brain
                              114           99
were similar to those of Zorn.     Traystman   using anesthetized dogs
showed that cerebral blood flow increased as a nearly linear function of
COHb.  Similar results were shown for  unanesthetized goats by Doblan
      26
et al.   who also showed that 02 delivery to the brain decreased as a
function of COHb and showed no clear threshold.  It would appear from
Traystman's and Dob!an's data that PQ2 might not fall as rapidly in
cerebral tissue as in other tissues because of increased cerebral blood
                                                                     62
supplies.  This hypothesis seems to be supported by Miller and Wood's
                       114             99
data but  not by Zorn's.     Traystman,  "on the other hand, did not
measure blood  flows in other body systems in order to test the notion
that there was not simply an overall vasodilatory response.  The amount
                                           88
of  hypoxia was indirectly assessed by  Sokal   using rats and measuring
glucose,  pyruvate, lactate and blood pH  levels in the brain after
                              3
exposure  to either 11,500 mg/m   (10,000  ppm) for four minutes or 4,600
     3
mg/m   (4,000 ppm)  for 40 minutes.  The slower uptake rates produced more
extreme effects.
10.3.5  CNS Pathology and Biochemical  Alterations
     Carbon monoxide poisoning studies where CO  levels  are very  high
have commonly  produced CNS lesions due to  local  and widespread anoxia.
                                     10-9

-------
Experimental results using high-level CO exposure have been used to


infer such brain damage as an explanatory mechanism   and have demon-

                                                 CQ                 03
strated ultrastructural evidence for such damage.    Preziosi et al.


exposed dogs on varying short-term exposures sufficient to produce COHb


levels of 40 to 50 percent and on various long-term exposure schemes


(six weeks) which produced COHb levels as low as 4-12 percent.  Short-


term, high-level exposures produced varying (only qualitatively described)


CNS pathologies ranging from mild microglial reactions to localized


necrotic lesions.  Long-term, low-level.exposures produced brain ventricu-


lar dilation but no other pathological signs.   From the article it was


difficult to judge the extent or frequency of the control-experimental


differences.  Lewey and Drabkin,   using dogs exposed for 11 weeks at

        3
115 mg/m  (100 ppm CO; 20 percent COHb), demonstrated localized CNS


lesions due to anoxia, similar to but much less  in extent than those in

                                        OCa
acute CO poisoning.  Ginsberg and Myers,    using pregnant rhesus monkeys


with short-term CO exposure just before delivery, showed that COHb


levels in offspring ranged between 10 to 20 percent for a few hours,


which was much lower than maternal COHb (60 percent).  Neurological


(CNS) damage in the offspring ranged from none to severe and was inverse-


ly correlated with arterial PQ« values present during exposure.  All


mothers showed no clinical effects after recovery, despite much higher

                                    94
levels of exposure.  Theodore et al.   showed no brain pathology in dogs

                                                         3
and monkeys after 168  days of exposure to 460 to 575 mg/m  (400 to


500 ppm) CO.  Histopathological examination of the brains of monkeys

                               3
exposed to  as much as  77.6 mg/m  (67.5 ppm) CO for 22 hrs./day for two
                                     10-10

-------
                                27
years were normal.  Dykyk et al.   reported  no  ultrastructural damage  in



either mothers or fetuses when mothers were  exposed to 100 percent CO



for 60 minutes just before delivery  (mother's COHb = 73.3 percent,



fetuses' COHb = 10.3 percent).  These investigators did, however, show



increased 02 uptake in CNS giant  reticular formation cells in fetuses



but a decreased Op uptake in the  same cells  in  mothers.
                  "•             "U

                      33                                3
     Fechter and  Annau   exposed  female  rats to 174 mg/m  (150 ppm CO;



15 percent COHb)  during their entire term of pregnancy and found reduced

                                                                  go

levels  of dopamine and CNS protein in offspring.  Miller and Wood,


                              3                        3
using rats exposed to 575 mg/m  (500 ppm) and 1150 mg/m  (1000 ppm) CO



until COHb equilibrium was reached,  showed changes in brain energy        J



metabolism;  however, the changes  were smaller than predictable from

                                                  3
theory.  At  high  levels of CO exposure  (1150 mg/m ; 1000 ppm; for four



hours)  Newby et al.   demonstrated decreased dopamine synthesis but no


                                                                93
alterations  in norepinepherine  levels in rats.   Szumanska et al.



 using 100 percent CO for 20,  60 and  90  minutes  did show decreases in

                                                               57
 norepinepherine and catecholamine levels.  Marks and Swiecicki,   however,



 exposed rats to CO for  120 minutes and  showed  increased CNS catecholamine



 levels.



 10.3.6   Summary and Conclusion  of Nervous System and Behavior  in



         Experimental Animals



      Table  10-1 shows  a summary of all  of the  reviewed  studies pertinent



 to experimental animals, CNS,  and behavior.   From the  data we  may



 conclude that  definite  effects  of CO may be  seen in  general  overt


                     3                                           3
 behavior at 230 mg/m   (200  ppm) and  possibly as low  as  115  mg/m   (100 ppm),
                                     10-11

-------
                  TABLE 10-1.  SUMMARY OF EFFECTS OF CO ON CENTRAL NERVOUS SYSTEM AND BEHAVIOR OF ANIMALS
   Reference
  Species
     Exposure*
COHb
   Dependent
    Variable
   Results
   Comment
        17
 Colmant
 Fechtet and
 Annau^ "
 Culver-, and
 Norton
r>oPlevovaand
  Franti \
  Lewey  and
  Drabkin  u
 Musselman
 et  al.55
      114
 Zorn
 Stupfe
-------
                                                       TABLE  10-1  (continued)
    Reference
             Species
              Exposure*
                         COHb
               Dependent
                Variable
                                                             Results
   Comment
  Goldberg-
  Chappell
            no
               Rat    200, 250 and
             n=16 in  500 ppm, 2 hr.
             each of
             2 tasks

               Rat    100 ppm, 2 hr.
              n-10
  Smith
  et al.
87
?Ator et al.
•—>
co
  Merigan and
  MeIntire
  Theodore
  et al.
  Johnson-
  et al.
Rat
n=4
               Rat
               n=4
               Rat
               n=4
              Rhesus
              Monkey
               n=12
200, 400, and 600 ppm,
for 60 min.  during
performance
       100, 250, 500, 750
       ppm, 2 hr.
            Lever press,  food
            reinforcer,  contin-
            uous and variable
            ratio tasks

            Fixed interval,
            lever press  for
            food

            Fixed consecutive
            number schedule,
            lever press  for
            food

22-57%      Differential
            reinforcement of
            low rate.  Lever
            press for food
155, 330, 520, and
700 ppm, 30 min.  pre-
performance plus up
to 1 hr. during per-
formance

400-500 ppm, 168 days    32-38%
              Rhesus  150, 200, 250, and
              Monkey  500 ppm, 1-8 days
               n=3
                                            Progressive  ratio
                                            schedule.  Lever
                                            press  for  food
                                            Complicated  series
                                            of shock avoidance,
                                            lever press
                                13-44%      Time  discrimination
                                            lever press  for
                                            food
                                                                 Reduced  rates  in
                                                                 both  tasks  and all
                                                                 levels
                                                                                       No effects
                                                          No  consistent
                                                          effect  until
                                                          600 ppm
                                                          No effect until
                                                          750 ppm
                                                          No  effect  until
                                                          500-700  ppm
                                                          No  effect
                                                          No  effect
Also collected
electrophysiological
measures.

Complicated schedule
might not be
affected.  Small
number of subjects.

Schedule produces
extremely stable
data.  Might not be
affected by COHb.
Small number of
subjects.

Complicated schedule
might not be
affected.  Smal1
number of subjects.
                                                     Aversive control
                                                     of behavior produces
                                                     stable results,  less
                                                     sensitive to environ-
                                                     mental effects.

                                                     Small  number of
                                                     subjects.

-------
                                                      TABLE 10-1 (continued)
Reference
Species
Exposure3
COHb
Dependent
Variable
Results
Comment
 McMillan
         60
 Carter
 et al.
14a
 Dyer et al.
 Dyer a
,_Annau
            29
             Pigeon   380, 490, 930, and
               n=8    1410 ppm, 1 hr.  +
                      test session
Rat      1000 ppm, 1.5 hr.
n=10     (Also added CO
             Rat      150 ppm for full
           n=41 pups  term of pregnancy
 Annau*
             Rat
             n=8
                    Rat
                    n=10
                    Rat
                    n=45
             Rat
             n=12
         150, 250, 500, and
         1000 ppm, 2 hr.
                      100 ppm, 2 hr.
                         15%
                      (maternal)

                        15-58%
         2500 ppm until
         ventral cortical
         nerve conduction
         stopped

         150, 250, 500, and
         1000 ppm
                                              60-70%
 Pankow
 et al.
75
Rat
n=47
Inject CO subcutane-  19% and 60%
ously in two levels
Multiple (fixed
interval, fixed
ratio).   Key peck
for food.

Fixed ratio, lever
press for food.
                                              Cortical  visual
                                              evoked potentials
                                                                   No effect lower
                                                                   than 500 ppm
                                                          Severe depression
                                                          of rate
                     Increased amplitude
                     but only in females
                                                                              Showed interaction
                                                                              of CO with d-ampheta-
                                                                              mine.
                                         Added C02 restores
                                         response rates to
                                         some extent.
Superior colliculus  Increased amplitude
visual evoked        at 500 ppm, decreas-
potential            ed amplitude at 1000
                     ppm

Superior colliculus  Increased ampli-
visual evoked poten- tude, decreased
tial                 peak latencies
                                     Cortical  visual
                                     evoked potentials
                                     and nerve con-
                                     duction velocity

                                     Lever press for
                                     hypothalamic elec-
                                     trical stimulation
                                     (reward)
Measure sciatic
nerve conduction
velocity
                     Decreased measures
                     at 60-70% COHb
                                         Measurements made
                                         while lever pressing
                                         on fixed interval
                                         schedule for food.

                                         Very high levels
                                         at high saturation
                                         rates.
                     Decreased rates
                     as a function of
                     CO beginning with
                     slight effects at
                     150 ppm

                     Decreased velocity
                     at both levels up
                     to 28 days but back
                     to normal at 90 days

-------
                                                      TABLE 10-1 (continued)
   Reference
 Species
       Exposure
                         a
   COHb
   Dependent
    Variable
   Results
   Comment
 Grunnet-and
 Petajan*3'
 Shul'ga86a
 2orn
     115
o
i
i—»
en
 Miller and
 Wood52
 Traystman
          99
 DobIan
 et al.


 Sokal88
       26
 Rat
 Rat
 n=24
Cat and
Rat
5-20 per
group
  Rat
  Dog
  n=23
 Goat
  n=6
  Rat
n=27-34
2500 ppm until
ventral nerve
conduction stopped

25 and 2 ppm for
8 hr/day, 10 wks.
100-700 ppm in
unanesthetized
animals
500 and 1000 ppm
in anesthetized
animals for 25 hr.

CO of various
amount to produce
target levels of
venous P^

CO of various
amount to produce
target levels of
venous PQ2
10,000 ppm, 4 min
and 4,000 ppm, 40
min
  60-70%
2.5-50%
0-70%
50%
Peripheral nerve
pathology
               Motor chronaxie,
               CNS pathology,  and
               porphyrin levels
               r02 and COHb in
               brain and liver
               r02 and COHb
               in brain and liver
Degenerated Schwann Very high levels
cell, regenerated   at high saturation
14-21 days          rates.

25 ppm increased    CNS damage and for
chronaxie, depressed
porphyrin and       not quantitatively
produced CNS gross  documented.
pathology
p
 Qy decreased at

a linear function
of COHb at same
rates for brain and
liver
p
 Qy decreased more

for liver than brain
Cerebral blood flow  Flow increased as
                     COHb increased
Cerebral blood
flow
Glucose, pyruvate,
lactate and blood
pH levels in brain
Flow increased as
COHb increased
Increases in all
levels except
decrease blood pH
Slow saturation rate
produced more extreme
effects.

-------
                                                       TABLE 10-1 (continued)
Reference
Norton ..and
Species
Rat
Exposure3 COHb
1000 ppm until
Dependent
Variable
CNS pathology
Results
Ultrastructural
Comment

Culver"0,
Norton et al.
                   Dog
Ginsberg and
Myers
o
I
 Theodore
 et al. *
 Dykyk
 et al.
 Eckardtn
 et al . 3U
 Fechtec and
      3^ 3d
    Rhesus
    Monkey
     n=9
  (pregnant
   females)

   Monkey
     n=9
  Dog, n=16
  Rat, n=136
Mouse, n=8Q

   Rat
  (Mothers
   n=28,
   Fetuses
   n=32,
   Neonates
   n=24)

  Cynomolgus
   Monkey
    n=27

      Rat
     n=16-32
      pups
                             respiration stopped
50-100 ppm, various
times per day
(4-24) up to 6 wks.
3000 ppm to produce
60% COHb.  Just
before delivery
                            400-500 ppm
                            168 days
                                                    7-12%
                                                      60%
                            Mothers exposed
                            to 100% CO for
                            60 min at term
   32-38%
 (dogs and
monkeys only)
                                                  Mothers 73.3%
                                                  Fetuses 10.3%
20 and 67.5
ppm, 22 hr/day
for 2 yr

150 ppm during full
term of pregnancy
 2.0-5.5%
   and
 4.8-10.0%

    15%
 (maternal)
                                                                  CMS pathology
                                                                  CNS pathology in
                                                                  offspring
                                                                  CNS pathology
                                      Qy consumption
                                      by reticular forma-
                                      tion giant cells.
                                      Histology exams
CNS histo-
pathology


Brain chemistry
                                      evidence  for
                                      brain  damage

                                      Brain  lesions  of
                                      various types
                                      similar to  CO
                                      poisoning but
                                      more localized

                                      Ranged from severe
                                      brain  damage to no
                                      effects
                                                           No effects
                                                                                               COHb  levels  lower
                                                                                               than  would be ex-
                                                                                               pected  from
                                                                                               exposure  level.
                                          COHb in fetuses
                                          did not nearly
                                          approach that of
                                          mothers'.
                                      Increased 4-fold in
                                      fetus.   Decreased in
                                      mothers.   No histo-
                                      logical differences
                                                                                       No effects
                                                                                       Reduced dopamine
                                                                                       and brain protein
                                                                                                            COHb varied
                                                                                                            unusually widely.

-------
                                                      TABLE 10-1 (continued)
   Reference
Species
       Exposure*
 COHb
   Dependent
    Variable
   Results
   Comment
 Millet and
 Wood52
 Szumanska
 et al.
 Rat
 Rat
500 and 1000 ppm
for 2.5 hr.
100% CO for 20, 60,
and 90 min.
33-52%
Brain chemistry
              Brain chemistry
Reduced energy
metaboli sm
                     Reduced noradrena-
                     lin and catechola-
                     mine levels.   Recov-
                     ered later
Smaller than
predicted from
theory.
 Newby
 et al.
 Rat
1000 ppm, 4 hrs.
              Brain chemistry
                     Popamine synthesis
                     rate decreased,
                     noradrenalin did not
I >^                            o                                                                 _


-------
depending on the species and test employed.  In learning and performance


the effect of the particular task being performed appears to be critical,

                                         3
with simple tasks affected above 174 mg/m  (150 ppm), but more complex

                                                           3
or demanding tasks not being affected until 575 to 690 mg/m  (500 to


600 ppm).  The effects of CO on learning might have varied among studies


as shown in Table 10-1 due to factors other than complexity of task or


contingencies on performance but these seem to be major variables.


Electrophysiological measures in the CNS seem to provide highly variable


data with only two studies by the same group showing consistent effects


below 500 ppm.  Methodological differences were very great in electro-


physiological studies and in any event, results are not as clearly


related  to function as are behavioral data.  Only one study measured

                                                                  fifia
peripheral nerve activity at very low levels of CO, and that study


should be replicated.  Cerebral blood supply measures seem to indicate a


close relationship between tissue PO« and COHb levels despite the fact


that cerebral blood supply is increased by COHb increases.  At higher


levels of COHb, brain damage and alterations in brain chemistry are


reported.


     The results reviewed in this document would be more easily inter-


pretable if the general quality of experimental procedures, design, and


analysis were improved.  In none of  the studies for instance was the use


of blind analysis reported.  This is important because (1) the handling


of animals can  influence the results of some experiments and


(2) unfortunately, the data are sometimes  treated only qualitatively.


In some  of the  studies, appropriate  control groups were not run.


Sometimes COHb  levels were not reported.
                                     10-18

-------
     An almost universal problem was the use of inappropriate statistical


tests such as the use of multiple t-tests where analysis of variance was


appropriate, or the use of univariate analysis where multivariate analysis


should have been used.  This kind of misuse of tests usually leads to


underestimated p-values and hence to overestimates of the number of


effects declared significant.  From the statistical consideration alone


one would be led to suspect that the effects of CO are less extreme than


reported in the literature but, fortunately, most authors obtained


results which were still significant when conservative corrections were


applied by the reviewer.


     For many studies,  it is difficult to answer such basic questions as


the  number of subjects  run, the statistical method used, the exact


experimental designs  employed, etc.  An effort has been made in this


literature review to  interpret the results from a consistent framework.


     Despite problems with the literature, the conclusions reached in


this summary are based  upon fairly solid ground.   Apparently the simpler


behavioral tasks and  general activity yield the lowest thresholds for CO

                                              3
effects; these appear at about 115 to 230 mg/m  (100 to 200 ppm) for


times  long enough to  approach saturation.


10.4  CARDIOVASCULAR  SYSTEMS


     The various tissues of the body must receive 0« at a rate adequate


to maintain their normal function.  Carbon monoxide, when present even


at very  low partial pressures, can seriously  impair the Op transport


system.  Experimental studies of  animals have provided  insights  into  the


mechanisms by which CO  modifies cardiovascular  functions.  The presence
                                     10-19

-------
of COHb interferes with tissue oxygenation by increasing the concentration



of carboxymyoglobin (COMb).  The ratio of COMb to COHb can increase from



1.0 to 2.5 in skeletal muscles and myocardium if the arterial 0^ tension



is 40 torr or lower.



10.4.1  Cardiac Performance and Damage


                 34
     Fusco et al .    found abnormal electrocardiograms (EKG) and changes



in ventricular and arterial pressures in dogs exposed to CO.   Lewey and
       RD
Drabkin   and Enrich et al.   exposed dogs to 115 mg/m  (100 ppm CO; 20



percent COHb) for 11 weeks, 5-3/4 hours per day, and showed EKG



abnormalities, cardiac hypertrophy, muscle degeneration and necrosis.


                 53                                3
Lindenberg et al .   exposed dogs to 58 and 115 mg/m  (50 and 100 ppm CO;



2.6 and 5.5 percent COHb) CO continuously and intermittently, seven days



a week for six weeks, and observed abnormal EKGs in all dogs and histo-



logical evidence of cardiac muscle degeneration in some subjects.


                                                                      83
Effects were more pronounced at the higher exposures.  Preziosi et al.


                                     3

exposed dogs continuously to 115 mg/m  (100 ppm) for six weeks and



reported abnormal EKG, right and left heart dilation, and myocardial



thinning.  Histologic examination showed old scarring in some cases and



fatty degeneration of heart muscle in others.  Carboxyhemoglobin levels



of 7 to 12 percent were lower than would be predicted from the exposure.


                 66                              3
Musselman et al .   exposed their dogs to 58 mg/m  (50 ppm) CO for 24



hours a day, seven days a week for three months.  No changes in the



electrocardiogram or heart rates were observed.  Examination of organs



and tissues revealed no pathological changes after exposure.
                                    10-20

-------
     Monkeys (Macaca irus) were exposed to 288 mg/m  (250 ppm; 20.6 per-



cent COHb) CO for two weeks by Thomsen.    In all animals so exposed,



the coronary arteries showed more or less pronounced widening of the



subendothelial spaces in which cells with or without lipid droplets were



accumulating.  He suggested that monkeys were more sensitive to CO than


                                    4                30
the rabbits studied by Astrup et al.   Eckardt et al.   exposed



cynomolgus monkeys (22 hours a day, seven days a week for two years) to

               3

23 or 77.5 mg/m  (20 or 67.5 ppm) CO.  Carboxyhemoglobin levels showed



considerable variation during the experimental period, from 2.0 to 5.5



percent and 4.8 to 10.2 percent for low and high CO ambient environments,



respectively.  No cardiac effects were noted at these low levels.


             78 79
Penney et al.  '   studied the influence of CO on the development of



cardiac hypertrophy in the rat.  Exposure to various CO levels of 115 to



575 mg/m  (100 to 500 ppm) for 20 to 46 days, leading to COHb levels of



9.2 to 41 percent, resulted in hypertrophy of both right and left


                               90
ventricles.  Stupfel and  Bouley   exposed mice and rats for 95 hours per

               o
week to 58 mg/m  (50 ppm) CO for either one to three months or for their



natural life expectancy of up to two years.  They made a large number of



measurements during exposure, in addition to pathological examination



after death.  They observed no important effects of the CO exposure on



their animals.


                          97                                         3
     Thomsen and Kjeldsen  exposed rabbits to 58, 115, and 207 mg/m



(50, 100  and 180 ppm; 4.5, 9.0, and 17.0 percent COHb) CO and demonstra-

                                                                          3

ted aortic  focal intimal  lesions beginning at exposure levels of  207 mg/m

                                           A C                              O

(180 ppm) for four hours.  Kjeldsen et al.,   exposing rabbits to 207 mg/m
                                     10-21

-------
(180 ppm) CO for two weeks (16.7 percent COHb), reported degenerative


changes such as contraction bands, myofibrillar disintegration, myelin


body formation, and dehiscence of the intercalated disks.  Thomsen and

        96
Kjeldsen   determined the threshold for such effects to be about

        3
115 mg/m  (100 ppm) for four hours (8.5 percent COHb).


     Cardiac hypertrophy was demonstrated by Tumasonis and Baker    in

                                                3
chick embryos which had been exposed to 490 mg/m  (425 ppm; 25.4 percent


COHb) for 144 and 168 hours.  Using a wide variety of animals exposed to

               3
460 to 575 mg/m  (400 to 500 ppm) CO (approximately 32 to 38 percent

                                                       94
COHb in dogs and monkeys) for 168 days, Theodore et al.   was unable to


demonstrate any cardiac abnormalities.


10.4.2  Cardiac Fibrillation Threshold

                                                          3
     Continuous exposure of cynomolgus monkeys to 115 mg/m  (100 ppm;


12.4 percent COHb) CO for three to six months resulted in demonstrable


electrocardiographic effects in both normal monkeys and monkeys with

                      21 23
myocardial infarction.  *    These investigations also considered the

                                                         22
susceptibility of the ventricles to induced fibrillation.    Normal and

                                          3
infarcted monkeys were exposed to 115 mg/m  (100 ppm) CO for six hours.


The voltage required to induce fibrillation was highest in monkeys


exposed to normal air and lowest for infarcted animals breathing CO.


Animals with either infarction alone or CO alone each required signifi-


cantly less voltage for fibrillation and when the two were combined, the


effects were additive.  In contrast with these findings it has been

                                                               3
shown that as a result of intermittent exposure to CO (575 mg/m  (500 ppm),


six-minute pulses of CO each hour for 12 hours each day over a period of
                                    10-22

-------
14 months), cynomolgus monkeys fed either a normal or a  semipurified



cholesterol diet, did not show myocardial infarctions or electrocardio-



graphic abnormalties.    In these animals, blood COHb reached 21.6



percent at the end of the daily period.  Aronow et al.   observed in a



blind randomized study that 21 dogs with acute myocardial  injury had a

                                                                        o

reduction in ventricular fibrillation threshold after breathing 115 mg/m



(100 ppm) CO for two hours (6.3 percent COHb).



10.4.3  Cholesterol and Sclerosis


                  4 5
     Astrup et al.  '  reported data showing increased aortic cholesterol

     7                                                        q

accumulation and atheromatosis in rabbits exposed to 196 mg/m  (170 ppm)



CO  for eight weeks  and then to 350 ppm for two more weeks  (17 to 33 per-


                            104
cent COHb).  Webster et al.,    using squirrel monkeys,  found no effects

                                                }

on  aortic or carotid vessels  nor on serum cholesterol, but did note a



greater incidence of coronary atherosclerosis  in groups  exposed to



115 to 345 mg/m  (100 to 300  ppm; 9 to 26 percent COHb)  CO on an inter-



mittent schedule for seven months.  Essentially identical  results as



found by Webster et al.    were reported by Davies et al.   using rabbits



exposed intermittently for 10 weeks to CO concentrations to produce

                                cc

20  percent COHb.  Mali now et  al.   reported no aortic or coronary athero-



sclerosis  in cynomolgus monkeys exposed on an  intermittent schedule for



14  months  so as  to  produce daily accumulations of 21.6 percent COHb.


                     89
     Stender et  al.,   in Astrup's group, attempted to resolve the



apparent conflict in the above studies, regarding aortic atherosclerosis,

                               o

by  exposing rabbits to 230 mg/m  (200 ppm) CO  continuously for 12 hours



per day for six weeks.  Instead of using a constant high cholesterol
                                     10-23

-------
diet for all subjects, the serum cholesterol was held constant by
variations in diet cholesterol.  In this case, no aortic cholesterol or
atherosclerotic differences were seen between CO-exposed and control
groups.  In reference to earlier results, Astrup et al.  now interpret
these data to mean that observed damage in earlier studies was attributa-
ble to greatly increased serum cholesterol in CO groups, although Davies
et al.,   Webster et al.,    and Mali now et al.    reported no increased
serum cholesterol either.  Differences in cholesterol buildup in aortic
tissue (due to CO exposure) might be related to observed differences due
to CO exposure in lactate dehydrogenase (LDH) enzymes in rabbits, as
                                                  OO               ~JQ ~?Q
observed in the aorta and by Hellung-Larsen et al.     Penney et al.   '
also reported increased LDH in rats.  However, in the most recent studies
by Astrup's group (Hugod et al.  a), non-cholesterol-fed rabbits exposed
only to CO (six weeks at 150-200 ppm or for 201-304 minutes at 2000-
4000 ppm) showed no evidence of histotoxic effects on intimal/subintimal
morphology of coronary arteries or aorta.  The weight of evidence suggests
that there is doubt as to the relationship between CO exposure and
atherosclerosis.
10.4.4  Coronary Blood Flow
     Carboxyhemoglobin increases result in an increased coronary blood
flow (CBF).1'7'8'40'112  This increase in CBF as a function of COHb is
apparently not sufficient to prevent a reduced 0« supply even at COHb
levels as low as 4 percent. a  This partly compensatory response is not
affected by autonomic nervous system blockage and is not mediated by
heart rate,    but is apparently due to auto-vasodilatory activity.
Increased CBF in response to COHb was no longer observed in atrioven-
tricular-blocked dogs being maintained by a pacemaker (Horvath  ).
                                    10-24

-------
10.4.5  Hemoglobin


     Carbon monoxide apparently induces  increases  in Hb which to an


unknown extent compensate for reduced availability of  Hb  for 02 carrying.

             78 79
Penney et al.  '   showed increased Hb levels  in rats  exposed to as

                  3
little as 115 mg/m  (100 ppm; 9.2 percent COHb) CO continuously, which


began early  in the exposure period and reached an  asymptotic value by


about 30 days of exposure.  These results were similar to those reported
               VI O                                    /"*/""
by Jones et  al.   using rats, and by Mussel man et  al.   using dogs con-

                            3
tinuously exposed to 58 mg/m  (50 ppm) CO for  three months.  Theodore

      94                                                              3
et al.   used monkeys  and dogs continuously  exposed to 460 to 575 mg/m


(400 to 500  ppm) CO for 168 days and showed  increased  Hb  levels which


reached asymptotic values at about 30 days but which began to decline


toward control values  at about 140 days.  This might represent a failure


of the compensatory Hb increases after very  long exposures, but further

                                                               41
study is needed to reach such a conclusion.  Jaeger and McGrath   exposed

                                 3
Japanese quail to 345  to 403 mg/m  (300  to 350 ppm; 30 percent COHb) CO


for  28 days  and observed increased hematocrit, Hb, plasma volume and


blood volume.  They also noted right ventricle hypertrophy.  Baker and

         Q
Tumasonis  reported vascular hypertrophy in  chick  embryos after 18-day

                            3
exposure of  eggs to 490 mg/m  (425 ppm;  6.15 percent COHb) CO.


     Apparently, continuous exposure to  CO  is  needed to show  increased

                                                 83
Hb levels at lower CO  exposures.   Preziosi et  al.   using dogs exposed


to 58 and 115 mg/m3 (50 and 100 ppm; 7 to 12 percent COHb) CO on various


intermittent schedules for  six weeks,  reported no  effects. A group  of

                             3
four dogs exposed to 115 mg/m   (100 ppm) continuously  for six weeks  also
                                     10-25

-------
                                          90
did not show effects.  Stupfel and Bouley,   using rats and mice exposed


          3                                                            30
to 58 mg/m  (50 ppm) CO intermittently for two years and Eckhart et al.


                                                        3

using monkeys exposed intermittently to 23 and 77.5 mg/m  (20 and



67.5 ppm; 2 to 10 percent COHb) did not demonstrate any COHb increases.


          35          54            84
Gasaskina,   Ljublina,   and Rylova,   using rabbits, guinea pigs, rats


                                            3

and mice exposed for long periods to 58 mg/m  (50 ppm) did not find any


                                        43a
blood morphology changes.  Kalmaz et al.     exposed rabbits to 50 ppm CO



for eight weeks and found no change in Hb concentration.  However, they



did find increased fibrinolytic activity consequent to the CO exposure.



The report may be subject to considerable doubt since their animals,



when exposed to ambient air, had COHb levels of approximately 5 percent



and their CO-exposed (50 ppm) animals had unbelievably high COHb levels —



in excess of 30 percent.



     Alterations in Hb have been reported for short-term CO exposures as



well as  long-term studies.  Ogawa et al.    report that in dogs a 30-


                           3

minute exposure to 690 mg/m  (600 ppm; 58.2 percent COHb) CO produced a



decrease in plasma volume resulting in hemoconcentration.  They attribu-



ted the plasma decrease to an increase in vascular permeability.


                     92               3
Syvertsen and Harris,   using 224 mg/m  (195 ppm) CO for 72 hours



(30 percent COHb), also reported increased Hb but attributed their



findings to increased erythropoiesis.  The latter study, which used



intermediate durations of exposure, probably suggests early Hb compen-



sation similar to the long-term findings.
                                     10-26

-------
10.4.6  Summary and Conclusion of Cardiovascular System in Experimental

        Animals

     Table 10-2 shows a summary of all of the reviewed studies pertinent

to experimental animals and cardiovascular systems.  From these data it

may be concluded that under most circumstances  EKG abnormalities may be
                                                                    o
noticed after relatively long-term intermittent exposure to 115 mg/m

(100 ppm; 8 to 13 percent COHb) CO and sometimes, depending upon the
                                                  3
species, exposure regimen, etc., as  low as 58 mg/m   (50 ppm; 4 to

7 percent COHb) CO.  Various  signs of cardiac damage are found at

similar levels.

     Decreased thresholds to  electrically induced fibrillation have been
                                             3
demonstrated at CO  levels as  low as  115 mg/m (100 ppm; 6 to 12 percent

COHb)  CO in exposures as short as two hours, but these findings are not

universal.  It is almost universally demonstrated that when experimental

animals are fed high cholesterol diets, they develop increased coronary

atherosclerotic damage  if they are exposed to CO levels as low as  115 to
        3
230 mg/m   (100 to 200 ppm; 9  to 18 percent COHb).  These exposures were

made  on long-term,  intermittent schedules.   Findings of similar increased

damage in  the  aorta are in greater dispute but  have  also been reported
                                       3
with  exposures to CO as low as 196 mg/m   (170 ppm; 17 percent COHb).
 Apparently such  damage,  and perhaps  other atherosclerotic  findings,  are

 due  to  CO- induced alterations  in serum cholesterol  and LDH alterations.

      As reported for CNS structures,  coronary blood flow apparently  is

 increased by vasodilation,  when CO is present, but  this increased flow

 rate is not sufficient to entirely compensate for the reduced 02 supply -
                                     10-27

-------
                     TABLE 10-2.   SUMMARY OF EFFECTS OF CARBON  MONOXIDE  ON  CARDIOVASCULAR  SYSTEMS OF ANIMALS
     Reference
  Species
       Exposure*
   COHb
   Dependent
    Variable
   Results
   Comment
   Lewey a
   Drabkin
   Erich
   et al.
         31
o
i
ro
00
   Lindenberg
   et al.
   Preziosi
   et al.83
   Musselgan
   6 w 3 I *
   Thomsen
          95
Dog
n=4-6
Dog
n=12
Dog
n=46
Dog
n=4

Macaca
irus
monkey
n=20
100 ppm for 11 wks.    20%
for 5-3/4 hr./day
               EKG and cardiac
               pathology
50-100 ppm for 6 wks.  2.6-5.5%
intermittently and
continuously
50-100 ppm for 6 wks.  7-12%
on various daily
schedules
               EKG and pathology
               EKG and pathology
50 ppm for 3 mo.
continuously

250 ppm
continuously
for 2 wk.
20.6%
EKG, heart rate


Cardiac
pathology
Some subjects
showed abnormal
EKG, most showed
increased heart
size, muscle
degeneration,
necrosis

Abnormal EKG,
changes in right
ventricular and
arterial pressures

Abnormal EKG,
heart dilation,
myocardial thinning,
some subjects
showed scarring and
degeneration in
heart muscle

No effects
Widening of
subendothelial
spaces of coronary
arteries with
accumulation of
cells with and
without lipid
droplets.
                                          COHb levels were
                                          low for exposure
                                          levels used
                                                         Very smal1  n
Lipid-laden
cell findings
indicate greater
sensitivity of
monkeys than
in rabbits (22)

-------
                                                        TABLE 10-2 (continued)
o
IN3
Reference
Eckhardt
et al.
Penney?ft 7q
et al.78'79
Species Exposure3
Cynomolgus 20 and 67.5
monkey ppm, 22 hr./day
n=27 for 2 yr.
Rat 100 ppm, 46 days
n=32 200 ppm, 30 days
500 ppm, 20-42 days
COHb
2.5 to 5%
and
4.8-10%
9.2%
15.8%
41.1*
Dependent
Variable
Cardiac
fibres is
Heart size
Results
No effects
Hypertrophy of
both left and
right ventricles
Comment
Unusually wide
variation in COHb
Also studied
hypoxic hypoxia
and lactate
dehydrogenase
i sozyme
   Stupfelftand
   Bouley*u
   Thomsen and
   Kjeldsen
   Tumasonis
   and Baker
,m
lul
        Rat
        n=336,
        mouse
        n=767
        Rabbit
        n=61
Kjeldseo
et al.
Thomsen and
Kjeldsen*0
Rabbit
n=16
Rabbit
n=42
Chick
embryo
50 ppm, 95 hr./wk.
whole natural life
expectancy up to
2 yr. (also short
term)

50, 100 and           4.5%
180 ppm for periods   9.0%
ranging from 30       17.0%
min - 24 hr.

180 ppm, 2 wks.       16.7%
                               50, 100, and 180      4.5%,
                               ppm for 2-48 hr.      8.5%,
                                                     17.0%
425 ppm for 144       25.4%
and 168 hrs.
                                                EKG,  organ
                                                weights
                                                          No effects
                                                Aortic damage
                                                        Myocardial  ultra-
                                                        structure

                                                        Myocardial
                                                        ultrastructure
                                                        Cardiac  size
Increased
focal intimal
lesions at
180 ppm, 4 hrs.

Signs of myocardial
damage

Ultrastructural
damage threshold
of 100 ppm for
4 hr.

Cardiac
hypertrophy
                     Also showed  no
                     effects on other
                     variables
                                                                               Blind study

-------
                                                       TABLE 10-2 (continued)
Reference
Theodogg
et al.








Species Exposure3
Monkey 400-500 ppm for
n=9, 168 days
Baboon
n=3,
Dog
n=16,
Rat
n=136,
Mouse
n=80
COHb
32-38%
(dogs and
monkeys
only)






Dependent
Variable
Cardiovascular
damage








Results Comment
No changes except
slight hypertrophy
in rat heart







DeBias
et al.
        91
CO
o
  Mali now/-
  et al.56
  Aronow
  et al.
      3a
  Astrup.
  et al.
Cynomolgus 100 ppm for 24 wks
Monkey     23 hr. per day
n=52
                 Cynomolgus 500 ppm, 6 min
                 Monkey     pulses with a
                 n=26       24 min declining
                            washout.  Pulsed
                            1/hr., 12 hr./day
                            for 14 mo.
                                                    12.4%
Dog
n=21
                            100 ppm, 2 hr.
                                 21.6%
                                 at the
                                 end of
                                 12 hr.
                                 period
6.3%
               EKG and suscepti-
               bility to induced
               fibrillation
               EKG and fibrilla-
               tion threshold
                     Abnormal EKG and
                     increased sensiti-
                     vity to fibrilla-
                     tion voltage
                     No effects
                     Infarcted animals
                     showed greatest
                     effect of COHb
                     on both dependent
                     variables.

                     Used subject on
                     normal and high
                     cholesterol diets
                 Rabbit
                 n=24
           170 ppm for
           8 wks., then
           350 ppm for last
           2 wks.
17-33%
Ventricular
fibrillation
threshold in
subjects with
acute myocardial
injury

Cardiovascular
pathology
Reduced
threshold
Conducted blind
study
1.  Increased aortic
atheromatosis and
cholesterol
2.  Local degenera-
tive signs and
hemorrhages in hearts

-------
                                                        TABLE 10-2 (continued)
Reference
Species
Exposure3
COHb
Dependent
Variable
Results
Comment

   Astrup,-
   et al.
GO
Davies
et al.
         9ft
         20
   Maii nowc
   et al.56
   Stende£Q
   et al.89
Squirrel   100-300 ppm
Monkey     4 hr./day, 5 days/wk.
n=22       for 7 mo. using
           a gradually increas-
           ing exposure until
           3 mo. then reduce to
           250 for 4 mo.

Rabbit     Low exposure for
n=24       8 wks., higher
           exposure for last
           2 wks.

Rabbit     4 hr./day,
n=24       7 day/wk.,
           10 wks.
                                                     9-26%
                                                  15%
                                                  and 30%
                                                     20%
                 Cynomolgus 500 ppm, 6 min
                 Monkey     pulses with a 24 min
                 n=26       declining washout,
                            pulsed 1 per hour,
                            12 hr./day for 14 mo.

                 Rabbit     200 ppm continuously
                 n=30       and 12 hr./day for
                            6 wks.
21.6%
at end
of 12
hr. period
17%
                                                                 Atherosclerosis
                                                                 in various cardiac
                                                                 structures plus
                                                                 serum cholesterol
               Aortic
               cholesterol
               Blood cholesterol
               and cardiovascular
               pathology
Aortic and
coronary
atherosclerosis
Cardiovascular
pathology
                                    Increased coronary
                                    atherosclerosis but
                                    no effects on
                                    serum cholesterol,
                                    aortic and carotid
                                    atherosclerosis
                     Increased
                     in CO exposed
                     groups
Increased
atherosclerosis
in coronary
artery but no
aortic differences
or plasma choles-
terol differences
No effects
No differences
in atherosclerosis
but CO produced
higher serum
cholesterol levels
                                          Subjects were
                                          on high cholesterol
                                          diets.
                     Study used
                     cholesterol
                     animals.
            fed
                                          Study disagrees
                                          with Astrup
                                          et al.
This study used
subjects on high
and low choles-
terol diets.
Disagrees with
Astrup et al.

In this study
serum cholesterol
was controlled by
individual adjust-
ments of diet.
Apparently coronary
atherosclerosis in
(17) was caused
by increased
serum cholesterol.

-------
                                                       TABLE 10-2 (continued)
Reference
HellungrLarsen
et al . 38
Species
Rabbit
n=16
Exposure3
170 ppm-550 ppm
In ascending
levels for 5-11
COHb
15-35%
Dependent
Variable
Lactate
dehydrogenase
enzymes LDH
Results
LDH increases
In aortic arch
Comment

   Penney7ft ,q
   et al.78'79
   Ayres
   et al.
7,8
           Rat
           n=32
Dog
n=40
o
oo
   Horvath
          40
           Dog
           n=5-7
   Young., and
   StoneAA*
           Dog
   Adams
   et al.
la
Dog
n=10
days

100 ppm 46 days
200 ppm 30 days
500 ppm 20-42 days

50,000 ppm for 30-
120 sec. and
1000 ppm for 8-15
min.
                                 9.2%
                                 15.82%
                                 41.12%
LDH
                                                           CBF
           Single dose of CO
           to produce desired
           COHb (3 levels)
                      6.2-35.6%
CBF
           1000 ppm until
              saturation reduced
              30%
                                     CBF
1500 ppm for
30 min.
                                                           CBF
LDH increases
due to CO
exposure

Increased CBF with
COHb
Increased CBF
with COHb
                     Increased CBF
                     with COHb even
                     when heart rate
                     paced at 150 beats
                     per min. or with
                     blocked autonomic
                     nervous system

                     CBF increased as
                     linear function of
                     COHb
Also studied humans
the results of
which agree with
dogs except dogs
were more resist-
ant to COHb
below 25%.

Atri oventri cular
blocked dogs,
maintained by
pacemaker, did not
show this effect.
                     CBF  increase was
                     not  enough to
                     compensate for
                     increased energy
                     expenditure.

-------

Reference
Jones .0
, 43
et al.







2^78.79


Theodore
et al.




Mussel man
DO
et al.
Preziosi
et al.


Stupfelnand
Bouleyyu



Species
Rat
n=35,
Guinea
pig
n=35,
Monkey
n=9,
Dog
n=6
Rat
n=32


Monkey
n=9,
Dog
n=16


Dog
n=4
Dog
n=46


Rat
n=336,
Mouse
n=767

Exposure3
51, 96 and 200 ppm
for 90 days




,


100 ppm 46 days
200 ppm 30 days
500 ppm 20-42 days

400-500 ppm for
168 days (contin-
uous)



50 ppm for
3 mo. continuous
50 and 100 ppm
for 6 weeks on
various intermittent
daily schedules
50 ppm for
90 hr./wk.
up to 2 yr.

TABLE 10-2
COHb
3.2-6.2%
4.9-12.7%
9.4-20.2%
dependi ng
upon species




9.20%
15.82%
41.12%

32-38%







7-12%






(continued)
Dependent
Variable Results
Hb levels Increases in
rats at both
exposure levels
Increases in
all animals at
200 ppm



Hb levels Increased even
at 100 ppm
levels

Hb levels and Increased Hb
blood volume and blood volume,
slight decrease
toward control
values after 140
days
Hb, hematocrit and Increased
red cell counts
Hb level No effects



Hb level No effects



Comment
Increased Hb in
rats at 96 ppm
was larger than
at 200 ppm.





About 30 days
until Hb
approached
asymptotic values
About 30 days
until Hb
approached
asymptotic values












-------
                                                   TABLE 10-2 (continued)
Reference
Eckhardt
et al.
Species
Cynomolgus
Monkey
n=27
Exposure3
20 and 67.5 ppm,
22 hr./day,
for 2 yr.
COHb
2-5.5%
and
4.8-10.0%
Dependent
Variable
Hematocrit, Hb
and erythrocyte
counts
Results
No changes
Comment
Unusually wide
variation in COHb
Ogawa 7,
et al.
Syvertsen and
Harris^
Dog
n=16
Dog
n=12
Jaeger
McGrath
                 Quai 1
                 n=40
Baker &
Tumasonis
Chick
embryo
n=90
6000 ppm for 30 min.   58.2%
195 ppm for 72 hr.
~30%
           300-350 ppm
           for 28 days
           continuous
                      30%
425 ppm during
first 18 incu-
bation days
6.15%
               Plasma volume
                                                                 Hematocrit and Hb
               Hematocrit,  Hb,
               plasma,  blood
               volume,  heart
               size fasting
               glucose  and
               carbohydrate
               stores
                                                                                     Decreased due to
                                                                                     CO
Increased concen-
trations but
inferred no
increase in plasma
volume

Hematocrit, Hb,
plasma and blood
volumes increased.
Right ventricle
hypertrophy.
Higher fasting
glucose muscular
carbohydrate.
Probably due to
increased vascular
permeability see
Parving et al.

Attributed change
to increased
erythropoiesis
                                                                 Vascular  structure,  Vascular  hypertrophy,
                                                                 Lactate dehydrogen-  increased lactic
                                                                 ase & serum albumin  dehydrogenase &
                                                                                     serum  albumin.

-------
Needless to say, these findings are not as consistent with all investi-


gators as might be desired.  It is difficult to resolve the disagreement,


in most cases, because of differences  in exposure regimens, experimental


animal species and analytic techniques, to name but a few of the common


problems of comparison.  Studies  utilizing bolus concentrations represent


"real world" conditions.  Animal  subjects are at risk to myocardial


effects for several minutes after exposure.


      Long-term exposure  to continuous  low concentrations of CO produces


increased Hb beginning about 72 hours  after exposure and maximizing at

              3
58 to 115 mg/m  (50 to 100 ppm) in about 30 days.  Short-term increases


in hemoconcentration  are apparently due to reduced plasma volumes.


      Despite the problems  in the  literature and the heterogeneity of


reported results,  it  seems safe to conclude that cardiovascular damage


can  be  demonstrated to occur as a result of long-term,  intermittent

                                                      3
exposure to CO concentrations  as  low as 58 to 115 mg/m  (50 to 100 ppm).


These results contrast with  neuro-behavioral data, which were usually


collected  from short-term  exposures and which demonstrated certain

                                                                      3
functional deficits which  occur at CO  levels as low as  115 to 230 mg/m


(100 to 200 ppm).   It would  seem  advisable to design studies that provide


more short-term exposures  during  cardiovascular tests and more long-term


results in neuro-behavioral  data.


10.5 OTHER DEPENDENT VARIABLES


10.5.1  Feeding, drinking, and body weight


      Koob  et  al.47 using two  strains of  rats exposed to 288, 575, and


1150 mg/m3 (250, 500, and  1000 ppm) CO for 24  hours, showed decreased
                                     10-35

-------
food and water intake and decreased weight gain during the exposure


                          32 33
period.  Fechter and Annau  *   reported slightly lower weight gains in


                                               3
rats whose mothers had been exposed to 174 mg/m  (150 ppm; 15 percent


                                                        94
COHb) CO during full term of pregnancy.  Theodore et al.   noted no



significant body weight effect in rats exposed for 168 days to 460 to

        3

575 mg/m  (400 to 500 ppm) CO, but the rats were apparently somewhat


                                     47
more mature than those of Koob et al.    No significant weight, feeding



or drinking effects were noted in three other studies:  (1) Musselman


       66                                                 o
et al.   using rats, rabbits, and dogs exposed to 58 mg/m  (50 ppm) for



three  months, (2) Campbell,    who exposed rats to 3450 mg/m  (3000


                                                         90
ppm) for a total of 300 days, and (3) Stupfel and Bouley,   using rats



and mice exposed intermittently for periods ranging from one month to



two years.  Since the only study which showed marked effects on weight



and intake was a short-term exposure, it is not possible to conclude



that weight gain and intake are affected by CO exposure, except possibly



in the early  stages of exposure and possibly only in growing organisms.



10.5.2 Biochemical Effects and Drugs


                  72 74
     Pankow et al.  '   injected CO subcutaneously in rats to produce



COHb levels of 40 percent to 50 percent and showed that only the higher



dosage increased leucine aminopeptidase activity in the liver after a



single injection.   Forty injections of the dose producing the lower COHb



over a period of 53 days also produced an enlarged liver.  Martynjuk and

        CO

Dacenko  showed increased aspartate and alanine aminotransferase


                           3                         49
activity after only 20 mg/m  (17 ppm).  Kustov et al.   exposed rats to


        3

58 mg/m (50  ppm) and showed depressed cytochrome oxidase activity and
                                     10-36

-------
increased succinate dehydrogenase activity in liver.  The latter two

studies indicate general hypoxic effects.
              91
     Sweicicki   exposed rats to CO and noted that an increase in

adrenergic system activity produced an increased carbohydrate metabolism.

Such metabolic alterations could explain weight changes if such changes

were verified.
                         CO                                 o
     Montgomery and Rubin   exposed rats to 288 to 3450 mg/m  (250 to

3000 ppm) CO  for 90 minutes in  several groups (20 to 60 percent COHb)

and then injected two dissimilar drugs (hexobarbital and zoxazolamine).
                                                                       3
They showed that CO exposure prolonged zoxazolamine effects at 288 mg/m

(250 ppm) CO  and hexobarbital effects at 1150 mg/m3 (1000 ppm) CO.

10.5.3  Miscellaneous
                   oc                                              o
     Schwetz  et al.   exposed pregnant rabbits and mice to 288 mg/m

(250 ppm) CO  for either 7 or 24 hrs./day for days 6 to 18 and 6 to 15 of

gestation.  No statistically significant differences in the number or

extent  of skeletal birth defects were noted.

10.5.4  Summary and Conclusions of Other Dependent Variables in

        Experimental Animals

     Table  10-3 presents a  summary of findings regarding CO and various

other  dependent variables.

     The data regarding feeding, drinking, and body weight suggest the

possibility of a short-term effect at 288 mg/m   (250 ppm) CO levels but

definitely  show no long-term effects.  Since only one  study showed

short-term  weight  loss, this finding  should be viewed  with caution.

Even if verified,  short-term (24 hours)  alterations  in feeding and
                                     10-37

-------
                                      TABLE 10-3.  SUMMARY OF CO EFFECTS UPON METABOLISM
'l
Reference Species
Koob
et al. '
Fechtec &,
Annau^'**
,_. Theodore
? et al.94
CO
<»
Musselgan
ex a i .

Campbell145

Rat
n=36
Rat
n=16-32
Rat
N=136
Rat
n=100,
Rabbit
n=40,
Dog
n=4
Rat
N=36-45
Exposure3 COHb
250, 500, and
1000 ppm for 24 hr.
150 ppm during full 15%
term of pregnancy (maternal)
400-500 ppm for
168 days
50 ppm for 3 mo.

Gradually increasing
exposure reaching
Dependent
Variable
Food & water intake
and weight
Body weight
of offspring
Body weight
Body weight

Body weight
Results
Decreased intakes
during exposure,
less weight gained
Nearly same at birth
but gained at
slightly lower rate
CO group had
slightly lower mean
but not significant
No CO effect

Slightly fewer gains
during 1st 100 days
Comment
True for 2
strains of rat.
Related to cate-
cholamine findings
200 g. starting
weight.
Differences
were very small
240 g. Starting
weight


1. No Signifi-
cance tests
                            3000 ppm at 100 days
                            intermittent exposures
                                                                   and then increased
                                              gain in last 200 days   differences
                                                                                    and slight

                                                                                    1st 100 days
                                                                                    represented
                                                                                    normal rapid
                                                                                    growth phase.
Stupfelft&
Bouley30
 Rat
n=336.
Mouse
50 ppm for 95 hr/wk
for whole natural
life up to 2 yr.
Also 1-3 mo exposure
groups
Body weight,
food & water
intake
No effect due
to CO

-------
                                                       TABLE  10-3  (continued)
Reference
Species
Exposure9
COHb
Dependent
Variable
Results
Comment
   PanRow
   Ponsold
,73
  Martynjuk &
  Dacenko °
o
i
CO
   Kustov
   et al.
49
Swiecicki
   Pankow &
   Ponsold;
   Pankow
  73
   et al.
         73a
               Rat    Subcutaneous injec-
            n=20-30   tion of 7.2 and 9.6
                      mMol/kg, CO.
                      40 injections in
                      53 days
                        Rat
                      17 ppm
                     Rat    50 ppm
                     n=92
                     Rat    CO exposure
                            combined with 1%
                            ethanol.
                                                   @ 50%
                                                   1 hr after
                                                   injection
               Leucine aminopep-     Single 9.6 mMol/kg
               tidase activity and  injection increased
               liver weight         enzyme.   Repeated
                                    7.6 mMol/kg injections
                                    increased enzyme
                                    and liver wt.

               Aspartate and   „     Increased during
               alanine aminotrans- Exposure
               ferase activity
               Cytochrome oxidase
               and succinate dehy-
               drogenase activity
               in liver

               Adrenergic system
                                                                              Depressed  cytochrome
                                                                              oxidase
                                                                              Increased  succinate
                                                                              dehydrogenase

                                                                              COHb  levels
                                                                              stimulate  system
                                                                                                       Increased
                                                                                                       carbohydrate
                                                                                                       metabolism
   Montgomery &
   Rubin155
               Rat
            n=10-20
          per group
                            250-3000 ppm in
                            various groups for
                            for 90 min.
20-60%
                                                         Rates  of metabolism
                                                         of hexobarbital  and
                                                         zoxazolamine
Prologed response to
hexobarbital at 1000
ppm and to zoxazolamine
at 250 ppm.

-------
                                                       TABLE 10-3 (continued)
Reference Species
Schwetzfi Pregnant
et al . female
Mouse
n=35-48
Pregnant
female
Rabbit
n=20-21

Dependent
Exposure COHb Variable Results Comment
250 ppm for either 7 10-15% Skeletal malfor- No teratogenic
or 24 hr/day on days mations in pups effects due to
6-15 of gestation CO
As above on days
6-18

Conversion of ppm to mg/m :
                                multiply by 1.15 @ 25C, 760 mm Hg.
o
i

-------
weight maintenance per se are  not particularly  serious  in an applied
sense.
     Biochemical findings suggest that  enzyme activities, etc., might be
measurably altered at extremely  low  levels  of CO  exposure but the  impli-
cation of these findings to  health effects  is not clear, since the
findings in  some cases are indicators of  hypoxic  effects which are known
from other data to exist.  By  themselves  these  data  do  not provide
information  about health concerns.   Taken in combination with other
findings, these data might be  used as supplementary,  explanatory results.
Extensions and verification  of these findings should provide interesting
interpretive data.
                                            CQ
     The findings of slowed  drug metabolism  might  have practical
import  in terms of CO exposure of subjects  who  are also under medical
treatment with drugs or  are  under the influence of illicit drugs.  The
findings in  this area are only suggestive;  thresholds need to be estab-
lished  for a much wider  range  of drugs  and animals.
      There is a paucity  of data  regarding the effects on offspring for
other than cardiac or CNS effects.   No  skeletal birth defects were noted
at relatively high levels of CO.
10.6  INTERACTIONS WITH  OTHER  POLLUTANTS, DRUGS AND  OTHER FACTORS
      Many materials  by themselves have  no biological effect  but  if
combined with other  substances,  levels  of exposure that do not by
themselves produce effects become harmful.   The effects of CO have been
explored in  only a preliminary fashion  with respect  to  such  interactions.
Carbon  monoxide exposure frequently  occurs in  the natural environment  in
                                     10-41

-------
combination with other pollutants, noise, and drug exposures such as


therapeutic drugs or alcohol.  Tobacco smoking raises COHb levels but


also has other effects which could act in combination with CO.


10.6.1  Other Pollutants

          12
     Busey   exposed rats for 52 weeks to various concentrations of
airborne pollutants (N02, SOp, CaSO., PbClBr, and CO), the CO levels of

                             3
interest being 23 and 77 mg/m  (20 and 67 ppm).  No consistent pulmonary


function changes were seen in any of the groups exposed to one of these


pollutants alone or in combination with any other single pollutant.


Hematological and biochemical measurements remained within normal limits

                               13
in all groups.  A similar study   was made on cynomolgus monkeys which


were exposed continuously for 104 weeks.  The CO concentrations were 22

           3
and 75 mg/m  (19 and 65 ppm).  Although some effects were observed with


the CO and N0? combinations, it was reported that no firm conclusion of

                                                                 3
any interaction was warranted.  The combination of S02 (26.2 mg/m ; 10

                            3
ppm) and CO (17 ppm; 20 mg/m ) resulted in a significantly increased


osmotic fragility of erythrocytes.


     Yamamoto    exposed mice and rats to combustion products from


gauze-PAN (Polyacylonitrile) which were analyzed and shown to contain

                           3
between 920 and 17,020 mg/m  (800 and 14,800 ppm) CO and between 209 and


435 ppm HCN, depending upon the intensities of exposure.  He concluded


that CO and HCN did not have additive or synergistic effects on survival


rates.  The effects of CO and CN  on the circulation and metabolism of

                                                          81
the brain of anesthetized dogs were studied by Pitt et al .    Cerebral


blood flow increased 130 and 200 percent when COHb levels were 30 and
                                     10-42

-------
51 percent.  Similar increments in flow were observed when blood CN~

concentrations were 1.0 and 1.5 M9/ml.  When CO and CN~ were administered

simultaneously, cerebral blood flow  increased additively.  Cerebral

metabolism increased only at the  higher levels of COHb and CN~ but, when

both substances at the lower levels  were presented to the animal,
significant decreases  in brain 02  consumption were  found.

     Murphy  a demonstrated  that COHb was  about 5 percent higher after
                                 3
simultaneous exposure  to 345 mg/m   (300  ppm) CO and 0.75 ppm 03 than
              3
after 345 mg/m   (300 ppm)  CO alone in mice, guinea  pigs, and rats

(25 percent vs.  30  percent COHb).   Oda et  al.70 did not detect any

effect  of simultaneous CO  and nitric oxide exposures of 460 ppm and

66 ppm,  respectively,  on the COHb  of mice, beyond that expected due to

CO alone.
                  cc
     Murray et al.   exposed mice  and rabbits to 25 and 70 ppm SOp,
                                            3
respectively and simultaneously, to 288  mg/m  (250  ppm) CO.  They studied

teratogenic effects on offspring and found no reliable defects due to

exposure to either  or  both substances.

10.6.2   Drugs

     Surprisingly little  systematic work has been done on the interactions

of various drugs and CO.   Pankow   ' a  observed that ethanol had additive

effects on some  enzymes in combination  with CO  if COHb levels exceed

50 percent.  McMillan60 noted that CO  attenuated the behavioral effects

of d- amphetamine in a  systematic  dose-dependent way for  CO  levels as  low
           Q                                  CO
as 575  mg/m   (500 ppm).  Montgomery and Rubin    showed that  the effects
                                     10-43

-------
of two dissimilar drugs (hexobarbital and zoxazolamine) were prolonged



by CO exposure in rats.



10.6.3  Halogenated Hydrocarbons



     Polybrominated and polychlorinated biphenyls are converted  ijn vivo


     14 84
to CO  *   or stimulate a catabolic process(es) that would produce CO.



The production of CO from dichloromethane (CH?C1«) was reported  to be



mediated by an enzyme present in the microsomal fraction prepared from


               39
hepatic tissue.    These studies indicated a direct role of cytochrome



P-450 in this process.  These observations are similar to those  reported


          2 25
by others.  '    Dogs were exposed for two hours to 500, 1000, 2000, and
5000 ppm of CHCl.   The rise  in COHb was  logarithmically related to
the CHpClp  exposure concentration.  Coronary blood flow increased 20 to


                                              3

25 percent  during all exposures above 573 mg/m .  Arterial pressure and



myocardial  contractility  (dP/dt)  increased with each concentration.



Heart  rate  was  not influenced by  CH^CK exposure but predisposed the



heart  to  arrhythmias.   Interestingly, combined exposures to CO and



CHpClp showed that CH?C1« had no  effect on the physiologic responses due



to CO,  but  CO antagonized the responses due to CH^Clp.



10.6.4 Other Variables



     Temperature appears  to  affect  the survival time of newly hatched


                             3

chicks exposed  to 11,500  mg/m   (10,000 ppm), with cooler temperatures



producing longer survival.    No  effort was made, however, to determine



whether cool temperatures might simply have slowed down physiologic



processes.  Variables relating  to body and/or environmental temperature



should be important but have not  been systematically studied.
                                     10-44

-------
     Variables relating to the method for the administration of CO have



received little systematic attention.  The uptake was shown to be


                               ' 82                             ^
important by Plevova and Frantik   who exposed rats to 230 mg/m  (200 ppm)

                               3
for 30 minutes and to 805 mg/m  (700 ppm) for 24 hours.  Both exposures



resulted in 20 percent COHb but the longer exposure produced more effect



on motor endurance.  This study is not definitive, however, since the



24-hour group would have reached saturation in two to three hours, thus


spending more time at 20 percent COHb.



10.6.5  Conclusions About Interactions



     Despite the paucity of data concerning CO and other substances and


conditions, there are enough  data to indicate that such interactions



might well be of importance to health effects.  Quite possibly some of



the commonly covarying pollutants and some of the commonly used drugs



(either therapeutic or otherwise) mjjjlxt  interact additively or syner-


gistically to make extremely  low levels  of CO dangerous.  This possibi-


lity  is based not only upon preliminary  evidence but is entirely within



the scope of reason on theoretical grounds.   In view of the potential



importance of such work,  it is surprising that more studies have not



been  reported.



10.7  MECHANISMS


      It has been generally assumed that  the manner in which CO produces



deleterious effects  is by reducing the O^carrying capabilities of



the blood.  This view  has been challenged  in  several ways, although



evidence  is still  very incomplete.
                                     10-45

-------
10.7.1  Hypoxic Hypoxia and CO Hypoxia



     If the effects of CO are limited to CO hypoxia, then CO effects



should be similar to the effects of hypoxic hypoxia, given that the



severity of the two hypoxias could be equalized.  It is easy enough to



calculate 0« arterial blood levels for CO and hypoxic hypoxias and thus



equalize exposures at asymptotic CO saturation levels.  It must be borne



in mind, however, that exposure to atmospheres with low 0« concentrations



produces a rapid reduction in arterial blood 0«, whereas with CO hypoxia



the reduction rate is much slower.  Attempting to decide the equivalence



of the two hypoxias in short-term exposures is not a trivial task.  In



long-term exposures where the equilibration process is a small proportion



of the exposure, equivalences can more easily be made.


                         92
      Syvertsen and Harris   exposed dogs to either simulated altitude



(18,000  feet) or to 225 mg/m  (195 ppm) CO for 72 hours and showed that



Hb and hematocrit rose to nearly the  same values by the end of the



period.  These blood measures rose gradually for the high altitude



group, beginning almost immediately,  but for the CO group began to rise



only  after 48 hours.  They also showed that erythropoietic levels



increased almost immediately for high altitude groups but did not begin



to increase  until about 24 hours in the CO group.  These differences can



probably be  explained by (1) the differences in the early levels of



hypoxia  being more extreme in the high altitude groups, and (2) the



chemosensory response to the high altitude condition.  This is not,



therefore, evidence  for some non-hypoxic effect of CO.  It does,  however,



appear that  compensation for CO effects is not as fast as for hypoxic



hypoxia.
                                     10-46

-------
                  7ft                                                 o
     Penney et al.   exposed groups of rats to 115, 230, and 575 mg/m


(100, 200 and 500 ppm) CO and to 18,000 feet simulated altitude for


periods of several weeks and showed that high altitude produced mainly


increased right ventricle weight, while CO produced overall heart weight


increases.  The levels of arterial blood 0« in high altitude subjects,


however, would not have produced equivalent exposures nor were durations


of exposure the same, so that this result is difficult to interpret.


     Winston    and Winston and Roberts   *    showed that pre-exposure


of mice to 500 or 1000 ppm CO for four hours resulted in a significant

                                                3
decrease  in mortality resulting from a 2875 mg/m   (2500 ppm) exposure


24 hours  later.  They also showed that the short pre-exposure did not


protect animals against hypoxic hypoxia.  Their conclusion was that

                                                                         108
selective redistribution of blood flow was responsible for their results.

          3
     Annau  showed that rats exposed for about two hours to 1000 ppm at


first  showed  depressed lever press rates in a behavioral study, but


after  the fourth  day of repeated testing, the decrement in behavior


began  to  approach pre-exposure  levels.   In contrast a group of rats


exposed to 8  percent Op (hypoxic hypoxia) for about two hours recovered


to normal by  the  second day of  repeated  testing.   This more rapid


recovery  by hypoxic animals than by CO-exposed animals is at least  a


control for possible practice effects.


     Koob et  al.47 exposed rats  for 24 hours to air containing 16,  14,


and  10 percent 02 and to 288, 576, and 1152 mg/m   (250, 500, and


1000 ppm) CO.  They showed no differences between  CO  and  lowered 02


groups in feeding, drinking and weight gain.  This result  implies that
                                     10-47

-------
CO has no effects on these variables other than hypoxic effects, but the



dependent variables are rather gross measures.



     That CO hypoxia and hypoxic hypoxia are similar in terms of survival


                                        15
effects was suggested by Clark and Otis,   who showed that adaptation to



CO produced increased tolerance of high altitude and vice versa.  Wilks



et al.    reported similar data.  It is difficult to evaluate the



equivalence of exposures in these studies, however.



     Careful effort to equalize hypoxic hypoxia and CO hypoxia were made


             99 100
by Traystman,  '    who measured cerebral blood flow in dogs.  Since his



subjects were held at constant ventilation, the effects of hypoxia-



induced hyperventilation were eliminated.  His data show that for



exposures of up to 40 minutes, with arterial 0« values ranging from 4



percent to 17 percent for both hypoxic hypoxia and CO hypoxia, the CO



hypoxia reduced cerebrovascular resistance significantly more than did



hypoxic hypoxia.  The difference between the two forms of hypoxia



diminished as the degree of hypoxia diminished.  These data  suggest that



CO produces a more extreme compensatory response than hypoxic hypoxia,



if ventilation is controlled.
           3
      Annau  exposed  rats  to  either 14, 12, 10, or 8 percent 0«  in "air"



 and  to  174,  288,  576,  or  1152 mg/m3  (150, 250, 500, and 1000 ppm) CO for



 daily exposures of 15  to  60  minutes.  He showed that brain-stimulation-



 reinforced responses were affected by both variables in about the same



 way  except for certain temporal  effects over  the course of several days



 exposure.  Apparently  CO-exposed rats recover response rates more slowly



 than low-02  exposed  rats.   It is unlikely that very much  adaptation to
                                     10-48

-------
CO would have taken place in the course of a few days of short exposures;


therefore, this result is difficult to interpret.   If replicable, these


data imply that CO has some non-hypoxic effect.


10.7.2  Elimination of Hemoglobin

                 36
     Geyer et al.   replaced the blood of rats with artificial blood.


Without Hb, these rats survived 17 hours of exposure to 115,000 mg/m3


(100,000 ppm) which killed controls immediately.  Although no other than


observation of "normal" behavior was  reported, this data imply that CO


has only hypoxic effects.


     Most insects do  not  have  Hb and  so may provide a source of material


which could be used to assess  the question as to whether or not CO has


effects on mammals in addition to those due to combination of CO with


Hb.  Haldane observed that a cockroach was unaffected by 18 days exposure


to an environment containing 80 percent CO and 20 percent Op.  Baker and


Wright   exposed Coccinella septempunctata (the seven-spotted ladybird)


and Carausis morosus  (the stick insect) to an environment of approxi-


mately 80 percent CO  and  20 percent 0^.  All ladybirds survived 10 days


or less of exposure but  longer periods under these  conditions hastened


death.  Ladybirds were less active and ate less food in this environment.


Stick insects  lived in an ambient atmosphere containing 20 percent CO, 5


percent 02, and  75 percent air.  Growth was arrested, but no deaths


occurred before  14 days;  all were dead by day 37.   In an 80 percent CO,


20 percent 02  environment, stick insects died between the 2nd and 21st


day of exposure.  It  was  postulated that the respiratory chain of enzymes,
                                     10-49

-------
although not inactivated, were inhibited to such an extent as to inter-



fere with the animals' well-being.  These insects also lack myoglobin.


                                                                   102
Certain bacteria can live and grow in a 100 percent CO environment.



Carbon monoxide-utilizing bacteria may perform an important function  in



natural aquatic environments and  in soil.



10.7.3  Conclusions About Mechanisms



     There is some evidence from  comparison of CO and hypoxic hypoxia



that CO has non-hypoxic effects but the evidence is only suggestive at



this stage and may derive from dose and saturation rate parameters.



There  is certainly also evidence  for CO having only hypoxic effects but



such evidence stems from the measurement of rather gross variables.



Although the evidence is difficult to interpret in terms of mammals,



insects having no Hb are apparently effected by CO but at very high CO



levels.



10.8   ADAPTATION, HABITUATION AND/OR COMPENSATORY MECHANISMS



     In this section consideration will be given to the question of



whether animals exposed to CO eventually develop some physiological



responses which tend to offset the deleterious effects.  While there  is



possibly a temporal continuum in  such processes, in this review the term



"adaptation" will be  used to refer to long-term phenomena, and the term



"habituation" will refer to short-term processes.  Allusions will be



made,  where possible, to the physiological chain of events by which



adaptation and habituation come about but extensive reductive explana-



tions  will be avoided and teleogical inferences shunned.  The term



"compensatory mechanism" will be  used to refer to those physiological
                                     10-50

-------
responses which tend to ameliorate deleterious effects, whether in the

long- or short-term case.


10.8.1  Adaptation (Long-Term)

            44
     Killick   exposed mice to successively higher concentrations of CO,


which in a period of 6 to 15 weeks reached levels of 2300 to 3278 mg/m3


(2000 to 2850 ppm) CO (60 to 70 percent COHb), showing that non-adapted


mice exhibited much more extreme symptoms when exposed to such levels.


A control group was used by Killick to partially rule out effects of


selection of CO-resistant individuals.  Clark and Otis15 exposed mice to

gradually increasing CO  levels over a period of 14 days until a level of
         3
1380 mg/m  (1200 ppm) was reached.  When exposed to a simulated altitude


of 34,000 feet, survival of the CO-adapted groups was much greater than


controls.  Similarly Clark and Otis   acclimatized mice to a simulated


altitude of 18,000 feet  and showed that these altitude-adapted mice
                                s

survived 2875 mg/m  (2500 ppm) CO better than controls.  Wilks et al.


reported similar effects in dogs.

                      34a
     Gorbatow and Noro    showed that rats given successive daily short-


term exposures could tolerate, without  loss of consciousness, longer and
                                                            3
longer  exposures.  Their CO levels were 2,875 to 11,500 mg/m  (2,500 to


10,000  ppm).  Increases  in tolerance to CO began to be evident as early


as the. fourth or fifth day of exposure  and were still occurring as late


as the  47th day.  Non-exposure for several days eliminated some of the

                                                          113
adaptation.  Similar results were reported by Zebro et al.

     As discussed in Section 10.4.5, Hb  increases  in  animals exposed to

                         ny
CO after about 48 hours,   and continues to  increase  in the  course of
                                     10-51

-------
continued exposure until about 30 days, depending perhaps upon exposure


level.  This hemopoietic response to long-term CO exposure is similar to


that shown for long-term hypoxic hypoxia, except that it is slower to


start, and tends to offset CO hypoxic effects.


     Most investigators have at least implied that this increased Hb


level is the mechanism by which adaptation occurs.  Certainly this


explanation is reasonable for the studies showing increased survival in

                                                    3
groups adapted for several days.  The study by Annau  made no such


inferences, and it is more likely that some behavioral explanation can


be found for his results, such as the possibility that hypoxic hypoxia


is more easily discriminable by the subjects and they more quickly

                                          3
develop state-dependent learning.  Annau1s  results might also be due to


some  mechanism as discussed by Winston    and Winston and Roberts   '

                                                     34a
or related to the effects shown by Gorbatow and Noro.


      While much has been written about compensatory Hb increases, little


has been done to elucidate the extent to which such increases offset


deleterious effects of  CO.  Only survival studies have been done to


unambiguously show adaptation.  The probability that some adaptation


occurs  is  supported theoretically due to Hb increases, and empirically


in the  findings of survival studies.


      Compensatory increases in Hb are not without deleterious conse-


quences of their own, such as cardiac hypertrophy.  The Hb increases are


also  not entirely compensatory at all CO levels in view of the fact that


deleterious effects still occur at some CO  levels for many physiological


systems.   It is possible, however, that without such mechanisms  as Hb
                                     10-52

-------
increases, CO effects would be worse and/or would occur at a lower
threshold.
10.8.2  Habituation (Short-term)
     Arguments have been made for the possibility that there exist
short-term habituation and/or compensatory mechanisms for CO exposure.
These mechanisms have been hypothesized (1) to account for certain
putative  behavioral findings, and (2) based upon physiological evidence.
     The  behavioral work upon which short-term habituation hypotheses
are predicated are mostly human  studies, where CO exposure at very low
levels or at very early exposure times (well before asymptotic saturation)
have shown performance decrements which were not apparent with either
higher exposures and/or longer exposures.  Depending upon the particular
                                                                      j
version,  the habituation hypothesis holds that if some short-term
compensatory mechanism were  operative, there might exist some threshold
value of  CO below which no compensation would be initiated, or that
there might be some sort of  time lag  in the compensatory mechanism so
that early CO exposures might produce effects which would later drop
out.  The question of behavioral data to  support this contention will be
reviewed  in the  context of human research, but in experimental animal
studies,  little  behavioral evidence for such thresholds or time lags  is
extant.   Many of the variable results in  the literature would be
attributable to  such threshold phenomena  if  independent evidence for
such were to be  demonstrated in  experimental designs, devised to
specifically test  such an  hypothesis.
                                     10-53

-------
     There is certainly physiological evidence for responses which would



compensate for the deleterious effects of CO in a very short time span.



As discussed in the section on nervous system and behavior, particularly



10.3.4, there has been demonstrated an increased CNS blood supply during



CO exposure which is apparently produced by cerebrovascular dilation.



It has also been shown, however, that the tissue PQ2 values for various



CNS sites fall in proportion to COHb, despite the increased blood flow.



Apparently the PQ2 values would fall considerably more without the



increased blood flow.  Although the graphs which were published on these



data did not show very short time intervals, it appears that tissue PQ2



falls  immediately and continuously as COHb rises.  There is no evidence



for time delays or for threshold effects.  It is also noteworthy that



only very high CO levels were employed, so that the saturation rates



were high and time lags or thresholds would be difficult to detect.



     As discussed in the section on cardiovascular effects', as COHb



rises, both coronary blood flow and 0« extraction in the peripheral



musculature increase.  These, too, are compensatory mechanisms which



have been shown to be only partly effective.  None of the studies present



evidence of time lag or threshold effects, since only terminal and near-



asymptotic values were reported.



     Increased blood flow and/or 0^ extraction have been demonstrated



for many body systems in response to CO exposure.  In some cases it has



been explicitly shown to be only partly compensatory, and by virtue of



the fact that at some CO levels deleterious effects still occur, it is



apparent that compensatory mechanisms are not entirely complete.
                                     10-54

-------
Disregarding time lags and threshold considerations, without the


compensatory mechanisms, CO would apparently  have a more deleterious

effect and the threshold for such effects would be lower.

10.9  SUBJECTS AT SPECIAL RISK


     From the theoretical and empirical  considerations of the foregoing

literature review and from additional data  reviewed below, some strong

conclusions may be drawn about  sub-groups in  the general population of

experimental animal  subjects which would be at especially high risk or

especially sensitive to the deleterious  effects of CO exposure.  What

follows will in some cases be based directly  upon studies designed to

test the given question, and in other instances will be deductions or

syntheses based upon extant data or theory.

10.9.1  Fetus and Uterine Exposure

     Several studies27'29'32'33'3639'86  have  exposed pregnant females

to  CO and in general have shown that the mothers have not been affected,

while the offspring  have shown  deleterious  effects.  In many cases the

deleterious effects  have been shown to disappear by adulthood, but the

inference of deleterious effects in childhood is of concern.

Additionally, impairment during maturation  can have effects on learning

and social behavior  which would be developing normally.  Most of the

studies cited above  did not measure COHb in the fetus during long-term


exposure.

     Longo and Hill55  studied the  uptake and  elimination of CO in fetal
                                                  3
and maternal sheep.  Following  exposure  to  58 mg/m   (50 ppm) CO, steady-

state maternal COHb  was 7.2 percent and  fetal COHb was 11.3 percent,
                                     10-55

-------
                          3
while exposure to 115 mg/m  (100 ppm) resulted in steady-state COHb



concentration of 12.2 and 19.8 percent, respectively.  The increase in



maternal COHb resembled a simple exponential process with a half-time of



1.5 hours.  The half-time for the fetus was five hours.  The decay curve



for CO elimination showed similar relations with fetal washout occurring



slower than in the mother.


                               55
     The data of Longo and Hill   on long-term maternal exposures suggest



that the fetus is at special risk because of higher COHb levels than



those of the mother.  Two studies using short-term exposures  *     also



measured COHb in the fetus and showed that it was much lower in the



fetus than in the mother, probably because of slower COHb rise times.



Since short-term exposures also adversely affected the fetus, these



studies  imply that not only is the fetus1 COHb higher than the mothers'



for  long-term exposures,  but that the fetus is apparently more fragile



and  more  subject to CO effects even if COHb is controlled.



     While the data clearly show that fetuses are especially at risk,



much more  information is  required regarding dose-response functions,



from which thresholds, extent of effects, and interactions with other



factors  may be estimated.



10.9.2   Impaired Groups



     There is clear evidence that subjects with impaired cardiovascular



functioning are especially sensitive to CO exposure because of the



already  reduced and/or marginal Op supply from the blood.  Any additional



loss of  Op due to COHb produces local or general hypoxias and deleterious


                                                       3a 21-23
effects.   This has been demonstrated for cardiac damage   '      and for
                                     10-56

-------
the effects of high cholesterol  levels  in  some cardiovascular structures.4'56
These results should hold for central nervous system structures but have
not been demonstrated.

     Subjects with significant pulmonary function  impairment might be at
special risk to GO exposure  because  of  the inadequate supply of 02 to
the blood, especially  during exercise.  Specific data on this subject in
experimental animal research are not available.
     There is one  large  group of subjects  in which several of the above
mentioned impairments  are commonly found,  i.e., the group  including aged
individuals.  When there is  any  of one  or  more impairments such as
cardiac damage, cholesterol  buildup  in  any vascular structures, anemia
and/or pulmonary  function impairment, especially during exercise, low
levels of CO could precipitate major adverse health effects.  Unfortu-
nately, there  is  no experimental evidence  for deleterious  CO effects in
many of these  areas other than cardiovascular impairment.  Certainly
more data are  needed  to  estimate dose-response curves so that the extent,
threshold, and pattern of those  problems  can be assessed.
10.9.3  Drugs
     Alcohol  has  already been  shown"  to  have additive effects with CO,   '
albeit at high exposure  levels.   More refined studies with other
dependent variables will very  likely show lower-level effects.  Sedatives
                                       63
and other drugs are potentiated  by CO.     Stimulant drugs  have  been
                              60
shown  to be  attenuated by CO;    dose-response functions and  a wide range

of dependent variables are  not known.
                                     10-57

-------
10.9.4  Unadapted Populations


     There is considerable evidence for long-term adaptation to high


altitudes in the form of increased Hb levels.  Individuals who have not


had such adaptation and are then simultaneously exposed to high altitude


and high CO concentrations would seem to be at higher risk because of


the simultaneous effects of hypoxic hypoxia and CO hypoxia.  Much data


are available, and estimates of threshold and dose-response functions


could be obtained by projecting arterial 0« content from simultaneous


hypoxic and CO conditions.


10.10  SUMMARY


     From the foregoing review of the literature pertaining to low-level


CO effects in normal experimental animals, it may be concluded that CO


produces deleterious effects mainly upon the cardiovascular systems and


the CNS.  While many particular conclusions are still in dispute, it


seems safe to conclude that cardiovascular effects can be demonstrated

                                   3
with CO exposures as low as 58 mg/m  (50 ppm; 4 to 7 percent COHb).

                                                             3
Behavioral and CNS effects seem to require a minimum 115 mg/m  (100 ppm;


12 to 20 percent COHb) to produce effects.


     The particular levels of CO in experimental animal studies are not


as important as the generalizations about the variables (dependent,


independent, and interactive) that are  likely to be important in humans.


Such knowledge also permits the prediction of specially sensitive popula-


tions and allows for anticipation of new effects not yet observed, and


sometimes too dangerous to produce, in  humans.  The particular level at


which such effects become important in  man is an empirical matter for


human research.
                                     10-58

-------
     While the foregoing review has discussed thresholds, and in some



cases dose-response functions, it is apparent that there remains a great



deal of ignorance regarding important health problems.  Too little is



known about interactions with other pollutants, drugs, or other environ-



mental conditions.  Much remains to be  specified regarding particularly



sensitive groups.  There is the suggestion that CO has other non-hypoxic



effects which  in  turn  suggests that CO  might have as-yet-unanticipated



health effects.   From  this discussion it  may be concluded that a great



deal more  information  about CO is required with respect to interactions,



groups at  special  risk,  and non-hypoxic CO effects.
                                     10-59

-------
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57.  Marks, E., and W. Sw1ecick1.   Effect of  carbon  monoxide, vibration and
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                                      10-64

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60.  McMillan, D. E., and A. T. MUler,  Jr.   Interactions  between carbon
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61.  MeHgan, W. H., and R. W. Mclntlre.   Effects of carbon  monoxide  on responding
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62.  Miller, A. T. , Jr., and J. J.  Wood.   Effects of acute carbon monoxide
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63.  Montgomery, M. R., and R. J. Rubin.   The effect of  carbon monoxide Inhalation
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     1971.                                                             	

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65.  Murray, F. J., B. A. Schwetz,  A. A. Crawford, J. W. Henck,  and R.  E. Staples.
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68.  Norton, S., and B. Culver.   A  golgi analysis of caudate neurons 1n rats
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70.  Oda, H., H. Nogaml, S. Kusumoto, and  T.  Nakajlma.   Nltrosylhemoglobin  and
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72.   Pankow, D. , and W. Ponsold.  Leucine amlnopeptidase  activity  in  plasma of
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73.   Pankow, D., and W. Ponsold.  The combined effects  of carbon monoxide  and
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             #
73a. Pankow, D., W. Ponsold, and H. Fritz.  Combined effects  of carbon  monoxide
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74.   Pankow, D., W. Ponsold, I. Grimm.  G. Gessner, and D.  Liedtke.   Enhancement
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75.   Pankow, D., W. Glatzel, K. Tietze, and W. Ponsold.   Motor  nerve  conduction
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76.   Parving,  H.-H.  The effect of hypoxia and carbon monoxide  exposure  on
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77.   Parving,  H.-H., K. Ohlsson, H. J. Buchardt Hansen, and M.  Rorth.   Effect
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78.   Penney, D., M. Benjamin, and E. Dunham.  Effect of carbon  monoxide  on
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79.   Penney, D., E. Dunham, and M. Benjamin.  Chronic carbon  monoxide exposure:
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80.   Petajan,  J. H., S. C. Packham, D. B. Frens, and B. G.  Dinger.  Sequelae  of
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81.   Pitt, B.  R., E. P. Radford, G. H. Gurtner, and R.  J.  Traystman.  Interaction
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82.   Plevova,  J., and E. Frantik.  The influence of various saturation  rates
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83.   Preziosi, T. J., R. Lindenberg, D. Levy, and M. Christenson.   An experimental
     investigation in animals of the functional and morphologic effects  of
     single and repeated exposures to high and low concentrations  of  carbon
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     Ann. NY Acad. Sci. 174:369-384, 1970.


                                     10-66

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83a. Purragganan, H. B., and A.  E.  McElfresh.   Failure of carbonmonoxy
     sickle-cell haemoglobin to  alter  the  sickle state.   Lancet 79-80, 1964.

84.  Rodkey, F. L., and H. A.  ColHson.  Biological  oxidation of [14C] methylene
     chloride to carbon monoxide and carbon  dioxide  by the rat.   Toxlcol.
     Appl. Pharmacol. 40:33-38,  1977.

85.  Rylova, M. L.  The application of Integral  methods of Investigation  to
     determine the  effect  of repeated  exposure  to carbon monoxide in  animals.
     In:  Industrial Toxicology.   Moscow, 1960,  pp. 264-270.

86.  Schwetz, B. A., B. K. J.  Leong, and R.  E.  Staples.   Teratology studies on
     Inhaled carbon monoxide and imbibed ethanol in  laboratory animals.
     Teratology 11:33A, 1975.

86a. Shul'ga, T.  New Data for the  hygienic  evaluation of carbon monoxide  in
     atmospheric air.   Iji:  U.S.S.R. Literature on Air Pollution and  Related
     Occupational Diseases.  Volume 9  in Two Parts.   B.  S.  Levine, ed., U.S.
     Department of  Commerce, Office of Technical Services,  Washington,  DC,
     1964.

86aa.     Sirs, J.  0.   The use of carbon monoxide to prevent sickle-cell
     formation. Lancet  1:971-972, 1963.

87.  Smith, M. D.,  W. H. Merigan, and  R. W.  Mclntire.   Effects of carbon
     monoxide on fixed-consecutive-number  performance in rats.   Pharmacol.
     Biochem. Behav. 5:257-262,  1976.

88.  Sokal, J. A.   Lack of the correlation between biochemical  effects on  rats
     and  blood carboxyhemoglobin concentrations in various conditions of
     single acute exposure to  carbon monoxide.   Arch.  Toxicol.  34:331-336,
     1975.

89.  Stender, S., P. Astrup, and K. Kjeldsen.   The effect of carbon monoxide
     on cholesterol in  the aortic wall of  rabbits.   Atherosclerosis 28:357-367,
     1977.

90.  Stupfel, M., and G. Bouley.  Physiological  and  biochemical  effects on
     rats and mice  exposed to  small concentrations of carbon monoxide for  long
     periods of time,   In:  Biological Effects  of Carbon Monoxide, Proceedings
     of a Conference, New  York Academy of  Sciences,  New York, January 12-14,
     1970.  Ann. NY Acad.  Sci. 174:342-368,  1970.

91.  Swlecicki, W.  The effect of vibration  and physical training on  carbohydrate
     metabolism in  rats intoxicated with carbon monoxide.   Med.  Pr. 24:399-405,
     1973.

92.  Syvertsen, G.  R.,  and J.  A.  Harris.   Erythropoietin production in dogs
     exposed to high altitude  and carbon monoxide.   Am.  J.  Physiol. 225:293-299,
     1973.

93.  Szumanska, G., M.  Sikorska,  and R. Gadamski.  Effect of acute carbon
     monoxide intoxication on  rat brain catecholamines.   Neuropatol.  Pol.
     15:75-84, 1977.


                                     10-67

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94.   Theodore, J., R. D. O'Donnell, and K. C. Back.  Toxlcological  evaluation
     of carbon monoxide in humans and other mammalian  species.   J.  Occup.  Med.
     13:242-255, 1971.

95.   Thomsen, H. K.  Carbon monoxide-induced atherosclerosis  in  primates.   An
     electron-microscopic study on the coronary  arteries  of Macaca  irus  monkeys.
     Atherosclerosis 20:233-240, 1974.

96.   Thomsen, H. K., and K. Kjeldsen.  Threshold limit for carbon monoxide-induced
     myocardial  damage.  Arch. Environ. Health 29:73-78,  1974.

97.   Thomsen, H. K., and K. Kjeldsen.  Aortic intimal  injury  in  rabbits.   An
     evaluation  of a threshold limit.  Arch. Environ.  Health  30:604-607,  1975.

98.   Tiunov,  L.  A., and V. V. Kustov.  Toxicology of carbon monoxide.  Leningrad,
     1969.   (In  Russian).

99.   Traystman,  R. J.  Effect of carbon monoxide hypoxia  and  hypoxic  hypoxia
     on cerebral circulation.  Ln:  Multi-disciplinary Perspectives in Event-Related
     Brain Potential Research, Proceedings of the Fourth  International Congress
     on Event-Related Slow Potentials of  the Brain (EPIC  IV), University  of
     North Carolina and U.S. Environmental Protection  Agency, Hendersonville,
     North Carolina, April 4-10, 1976, D. A. Otto,  ed., EPA-600/9-77-043,  U.S.
     EPA, RTP, NC, December 1978.  pp. 453-457.

100. Traystman,  R. J., and R. S. Fitzgerald.  Cerebral  circulatory  responses
     to hypoxic  hypoxia and carbon monoxide hypoxia in carotid baroreceptor
     and chemoreceptor denervated dogs.   Acta Neurol.  Scand.  Suppl. (64):294-295,
     1977.

101. Tumasonis,  C. F., and F. D. Baker.   Influence of  carbon  monoxide upon
     some respiratory enzymes of the chick embryo.  Bull. Environ.  Contam.
     Toxicol. 8:113-119, 1972.

102. Uffen,  R. L.  Anaerobic growth of a  Rhodopseudomonas species in  the  dark
     with carbon monoxide as sole carbon  and energy substrate.   Proc. Nat!.
     Acad. Sci.  U.S.A. 73:3298-3302, 1976.

103. Committee on Medical and Biologic Effects of Environmental  Pollutants.
     Carbon  Monoxide.  National Academy of Sciences, Washington, DC,  1977.
     pp. 68-167.

104. Webster, W. S., T. B. Clarkson, and  H. B. Lofland.   Carbon  monoxide-
     aggravated  atherosclerosis in the squirrel  monkey.   Exp. Mol.  Pathol.
     13:36-50, 1970.

105. Wilks,  S. S., J. F. Tomashefski, and R. T.  Clark, Jr.  Physiological
     effects  of  chronic exposure to carbon monoxide.   J.  Appl. Physiol.  14:305-310,
     1959.

106. Winston, J. M.  A Study of the Mechanism of the Alteration  of  Carbon
     Monoxide-Induced Lethality.  Ph.D. Thesis,  University of Iowa,  Iowa City,
     IA, 1976.
                                      10-68

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107. Winston, J. M. , and R. J. Roberts.   Influence  of carbon monoxide,  hypoxic hypoxia
     or potassium cyanide pretreatment  on acute  carbon monoxide and hypoxic
     hypoxia lethality.  J. Pharmacol.  Exp.  Ther. 193:713-719,  1975.

108. Winston, J. M., and R. J. Roberts.   Glucose catabolism following carbon
     monoxide or hypoxic hypoxia  exposure.   Biochem.  Pharmacol.  27:377-380, 1978.

109. Xintaras, C.,  C.  E. Ulrich,  M.  F.  Sobecki,  and R.  E.  Terrill.   Brain
     potentials studied by computer  analysis.  Arch.  Environ.  Health 13:223-232,
     1966.

110. Xintaras, C.,  B.  L. Johnson,  C.  E.  Ulrich,  R.  E.  Terrill,  and  M.  F. Sobecki.
     Application of the evoked response technique in air pollution  toxicology.
     Toxicol. Appl.  Pharmacol. 8:77-87,  1966.

111. Yamamoto, K.   Acute combined effects of HCN and CO, with the use of the
     combustion products from PAN (Polyacrylonitrile)-gauze mixtures.   2.  Rechtsmed.
     78:303-311, 1976.

112. Young, S. H.,  and H.  L.  Stone.   Effect of a reduction in arterial  oxygen
     content (carbon monoxide) on coronary flow.  Aviat.  Space  Environ. Med.
     47:142-146, 1976.

113. Zebro, T., R.  J.  Littleton,  and E.  A.  Wright.   Adaptation  of mice  to
     carbon monoxide and the  effect  of  splenectomy.   Virchows Arch.  A:  371:35-51,
     1976.

114. Zorn, H.   Learning of conditioned  reflexes  of  the Wistar rat under intermittent
     action of  low CO  concentrations.   Staub Reinhalt.  Luft 32:36-38, 1972.

115. Zorn, H.  The partial oxygen pressure in the brain and liver at subtoxic
     concentrations of carbon monoxide.   Staub  Reinhalt.  Luft 32:24-29, 1972.
                                      10-69

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               11.   EFFECTS OF LOW-LEVEL CO EXPOSURE ON HUMANS







11.1  INTRODUCTION



     Carbon monoxide (CO) poisoning is a common form of poisoning



occurring both accidentally and voluntarily.  The potentially serious



effects of overdosage must always be considered by those concerned



with this contaminant.   The early history (from the days of Aristotle)


                                                                  130
of CO and its effects on mammals has been well described by Lewin.



The clinical-pathological effects, especially of large increments in



carboxyhemoglobin (COHb), are adequately documented in several


           ?ft ~\ ^? 16^ ?0? ??fi
monographs.  '   '   '    '     Neurological signs and sequelae as well



as anatomical alterations in various tissues are presented in these



reviews, as are the occurrences of CO intoxication, clinical symptomology,



complications, progressions, and emergency and subsequent treatment.


                                                                         47
An extensive bibliography of abstracts up to 1966 was compiled by Cooper.



These severe effects of exposure to high concentrations of CO are not



directly germane to the problems of individuals exposed to current



ambient levels of CO but are valuable in that they indicate the potential



effects of accidental overdose.
                                   11-1

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     Extensive studies have been conducted using various animal species
as subjects.  Under the varied experimental protocols employed by
investigators, considerable information has been obtained on the toxicity
of CO, its effects on blood, tissues, metabolism, etc.  The effects
observed on experimental animals have provided some insight into the
potential role CO plays in cellular metabolism.  A certain degree of
caution must be employed in extrapolating the results obtained from
these data to man.  Not only are there questions related to species
differences, but exposure conditions differ markedly in the studies
                                     204
conducted by different investigators.
     Human  research is especially fraught with methodological problems.
As with the experimental animal literature, there are many methodological
and reporting problems which make the reported research data difficult
to interpret.  These  include:  failure to measure blood COHb levels;
failure to  distinguish between the physiological effects of a CO dose of
high concentration or the slow, insidious increment in COHb over time
with lower  inhaled CO concentrations; the amount of CO brought to or
removed from the  lungs by changes in alveolar ventilatory volumes; and
the small number  of subjects.  Other factors involve failure to provide
control measures  (via double-blind administration), for experimenter
bias and experimenter effects control periods so that task-learning
effects do  not mask negative results, homogeneity and the groups labeled
"smokers",  control of possible boredom and fatigue effects, and poor or
inadequate  statistical treatments.
                                    11-2

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     An almost universal problem in this area of research is the use of
inappropriate statistical techniques for data analysis.  Experimenters
commonly use tests designed for simple two-group designs when analysis
of variance is required, or use several univariate tests when more than
one dependent variable  is measured and multivariate tests are appropriate.
Such inappropriate statistics usually yield results in which the p-value
is too small, so that the possibility exists that too many results were
falsely declared to be  statistically significant.  In this review, an
effort will be made to  account for such problems whenever possible by
making appropriate corrections and/or discussing the possible consequences
of such an error in context.
     The above problems are not unique to human research data (as dis-
cussed in Chapter 10).   A problem that is unique to human research is
that only low levels of CO exposure may be safely and prudently used.
In such instances of low-level exposure, research findings necessarily
deal with near-threshold effects.  The so-called "threshold" for an
effect is conceptually  defined as a CO level below which no deleterious
effect on the dependent variable occurs and above which an effect is in
evidence.  In practice, a threshold must be defined as a CO level above
which  an effect  upon a  dependent variable is produced  a certain per-
centage of the time it  is administered.  Usually, a threshold is defined
in terms of the  point where an effect  is noted 50 percent of the time,
although many other, possibly better,  definitions are  in use.  When
research is necessarily restricted to  such barely-noticeable effects it
may be expected  that (1) results will  be more variable due to statistical
                                    11-3

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sampling fluctuations and (2) other uncontrolled variables which also



effect the dependent variable in question will be of major importance



and will increase the variability of results.  For these reasons, human



data, while being of prime interest, will also be of highest variability.



Such high variability must be resolved with (1) large groups of subjects



(2) theoretical interpretation of results using knowledge gained from



experimental animal data, and (3) consideration of consistency of the



data within and across experiments.



     This chapter is intended to review data from studies in which



humans  have been either accidentally or intentionally exposed to low



levels  of CO.  The summary and conclusion of each section of this chapter



will integrate the relevant material from studies which have used exper-



imental animals.  Unless otherwise stated, all subjects are considered



to be normal (i.e., without debilitating disease).



11.2  NERVOUS SYSTEM AND BEHAVIOR



     The demonstrable changes in central nervous system (CNS) function



in individuals who were inadvertently exposed to high levels of ambient



CO in illuminating gas and in automobile exhaust stimulated psychophysi-



ological research.  These studies attempted to determine psychomotor and



psychological aberrations in individuals having lower levels of blood



COHb than those observed in CO-poisoned individuals.  Reports of the



earlier studies suffer from a number of deficiencies.  These deficiencies



are related to inadequate understanding of the significance of behavioral



changes, the inability to distinguish between simple perceptual motor



performance, and the more complex performance involving sustained and/or
                                   11-4

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selective attention, short-term memory, and decision-making among the



possible alternatives.



11.2.1  Sleep and Activity

                    -I CO

     O'Donnel et al.    sought to determine how overnight exposure to



low levels of CO (COHb levels up to 12.6 percent) affected sleep and



found small but unreliable changes that they  interpreted as a possible


                                                            86
reduction in central nervous activation.  Groll-Knapp et al.   and


             95
Haider et al.   reported a significant reduction of rapid eye movement

                                                                         3

(REM) sleep in subjects of both sexes exposed for seven hours to 115 mg/m



(100 ppm) CO.



11.2.2  Vigilance



     Vigilance is an  individual's ability to  detect small changes in his



environment that take place at unpredictable  times, thus demanding



continuous attention  for long periods of time.  In monotonous tasks,



subjects miss signals that they would not have missed when starting the



task.  Such signals are usually presented visually or aurally.



     Fodor and Winneke   used an auditory vigilance task in which they



presented short bursts  (0.36 second) of white noise at 2-second  intervals



as  the stimuli.  About  three out of every hundred of these noises were



slightly less intense and were the signal to  which the subjects  were to



respond by pressing a button.  Twelve non-smokers (male and female) were

                      3

tested at 0 to 57 mg/m  (0 to 50 ppm) CO  for  80 minutes prior to the



first of three vigilance experiments.   Carboxyhemoglobin was estimated



to  be 2.3 and 3.1 percent, at the beginning and the end, respectively,



of  the first vigilance  test.  Subjects  were likely to miss more  signals

-------
during the initial test than during the next two vigilance tests; COHb



reached an estimated 4.3 percent at the end of 210 minutes of CO exposure.



These data suggested an initial effect, possibly followed by a compen-



satory response.  Compensatory mechanisms might not have been operative



during the first test because of either a threshold level of COHb below



which no compensatory response would be initiated or a time lag in



compensatory responses.

                       oc                                             o

     Groll-Knapp et al.   exposed subjects to 0, 57, 115, and 172 mg/m



CO (0, 50, 100, and 150 ppm; 0.0, 3.0, 5.4, and 7.6 percent COHb) for



two hours.  They used a 90-minute auditory vigilance test which showed



a dose-related decrement due to CO although their statistical documen-


                                                95
tation is absent.  The same group (Haider et al.  ) was later unable to


                                    23         217
replicate the results of this study.    Winneke    utilized the same



test  in studies which used 0, 57, 115, and 172 mg/m3 (0, 50, 100, 150 ppm)



CO as well as exposure to methylene chloride (CH^CK), a compound which



causes an elevation in COHb.  His results from the CO exposures were



negative, in marked contrast to the previous data, despite an estimated


                                                                3

COHb  level of approximately 9 percent at the end of the 172 mg/m



(150  ppm) exposure.  He did find that his subjects, as a consequence of



CH2C12 exposure, exhibited a striking decrement in vigilance.


                         19                                            3
      Beard and Grandstaff   exposed subjects to 0, 57, 200, or 286 mg/m



CO (0, 50, 175, or 250 ppm; 1.8, 5.2, and 7.5 percent COHb estimated



from  alveolar breath) for 1.5 hours during which the subjects performed



a visual vigilance task.  They reported a statistically significant



decrement in performance at the two lower CO levels but not at the
                                    11-6

-------
highest level.  Their data raise again the question of compensatory


                                                                          23
mechanism thresholds but their statistical procedure is also questionable.



     Horvath et al.    utilized a visual vigilance test and were the



only group of earlier investigators to measure COHb.  They also required



two responses, one for the non-signal stimuli as well as the usual



response to the signals.  Their subjects were pre-exposed for one hour



to 0, 29, and 126 mg/m3 (0, 25, and 110 ppm) CO and then continued the



CO exposure during a 1-hour vigilance task.  The COHb levels at the



beginning of the vigil were 0.9, 1.6, and 2.2 percent, respectively, and



at the end of the vigil were 0.9, 2.3, and 6.6 percent.  They noted no



initial effects of CO but by the end of the vigil the 110 ppm group

                   3

exposed to 126 mg/m  (110 ppm) showed a statistically significant decre-


                                             218
ment in performance.  Recently Winneke et al.    attempted to replicate

                  -I QTT                                       218
the Horvath et al.    study without success.  Winneke et al.    apparently,



however, provided  less  sensory deprivation in their study and this may



have raised the arousal level of their subjects, keeping them more


                        39
alert.  Horvath's  group   also attempted to replicate an earlier study



by Horvath et al.    using a less isolated (clear plastic) chamber and



failed to observe  a statistically significant decrement due to CO, but



their COHb levels were  also marginally lower.


                    23
     Bern"gnus et al.    utilized a visual numeric monitoring task with



subjects exposed to 0,  115, and 229 mg/m3 CO (0, 100, and 200 ppm CO;



0, 4.6, and 12.6 percent COHb).  No CO exposure  levels produced any


                                                                  23
effect on vigilance performance.  The task used  by  Benignus et al.   was



a fairly complex task with high probabilities of signals so that the
                                    11-7

-------
subjects might have been more aroused than they would have been on a



simple vigilance task.



     Putz et al.     used an auditory and visual monitoring task and


                                     3

exposed subjects to 6, 40, or 80 mg/m  CO (5, 35, or 70 ppm CO; 1, 3, or



5 percent COHb) for four hours.  Their results showed no CO-related



decrements, although they did report electrophysiological effects (to be



discussed later).  Their signal rates were also fairly high and the



performance periods were short, so that their subjects, too, might have



been too aroused to show behavioral vigilance decrements.


                       125
     Krotova and Muzyka    studied individuals working for about two years



in an environment containing CO.  They had approximately 4 percent COHb



after work.  Only 11 of the 56 workers reported a loss of vigilance.



11.2.3  Sensory and Time Discriminations



     The first demonstrable influences of CO on CNS functions were noted


                   142
by McFarland et al.    in conjunction with their studies on the effects



of altitude and CO on visual thresholds.  They observed decrements in



visual  sensitivity at COHb levels as low as 5 percent and extrapolation



of their dose-response curve implies that impairment would occur at even


                              97
lower levels.  Hal perin et al.   reported that visual function was



impaired at COHb  levels as low as 4 percent and that greater impairment


                                                97
occurred at higher COHb levels.  Hal perin et al.   further noted that



recovery from  the detrimental effects on visual function lagged behind


                                 141                     143
the  elimination of CO.  McFarland    and McFarland et al.    were unable



to demonstrate statistically significant differences in  dark adaptation



and  glare  recovery for COHb levels of 6 to 17 percent.   Ramsey    *
                                    11-8

-------
was unable to demonstrate any CO effect on visual brightness discrimi-
nation or depth perception.
                    187b
     Seppanen et al.     evaluated the effect of increasing COHb on
visuoperceptual and psychomotor performance in smokers and nonsmokers.
Subjects breathed 1100 ppm carbon monoxide intermittently to eventually
reach COHb levels of up to 18 percent.  Interspersed between the inhala-
tion of CO were periods breathing air during which the tests were
performed.  No effect on perceptual speed and accuracy was observed.
Visual perception as measured by critical flicker frequency was decreased
linearly with  increasing COHb.  This study was unusual in the methods
utilized to increase COHb and its significant findings open to questions
of technique.
     A perceptual test and a standard cortical function test, critical
flicker fusion frequency (CFFF), apparently is not influenced even by
COHb levels of 10 to 12.7 percent.88,170,171,213,217  Guest et al 88

also utilized  an auditory analogue of CFFF, the auditory flutter fusion
threshold.  This threshold was  not affected by COHb levels of 10 percent.
                 83
Grandstaff et  al.   have recently reviewed these studies.
                                  18
     Studies by Beard and Wertheim   suggested an alteration in CNS
function because the ability to discriminate  slight temporal differences
in successive  short tones was impaired  in subjects having estimated COHb
levels of 2 to 3 percent.  These data imply an orderly dose-response
function with  increasing decrements  in  performance as CO levels  increase.
Although these data represent the lowest  levels  of COHb to produce  a
significant alteration  in  behavioral performance, considerable questions
                                    11-9

-------
as to the validity of the observations have been raised.  Attempts to

replicate these particular findings have been less than satisfac-

tory158'159'193'197 even though the subjects of all of these other

studies attained higher COHb levels.  Some of the failures to replicate

may be explained on the basis of differing protocols and the environmental

conditions under which the tests were conducted.  Some investigators

designed their experiments to minimize boredom and fatigue while others,

conversely, attempted to minimize external influences and conducted
                                                           -I c~l a
their experiments for a relatively  long time.  Otto et al.,     however,

made strong efforts to replicate the study accurately and presented a

strong rationale indicating that time discrimination is probably not

affected by low COHb levels.

11.2.4  Complex Sensorimotor Tasks  and Driving

     A number of investigators have used broad sensory and/or motor

screening batteries in an effort to discover what types of behavior

might be affected by low-level CO exposure.  From the standpoint of

experimental and statistical design, such studies are not always easy to

interpret.  When many dependent variables are measured, the chance that

one  or more of them will erroneously be declared statistically signifi-

cant is  increased, and in order to  account for this increased probability

of an inferential error more exotic statistical procedures must be used.

Such procedures usually involve multivariate techniques or at least

conservative corrections.  Usually  an increased number of dependent

variables requires a concomitantly  increased number of subjects.  In none

of the cases of behavioral screening batteries reported below did
                                    11-10

-------
researchers take appropriate account of this problem.  Attempts were



made on the part of the reviewers to account for this problem by the



application of conservative corrections.


                  1 ftR
     Sayers et al.    found no significant changes, despite COHb levels



of approximately 20 to 30 percent, in hand-eye coordination and steadiness,



tapping speed, arithmetic (continuous addition), location memory, and


                                          21 22
simple reaction time tests.  Bender et al.  '   found a decrement in



learning of meaningless syllables and in  hand-eye coordination when the



COHb levels of his subjects were about 7  percent.  Other tests which



they administered failed to show decrements in performance at these

                        -IOC                            O
levels of COHb.  Schulte    exposed firemen to 115 mg/m  (100 ppm) CO



for variable time periods and reported large changes in performance of a



series of complex tasks.  In a test where subjects were required to



underline all plural nouns in prose passages, decreased performance was



noted when COHb was approximately 8 percent.  The mean time to complete



an arithmetic test significantly increased at similar or slightly lower



COHb levels.  This investigator may have  underestimated his COHb levels



since his subjects, mostly smokers, had initial measured values close

                          •I CQ

to zero.  0'Donne!1 et al.    studied the ability of four subjects to



perform arithmetic problems without pencil and paper.  Their subjects



required a longer  time to complete the answers (89.76 versus 98.64 seconds


                                                                141 143
when COHb levels 5.9 and 12.7 percent, respectively).  McFarland   '



tested subjects' performance of complex psychomotor tasks involving



reaction times to  central and peripheral  stimuli and showed some minimal



effects of CO (11  and 17 percent COHb) on attention to peripheral
                                    11-11

-------
                   183
stimuli.   Salvatore    reported increased reaction times to peripheral



stimuli at COHb levels of 4 to 8 percent.  Putz et al.     reported



decrements in hand-eye coordination, response times during a complex



monitoring task, and tracking accuracy in subjects exposed to 35 and



70 ppm CO (3 and 5 percent COHb).


                   114 115
     Johnson et al.   '    studied employees who worked at a U.S.-Mexico



border crossing and toll collectors at a toll highway.   They believed



that more valuable information would be obtained from these workers than



from the usual studies on university students.  Toll collectors had COHb



levels ranging from 1.5 to 11.7 percent with a mean value of 3.9 percent



and exhibited slowed eye-hand coordination requiring fine motor control



and disruption of performance on two concurrent tasks.



     The potential influence of ambient levels of CO on vehicle operators



as well as the additional increments in blood COHb levels has received



minimal attention.  Suggestive but not conclusive evidence has been



reported indicating that drivers in fatal accidents have higher levels


        220                                        70
of COHb.     In the early studies of Forbes et al. ,   five subjects were



exposed to CO sufficient to raise COHb levels as high as 30 percent and



their  reaction times, coordination, and perceptual skill were determined



within the context of a test of driving skill.  They showed no CO effect


                        219
on skill.  Wright et al.    used a driving simulator with both smokers



and nonsmokers as subjects (final COHb levels were 5.6 and 7.0 percent,



respectively).  They suggested that a 3.4 percent increase in COHb was



sufficient to obviate safe driving.  McFarland et al.    '    studied



subjects that actually  involved driving  instrumented automobiles under
                                    11-12

-------
highway conditions while exposed to CO concentrations producing 17 percent



COHb.   They concluded that such COHb levels do not seriously affect



driving but they did show statistically significant increases in roadway



viewing time, though no differences occurred in steeering wheel reversals.



Preliminary data from Rockwell and others,175'177'178'215 in studies in



which subjects drove instrumented automobiles while exposed to CO levels



producing 0, 6, and 13 percent COHb, imply that at COHb levels of 6 and



13 percent subjects showed increased variations in automobile speed,



decreased ability to maintain fixed following distances, and decreased


                                     181
steering motions.  Rummo and Sarlanis    reported that during a 2-hour



vigilance driving-simulator task subjects with 6 to 8 percent COHb were



significantly slower in responding to changes in speed by the lead car.



11.2.5  Central Nervous System Electrical Activity


           54
     Dinman   analyzed evoked photic responses in subjects with 22 and



37 percent COHb and found no changes in latency or voltage following


                          109
photic stimulation.  Hosko    reported changes in CO-induced visual



evoked response but only at COHb levels of about 20 percent.  Putz



et al.    reported an increase in the amplitude of auditory evoked

                                          o

potentials for CO levels of 40 and 80 mg/m  CO (35 and 70 ppm CO; 3 and

                             oc

5 percent COHb).  Groll-knapp   measured slow-wave brain potentials (the



so-called contingent negative variation or CNV) and noted a diminution



in the voltage reached by the CNV and the extent of the drop seen after

                                                          3

response stimulus given consequent to CO exposure 172 mg/m  (150 ppm).



Otto et al.,161b  in a preliminary report of evoked slow potentials
                                    11-13

-------
                                                o
during vigilance performance at 115 and 229 mg/m  CO (100 and 200 ppm


CO; 4.6 and 12 percent COHb), showed that CNV amplitude decreased as

                       pc
reported by Groll-Knapp   and showed that a positive potential with a


latency of about 100 msec increased with CO.


     Ikuta    evaluated 87 male adults who had suffered from CO poisoning
at an accidental explosion in a coal mine.  Older individuals showed the


greatest degree of impairment.


11.2.6  Conclusions and Discussion of Nervous System and Behavior in Humans


     Table 11-1 shows a summary of research results concerning the


effects of CO on CNS and behavior.


     Experimental animal data point toward disturbed sleep patterns

                                                             3
which have also been reported in humans at levels of 115 mg/m  (100 ppm) CO.


General activity levels in humans have not been specifically studied.


     Effects of CO on vigilance are in considerable dispute but some


evidence suggests that, if relevant variables are controlled, there is a


decrement in vigilance due to CO at threshold level of about 4 to 6 per-


cent COHb.  Human and animal studies point toward such factors as arousal,


environmental temperature and humidity, CO dose rate, task variables,


and subject cerebrovascular health as important and usually uncontrolled


variables.  Research is required to clear up this confusion.


     Apparently, visual system impairment at low illumination levels or


at quickly-changing illumination  is affected by CO exposure at levels


approaching zero in a dose-related manner, but these data are old and


should be replicated.  Other sensory systems could also be affected but


have not been extensively studied.  Time  discrimination does not seem to


be affected by  low CO levels.
                                    11-14

-------
                        TABLE 11-1.  SUMMARY OF DATA ON EFFECTS OF CO ON HUMAN BEHAVIOR AND CNS

et
Reference
al.
No. of
subjects
4

Exposure
9 hours to
150 ppm dur
a
75 and
ing
COHb
5.9%
12.7%
Dependent variable
Sleep

No
to
Results

Comment
changes large enough
be significant but
Groll-jCnapp
et al.

Haider et al.
             95
Fodor and
Winneke
       07
Groll-Knapp
et al.
Beard and
Grandstaff
          19
Horvath et al.
              107
Winneke
       217
                     10
                     20
20


 9


 10
                      18
                           sleep
      100 ppm 7 hours
      (2nd experiment)

      2-7 hours
      (50-150 ppm)
                           5 hours (50 ppm)
2 hours
(50-100 ppm)

90 minutes
(50, 175 & 250 ppm)

1 - 2 1/2 hours
(26 and 111 ppm)
      5 hours (50
      and 100 PPM)
                            2-5%
                                                 3-7.6%
                                                 1.8-7.5%
Sleep stages


EEC in sleeping



Vigilance


Auditory vigilance


Visual vigilance
                                                 2.3 and 6.6%   Visual vigilance
                      5.1 and 10%
                      respectively
Vigilance, visual
CFFF, and psycho-
motor tasks com-
paring effects of
CO and methylene
chloride.
trends toward deeper
sleep with CO

Altered proportion of
sleep stages.

REM and stage 2 sleep
depressed but greater
amount of deep sleep.

Vigilance at first
decreased, then increased.

Decreased vigilance
performance.

Significant reduction
in vigilance.

Signal identifica-
tion performance
deteriorated and mono-
tony effect was
potentiated.

No impairment of performance
due to CO exposure could
be demonstrated, while CNS
depression was shown after ex-
posure to methylene chloride
for only 3-4 hours at concentra-
tions as low as 300 ppm.

-------
                                                     TABLE 11-1 (continued)
                 No. of
  Reference     subjects
                               Exposure*
                      COHb
Dependent variable
   Results
Comment
Benignus and       52
Otto"
Putz et al.167     30
                            3 1/3 hours
                            (100 + 200 ppm)
                      4.61-12.62%
                            4 hours (5-70 ppm)    1-5%
Vigilance            No effect on
performance          vigi1ance
(numeric monitoring  performance.
task)

Auditory and visual  No effects.
monitoring
McFarland et al.
                142
Halperin
        97
McFarland141 and
McFarland
et al.™
      170
Ramsey
Weber et al.
                   20
                   20
                            4 hours               0-11%
                            (concentrations high
                            enough to achieve
                            stated COHb levels)

                            3-4 hours (at concen- 3-6.2%
                            trations high enough
                            to achieve COHb levels
                            stated)
                            Exposure time         6-17%
                            sufficient to
                            achieve stated blood
                            concentrations (700 ppm)
                                    Visual sensitivity
                                    Visual sensitivity
                                    to differences in
                                    light intensity
                                    Dark adaptation
                                    and glare recovery
                     Low COHb levels
                     were found to
                     reduce visual
                     sensitivity.

                     Reduced sensitivity
                     Recovery from effects
                     of CO lags behind
                     elimination of CO
                     from the blood.

                     No statistically signifi-
                     cant effects were
                     demonstrated.
45 minutes (300 ppm)  11.28-15.66%  Brightness discrimi- No significant
                                    nation depth percep- effects demon-
                                    tion and CFF         strated.
3.5 hours (150 ppm)   9-11%
Critical flicker
fusion frequency
Exposure did not
affect CFFF
either in mono-
tonous or activating
situation.

-------
                                                       TABLE 11-1  (continued)
Reference
Guest 00
No. of
subjects
8
Exposure3
65 minutes
COHb
10%
Dependent variable
Auditory flutter
Results
No significant
Comment

   et  al.
          217
  Winneke
   Beard   and
   Wertheim
~
             18
             18
                      (concentrations high
                      enough to achieve
                      stated blood level)
5 hours (50 and
100 ppm)

2 1/2 hours
(50-250 ppm)
                      9 hours to 75 and
                      150 ppm
5.1 and 10%
respectively

Estimated
2-3%
                      5.9% and
                      12.7%
fusion threshold
and critical flicker
fusion frequency
with phenobarbitone

CFF
Discrimination of
short intervals of
time
                                                         effects demonstrated.
No impairment could be detected
due to CO exposure.

Performance deterio-
rated increasingly with
progressively higher
concentrations.
                                                                   Time  discrimination  No effects.
                                                        Not precise
                                                        replications of
                                                        Beard and Wertheim.
   Stewart—
   et al.
    197
             18
4-7 hours
25-100 ppm
              Time discrimation
                     No effects.
                     Not precise
                     replications of
                     Beard and Wertheim.
   Otto
   et al.
161a
   Bender et al.
                21
             13
             42
0, 75 and 150 ppm
for 3 hours
.16, 3.8 and
7.8%
Time discrimination  No effects.
3.5 hours (100 ppm)   3.8-8.2%      Level of activation,  Level  of activation and
                                                                   visual  perception
                                                                   psychomotor  per-
                                                                   formance,  learning
                                                                   and retention,
                                                                   Amthauer's I.S.T.,
                                                                   subjective condition
                                                                               1ST showed no difference.
                                                                               Performance declined in
                                                                               visual  perception,  learning
                                                                               and memory and in psychomotor
                                                                               testing.

-------
CD
                                                   TABLE 11-1 (continued)
Reference
OMtanna
No. of
subjects
4
Exposure3
9 hours to 75 and
150 ppm
COHb
5.9% and
12.7%
Dependent variable
Mental arithmetic^
Results
No effects.
Comment

   Bender et al.
                22
  42
   McFarland141
   and McFarland
   et al.
   Salvatore
            183
   Putz et al.
   Johnson,A
   et al.
              167
(not
given)
2 1/2-8 hours
(100 ppm)
           700 ppm until
           COHb level achieved
           20 minutes
           (800 ppm)
(not given)
           8 hours (22.8 ppm)
           TWA
7.2%-11.6%
                      6-17%
                      4-8%
(not given)
                      1.5-11.7%
Visual perception
ability to learn,
manual dexterity
Visual perception
was not affected,
manual dexterity
was diminished, learning
performance deteriorated.
              Complex psychomotor  Only "minimal"
              tasks                effects.
              Visual function
              performance
                     Detection time was
                     significantly increased.
                     No other effects were
                     noted.
Hand-eye coordina-   Decrements in all measures.
tion complex monitoring,
tracking

Eye-hand coordina-   Eye-hand coordination
tion, time estima-   was impaired.  Perform-
tion, visual percep- ance on two concurrent
tion, complex arith- tasks was disrupted.
metic, choice reaction
time, CFF, task time
sharing

-------
                                                   TABLE  11-1  (continued)
                    No.  of
     Reference      subjects
   Exposure
           a
COHb
Dependent variable
   Results
   Comment
                      10

8 hours (0-41 ppm)    1.66-2.5%
   Forbes  et  al.
                70
VO
                jnq
  Wright et al.       50
   McFarland141
   and McFacland
   et al.
   Ray and
   Rockwell
   Rockwell  and
   Weir177
1 hour (90 ppm)
(Duration of
exposure sufficient
to raise COHb levels
by 3.4% (20,000 ppm)

Exposure with
700 ppm to produce
COHb.

4-6 hours
(950 or 1900 ppm
given every 35
minutes in quanti-
ties sufficient to
maintain COHb levels
of 10 or 20% res-
pectively
22.4-47.2%
1.24-6.97%
6-17%
              Mental arithmetic,
              audio digit moni-
              toring, hearing
              acuity, divided
              attention, choice
              reaction time, CFF,
              eye-hand coordina-
              tion, subjective
              feelings
Reaction time,
depth perception,
visual perception,
motor performance
in driving
Hearing acuity and
CFF were decreased.
Choice reaction time
was increased.  No
difference was noted
due to CO in mental
arithmetic, divided
attention, digit
monitoring and
subjective feelings.

No impairment of
function up to
30% COHb.
Poor control data.
Simulated driving    Impairment of
                     varying degrees
was demonstrated.
Driving performance  No effects.
                     Poor analysis
                     of results.
10 and 20%    Driving tasks
                     Increased response   Only preliminary
                     time to distance and analyses.
                     velocity, decreases in
                     time estimation, decrease
                     in driving precision.

-------
                                                  TABLE 11-1 (continued)
    Reference
         No. of
        subjects
               Exposure*
                      COHb
Dependent variable
   Results
Comment
  Weir and
  Rockwell
215
  Rummo  ancL,
  Sal amis101
  Hosko
        109
ro
o
  Putz et  al.
  Groll-
  et al.
              167
6-12
(for
various
tests)
   Ikuta
       110
           12
           30
           20
  Otto et  al.161b     28
           87
90 and 120 minutes    7-20%
(100 and and 490 ppm
respectively)
                    20 minutes (800 ppm)  6-8%
            0.5-24 hours
            (1-1000 ppm)
            (not given)
            2 hours (50, 100
            and 150 ppm)
            2.5 hours
            (100 amd 200 ppm)

            (unknown)
                      Max. 33%
                      (not given)


                      3-7.6%
                      4.95 and
                      12.04%

                      (unknown)
                                                        velocity variance,
Reaction time to
speed changes,
steering reversal
responses

Visual evoked
response (VER)
Auditory evoked
potential

Computer analyzed
brain potentials
                                                        Event related
                                                        potentials
Mean velocity and    No performance decre-
ment with normal
gas and brake pedal  driving tasks.
actuations, steer-
ing wheel reversals,
headway, visual
behavior

Significant increase
in reaction time and
fewer steering wheel
reversal responses.

VER alterations
associated with
COHb levels of
20-22%.

.Increased amplitude.
CNV amplitude        No significant
reduced proportional test data.
to progressively
higher COHb concen-
trations.
                     CNV decreased,
                     P100 increased.
                     Preliminary data.
                                          Data obtained
                                          3 years after a coal
                                          mine explosion.
  al ppm CO = 1.145 mg/m3  CO  and  1 mg/m   CO =  0.874 ppm  CO, at 25°C and 760 mm Hg.

-------
     Complex tasks involving large behavioral loads or fine discrimi-



nation are usually not affected by CO, especially if the duration of the



task performance is short; although the data by Putz et al.    appear to



show such effects.  Vigilance and sensory functions, which are certainly



components of more complex tasks such as driving, appear to be affected;



thus one would expect an effect on the overall task.  It is probable



that research in both experimental animals and man has not shown reliable



effects because:  (1) the tasks are highly redundant, so that a great



impairment is required before decrements are noticed; (2) performance



measures of end-result behavior are sometimes gross and insensitive;



and/or (3) the tasks' components stimulate the subject with their variety



and thereby keep alertness high.  More sophisticated studies are required.



     Quantitation of electrical activity of the CNS as affected by CO



has just begun.  While alterations have been demonstrated in both exper-



imental animals and man,  interpretation of these results still rests on



their correlation with behavioral data because of the lack of general



theoretical data  about CNS electrical activity.



11.3  CARDIOVASCULAR SYSTEMS



      Experimental animal  studies have suggested that one of the principle



effects of CO occurs in the cardiovascular system.  This section reviews



cardiovascular  data from  studies of both healthy and impaired human



subjects exposed  to CO.



11.3.1  Cardiovascular Damage and EKG Abnormalities


                  48
      Corya et al.   presented the first evidence for left  ventricular



abnormality in  five cases of non-fatal CO poisoning  (20 percent COHb).
                                    11-21

-------
Abnormal left ventricular wall motion was shown by echocardiograph in


three of five cases.  A similar number showed mitral valve prolapse.

             221
     Zenkevic    conducted clinical and physiological hemodynamic studies


on two groups of subjects:  individuals in constant contact with CO and


individuals having no evidence of chronic CO intoxication.  He noted


considerable cardiovascular abnormalities in the CO-exposed group.

                                            57
A study of cast iron workers by Ejam-Berdyev   also suggested a larger


frequency of cardiovascular, as well as CMS disturbances, in these


workers that was related to their increased blood COHb content.


     Hemp processing in Japanese villages is conducted in small rooms

                                                                    3
heated by charcoal.  Ambient CO concentrations average about 80 mg/m

                                                o
(70 ppm) and reach peak levels of about 344 mg/m  (300 ppm).   The inci-


dence of myocardosis was found to be excessively high.  Deaths from


cardiac failure in these villages was reported to be 6.8 times greater

                                                         123a
than the anticipated numbers for the Japanese population.


     Only one study has been reported on patients having peripheral


vascular disease.   Ten men with angiographically documented occlusive


arterial disease were exercised on a bicycle ergometer until  leg pain

                                                                 3
occurred.  These patients then breathed filtered air 0 or 57 mg/m  (0 or


50 ppm) CO for a 2-hour period.  Exercise after this time showed that


COHb levels of about 2.8 percent significantly decreased the time to


onset of pain compared to controls.  Alexieva and Simitrova  studied a

                                                                3
large group of workers exposed to an ambient CO level of 57 mg/m


(50 ppm) and reported changes in peripheral vessels suggesting impaired


vascular tone.
                                   11-22

-------
                  25
     Bogusz et al.    related electrocardiographic changes in blood
lactate levels, and aspartate aminotransferase activity to levels of COHb.
      81
Gorski   utilized the ballistocardiogram to demonstrate hypoxemia of the
myocardium in similar cases.  Goldsmith and Aronow   have reviewed the
available evidence relating CO exposure to the rate of development of
arteriosclerotic heart disease (ASHD).
11.3.2  Blood Flow and Related Variables
     The heart has a specialized circulatory system in which the primary
response to increased metabolic demands can only be secured by an
increased cardiac blood flow.  Even under no-stress conditions (rest)
there  is an almost complete extraction, roughly 75 to 80 percent, of the
available 0« supply from the blood.  The increased capacity for flow to
compensate for the small benefit obtainable from more complete extraction
from  the perfusing blood has been  shown to be on the order of several
hundred percent.          \
      The studies of Ayres et al. on the hemodynamic and respiratory
                                                                      14 15
responses of man were made  during  diagnostic cardiac catheterizations.   '
                                                               3
They  gave these  subjects a  fixed amount of CO, either 1145 mg/m  (1000 ppm)
                                3
for 8 to 15 minutes or 5725 mg/m   (5000 ppm) for 30 to 45 seconds.
These procedures induced COHb  levels of between 6 to 12 percent.  Two
groups of patients, those with and those without coronary heart disease
(CHD), were studied.  The normal individuals responded to the presence
of elevated COHb by increasing their cardiac output and minute ventilation,
......         .    4.   •  i n  •   Increased extraction of 00 from
but with a decrease in arterial PQ2                            2
arterial blood occurred, as evidenced  by the increased extraction rates.
                                    11-23

-------
      v,Qr,m,c D   decreased from 39 to 31 torr, probably as a result of
      VcllOUS ' rt o
the left shift of the 00 dissociation curve.  Arterial Pn«
These changes and mixed venous PQ2
In contrast to normal subjects, patients with cardiac heart disease
(CHD) did not show an increase in cardiac output.  Cardiac blood flow
                                                             3
(CBF) increased significantly in all patients given 5725 ug/m  (5000 ppm)
CO for 30 to 95 seconds (COHb about 9 percent), but it only increased in
                                             3
the CHD patients when they breathed 1145 mg/m  (1000 ppm) CO for 8 to
15 minutes  (COHb about 12 percent).  It should be noted that most of
these individuals had relatively high initial COHb concentrations.  The
myocardial  arteriovenous 0« difference decreased in both situations,
with the greatest percentage decrease occurring at the lowest COHb
concentration.  In all but two of those patients, coronary sinus PO«
decreased,  suggesting that the increase in CBF was insufficient to
compensate  for the decreased Op delivery caused by the presence of COHb.
Further evidence of  anaerobic myocardial metabolism was suggested by the
decreased lactate extraction, with four patients showing lactate produc-
tion by the myocardium with no lactate extraction.  Ayres reported
                                                        14 15
similar changes in concurrent studies conducted on dogs.  '    These
observations on man  suggest that CO inhalation would have a significant
  ff  +      +   • n n  in patients with lung disease as well as certain
eTTecL on arterial 'no
cardiovascular disorders.
     The potential toxicity of CO present in transfused blood has received
                                 120
little attention.  Kandall et al.    measured COHb concentrations in
donor blood and in relatively healthy infants receiving exchange blood
                                    11-24

-------
transfusions.  The mean pre-transfusion COHb in six cases was 1.34 percent.



Donor blood contained 5.17 percent COHb, resulting in a mean value of



4.92 percent COHb in the transfused infant.  In one infant transfused



with blood containing 8.87 percent COHb, the resultant COHb value in the



infant was 7.43 percent.  Although it was stated that the infants did



not appear to be adversely affected by the COHb levels reached during



exchange transfusion, it should be noted that although measures were



gross, adverse effects at these levels of COHb have been observed.



Furthermore, in individuals whose 0? transport system or cardiovascular



reserve is already compromised, the presence of additional COHb from



transfused blood may result in a further and more potentially dangerous



decrement in arterial, mixed  venous, and coronary sinus 02 tensions.  It



should be recalled that some  blood samples collected from blood donors



had COHb values that exceeded 18 percent.



     An additional hazard to  patients, especially those undergoing


                                                                        146
cardiovascular surgery, may develop during anesthesia.  Middleton et al.



have reported markedly elevated expired CO levels in patients undergoing



cardiac bypass surgery.  This increment would be related in part to the



CO present  in transfused blood and/or to the closed-circuit method of



anesthesia which precludes the loss of endogenously produced CO.



11.3.3  Angina


                                257
     Two groups of investigators  '  '  reported studies on patients with



angina pectoris.  Aronow et al.  studied the influence of riding  in an



open car on  a major  Los Angeles freeway.  Two trips of 90 minutes duration



were made;  on one the patients breathed compressed CO-free air and  on
                                    11-25

-------
                                                       q
the other the ambient CO concentration averaged 61 mg/m  (53 ppm).

Carboxyhemoglobin levels after this ride averaged 0.65 percent, in contrast to

the 5.08 percent observed in the trip in the open car.  Exercise time, on a

bicycle ergometer, to the onset of angina, was determined prior to and after

the completion of the exposure.  Although no changes in time of exercise to

onset of anginal pain were noted from the ride while breathing compressed air,

a significant reduction from a mean time of 249 to 174 seconds was found when

COHb was elevated.  Ischemic ST-segment depression of at least 1 mm after

exercise-induced angina pectoris occurred earlier, after less exercise.
                                                                    V
               p
Anderson et al.  conducted a study in which patients with stable angina walked

on a treadmill.  They then breathed, while at rest, air containing 57 or
        3
114 mg/m  (50 or 100 ppm) intermittently over a period of four hours,  raising

their COHb levels to 2.9 and 4.5 percent, respectively.   The repeat exercise

tests clearly demonstrated a reduction in walking time to onset of angina.   No

differences in time of angina onset were observed at the two induced COHb

levels although the duration of the pain was longer at the higher COHb levels.

Five of the ten patients had deeper ST-segment depression after CO exposure.

Other measures of cardiac function--systolic time intervals, left ventricular

ejection time, pre-ejection period index, and pre-ejection peak to ejection

time ratio—remained within normal limits.
                                       5
     Another study by Aronow and Isbell  was somewhat similar to the

                                 2                   5
work performed by Anderson et al.    Aronow and Isbell  exposed patients
                                               o
(nonsmokers at the time of the test) to 57 mg/m  (50 ppm) CO, resulting
                                                           s

in a COHb concentration of 2.68 percent.  This study was also conducted
                                   11-26

-------
as a double-blind random trial in which subjects breathed CO on two days and
compressed CO-free air on two other days.  All patients had their angina
pectoris documented by history and coronary angiography.  A 16 percent
reduction in exercise time (bicycle) resulted following the CO exposures.
Ischemic ST-segment depression after exercise-induced angina occurred earlier
after less exercise and at a lower product of systolic blood pressure times
heart rate at the onset of angina after the patients breathed CO.  Plotting of
the data suggests that there was a linear relationship between COHb levels and
the decrease in time to angina.  Table 11-2 summarizes the above data.
         TABLE 11-2.  EXERCISE-INDUCED ANGINA AND CARBON MONOXIDE
                       (Each Study had 10 Subjects)
Carboxyhemoglobin Ambient3CO
Investigator percent (mg/m )
Initial
Aronow et al. 1.12
5
Aronow and Isbell 1.07
2
Anderson et al. 1.40
Einal
5.08 61*
2.68 57**
2f\r\ r*"7^^*fc
VI II t* / /\ /S /\
* -J\J 
-------
while they sat in ventilated or unventilated rooms with other individuals



who were smoking cigarettes.  It is possible that in addition to carbon



monoxide and nicotine, other components of tobacco smoke, including



oxides of nitrogen and hydrogen cyanide, and possibly psychological



factors, may have contributed to the decrease in exercise performance.



11.3.4  Epidemiological Evidence



     Epidemiologic studies   '  '    in the Los Angeles area have suggested



the possibility of increased mortality from myocardial infarction, associated



with high atmospheric levels of CO.  Some differences of opinion have



been raised concerning interpretation of these data.  A study similar in


                                       128
design has been completed in Baltimore.     The Baltimore data indicated



no apparent relation between either the incidence of myocardial infarction



or sudden death due to ASHD  and the average 24-hour ambient CO



concentrations.  Neither group of  investigators was able to detect any



relation between postmortem  COHb levels and causes of sudden death.  The



Baltimore study was superior in that the diagnoses of disease state were



more precise and the population base more clearly defined than in the



other studies.  The ambient  levels of CO in Baltimore appeared to be


                                                              103
considerably lower than those reported for Los Angeles County.



During a 92-day seasonally excessive period of ambient CO, Kurt et al.



identified cardiorespiratory complaints (CRC) of a non-traumatic origin



from each of 8556 patient encounters at the Emergency Room of Colorado



General Hospital.  Excessive numbers of CRC were seen above a threshold


               3                                                 3
limit of 6 mg/m  (5 ppm) for the 24-hour mean and for the 13 mg/m



(11 ppm) one-hour mean maximum ambient CO.
                                    11-28

-------
     Whether this incidence is partially or totally related to CO exposure
and high altitude at which these observations were made needs further
                       -JCO
investigation.  Radford    evaluated patients admitted to the myocardial
infarction research unit at Johns Hopkins Hospital.  While their diagnoses
were consistent with both an acute and chronic effect on the myocardium of
long term exposure to CO, the effects observed clearly could not be related
to that factor.  Therefore, the possibility of an association between CO
levels in ambient air and incidence of myocardial infarction or sudden
deaths remains in question.  It is apparent that more comprehensive and
extensive epidemiological studies need to be conducted in order to
clarify this  issue.
11.3.5  Conclusions and Discussion
     Table 11-3 summarizes the data on cardiovascular effects of CO
exposure.  While the data are extremely limited due to the lack of
research on human exposures, it is possible that cardiac damage may result
                                                       o          123a
from chronic  exposure to CO at levels as low as 80 mg/m  (70 ppm).
Since more extensive data from animal studies show that such damage is
systematically observed in chronic exposures, the results of human
studies are not unexpected.  The particular threshold level for cardiac
damage in humans has not been reliably determined, however, inasmuch as
                                                o
only one study reports a level as low as 80 mg/m  (70 ppm).  Studies
utilizing bolus concentrations represent "real world" conditions.
Animal subjects are at risk to myocardial effects for several minutes
after exposure.
                                   11-29

-------
                       TABLE 11-3.   SUMMARY OF DATA ON EFFECTS OF  CO  ON  HUMAN CARDIOVASCULAR SYSTEM
Reference
No. of
subjects
Exposure3
COHb
Dependent variable
Results
Comment
    Corya et al.
                48
CO
o
    Aronow,
    et al.
    Alexieva and
    Simitrova

    Bogusz et al.
       10
25
       47
    Ayres et al.
                15
       26
   Ayres  et al.14      26
                       and

                        15
               (unknown)
                     16-25%
2 hours
(50 ppm)
2.77%
1-6 hours (mean
1 hour 20 min.)
5 hrs 30 min. mean
average
35%
average
17%
8-15 min
(1,000 ppm)
30-45 sees
(5,000 ppm)

(time sufficient to
produce stated COHb
(5,000 ppm 5%)
8-15 minutes
(1,000 ppm - 0.1%)
mean
8.96%
                                    5-25%
            Echocardiographic
            findings after acute
            CO poisoning
Symptoms of inter-
mittent claudication
Aspartate amino-
transferase (AspAT),
lactic acid dehydro-
genase activity,
and lactate level
in lighting-gas com-
pared to coal-stove
poisonings.

Systemic and myocar-
dial hemodynamic
responses
            Myocardial  and
            systemic responses
                       Echocardiographic
                       (ECG) findings in
                       4 of the 5 cases
                       indicated prolapse
                       of the mitral  valve,
                       suggesting that
                       myocardial damage
                       may occur in cases of
                       non-fatal CO poisoning.
                       Patients were ad-
                       mitted to a hospital
                       the same day they
                       suffered acute CO
                       poisoning due to a
                       faulty water heater.
Intermittent claudication
was significantly aggra-
vated due to CO exposure.
Enzymatic changes increase
with length of exposure.
Changes enzyme activity and^
lactate level parallel ECG and
clinical changes AspAT activity
was increased even without ECG
or clinical changes.
Coronary blood flow increased,
and extraction ratios decreased.
Systemic oxygen extraction was
increased.

Increased cardiac output and
coronary blood flow.  Signs
suggesting myocardial hypoxia
were observed in patients with
coronary artery disease.

-------
                                               TABLE 11-3  (continued)
    Reference
 No.  of
subjects
   Exposure*
COHb
Dependent variable
   Results
Comment
  Randal
  et al.
    15
(none)
  Middletpn
  et al145
    22
  Aronow.
  et al.'
oo
  Anderson  et  al.
    10
    10
  Aronow     ,
  and  Isbell
   Kuller  et  al.
                128
    10
   1397
1 1/2 hours
(20-210 ppm)
90 minutes
(42-63 ppm)
4 hours
(50 and 100 ppm)
2 hours
(50 ppm)
7.7-14 ppm
mean        Change in COHb with
1.34-4.92%  exchange blood
            transfusions
(not known) Carbon monoxide
            accumulation in
            closed circle anes-
            thesia systems.
3.8-1
mean
2.9% and
4.5%
mean
2.68%
Symptoms of angina
pectoris.
Onset and duration
of angina pectoris.
Exerci se-i nduced
angina pectoris.
0.9 to 9.9% Relationship between
            exposure and heart
            attacks\.
Elevations in COHb due to
receiving transfused blood
could not be shown to have
any adverse effect on the
recipient.

Closed system anesthetic
techniques allow the accumu-
lation of endogenous and ex-
ogenous CO, producing minimal
decremental effects.

Angina pectoris developed sooner
after less work, following ex-
posure to highway air.

Exposure to low concentrations
of CO produced anginal  pain
of greater duration after less
exercise.

Exposure to CO produced
symptoms of angina sooner and
after less cardiac work.
                       No relationship was
                       established between
                       ambient CO levels
                       and onset of sudden
                       death and myocardial
                       infarction.
                       This study covers a
                       two-year period and
                       involves deaths due
                       to coronary disease
                       occurring in the
                       Baltimore area.

-------
  Hexter  andft~
  Goldsmith1^
                                              TABLE  11-3  (continued).
Reference
No. of
subjects
Exposure
COHb
Dependent variable
Results
Comment
(not
given)
7.3-20.2 ppm
8-17%
Community air
pollution and
mortality—total
number of deaths,
day of occurrence,
maximum temperature,
average CO concentration.
A greater number of
deaths was shown to
have occurred when
ambient CO concen-
trations were
This study covers
a period of 4 yrs
in Los Angeles
County.

higher.
  al  ppm  CO  = 1.145 mg/m3 CO and
               mg/m3 CO = 0.874 ppm CO,  at 25°C and 760 mm Hg.
GO
PO

-------
     Certainly the alterations in blood flow observed  in man agree with
those observed in experimental animals.  Human data have been reported
which show that such compensatory changes do not occur as readily or
extensively, however, in cases of cardiac pathology.
     The limited studies on patients having cardiovascular disease
suggest that the critical level of COHb is 2.5 to 3.0  percent.  Additional
and confirmatory studies are definitely needed to determine the lowest
concentration of COHb at which no alterations in performance can be
detected.  The available studies on patients do not give much information
about the role of CO in the development of the disease but do give some
indication of their dose-response relationship.  The validity of these
data is strongly reinforced by complementary experimental animal studies
which show very similar dose-response  curves.
     The U.S. National Health Survey Examination reported that there
were 3,125,000 adults, ages 18 to 79 years, with definite coronary heart
disease and another 2,410,000 with suspected heart disease.  Many of
these individuals, as well as others in the general population, have
COHb levels equal to or above 2.5 percent.  It would be rash even to
suggest that the above-mentioned studies implicate CO  as a factor in
determining the natural history of heart disease in a  community.  The
necessary epidemiological evidence for an association  between frequency
of episodes of angina pectoris and community ambient CO levels  is lacking;        /
however, it is not presumptuous to state that individuals with  cardiac
                -"- - •-- ~^.,,.,_._ — ^                                                            .
                                                                                  P
ailments are especially at risk to CO  exposures sufficient to produce
2.5 to 3.0 percent COHb.
                                    11-33

-------
11.4  PULMONARY FUNCTION AND EXERCISE
     Maximal exercise can increase the 0« uptake of the whole body in
excess of 20 or more times the resting uptake and will stress the 0«
transport system maximally.   Any impairment of 0« transport, such as
could occur when COHb is present, could limit maximal aerobic capacity
        ).  In fact, it has been appreciated for some time that individ-
  02 max
uals having a large burden of CO experience difficulty in performing
work.
                         180
     Roughton and Darling    suggested, on theoretical grounds, that
work capacity would be reduced to zero when COHb approached 50 percent.
11.4.1  Maximal Work
                  oc
     Chiodi et al .   in 1951 showed that subjects were unable to perform
tasks requiring only low levels of physical exertion when their blood
COHb reached 40 to 50 percent.  Several collapsed while attempting to
                                                 37
perform routine laboratory tasks.  Chihaia et al.   have reported that
heavy physical work at low ambient CO levels can induce states of CO
                     74
poisoning.  Goldsmith   reported that competitive swimmers have impaired
performance when competitive events are conducted in atmospheres con-
               3
tain ing 34 mg/m  (30 ppm) CO originating from traffic.
11.4.2  0« Uptake and Heart Rate
     In studies using submaximal exercise for short durations (5 to
60 minutes) it appears that 0« uptakes during work were unchanged despite
the presence of coHb.31'35'59-60'73.89'155-165-207'208  The only clear
indication of physiological load appeared to be  a slight increase in
                             qc                  1 pq
heart rate.  Chevalier et al .   and Klein et al . ,    studying men working
                                    11-34

-------
at a light work load for a period of five minutes,  reported that while



the Op uptake was not affected when COHb levels were approximately



4 percent (estimated Values), there was a significant  increase  in Op



debt when this was related to the total Op  uptake.  Nobody has  yet



replicated these results on Op debt.   Five  subjects studied by  Pi may

      -I CC

et al.    performed work for 15 minutes at  an  Op  uptake of 1.5  liters



per minute.  No differences in Op uptake were  found, even though COHb



reached 15 percent.  In a rather involved study in  which COHb fluctuated


                                        122
between 5 and 17 percent, Klausen et al.     found no differences related



to CO in energy expenditure when subjects exercised for 15 minutes at



50 percent of their Vno     '  Vogel et a1-208  and Vogel and Gleser207
                     \j£. max


and Pirnay et al.    reported consistently  higher heart rates for given



selected submaximal work loads, and increased  ventilatory volume



exchange per unit  of Op uptake, with COHb levels  of 15 to 20 percent.


                   73
      Gliner et al.   studied the responses  of  two groups of 10  men each



(mean age 23.0 and 48.4 years, respectively),  one-half of each  group


,  .      ,       A    •  n  -i  * oc       4. vi      was  selected  (untrained
being smokers.  A  work  load of 35 percent Vn9  max/              v
                                            \jtL  iTIaX

men can work at this level  for approximately eight  hours with minimum



physiological changes), and the men worked  for four hours in an environ-


                        o

ment  containing 57 mg/m  (50 ppm) CO.   Final COHb's were 10.3 and



13.2  percent, respectively, for nonsmokers  and smokers.  Ambient temper-



atures were 25°C and 35°C,  with relative  humidities of 30 percent.  The



only  significant change was a  higher  heart  rate in  the CO environment



 irrespective of age of  subjects, confirming observations previously
                                    11-35

-------
reported.   Since cardiac index remained constant at approximately


                 2                                 3
6 liters/minute'm  in both filtered air and 57 mg/m  (50 ppm) or up to

        3

115 mg/m  (100 ppm) CO, stroke output was decreased.  The full signifi-



cance of this change in long-term performance in co-polluted environments



is not apparent at this time.



     Despite the wide variability in experimental conditions—duration



and magnitude of exercise, level of COHb, methods for giving CO to the



subjects, small number of subjects exposed, and their limited age range—



the results from all studies were essentially similar.



11.4.3  Aerobic Capacity



     In short-term maximal exercise of several minutes'  duration, where



capacity for effort is dependent mainly on aerobic metabolism, it is



anticipated that maximal aerobic capacity would be diminished approxi-



mately in proportion to the  level of COHb present in the blood.  Such


 ...   ..    .  „       when COHb is between 7 and 33 percent has been
diminution  in Vfto
               02 max

conclusively observed by a number of investigators.



In the majority of these studies, exercise bouts ranged from 2 to 6 min-



utes and CO was administered either by breathing relatively high concen-



trations of this gas or by breathing a fixed amount with additional CO



to maintain the desired levels of COHb.  Subjects were not always iden-



tified as to their smoking habits.


             187a
     Seppanen     determined the physical work capacity of cigarette



smokers  (20 cigarettes/day)  following either smoking or inhalation



of CO.  A progressive bicycle test to max was conducted after  breathing



room air (2.8 percent COHb), after smoking (9.1  percent COHb), and  after
                                    11-36

-------
bolus breathing of 1100 ppm CO (9.1 percent COHb).  The physical work
capacities at heart rates of 130, 150, and 170 beats per minute decreased
after both CO inhalation and cigarette smoking.  The greatest decrease
in calculated maximal work was observed after CO inhalation.
     In the above-mentioned studies, the  levels of COHb were considerably
in excess of those occurring in men exposed to the outdoor air of certain
metropolitan areas.  The initial  studies  by Horvath's group  '*
                                       o
were made on subjects breathing 57 mg/m   (50 ppm) CO at either of two
thermal ambients, namely 25°C or  35°C, with a relative humidity of
20 percent.  They utilized a walking test (requiring some 15 to 24 min-
utes to complete) with progressively increasing grade in order to measure
v      .  The two populations consisted of 20 young (24+ years) and
  02 max
16 middle-aged  (48+ years) subjects, both smokers and nonsmokers.  The
middle-aged  subjects demonstrated the  anticipated decrease in  .nv
 associated with  advancing age.   However,  the  middle-aged  nonsmokers had
   v       some 27 percent greater than that of smokers  of the  same age.
 a V02 max
 During the progress  of the test,  COHb  levels  in nonsmokers increased
 from 0.7 to approximately 2.8 percent, while  levels  in  smokers rose from
 2.6 to 3.2 percent to 4.1 to 4.5 percent.   Control studies conducted  on
 these subjects while they breathed filtered air indicated that COHb
 decreased in both smokers and nonsmokers.   The results  from these
 studies56'73'173'174 failed to demonstrate any reduction  in VQ2 max*
 The decrement in Vno  „
                   02 max
 the hot environment was greater than the  changes that occurred from
 breathing CO.  Other cardiovascular, respiratory, metabolic, and
                                    11-37

-------
temperature measurements made concurrently with the 0« uptake studies



also failed to show any decrements associated with the CO exposure.  The



only significant effect related to CO was a decrease in absolute exercise



time.  This was consistently observed in the nonsmoking subjects but not



in the smokers.  These observations confirmed those found earlier by


               59
Ekblom and Huot   who, however, reported a surprisingly large decrease


                                                                3

(38 percent) in work time at 7 percent COHb.  Aronow and Cassidy  found



a slight decrease in work time during a maximal exercise test on 10



middle-aged (50.7 years) subjects.  Their reported levels of 4.0 percent

                                          3

COHb in subjects who had breathed 115 mg/m  (100 ppm) CO for one hour is



what would be  expected with initial control levels of 1.67 percent.  One



of ten subjects developed ischemic ST-segment depression after maximal



exercise following CO exposure.  No electrocardiographic changes were



observed in the subjects studied by Horvath's group.  '  '   '


       155
Nielsen    found that subjects exercising under a CO load developed



higher internal body temperatures.  Reductions in skin conductance



suggested a redistribution of the circulation to the working muscle and



away from the  skin.



     Horvath and coworkers  '  '   '    had some concern about the



changes in COHb levels in their smokers and nonsmokers as well as the


,  ,  f  .       .  „       under the ambient and exercise conditions
lack of change in Vn/,
            M      02 max

previously employed.  They developed a more precise method to regulate


                                            50
relatively low levels of COHb (Figure 11-1).    It is of some importance



that they found that a low ambient level of CO can be quite effective in



maintaining a  previously produced high blood COHb concentration.  These
                                    11-38

-------
                  C    -15    -10    -50
5           10          15

       TIME, minutes
Figure 11-1.   The maintenance of requested COHb level in a subject during rest and at^various work levels with a widely ranging
ventilatory exchange. Control level of COHb was 0.6% prior to the administration of the initial bolus of CO to raise COHb to
desired level; a total of 34.2 mlof CCTSTPDI was given. (Used with permission of The American Physiological Society 38:366-368,1975.)
                                                           11-39

-------
data suggest that the ambient level of CO may have little to do with the



absolute level of COHb present in an individual.  In these experiments a



double-blind study was again utilized in which subjects breathed either



filtered air, or air with CO which resulted in stable levels of COHb.



The data obtained clearly indicate that a threshold level of COHb must



be present before significant physiological alterations can be demon-



                                                         were noted when
strated.  Statistically significant decreases in V     v
                                                     max
COHb levels exceeded 4.3 percent.  Although this was a double-blind,



randomized study in which neither the investigators nor the subjects



knew the composition of the air breathed, it was subsequently determined



that all subjects correctly identified the experiment in which they had



been exposed to the highest level of ambient CO.  In all instances they



noted  a heaviness of the lower extremities and greater difficulty in the



task.  Ekblom et al . ,   utilizing a similar technique, raised COHb to



15 percent.  The reduction in VQ2 max was e*Pected-  Maxl'mal cardiac


output was decreased,  however, due to a decreased stroke volume.  Mean


     ,  ..  n   was found by Clark and Coburn40 .    .         .
myoglobin P                                   "to decrease during exercise
  .  T/          During  exhaustive exercise, Pn  increased, suggesting

 at  V02  max                                U2

 facilitation  of  Op offloading; but when a COHb level of 5 percent was



 present during exercise,  P5Q decreased.  Though the experiment was



 conducted in  Denver  (1700 m altitude), subjects having a burden of



 5 percent COHb exhibited  a decrement  in maximum performance similar to



 that  observed by others in subjects at sea level.



      The data obtained by Horvath's group and others are summarized in



 Figure  11-2.  .There  is a  linear  decline in Vn, mav when COHb  1eve1s
                                               lllct/\
                                    11-40

-------
    40
    30
 0)
 a
 *
X
<
UJ
CO
<
UJ
DC
O
UJ
Q
     20
     10
                                         SMOKERS


                                           I	I
                            15             25
                                PERCENT COHb
35
Figure 11-2. Relationship between COHb and decrement in maximum aerobic
power.
                                   11-41

-------
range from 4 to 33 percent COHb.  This can be expressed as:  percent
decrease in V       =0.91 (percent COHb) + 2.2.  It should be noted
             02 max
that this does not apply to smokers in Horvath's series, who had COHb
levels considerably in excess of 4 to 5 percent with no decrement in
their respective VQ2 ^ values'
11.4.4  Conclusions and Discussion
     Table 11-4 summarizes the  studies regarding pulmonary function and
exercise and the effects of CO  exposure.  There is some evidence that
                                                        3          205
work capacity is affected at CO levels as low as 34 mg/m  (30 ppm),
but the study yielding those results was poorly controlled, since ambient
CO levels were used rather than systematic exposures.
     Oxygen uptake during short exposures and submaximal work are
apparently not affected even when COHb levels are 15 to 20 percent.
These studies were usually done on healthy individuals and, frequently,
too few subjects were run for the study to be definitive.
     The most carefully executed and extensive studies are those
involving aerobic capacity.  Obviously, CO can modify these physiological
responses.  The level of blood  COHb required to induce these effects
appears to be approximately 5 percent.  The concentration of CO in the
blood may be the most sensitive indicator of effect rather than the
ambient levels of this pollutant.
11.5  INTERACTIONS WITH OTHER POLLUTANTS AND DRUGS
11.5.1  Other Air Pollutants
     There are many other compounds in polluted atmospheres that have
been demonstrated to have deleterious effects on physiological functions.
                                    11-42

-------
                       TABLE 11-4.   SUMMARY OF  DATA ON  EFFECTS OF CO ON HUMAN PULMONARY FUNCTION AND  EXERCISE
       Reference
                  No.  of
                 subjects
              Exposure*
                  COHb
               Dependent variable
                            Results
                         Comment
     Chiodi  et al.
                  36
                     dogs
                     n=2
                     men
                     n=4
CO
     Chihaia et al.
                   37
     Goldsmith
              74
                    (not
                   given)
Chevali
et al.
     Pirnay
     et al.
            er
10
           >70 minutes
           (0.15-0.35%)
                                                       16-52%
                                Job exposure
           Up to 2 hours
           (11-30 ppm)
                             up to
                             50%
2%-3% minutes
(0.5%)


(not stated)
3.95%
                                                  15%
                                 Pulmonary ventila-
                                 tion,  cardiac  output
                                 and plasma pH.  Res-
                                 piratory response
                                 to high  CO.
                                 Physical  work
                  (not given)     Performance  of
                                 competitive  swimmers
Oxygen uptake
                                            Muscular  exercise
                                            during  CO intoxica-
                                            tion.
No hyperpnea observable during
rest with acute and severe CO
poisoning.
Arterial pCO? increased and pH
became acidic.  In severe
poisoning, respiratory center
was depressed.  Cardiac output
was increased slightly with COHb
up to 30%, increased as much as
1/2, up to 50% COHb.  The direct
action on the respiratory center
of acute hypoxemia produced by CO
poisoning that is severe while
being still compatible with life
is purely depressive in nature.

Unable to perform low-
oxidation level work after
40 to 50% COHb
It was found that     COHb was established
exposure to ambient   by measuring expired-
CO raised COHb        air CO samples.
levels to compare
with inhaled cigarette
smoke and affected
performance of swimmers.

Greater oxygen debt per
greater oxygen uptake when
compared with nonsmokers.

Maximal 0~ consumption lowered.
Greater ventilation was induced
during exercise.   02 uptake
not affected.

-------
                                                     TABLE 11-4 (continued)
  Reference
          No.  of
         subjects
   Exposure*
COHb
Dependent variable
   Results
Comment
Ekblom
and Huot
59
             10
Horvat
et al.
Neil sen
       155
            (not
            given)
Pirnay165
et al.
Drinkwater
et al.56
             20
15 minutes (in quan-
tity theoretically
determined to obtain
stated blood values)
7 and 20%
Build-up and main-
tenance dose
(75 and 100 ppm) for
a period 15 min +
exercise time

(not given)
                                             2.7, 4.5
                                             and 5.2%
Response to maximal
and submaximal  work
load at different
COHb levels
            Maximal  aerobic
            capacity at dif-
            ferent levels of
            COHb.
(not given) Thermoregulation
            and work
                      (not stated)
                       15%
50 ppm
3.17%
            Muscular exercise
            during CO intoxica-
            tion.
Exercise and heat
stress
Maximal physical performance
was reduced with increasing
levels of COHb, as was VQ2
   .  Highest heart rate
aicVeased at 20% COHb during
maximal work and increased
during submaximal work at both
7% and 20% levels.   There was
a more significant change in
Oy deficit at 20% COHb than
at 7% COHb.

VAO     lower for COHb levels
 02 max
of 4% or greater.  Ventilatory
volumes were significantly
lower with COHb 3.2-3.4%.
Equilibrium body temperature
was higher.  Acute exposure to
altitude left temperature level
unchanged.

Maximal 0? consumption was
lowered.  Greater ventilation
was induced during exercise.
02 uptake not affected.

Exposure effectively reduced
work time of nonsmokers and
elicited changes in respiratory
patterns of both smokers and
nonsmokers.

-------
                                                         TABLE 11-4 (continued)
      Reference
            No.  of
           subjects
   Exposure*
COHb
Dependent variable
   Results
Comment
    Raven
    et al.
174
               16
50 ppm
2.31-5.54%
    Aronow and
    Cassidy^
    Raven
    et al.
173
               10


              16
en
     Ekblom
     et  al.
60
     Clark
     and Coburn
    40
              21
1 hour
100 ppm

(no exposure
time given)
50 ppm
15 minutes
(repeated once)
levels to produce
stated COHb
(not given)
3.95%
Increased
(14% for
smokers)
200% for
for non-
smokers
Age, smoking habits,
heat stress, & CO on
body temperature,
cardi orespi ratory
and metabolic
responses.

Maximal treadmill
exercise

Body temperature,
cardi orespi ratory
and metabolic
responses during
tests of maximal
aerobic power under
2 temperature condi-
tions (25o
                                               12.8-15.8%
            Changes in arterial
            0« content in rela-
            tion to circulation
            and physical
            performance.
(not given) Mean myoglobin oxy-
            gen tension during
            exercise at maximal
            oxygen uptake
Total working time reduced with
exposure to CO at lower  (25 C)
temperature.  Older nonsmokers
                   V
had a decrement in  02 max*
Mean exercise time significantly
reduced.
No significant change in maximum
aerobic power.  Total working time
was decreased in 25 C ambient
temperature.  Older nonsmokers
                    w
showed decrement in  02 max*
Older smokers showed no change.
Regardless of ambient conditions,

smokers had a significantly lower
aerobic power than nonsmokers.
Aerobic power of older smokers
was 26% lower than that of younger
smokers.

Maximal physical performance de-
creased after CO exposure.  Lower
cardiac output during CO-induced
hypoxia.  Maximum heart rate was
significantly lower in 1 subject
at levels >13%.

During exercise of max 0? con-
sumption, CO shifted out of the
vascular compartment.   It was
implied that the CO was taken up by
muscle tissue containing myoglobin.

-------
                                                     TABLE 11-4 (continued).
Reference
Klausen99
et al.
No. of
subjects
8
Exposure
(not given)
COHb
(not given)
Dependent variable
Circulation, metabo-
lism, ventilation
Results Comment
No change in ventilation at
rest, but changes present
in work.
Vogel
and Gleser
          207
                     16
                     8
Gliner et al.
             73
                     19
Collier.
et al.
                              1 hour
                              225 ppm
225 ppm
4 hours
50 ppm
                              Loading dose:
                              10,000 ppm to
                              produce mean COHb
                              of 8.9% maintenance
                              dose:  60-70 ppm for
                              5 mins (to produce
                              mean of 7.8%).
                       17-18%      Physical work
                                   capacity
18-20%      Effect on 02 trans-
            port during exer-
            cise, compared with
            hypobaric hypoxia
4.6 to      Physiologic response
6.8%        to long-term work
            and thermal stress
                       8.9% and    Physiological  adapt-
                       7.8%        ations  and exercise
                                   in normal  healthy
                                   males.
No impairment in ability to
do heavy work as a result of
elevated COHb was observed.

No significant differences in
0~ transport were detected,
tnough with CO hypoxia a lack
of cardiovascular response at
rest and a lesser ventilation
with exercise was apparent.

Decrement of stroke volume
which increased with higher
ambient temperature was
observed.  Heart rate was
increased in CO.

CO produced minute volume +
breathing frequency increased
only during exercise, 0?
consumption and arteriovenous
00 content difference during
                                                                                          ">
                                                                                          exercise.   Venous  0« content
                                                                                          and venous  PO? was Decreased

                                                                                          with exercise and  at rest.

-------
                                                     TABLE 11-4 (continued)
Reference
Klein ^
et al.
No. of
subjects
4
Exposure3
(not given)
V
COHb
4-12%
Dependent variable
Hemoglobin affinity
for oxygen in rela-
Results Comment
Maximal exercise induces
a change facilitating 0«
                                                                 tion to exercise and
                                                                 chronic elevation
                                                                 of COHb
                                                         offloading,  but the mecnanisms
                                                         and significance of the change
                                                         remains  to be established.   Re-
                                                         duction  of Ca02 during moderate
                                                         elevation of COHb does not in-
                                                         duce compensatory changes in P_Q
                                                         to facilitate tissue oxygenation.
al ppm CO * 1.145 mg/m3 CO and 1
mg/m  CO = 0.674 ppm CO, at 25°C and 760 mm Hg.

-------
Horvath and his group  » 3»173»174 have shown that combinations of
       3                          3
57 mg/m  (50 ppm) CO and 1.33 mg/m  (0.21 ppm) peroxyacetylnitrate (PAN)
exerted no greater effect on work capacity of healthy men--young and
middle-aged, smokers and nonsmokers—than that of CO alone.  However, it
appeared that slightly greater concentrations of either component could
                                                                92 93
have led to significant differences in response.  Hackney et al.  *
found no consistent changes (synergistic or additive) in pulmonary
functions in a 2-hour exposure of young male subjects to a combination
                                              3
of three pollutants - S02, 03, and CO (34 mg/m  ; 30 ppm).  It has been
                        139
reported by Mamacasvili,    who exposed human volunteers to low concen-
trations of CO and S0«, that each component produced independent delete-
rious visual effects on light and color sensitivity.  An 8-hour exposure
to mean ambient concentrations of CO and ammonia resulted in insignifi-
                                                                       202
cant physiological and biochemical effects on young healthy nonsmokers.
An additive effect was observed by Elfinova et al.   for a combination,
at low concentrations, of CO, phenol, and dust.
               90
     Gzegocskij   reported that the presence of CO and nitrogen oxides
in dust-laden air could reinforce the toxic effect of silicon dioxide
and hasten the development of silicosis.
11.5.2  Other Environmental Parameters
     The organisms' response to the presence of CO may well be modified
by the presence of other environmental factors  such as ambient temperature,
                                                         124
relative humidity, and barometric pressure.  Korenevskaja    indicated
that high ambient temperatures reinforce the toxic effect of CO and that
the presence of CO lowers the body's resistance to overheating.  Men
                                    11-48

-------
working for four hours in an ambient temperature  of  35°C  and  20 percent



relative humidity and exposed to a CO  concentration  of  57 mg/m3 (50 ppm)



failed to demonstrate synergistic effect.   *    Horvath's group



reported reduced working time with CO  at  25°C  but not at  35°C.



Experimental animal  studies have shown the  importance of  temperature



effects on survival  at high CO  exposure levels.



11.5.3  Alcohol



      Rockwell  and Weir    evaluated the interactive  effects of CO  and



alcohol on highway  driving performance using  four young,  nonsmoking



college students.   Carboxyhemoglobin  levels were  0,  2,  8  and  12 percent



and blood alcohol was 0.05 percent.   Perceptual  narrowing and decreased



visual activity were noted under increasing COHb  levels but there  was  an



alcohol-CO synergistic  interaction only in  curve  negotiation  tasks at



the 12 percent COHb level.



      Stewart's group    has  recently  evaluated behavioral functions in



 relation  to  the  hypothesis that alcohol ingestion (59 mg  percent blood



 level) would potentiate  any  deleterious CO  effects.  Neither  the presence



 of COHb  levels of 8.8 percent  or the  blood  alcohol levels produced



 deleterious  performances.



 11.5.4   Smoking



      A common source of  CO for the general  population comes  from tobacco



 smoking,  with other primary  sources  arising from the environment.



 Exposure  to  smoking primarily  affects the COHb level of the  smoker



 himself119'129 but  in some circumstances, such as in poorly  ventilated



 space, smokers provide  a source that may  affect other  occupants.   In
                                    11-49

-------
addition to CO, other products inhaled by the smoker may produce subtle



physiological and biochemical effects on both the smoker and those



individuals breathing either the pre-inhaled materials or the smokers'


                 182 191
exhaled products.   '     The possible interaction of CO and other



constituents of smoke which may occur in the lungs and other tissues and



so induce pathological changes remains to be elucidated.



     Those interested in the problems related to smoking tobacco, i.e.,



carcinogenesis, and cardiovascular and pulmonary disease, should refer



to documents specifically concerned with these matters.   '  *



Prospective and retrospective epidemiological studies have identified



cigarette smoking as one of the major factors in the development of



coronary heart disease (CHD).  The risk of developing CHD for pipe and



cigar smokers is apparently much less than it is for cigarette smokers



but more than it is for nonsmokers.  Tobacco smoking may contribute to



the development and aggravation of CHD through the action of several



independent or complementary mechanisms, one of which is the formation



of significant levels of COHb.168



     In the report of their epidemiological study in Baltimore, Kuller


      128
et al.    have stated that if there is an association between CO and



heart attacks, the significant exposures are probably related to micro-



environmental factors and cigarette smoking rather than community air



pollution.  They did note that relatively few heart attacks occur while

                                             11
an individual is smoking a cigarette.  Astrup   has suggested that



intermittent exposure to CO may be regarded as putting smokers at a much



higher risk than nonsmokers for the development of arterial diseases.



Wald et al.    and Ball and Turner   have come to similar conclusions.
                                   11-50

-------
     Smoking of cigarettes has been found to result in higher COHb

                                                04. TOO
levels than exposure to street air levels of CO.  '     Manual workers



had lower COHb levels than sedentary workers (both smokers), probably



related to the increased ventilation required in the occupations of the


               34 184      191
manual workers.  '     Srch    performed tests on two smokers and two



nonsmokers in a small car.  Before entering the car the smokers and



nonsmokers had COHb levels of 5 and 2 percent, respectively.  Each



smoker smoked five cigarettes with the windows and doors closed.  At the



end of the 60-minute test, the respective COHb in the smokers and non-



smokers had increased to 10 and 5 percent.  Other studies have reported



essentially similar patterns of accumulation in nonsmoking  individuals



exposed to smokers in other closed spaces.  The pattern of  accumulating


                                                                  49 113 214
CO (as well as other products) in closed spaces has been reported.  '   '



A mathematical model for calculating the build-up of CO and the resultant


                               118
COHb  levels has been developed.



      The quantity of CO actually entering the lung depends  upon the form



in which tobacco is smoked, the pattern of smoking, and the depth of



inhalation.  Very little CO is absorbed in the mouth and larynx



(approximately 5 percent), so that most of the CO available for transfer



to Hb must reach the alveoli in order to raise the level of COHb present



in the blood stream.  Cigarette smokers inhale more than cigar  smokers,



and the latter less than pipe smokers; but individual differences in



this  pattern are quite marked.  Heavy cigarette smokers have COHb levels



as high as 15  to 17 percent.  The CO concentration in cigarette smoke  is



approximately 4.5 percent. 65»"»100»2l0a  it has been estimated that the
                                    11-51

-------
                                                  o

cigarette smoker may be exposed to 458 to 572 mg/m  (400 to 500 ppm) CO



for the approximately six minutes utilized to smoke a cigarette.


      129
Landaw    noted that a smoker's COHb level increased 1 to 9 percent



during periods of active smoking.  He also presented data suggesting



that the half-time of CO elimination in smokers was approximately


                              188 189
291 minutes.  Smith and Landaw   '    reported that smokers (mean COHb



of 11.6 percent) had an increased red-cell volume or a reduced plasma

                                -I CO

volume (or both).  Pankow et al.     have raised the question as to



whether or not these changes represent an adaptive response.  Figure 11-



3 illustrates the pattern of change in COHb in a typical heavy cigarette


       129
smoker.     An indwelling venous catheter permitted the frequent sampling



of this smoker's blood.  The subject smoked only during his working



hours.  When he began to smoke the next day, he still had a body burden



of 1.7 percent COHb.  Cigarette smokers generally are excreting CO into



the air rather than inhaling it from the ambient environment.



      Low-toxicity cigarettes produce significantly smaller amounts of



CO.   However, the smoking pattern of the individual markedly .alters the



absolute amount of CO inhaled.



      Frankenhaeuser et al.   have reported another response to cigarette



smoking that may have important consequences to the smoker.  They observed



a progressive increase in adrenaline (epinephrine) excretion with number



of cigarettes smoked.  These investigators have also found that certain



psychophysical performance measures did not deteriorate if moderate



smokers smoked during the testing in contrast to the decrement observed



when  they did not smoke during testing.
                                    11-52

-------
.0
X
o
u
UJ
o
cc
LU
Q.
     3 -
                             SMOKING

                       29CIG. @1/14MIN
                           I
1
                           10
15
                               HOURS
20
          (05:18)
25
Figure 11^3. Pattern of change in COHb in a typical cigarette
                               11-53

-------
                  p
     Aronow et al.   studied eight angina patients who smoked cigarettes

or were given CO to breathe so that the final COHb levels were approxi-

mately equivalent (3.90 and 3.86 percent).   These patients were smokers,

and their initial COHb levels were above 2 percent.  Catheterization of

both left and right ventricles permitted an evaluation of the functions

of the myocardium.   The major differences observed under the two condi-

tions were as follows:  (1) cardiac output decreased with CO inhalation

and did not change with smoking; (2) systolic and diastolic arterial

pressures did not change with CO but increased with smoking; (3) left

ventricular change in pressure with time (dp/dt) decreased with CO but

did not change with smoking; (4) left ventricular end diastolic pressure

increased in both situations; and, (5) the partial pressure of Op in

arterial, mixed venous, and coronary sinus blood decreased with CO

exposure and with smoking.  Furthermore, CO causes a negative inotropic

effect on the myocardium; which decreases left ventricular dp/dt,

decreases stroke index, decreases cardiac index, and increases left

ventricular end diastolic pressure.  These divergent effects need to be
                                 P
further evaluated.   Aronow et al.  stated that the increased systemic

blood pressure and heart rates that are observed following cigarette

smoking were related to the nicotine in the cigarette.

     A critical problem arises in attempts to separate the CO effects of

cigarette smoking from the effects of other substances present in the

                                       9
inhaled cigarette smoke.  Aronow et al.  had male angina patients smoke

lettuce leaf, non-nicotine cigarettes, which resulted in blood COHb

levels of 7.8 percent.  Heart rate and blood pressure were unaffected by
                                   11-54

-------
this smoking but again angina, on effort, occurred earlier.  These data



may suggest that the presence of COHb following smoking of cigarettes



may be the major factor in the development of angina pectoris during



exercise.  Chest pain and electrocardiographic changes have been associ-



ated with acute CO poisoning.  Wald and Howard     have stated in their



overall review on smoking, CO, and arterial disease:



     "There is at present only indirect evidence that CO may be a cause



     of atheroma in man and  for the present, however, it is necessary to



     reserve judgment on whether CO is a cause of arterial disease,



     while at the same time  suspecting that it may be the principal



     agent in tobacco smoke."
           5                                           2
     Aronow  and coworkers,  as well as Anderson et al.,  have shown that



 in patients with ischemic  heart  disease, exercise-induced angina occurs



 earlier when the patients  are exposed to low  levels of CO.  Carbon



 monoxide  exposure  also  exacerbates  and prolongs the pain of intermittent



 claudication in patients with this  disease.   The potential deleterious



 influence of cigarette  smoking and/or CO exposure on the pregnant woman,



 fetus, and neonate will be considered elsewhere.  The only direct evidence



 that CO adversely  influences fetal  development was derived from studies



 conducted on rabbits    and rats.   '



     A number  of studies have suggested that  cigarette smoking reduces



 work capacity,733'1243'206 in direct relation to the level of COHb



 present in the working  subject.   In young  smokers, 21 to 30 years of



 age, no differences  in  maximal aerobic power  were observed despite


                                                              173
 reductions in  vital  capacity and maximum breathing capacities.     Older



 smokers (40 to 57  years of age)  had significantly lower  (27 percent)


                                              174
 aerobic power  than comparably aged  nonsmokers.     Younger smokers had



                                    11-55

-------
only a 6 percent lower aerobic power than nonsmokers of similar age.


              144
McHenry et al .     found that the duration of maximal exercise and maximal



heart rate was significantly shorter in smokers and former smokers than



in nonsmokers.   Maximal systolic blood pressure during exercise was

                                                            •

greater in smokers.  Tobacco smoking decreased Vn9     even in ^   ^
                                                   max
moderate smokers.     The effect of passive smoking (i.e., exposure to



three individuals smoking five cigarettes each) on nonsmoking patients


                                               "y\\
with exercise-induced angina has been reported.    Their exercise time



to the onset of angina was decreased 22 and 38 percent, respectively,



from exposure in a well ventilated versus an unventilated room.  Blood



COHb levels were 1.77 and 2.28 percent, respectively, in these patients.



There still remains some question as to the role of other materials in



cigarette smoke in producing this reduced performance.



     Smokers may have early closure of small airways, especially when



supine.     The diffusing capacity for CO in young smokers as well as



older smokers is impaired.   '     Other physiological changes have also



been reported.    The potential hazard of rapid smoking utilized in the



stimulus-satiation method to help smokers break the smoking habit has


                                147
been identified by Miller et al.     Carboxyhemoglobin levels above



22 percent can occur.



11.5.5  Conclusions and Discussion



     While it is important from the point of view of  general and theo-



retical information to know how CO alone affects various physiological



and behavioral systems; CO does not occur by itself in the actual



environment.  The data relating CO to other pollutants is so sparse,
                                    11-56

-------
however, that almost no pattern can be discerned.  Both human and labora-



tory animal studies suggest cases in which CO either additively or



synergistically combines with other airborne pollutants to produce



increased effects; but there is usually only one study per pollutant



combination and even those do not give parametric data from which dose-



response curves or thresholds might be estimated.  There is a definite



need to obtain in a systematic manner information about real-life combi-



nations of other pollutants with CO.



     In both human and experimental animal studies, the data regarding



alcohol in combination with CO are only suggestive.  This frequently



occurring combination is of such import as to urgently require further



research, especially with  regard to behavior and psychomotor performance.



Other  drugs (both therapeutic and illicit) which would be expected to



interact with CO have not  been studied.   It would seem to be of paramount



importance to know the combined effect of CO and such drugs as



tranquilizers, sedatives and illicit psychotropic drugs.  Data from



experimental animal studies strongly indicate that the effects of such



drugs  are potentiated and/or altered by CO exposure.  The possibility



that CO may potentiate or  counteract the  effects of drugs designed to



alleviate cardiovascular or pulmonary conditions is quite important in



view of COHb levels attributable to environmental sources and smoking.



     Smoking is both another source of CO to the smoker and others as



well as a  source of other  chemicals with  which  environmental CO  levels



could  interact.  Available data strongly  suggest that chronic CO exposure



via smoking produces cardiopulmonary damage, but the  interaction with
                                    11-57

-------
other products of smoking confounds the results.  Data on the effects of


environmental CO increments in addition to COHb built up due to smoking


have produced results which in some cases imply additive effects and in


other instances imply adaptation to COHb.  There is need for further


systematic and parametric research to descry these relationships.


11.6  HIGH/ALTITUDES - MECHANISMS


     Precise data on the potential scope of the problems attributable to


CO for high altitude residents and visitors are not available.


Approximately 2.2 million people live at altitudes (land elevations)


above 1524 meters in the United States.  These figures do not present a


complete picture of potential numbers of individuals who may be subjected


to CO at these altitudes because the tourist population in these areas


is high in both summer and winter.  Furthermore, proper tuning of automo-


biles for high altitude traveling is uncommon, and the influx of visitors


and cars with their greater emissions of CO and other contaminants may


prove to be an important factor in raising pollution exposure to an


unacceptable point.  At 1540 meters, each cubic meter of air contains


approximately 18 percent less oxygen than at sea level.  Therefore,


concentrations of carbbn monoxide in air in a city like Denver will be

                                                    3
22 percent higher than at sea level (i.e., a 10 mg/m , 8-hour average is

                       3
equivalent to 11.8 mg/m  at Denver's altitude).


11.6.1  Physiological Results


     Carbon monoxide exposure may aggravate the Op deficiency present at


high altitudes.  When high altitude and CO exposures are combined


(Table 11-5), the effects on 0« availability in blood are apparently
                                    11-58

-------
additive.  It should be noted,  however,  that each of these,  decreased

PQ2 in the air and increased  COHb,  produce  different physiologic responses,

They have different effects on  blood PQ2, on the affinity of CL for Hb,

on the extent of 02Hb  saturation  (CO hypoxemia shifts the OJHb dissoci-

ation curve to the left,  and  a  decrease  in  PAQ2 shifts it to the right),

and on ventilatory drive.

     TABLE 11-5.  APPROXIMATE PHYSIOLOGICALLY EQUIVALENT ALTITUDES
                 AT EQUILIBRIUM WITH AMBIENT CO LEVELS
——•.—-.—-.———————_________ _ _ ______ «._....___...__i.,.._—__..________.. _.. ____ _______
     Ambient                       Actual Altitude (meters)
CO concentration          0  (sea level)       1524      3048
mg/m        ppm
Physiologically Equivalent
0
28.6
57.3
114.5
0
25
50
100
0 (sea level)
1829
3048
3749
1524
2530
3658
4663
Altitudes with COHb
3048
3962
4694
5486
                   69
      Forbes  et al.    reported that during light activity at an altitude

 of  4875  meters,  CO uptake was increased,  probably because of the hyper-

 ventilation  at altitude caused by the respiratory stimulus of decreased

 Pn?.   Evidence that CO elimination was similar at sea level and at
                                                                     80 187
 altitudes  up to 10,000 meters was obtained by several investigators.   *

 Increased  ambient temperatures up to 35°C and hard physical work increased

 the rate of  elimination.      Pitts and Pace    stated that every 1 per-

 cent increase in COHb (up tp 13 percent)  was equivalent to a 109-meter

 rise in  altitude if the subjects were at  altitudes of 2100 to 3070 meters.

 Their observations were based on changes  in the heart rate response to

 work.  Subjects who may have been smokers were not identified.
                                    11-59

-------
     Two groups of investigators have presented data comparing the



physiologic responses of subjects to altitude and CO where the hypoxemia



due to altitude and the presence of COHb were approximately equivalent.


            23
In one study   the COHb varied around 12 percent (although the mode of



presentation of CO was such that COHb ranged during the CO exposures



from 5 to 20 percent) and the altitude study was conducted at 3977 meters,


                187
The second study    compared responses of subjects at altitudes of



4000 meters and a COHb content of 20 percent.  In both studies, COHb



content was in excess of that anticipated for typical ambient pollution.



However, it was suggested that the effects attributable to CO and to


                                        209a
altitude were equivalent.  Wagner et al.      studied smokers and non-



smokers who exercised at 53 percent of their Vno     and at 760 and
                                              02 max


523 torr.  Carboxyhemoglobin levels were raised to 4.2 percent.  While



at altitude and in an altitude chamber with elevated COHb levels, non-



smokers increased their cardiac output and decreased their arterial-



mixed venous 0« difference.  Smokers did not respond in similar manner.



Smokers may have developed some degree of adaptation to altitude.



     Parving     exposed humans to CO to produce 20 percent COHb and to



simulated high altitude sufficient to produce an equivalent arterial



blood oxygen saturation.  Exposure times were three to five hours.  The



results showed increased capillary permeability for proteins during



exposure to CO but not during exposure to simulated high altitude.  It



was also shown that plasma volume decreased significantly during the



simulated high altitude exposure but not during CO exposure.  The plasma



volume was explained as due to hypoxia-induced hyperventilation but the
                                   11-60

-------
effect on capillary wall permeability appears to be unique to CO and
therefore apparently represents a non-hypoxic short-term effect.
     It was recommended on theoretical grounds that the ambient CO in
tunnels being constructed at 3859 meters should not exceed 29 mg/m
         149
(25 ppm).     The maximal aerobic capacity  is reduced approximately
20 percent in individuals exposed to an altitude of 3085 meters.  Weiser
      216
et al.    reported that max VQ2 was significantly  impaired in subjects
living at 1700 meters when their COHb levels were  5 percent.  However,
this decrement is similar to that seen in sea level residents.  No data
                                                   29
are available for higher altitudes.  Brewer et al.   conducted a study
on residents of  Leadville, Colorado (3085 meters).  The mean COHb level
in smokers at altitude was higher than that of smokers at sea level.
This  increased degree of hypoxemia may have contributed to the elevated
red cell mass observed  since individuals who stopped smoking demonstrated
                                                128a
a reduction  in their red cell  mass.  Kurt et al.     demonstrated that
ambient  CO levels in Denver, Colorado had a significant, low-level
association  with a  number of patients with  acute morbid cardiorespiratory
complaints presenting themselves  in an emergency room.
11.6.2   Behavioral  and  Central  Nervous System
      The most supportive information on the additive nature of CO hypoxia
and hypoxic  hypoxia originates from psychophysiologic  studies and even
                                                            24
these are  not as persuasive as one would  desire^   Blackmore   analyzed
the cause  of aircraft accidents in Britain, finding that COHb levels
provided valuable information  relative to altitude and CO  sources.  The
relatively high  levels  found could be attributed to equipment failure,
                                    11-61

-------
smoking, and fires.  No data are available on the effects of CO on



native inhabitants of high altitudes or on the reactions of these natives



when they are suddenly removed to sea level and possible high ambient CO



concentrations.


                     142
     McFarland et al.    showed that changes in visual threshold occurred


                                                                     209
at a simulated altitude of approximately 2425 meters.  Vollmer et al.



studied the effects of CO at simulated altitudes of 3070 and 4555 meters



and reported that there were no additive effects of CO and altitude.



They suggested that the effects of CO were masked by some compensatory



mechanisms.  The data presented were not convincing.  Lilienthal and


      133
Fugitt    indicated that a combination of altitude (1540 meters) and



5 to 9 percent COHb induced a decrease in flicker fusion frequency,



although either one alone had no effect.  They also reported that the



presence of 8 to 10 percent COHb was effective in reducing altitude



tolerance by some  1215 meters.



11.6.3  Conclusions and Discussion of Carbon Monoxide and High Altitude



        Combinations



     Data from both physiologic and behavioral studies on humans seem to



indicate a simple  additive effect of CO and high altitudes.  They both



reduce 0? availability, and there are data which allow estimation of



their common effect on 0« levels.



     It would be erroneous to infer that CO hypoxia and hypoxic hypoxia



are equivalent states or produce equivalent results.  They apparently do



at equilibrium states, but CO uptake and elimination produce a  slower



rate of 0« change  than hypoxic hypoxia.  Hypoxic hypoxia also produces



hyperventilation;  CO hypoxia does not.
                                    11-62

-------
     Data from experimental animal studies imply that for some physiolog-



ical  functions, CO has additional non-hypoxic effects which might act to



impair functioning of some systems.  Although such additional impairment



might represent unanticipated, more-than-additive effects of CO and high



altitude, data from human studies on this are lacking.



11.7  ADAPTATION, HABITUATION, AND COMPENSATORY MECHANISMS



     Extensive discussion of these topics was given in Chapter 10.



There, for purely logistical reasons, the term "adaptation" was used to



refer to long-term effects, and the term "habituation" was used to refer



to short term effects.  This convention will be continued here.



     In Section 10.8, discussion was made of experimental animal data



showing that COHb levels produced physiological responses which by their



nature tended to offset other deleterious effects of CO.  Such responses



were:  (1) increased  coronary blood flow, (2) increased cerebral blood



flow, (3) increased hemoglobin via increased hemopoeisis, and



(4)  increased 0? consumption in muscle.  Where possible, an evaluation



of the completeness of such so-called compensatory responses was made



and, in general, the  compensation appeared to be only partial in nature.



There was also some evidence that such compensation on a long-term basis



might have undesirable side effects.



11.7.1  Adaptation and Other Long-Term Effects



     The presence of  a clinical  state of chronic CO poisoning with the



implication that adaptation to CO occurs in humans has not been verified.



If it existed, such a state should have been identified by studies on



long-term heavy smokers or on individuals exposed to  environmental
                                    11-63

-------
sources of CO.   Early concern in England and Scandinavia with CO intoxi-


                                                                     87 121
cation led to studies suggesting the possibility of such a condition.  *



However, problems regarding the employment of high levels of inspired CO



(several hundred parts per million) and inadequate experimental methods



have resulted in some skepticism of the conclusions presented.


        121
Killick,    using herself as a subject, reported that she developed



acclimatization as evidenced by diminished symptoms, slower heart rate,



and the attainment of a lower COHb equilibrium level following exposure



to a given inspired CO concentration.  Interestingly, Haldane and


        96
Priestly   had earlier reported a similar finding as to the attainment



of a different COHb equilibrium following exposure to a fixed level of



CO in the ambient air.  Additional information on other possible adap-



tation effects in the pre-1940 literature can be found in KiHick's



review.



     The mechanism by which long-term adaptation is assumed to occur, if



it could be demonstrated in humans,  is an increased Hb concentration via



a several-day increase in hemopoeisis.  If, in fact, such data from



human studies were available, the question of the completeness of the



adaptation would be very important as would the question of the undesir-



able chronic side effects of the compensation.  If an appreciable amount



of compensation occurs in man, then  it may be inferred that in subjects



with impaired compensatory mechanisms, CO effects might be much more



extreme.
                                    11-64

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11.7.2  Habituation and Short-Term Effects
     The only evidence for short-term COHb compensation in man is indirect.
From experimental animal studies  it  is  known that coronary blood flow is
increased with COHb, and from human  studies it  is known that subjects
with impaired cardiac functioning have  the lowest threshold to CO-
induced decrements.  The implication is that in some cases of cardiac
impairment, the  short-term compensatory mechanism is impaired and thus
the threshold is lowered.
     In a few instances of behavioral testing,  it has appeared that
decrements  due to CO have occurred only at very low levels or at early
exposure times and  have, in  the  same studies, not appeared at higher or
longer exposures.   This has  led  to the  hypothesis that there might be
some threshold or time  lag in a  compensatory mechanism, such as increased
cerebral blood flow (CBF).   Not  only is there no direct physiological
evidence from human or  experimental  animal studies for such a threshold
or time  lag, but it would appear to  be  more conservative  to assume that
the behavioral effects  which were observed were due to possible non-
random sampling.
     The idea of a  threshold or  a time  lag in compensatory mechanisms
should not  be rejected.  There  simply  is  no direct evidence.  Studies
should be performed which  (1) measure  CBF and tissue PQ2  with low COHb
levels at various saturation rates  to  determine early  and low level
effects  accurately  and  (2) design behavioral  studies where threshold
effects  or  time  lags are  factors in  the experimental design that can  be
explicitly  studied.
                                    11-65

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11.8  SPECIAL GROUPS AT RISK



     As discussed in Chapter 10, it is known from both theoretical and



empirical experimental animal research that certain groups in the popu-



lation are at a higher than normal risk of detrimental effects of CO



exposure.  The list of such groups from Chapter 10 included the fetus,



subjects with health impairments, subjects who are under the influence



of drugs, and subjects who have not been adapted to high altitude and



are then exposed to a combination of high altitude and CO.  Even in



laboratory animals, there is too little information about CO effects in



these special risk groups so that an assessment of the extent of the



increased risk and the circumstances under which it might occur is



difficult.   In this section, human studies will be reviewed in an attempt



to deduce the extent of the problem which has been described in



experimental animals.



11.8.1   Fetus



      It  has  been shown in experimental animals that short-term maternal



CO exposure  results in lower COHb levels in the fetus than in the mother,



but has  greater detrimental effects in the fetus than in the mother.



Long-term maternal CO exposure has been shown to lead to higher fetal



than  maternal COHb.  Fetal uptake and elimination of CO has been shown



to be slower than maternal.  These data are reviewed in Chapter 10.



      Pregnant mothers and their fetuses may be exposed acutely or chron-



ically to CO either by maternal smoking or by environmental pollution.



The biologic effects of CO exposure on fetal tissues during intrauterine



development  or during the newborn period require clarification.  Of the
                                   11-66

-------
several mechanisms that may account for the  influence of CO on developing



tissue, the most important is the interference with tissue oxygenation.



Carbon monoxide decreases the capacity of Hb to transport 0? and shifts



the 02 saturation curve to the  left.  The normal arterial PQ2 supplying



fetal tissue is approximately 28 torr.  This additional shift to the



left will tend to decrease further the Op gradient from maternal to



fetal blood across the placenta! tissue.  The decreased PQ2 and the



diminished 02 transport due to  the presence  of COHb may also produce



undesired influences  on the fetus.



     One of the possible mechanisms by which CO or other components of



tobacco smoke may adversely influence fetal  development is through



interference with the metabolic function of  placental cells.  These



cells  have a role in  hormone metabolism, as  well as in the transport of



vitamins, carbohydrates, ami no  acids, and other substances, through


                                         201
their  energy-dependent processes.  Tanaka    reported that the 02



uptake of placenta tissue  slices from smoking mothers varied inversely



with maternal carboxyhemoglobin (COIIb), being markedly reduced when



CO Hb  was greater than 7.0 percent.  The preponderance of evidence



concerning CO Hb  levels, along  with  fetal and perinatal exposure, tends



to warrant the minimization of  exogenous CO  sources to which this group


                        T36
might  be exposed.  Longo    has reviewed the pertinent literature up to

                     inc
1977 and Hill et  al.    have provided a mathematical model for the



exchange of CO between the fetus and the mother.



     Another factor  that may produce differential  effects on the  fetus



is related to the endogenous production of  CO by pregnant women.
                                    11-67

-------
     135
Longo    indicates that nonsmoking pregnant women produce 0.9 ml CO/hr;
                                         137
non-pregnant women produce 0.39 ml CO/hr.     Fetal endogenous CO production
accounts for 3 percent of the total COHb present in the blood of a nonsmoking
normal pregnant woman.  The source of the remainder is unknown although it may
be partly accounted for by the increased red cell mass of the pregnant woman.
Even though the hyperventilation of pregnancy may partially compensate for the
increased CO production in the absence of exogenous exposure, the CO Hb still
                                                                     135
remains at about 13 percent above that which is in nonpregnant women.     It
should be noted that post-partum (24 hours) females may be producing three
times as much CO as a near-term nonsmoking pregnant woman.  Hemolytic disease
of newborn infants (physiological jaundice) produces a high level COHb
resulting from endogenous production and so provides a further stress to the
infant.161'154
     Smoking mothers have been reported to have from 2 to 14 percent COHb,
while COHb levels in the fetuses ranged from 2.4 to 9.8 percent.  These values
may not represent conditions present during pregnancy, since these data were
obtained just prior to birth.  The newborn are also subject to ambient levels
                      20
of CO.  Berhman et al.   measured COHb in 16 relatively normal newborns in a
downtown Chicago nursery.  Carboxyhemoglobin was found to be as high as 6.98
percent.  These investigators indicated that the absolute COHb levels were
related to ambient levels of CO.  Some doubts as to this conclusion exist
since the monitoring reference site was some 1.5 miles from the nursery.  The
investigators reported no untoward clinical effects from these levels of COHb.
                                   11-68

-------
However, the high levels of COHb in neonates are of  some concern and



warrant further investigation.


                    13 138
     Several studies   *    have demonstrated that babies delivered of



mothers who smoke cigarettes weigh less  than those delivered of non-



smoking mothers.  Relative maternal,  fetal, or placenta! hypoxia may be



responsible, as suggested by the observation that infants born at higher


                                                       l ^1
altitudes also weigh  less than those  born  at sea level.     The New Mexico



Department of Health  (1975) has provided additional  confirmation of the



relationship between  altitude and birth  weight.



     Maternal smoking probably constitutes the most  frequent source of



fetal  exposure to CO.  There  is some  question as to  the relationship of



fetal  deaths to maternal  smoking but  there is no doubt that such smoking



results  in  higher than normal fetal COHb.    *     Gennser et al.



found  that  maternal  cigarette smoking abruptly decreased the proportion



of time  that the  fetus made breathing movements.  The relation to CO is



not clear.  The effect of maternal smoking on surviving children is not

                                                              -1 OC

well  known.  Discussion  of this point is available from Longo.     There



remain a considerable number  of  unanswered questions as to the influence



which  various  levels of  COHb  have  on  the mother  and  on the fetus.



11.8.2  Impaired  Groups



      As  pointed out in the  section on cardiovascular effects, the lowest-



effects  level  of  CO (about  2.5  to  3 percent COHb)  has been shown in



subjects with  cardiovascular  damage.   Such impairments produce low CO



thresholds  because  there is  already  sufficient  hypoxia of  cardiac tissue



to produce  impairment, so that  there  is no reserve  or  compensatory



capacity.
                                    11-69

-------
     Another group which also has impaired Op delivery is composed of



individuals with impaired cerebrovasculature.  This group consists



mainly of persons with obstructed vasculature due to cholesterol buildup



and to previous cerebrovascular injury.  While on theoretical grounds it



is probable that subjects with impaired cerebrovasculature would have



very low thresholds for detrimental effects of CO exposure, there are no



direct experimental data on the subject in either humans or laboratory



animals.  The possible effects of reduced 02 supply to the CNS range



from all of the behavioral effects reported to be caused by CO, to the



possibility of precipitation of motor seizures or cerebrovascular



accidents.



     Subjects whose blood has reduced 0« carrying capability because of



either dietary or pathological anemia should also be at special risk to



CO exposure.  Unfortunately, the effects of CO on anemic patients or



experimental animals have not been adequately studied.  It can be assumed,



a priori, that anemic persons could be at greater risk than normal



persons  because the capacity of the 0« transport system is reduced.



Tissue oxygenation may be initially compromised due to the anemic state



since mixed venous PQ2 accompanying a particular COHb value is somewhat



greater  in anemic than in normal subjects.   In patients with hemolytic


                               fi?
anemia and sickle cell disease,   the rate of endogenous CO production



from heme catabolism is increased.  Normal subjects produce approximately



18 moles CO/hr, resulting in COHb levels of  0.5 to 0.8 percent.  Carbon


                                      41 134
monoxide production in anemic patients  '    has been reported to vary



from 31  to 158 moles/hr, producing COHb levels of 1.3 to 5.2 percent.
                                   11-70

-------
     Anemic individuals approach equilibrium levels of COHb more rapidly

than those with normal Hb levels at any given exposure to CO.  Exposure
            3
to 21.9 mg/m  (25 ppm) CO for approximately four hours in an individual

with 7 g percent of Hb could result in 4 to 5 percent COHb, compared to

an anticipated level of 2.5 percent for normal individuals.  Exogenous

CO exposure of anemic individuals could result, in conjunction with

higher endogenous production, in critical levels of COHb.  Subjects

whose blood has low 02 carrying capabilities due to anemia would be

expected to be more sensitive to the effects of CO exposure because of

the already marginal Op delivery system.  While dietary anemias are not

as great a problem as in former times, anemias resulting from various

pathological conditions are still major health problems and low levels

of CO exposure could pose a health threat to such groups.

     Patients with chronic obstructive pulmonary disease are probably at

high risk although few studies on them have been reported.  Any increase

in hypoxia could result in respiratory failure or other effects due to

reduced 0« supply.  However, these individuals may absorb less CO due to

their disease and may have compensated for their hypoxia by increased

erythropoiesis and a  shift of the Op dissociation curve to the right.

Ogawa et al.    have presented evidence on the development of pulmonary

edema and discussed possible mechanisms of the role of CO in the disorder.
        -i qrj
Sofoluwe    has described the potential further irritation of the lungs

of children having bronchiolitis and bronchopneumonia by their exposure
                                                                       4
to CO derived from wood fires used for cooking purposes.  Aronow et al.

studied 10 patients with chronic obstructive pulmonary disease who had
                                    11-71

-------
been exposed for one hour to CO which raised the COHb level to 4.1 percent.



When they exercised on a bicycle ergometer, dyspnea occurred within



146.6 seconds.  However, 218.5 seconds elapsed before dyspnea occurred



when they exercised with COHb levels at 1.48 percent.  The investigators'



conclusion was that their limited exercise performance was probably a



cardiovascular limitation rather than a respiratory one.



11.8.3  Drugs



     Drugs such as alcohol, tobacco smoke, therapeutic drugs, and illicit



drugs as they interact with CO exposure have been discussed in Section 11.5



on  interactions with other pollutants and drugs.  Although there is



little empirical data on these interactions in either man or animals,



the  little evidence and the theoretical expectations strongly indicate



that individuals taking various drugs would be at special risk.   The



group of people under the influence of some form of drugs at any given



time is so large as to include a very major part of the general  population.



Since interactions could be serious and the potential for them appears



to  be ubiquitous,  it is imperative that further research be done on this



subject.



11.8.4  Unadapted  Individuals



     Adaptation in humans has been discussed extensively in Section 11.6



on  high altitudes, and on animals in Sections 10.7 and 10.8.  The prepon-



derance of evidence to indicate that people who have not adapted to high



altitudes and are  then exposed to both high altitude and CO simultaneously



are  at greater risk.
                                    11-72

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11.8.5  Occupational



     Certain occupational groups are at special risk because of the



especially high exposures to CO peculiar to their work.  These groups



include garage personnel, traffic policemen, steelworkers, firefighters,



and workers in petroleum and chemical  industries.  The presence of



chronic low-level CO poisoning may  have significant influences on the



health and efficiency of these workers but this awaits further study.



Many other occupational exposures occur, but most studies of such exposure



are complicated by  the  unknown or unreported smoking habits of the


                    87
workers under study.    Table 11-6  illustrates the potential emission



rates of  CO for certain industries.



     A study of blood COHb  in the U.S. general public was carried out by


                            198 199
Stewart and his associates,    *     who sampled blood drawn at blood



donor mobile units  in 17 urban areas and in some small towns in


                                                   52 119 212
New Hampshire and Vermont.   Kahn and his associates   '    '    evaluated



COHb  levels in metropolitan St.  Louis, where a total of 45,649 donors



provided  blood for  analysis.  Stewart  had 29,000 individuals (1,018  from



St. Louis) and Kahn had 16,649 (all from St. Louis) in their respective


                                                  199
samples.   It should be  noted that Stewart et al.'s    subjects were


                                       119
studied  in March  1971 and  Kahn et al.'s* y during October 1971 to



October 1972.  The  highest COHb  values were 13.0 and 18.2 percent,



respectively,  in  Stewart et al.'s and  Kahn et  al.'s samples.  Tables 11-



7 and 11-8 present  Horvath's summary     of the  findings of these two

                        1 QQ
groups.   Stewart  et al.    concluded that 35 percent  of the  nonsmoking



donors  in St.  Louis were exposed to ambient CO which  led  to  COHb  levels
                                    11-73

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                              TABLE 11-6.  NATIONWIDE EMISSION ESTIMATES, 1977



                                          (10  metric tons/year)
                                                                              223
Source Category
Transportation
Highway vehicles
Non- highway vehicles
Stationary fuel combustion
Electric Utilities
Industrial
Residential, commercial,
and institutional
Industrial processes
Chemicals
Petroleum refining
Metals
Mineral products
Oil & gas production & marketing
Industrial organic solvent use
Other processes
Solid waste
Miscellaneous
Forest wildfires
Agricultural burning
Coal refuse burning
Structural fires
Miscellaneous organic solvent use

TOTAL
TSP
1.1
0.8
0.3
4.8
3.4
1.2
0.2
5.4
0.2
0.1
1.3
2.7
0
0
1.1
0.4
0.7
0.5
0.1
0
0.1
0

12.4
S0x
0.8
0.4
0.4
22.4
17.6
3.2
1.6
4.2
0.2
0.8
2.4
0.6
0.1
0
0.1
0
0
0
0
0
0
0

27.4
N0x
9.1
6.7
2.5
13.0
7.1
5.0
0.9
0.7
0.2
0.4
0
0.1
0
0
0
0.1
0.1
0.1
0
0
0
0

23.1
VOC
11.5
9.9
1.6
1.5
0.1
1.3
0.1
10.1
2.7
1.1
0.1
0.1
3.1
2.7
0.3
0.7
4.5
0.7
0.1
0
0
3.7

28.3
CO
85.7
77.2
8.5
1.2
0.3
0.6
0.3
8.3
2.8
2.4
2.0
0
0
0
1.1
2.6
4.9
4.3
0.5
0
0.1
0

102.7
Percentage of
Total CO
83.4
75.2
8.2
1.2
0.3
0.6
0.3
8.1
2.7
2.3
2.0
0
0
0
1.1
2.5
4.8
4.2
0.5
0
0.1
0

100 100
NOTE:  A zero indicates emissions of less than 50,000 metric tons.

-------
TABLE 11-7.  AVERAGE PERCENT OF CARBOXYHEMOGLOBIN SATURATION
           IN SMOKERS AND NON-SMOKERS IN ST. LOUIS1Ub
Non-smokers


Kahn et al.119
199
Stewart et al . L
No.
of donors
10,157
673

Mean
0.85
1.35
Smokers
No.
of donors
6,492
345

Mean
4.58
5.47
 TABLE  11-8.   AVERAGE  PERCENT  OF  CARBOXYHEMOGLOBIN SATURATION106
Non-smokers


Kahn et
(St.
Stewart
(U.S.


al . 119
Louis)
. , 199
et al .
A.)
No.
of donors
10,157

16,036


Mean
0.85

1.43

Smokers
No.
of donors
6,492

11,289



Mean
4.58

5.21

                             11-75

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                                            119
greater than 1.5 percent, while Kahn's group    reported that 15.3 per-



cent of their St. Louis nonsmoking blood donors had levels above



1.5 percent.  Kahn's group also stated that 21.9 percent of their donors



who were nonsmoking industrial workers had COHb levels of 2 percent or



more and only 5.7 percent of the remainder of the nonsmoking sample had


                                            194
levels of 2 percent or more.  Stewart et al.    have compared COHb



levels found in  subjects in Chicago in 1970 and 1974.   They reported a



substantial reduction in COHb levels in blood donors over this time



frame, and  suggested that the reduction was caused by a decrease in



ambient CO  levels.


                   199
     Stewart et  al.    concluded that there were significant differences



between the COHb saturations of the occupational groups studied.



Students and housewives had the lowest COHb concentrations.  Other low



COHb groups included those associated with mental health services,



education,  library science, religion, art, road paving, and entertainment.



The vehicle-related occupational groups had higher COHb saturations than



most groups.  Other high COHb groups included those associated with



metal processing, chemical processing, stone and glass processing,



printing, welding, electrical assembly and repair, and graphic arts.



They concluded that a significant percentage of the population studied



was continuously exposed to ambient CO concentrations in excess of those



permitted by U.S. air quality standards.


                                          119
     On the other hand, Kahn and coworkers    concluded that ambient CO



exposure was responsible for only very small increases in COHb  levels  in



their sample.  They suggest that their data indicate two major  sources
                                    11-76

-------
of COHb in their subjects:  smoking and work-related exposure.  They



stated that almost 20 percent of their sample population were industrial



workers who carried an added COHb burden of 1.15 percent compared with



non-industrial workers.  They attributed higher COHb levels not to



ambient atmospheric CO but, overwhelmingly, to smoking and occupation.
Most individuals with 2 percent COHb or more were industrial workers or



smokers or both.  A similar conclusion was reached by Torbati et al.


           38
     Chovin   has provided some of the most complete information on



Paris policemen, illustrating some of the concerns related to this



occupational group.  Similar information is provided by the studies of



Balabaeva and Kalpaznov   on traffic policemen  in four large towns in


                       82
Bulgaria.  Gothe et al.   found relatively low  levels of COHb in Swedish



traffic policemen.


           T69
     Ramsey     reported a rise in COHb from 1.5 to 7.3 percent in



14 nonsmoking parking garage employees exposed  to an average working-day

                           3
ambient CO level of 68 mg/m  .  He also noted that smokers exposed to the



above environment  had an  initial average COHb level of 2.9 and an average



COHb level of 9.3  percent at the end of the day.  Nonsmokers exposed to



this environment had final levels of only 3.9 percent.  Ramsey stated



that occupational  exposure was more  important than smoking in increasing


                                                           32
COHb levels.  A contrary  opinion was expressed  by Buchwald,   who report-



ed that cigarette  smoking was  a more significant contributor to  the high



 levels of  COHb  which he found  in Canadian garage and  service workers.



Of the smokers, 70 percent had levels  in  excess of 5  percent, while only



30 percent of the  nonsmokers had  such  levels.   A study  of  employees of
                                    11-77

-------
 the Triborough Bridge and Tunnel Authority, New York City,   indicated
 that methemoglobin was slightly, although statistically, increased in
 these workers occupationally exposed to automobile exhaust.  The role of
 cigarette  smoking was not clarified.  Fristedt and Akesson    found a
 slight increase  in COHb  in workers employed in service installations of
 enclosed parking areas,  but attributed the discomfort that the workers
 experienced  to other components of automobile exhaust.
                       30
      Breysse and Bovee   used expired air samples to determine the
 exposure to  CO of stevedores, gasoline-powered lift-truck drivers, and
 winch  operators.  Of some 700 estimates of COHb in these workers, almost
 6  percent  (5.7)  of the workers exceeded COHb levels of 10 percent.
  Levels of  COHb greater than 10 percent were found in 7 percent of the
  stevedores and 18 percent of the lift-truck operators.  Smoking contributed
                                                                    164
  substantially to the attainment of the high levels of COHb.  Petrov
  also  studied dock workers and found COHb levels as high as 10 percent.
                                  74
  Goldsmith's  study of  longshoremen   suggested that the alveolar concen-
  trations  of CO were age-related regardless of smoking history.  Pack-a-
  day smokers  in the 45-to-54-year age bracket had alveolar values of
         3                                                             3
  31 mg/m  ,  while  75-to-84-year-olds' alveolar values were only 16 mg/m .
  Nonsmokers did not exhibit this age-related pattern, since even in
  subjects  up to 84 years  of age, alveolar concentrations remained at the
  same  level.
       Inspectors  at U.S.-Mexico border crossing stations are  exposed to
                                                           3  43
,  ambient  levels of CO that fluctuate between 6 and 195 mg/m  .
  Carboxyhemoglobin  levels of  smokers and nonsmokers prior to  their duty
                                     11-78

-------
as inspectors were 4.0 and 1.4, rising to 7.6 and 3.8 percent, respectively.

              114
Johnson et al.    studied six fare collectors working at a toll highway.

                              3
Ambient CO levels were 26 mg/m  (8-hour time-weighted average for 12 days).


On three days ambient CO exceeded 40 mg/m .  Post-shift COHb ranged from


1.8 to 8.6 percent, with a high of 11.7 percent.


     Nonsmoking British steelworkers had end-of-shift values of 4.9 percent.


Non-exposed,  nonsmoking controls reached 1.5 percent.  Smokers had


higher values, reaching levels of 7.4 percent.  The  highest COHb value

reported was  14.9 percent.


     Another  major source of CO is the internal combustion engine, which


may in some cases be considered an occupational source since it provides


many forms of transportation.  Community CO  levels in ambient air follow


a regular diurnal pattern of variation, however, and different

                                                                   112
concentrations have been measured at different  sites.  Jech and Ubl

measured alveolar concentrations of CO in individuals during a 2-hour


stay on a busy street and reported a considerable increase in expired CO


levels during that period.   Likewise, the passenger  compartment of


vehicles provides a potentially hazardous occupational area.  Carbon

monoxide may  enter this compartment from faulty or damaged exhaust


systems or from  the air surrounding roadway  traffic.  Carbon monoxide


levels in the compartment may  be higher than those found outside the


vehicle.  Haagen-Smit   found  average concentrations in a vehicular
                                   3
passenger compartment to be  42 mg/m  on a  Los Angeles freeway during
                                                      3
rush hour traffic  (higher concentrations up  to  80 mg/m  have been  report-


ed recently).  It  has been  reported that concentrations in excess  of

        3
115 mg/m  occur  in some vehicle  interiors.
                                    11-79

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     Direct measurement of COHb in firefighters engaged in fighting



fires of extremely long duration indicated that 10 percent of these


                                                    78
individuals had COHb values in excess of 10 percent.     Sammons and


       184
Coleman    reported that firefighters had changes in those enzymes



related to myocardial damage and that these changes were related to



their COHb levels.  However, the high levels of COHb in their control



(non-firefighters) and test (firefighters) groups make their conclusions



somewhat suspect.



     Besides contributing to exposure of employees to CO, industry also



contributes to the pollution of the surrounding atmosphere.   Gas generator



plants,157 smelters,150 steelworks,33'117'140 plastic works,23 electric



power generating plants,   and mines    have all been suggested as



sources of environmental CO pollution.  Workers in a cast iron foundry



were also found to have high COHb levels associated with various CNS and
                         co

cardiovascular disorders.    Hernberg et al.    evaluated 1000 foundry



workers who were exposed to CO, heat, and strenuous physical work.  The



presence of angina pectoris showed a clear dose-response relation with



regard to CO exposure from either occupation or smoking, or both.



     Rural work establishments, especially those involving intensified



livestock production facilities, can produce high ambient levels of CO.


                                             3

Carbon monoxide concentrations up to 229 mg/m  have been found in these



facilities, with both the animals and workers having high levels of


     153
COHb.     Recreational facilities may also be problem areas.  Excessive



levels of CO were found in ice-skating arenas where ice- resurfacing


                                               3

machines were used.  Levels as high as 348 mg/m  (400 ppm) CO were found
                                   11-80

-------
in such an arena after complaints of  illness  in children  skating  there



were reported to the local health department.     Johnson et al.116a



reported on eight school children who became  sick from CO while in a



school bus.  Subsequent testing  for ambient CO concentrations  in  school



buses showed that 36 percent of  bus interiors tested  had  levels of CO in           7



excess of  EPA standards for an 8-hour exposure.  Improperly regulated



space heaters in enclosed  areas  can also  produce high concentrations of


                 ?fi
CO.  Bondi et al .   reported that on  a  submarine patrol of 40  days the



COHb levels of  subjects were 2.1 and  1.7  percent at the beginning and



end of the patrol .



     The belated discovery that  at  least  one  chemical substance utilized



 in industry and commerce  is degraded  within the body  to CO has potentially



 significant epidemiological and  clinical  implications.  Halogenated



 hydrocarbons  have been widely  utilized  as organic solvents, replacing


                                           195
 carbon tetrachloride.  A  chance  observation     indicated  that  the inha-
 lation of one of these,  dichloromethane (methyl ene di chloride,



 was followed by a sustained elevation of COHb concentration.   Inhalation



 of 500 to 1000 ppm of CH^CK (Industrial Threshold Limit Value  is  500  ppm)



 for one or two hours resulted in COHb levels exceeding 14 percent.



 This elevation of COHb continued beyond the time of exposure  and gradually



 returned to normal during the next 24 hours.  Fodor and Roscovanu



 exposed human volunteers to 500 ppm CH2C12.  After eight hours  of  exposure,



 COHb levels were approximately 12 percent.   Exposure to 100 ppm resulted



 in raising COHb levels to 5 percent.   Elimination of CO was slow,  so



 that 24 to 26 hours were required to reestablish the control  COHb  levels.
                                    11-81

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Residual alterations in pulmonary function were still noted three months

later.

     Several investigators have studied the influence of CHpClp on

physiological function.  Astrand et al.   examined the effects of ChLClp

on work performance.  Central nervous system depression was observed in
              196          217
some subjects.      Winneke    compared the effects of exposure to
                          3
ambient CO (up to 115 mg/m ) and CHCl  on vigilance performance.
Although he noted no effects related to CO, he found a striking decre-

ment in vigilance consequent to ChLClp exposure.   A potentially more

dangerous complication of CHpCK exposure has been indicated by Stewart
         192
and Hake:  ^

     "... because it is so sustained following exposure, the cardio-
     vascular stress produced by elevated COHb levels, derived from
     CH2C12 metabolism, is greater than that resulting from equally high
     CORb levels derived from CO."

They report on an individual who experienced three episodes of myocardial

infarction, each following the use of a paint remover.  About 80 percent

of CH2C12 is metabolized to Co;55»68>127»148»172»179 the mechanism

                                      179
remains to be elucidated.  Roth et al .    have noted that animals rarely
succumb to CHpClp (11,520 ppm), possibly because of saturation of the

pathways by ChLClp metabolism and/or rates of CO excretion.

     The possible detrimental health effects of chemical compounds that

may be metabolized to CO deserve further investigation.

11.9  SUMMARY

     From the foregoing review of the literature pertaining to the

effects of low- level CO exposures of humans and experimental animals,
                                   11-82

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it may be concluded that CO deleteriously affects mainly the cardiovascular
and central nervous systems.  While many data are ambiguous, poorly
documented, and often in dispute, it still seems safe to conclude that
cardiovascular effects can be demonstrated with CO exposures as low as 17 to
       o                                    '       	'"
21 mg/m  CO (15 t^JJB ppm CO for an 8-hour exposure; 2.5 to 3.0 percent COHb).
For behavioral and CNS effects, a minimum of 29 to 34 mg/m3 CO (25 to 30 ppm
CO; 4 to 6 percent COHb) seems to be required.  Visual sensitivity might be
affected as a continuous dose-response function without an obvious CO
threshold, but such data are presently tenuous.
     There are important data to be acquired before an appraisal can be made
of the general health effects of CO.  Fragments of data seem to point to the
importance of CO and its interactions with other pollutants with which it
commonly occurs.  Far too little information exists regarding the effects of
exposures  to CO in combination with other pollutants, as opposed to the
effects of CO by itself.
     There are suggestions that CO might interact with drugs in a significant
way.  Apparently fetuses, health-impaired individuals, individuals under the
influence  of drugs, and persons not previously adapted to high altitudes or CO
exposures  are at special risk, but the nature of the risk, much less its
magnitude, cannot even be estimated from the present literature.
                                                        3
     It appears that acute CO exposures to 17 to 21 mg/m  (15 to 18 ppm)
may^be adverse to human health.  This range of values represents the
level at which the first detectable effect occurs in persons with
                                    11-83

-------
cardiac impairment.   The question of the significance of this and other



findings is a matter of general dose-response functions.  While only



preliminary information is available on this subject, as discussed



above, the findings in the present literature may be summarized in



Table 11-9.  These data are of little use, however, if drugs and other



pollutants alter the responses of individuals who have multiple



impairments.  It represents a minimum known set of effects which could



under some circumstances be much worse or which could occur at lower



thresholds.  Further data are urgently needed.
                                   11-84

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       TABLE 11-9.   ESTIMATED HEALTH EFFECTS LEVELS FOR CARBON MONOXIDE EXPOSURE*
Effects
Approximate Ambient
CO levels to produce
COHb concen- stated COHb, mg/m
tration, % in resting individuals Reference
Ref.
No.

                                   1-hour
                                            8-hour
Physiologic norm

Passive smoking**
aggravates angina
pectoris
                0.30-0.7

                1.8-2.3
  0              0          Coburn, et al.,  1969   222.

(29-70 ppm)    (6-15 ppm)   Aronow, 1978           2b.
Decreased excercise   2.5-3.0
capacity in patients
with angina pectoris,
intermittent claudi-
cation, or peripheral
arteriosclerosis

Impairment of vigi-   3.0-6.5
lance tasks in
healthy experimental
subjects

Increased angina***
attacks for freeway
travel

Impairment of myocardial**
function in patients with
coronary heart disease

Decreased exercise
performance in normal
persons

Decreased exercise
performance in
patients with chronic
obstructive pulmonary
disease

Linear relationship   5-20
between COHb and
decreasing maximal
oxygen consumption
during strenuous
exercise in young
healthy men

Statistically signi-
ficant diminution of
visual perception,
manual dexterity or
ability to learn
                             79-97
                             (70-85 ppm)
                             97-239
                             (85-207 ppm)
               17-21        Aronow and Rokaw, 1971 9.
               (15-18 ppm)  Anderson et al., 1973  2.
                            Aronow and Isbell,1973 5.
                            Aronow et al.,  1974    6.
               21-52        Horvath et al., 1971   107.
               (18-45 ppm)  Groll-Knapp et al.,    85.
                              1972
                            Fodor et al., 1972     67.

                            Aronow et al., 1972    7.
                                                         Aronow et al.,  1974    8.
                                                         Aronow and  Cassidy, 1975
                                                         Aronow et al., 1977    4.
                             176-887        38-193       Ekblom et al., 1972    59.
                             (155-175 ppm)  (33-170 ppm) Horvath, et al., 1975  108.
                                                         *Ayres, Papers         14,15
                                                         Bender et al., 1971    22.
**

***
High variability in COHb levels is found between  individuals exposed to  similar CO  levels.
Partial effects may be due to other pollutants found  in cigarette  smoke.
Partial effects may be due to other pollutants found  in automotive exhaust  and
the ambient air.
                                             11-85

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162.    Pankow, D., B. Pankow, and W. Ponsold.  Are there adaptation  reactions
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163.   Pankow, D., W. Ponsold, and  H.  Fritz.   Combined effects  of carbon
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163a.  Parvlng, H.-H.  The effect of  hypoxla and  carbon monoxide  exposure  on
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164.   Petrov, P.  Chronic CO intoxications  in Workers engaged  1n loading  and
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170.   Ramsey, J. M.  Carbon monoxide, tissue  hypoxia,  and sensory  psychomotor
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173.   Raven, P.  B., B. L. Drinkwater, S.  M. Horvath,  R.  0. Ruhling, J.  A.  Gliner,
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                                      11-99

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174.    Raven, P. B., B. L. Drinkwater, R. 0.  Ruhling,  N. W.  Bolduan,  S.  Taguchi,
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182.    Russell, M. A.  H., P.  V. Cole, and E.  Brown.  Absorption  by non-smokers
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183.    Salvatore, S.   Performance decrement caused  by  mild carbon monoxide
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184.    Sammons, J. H., and R. L. Coleman.  Firefighters' occupational  exposure
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185.    Sayers,  R. R.,  W.  P. Yant, E.  Levy, and W. B. Fulton.   Effect  of Repeated
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187.   Sedov, A. V., L.  I. Zhukova,  and G.  E.  Mazneva.   Carbon monoxide excretion
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188.   Smith, J. R., and S.  A.  Landaw.   Smokers'  polycythemia.   N. Engl.  J.
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190.   Sofoluwe, G. 0.   Smoke pollution in  infants with bronchopneumonia.
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191.   Srch, M.  The significance  of carbon monoxide  in cigarette smoke  in
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192.   Stewart, R.  D., and C.  L. Hake.   Paint-remover hazard.   J.  Am.  Med.
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193.   Stewart, R.  D., P.  E. Newton, M.  J.  Hosko, and J.  E.  Peterson.   Effect of
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194.   Stewart, R.  D., C.  L. Hake, A. Wu, T.  A.  Stewart, and J. H. Kalbfleisch.
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195.   Stewart, R.  D., T.  N. Fisher, M.  J.  Hosko, J.  E.  Peterson, E.  D.  Baretta,
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196.   Stewart, R.  D., T.  N. Fisher, M.  J.  Hosko, J.  E.  Peterson, E.  D.  Baretta,
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197.   Stewart, R.  D., J.  E. Peterson, E. D.  Baretta, R. T.  Bachand, M.  J. Hosko,
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198.   Stewart, R.  D., E.  0. Baretta, L.  R. Platte, E.  B. Stewart, J.  H.
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199.    Stewart, R. D., E. D. Baretta, L. R. Platte, E. B. Stewart,  J.  H.
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202.    Tiunov, L. A., and V. V. Kustov.  Toxicology of carbon monoxide.
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207.    Vogel, J. A., and M. A. Gleser.  Effect of  carbon  monoxide on oxygen
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208.    Vogel, J. A., M. A. Gleser, R. C. Wheeler,  and B.  K.  Whitten.   Carbon
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209.    Vollmer, E. P., B. G. King, J. E. Birren, and M. B. Fisher.   The effects
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209a.  Wagner, J. A., S. M. Horvath, G. M. Andrew, W. H.  Cottle,  and J. F.  Bedi.
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210.    Wagner, J. A., S. M. Horvath, and T. E. Dahms.  Cardiovascular  adjustments
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210a.   Wald, N., and S. Howard.   Smoking,  carbon  monoxide and arterial  disease.
       Ann. Occup. Hyg. 18:1-14,  1975.

211.   Wald, N., S. Howard, P. G.  Smith, and  K. Kjeldsen.   Association  between
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212.   Wallace, N. D., G. L.  Davis,  R. B.  Rutledge,  and A.  Kahn.   Smoking and
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213.   Weber, A., C. Jermini,  and E. Grandjean.   Effects of low carbon  monoxide
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215.   Weir, F. W., M. M. Mehta,  D.  F. Johnson, D. M. Anglen,  T.  H.  Rockwell,
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216.   Weiser, P. C. , C. G. Merrill, D. W.  Dickey, T.. L.  Kurt,  and G. J.  A. Cropp.
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219.   Wright, G., P. Randell, and R. J. Shephard.   Carbon  monoxide  and driving
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220.    Yabroff, I., E. Myers, V. Fend, N. David, M. Robertson, R. Wright,  and
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       August 1977.
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                             APPENDIX A: GLOSSARY

Abscissa:  The horizontal or x axis of a graph.
Abscission:  The process of cutting off, as in the dropping of leaves.
Absorbance:  The ability of a layer of a substance to absorb light
     or other radiation, expressed mathematically as the negative
     logarithm of the fraction of light intensity transmitted.
Absorptivity:  The absorbance of a solution of unit concentration in a
     layer of unit thickness.
Adiabatic:  A process occurring without loss or gain of heat.
Adrenaline:  British name for epinephrine, a potent stimulator of the
     autonomic nervous system.
Adsorption:  The adhesion of molecules in an extremely thin layer to
     the surfaces of solids or liquids with which they are in
     contact.
Alveolar:  Pertaining to the alveoli or small air pockets of the lungs.
Alveolar-arterial pressure difference (A-aDQp):  Difference in oxygen
     pressure between the lung alveoli and the arterial blood.
Ambient air:  The surrounding, well-mixed air.
Aminotransferase:  Any of a class of enzymes that catalyzes the transfer
     of an ami no group from one molecule to another, typically
     from an alpha-ami no acid to an alpha-keto acid.
d-Amphetamine:  A central nervous system stimulant.
Anaerobic:   Living, or active, in the absence of free oxygen.
Anemia:  A reduction below normal in the number of erythrocytes
     (red blood cells) per cubic millimeter, in the quantity of hemoglobin,
     or in the volume of packed red cells per 100 mi 11ilHers of blood.
Angina pectoris:  A paroxysmal thoracic pain, with a feeling of
     suffocation and impending death, due usually to anoxia of the
     heart muscle, and precipitated by effort or excitement.
                                      A-l

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Angiogram:  An Xray picture of a blood vessel filled with a contrast
     medium.
Angstrom:  A unit of wavelength of light, equal to one ten-billionth
     of a meter, or 10   cm.
Anoxia:  Absence or lack of oxygen; reduction of oxygen in body
     tissues below physiologic levels.
Anthropogenic:  Relating to the impact of man and his activities on
     the natural world.
Aortic intima:  Innermost lining of the aorta (main trunk from which
     the body arteries proceed).
Arteriosclerotic heart disease (ASHD):  Sclerosis and thickening of
     the walls of small arteries (arterioles) of the heart.
Asanguineous:  Bloodless; the blood is replaced by another fluid.
Atheroma:  A mass of plaque of degenerated, thickened arterial lining
     occurring in atherosclerosis.
Atheromatosis:  The process involving fatty degeneration of the inner
     coat of an artery.
Autonomic nervous system:  The portion of the nervous system concerned
     with regulation of the activity of the heart muscle, the smooth
     muscle, and the glands; self-regulatory.
Autotrophic:  Needing only carbon dioxide or carbonates as a source
     of  carbon, and a simple inorganic nitrogen compound for metabolic
     synthesis.
Auxin:   Plant "hormone" that promotes growth in plant cells and tissues.
Bacteroids:  Enlarged, branched bacteria found in the nodules of
     leguminous plants.
Ballistocardiogram (BCG):  Tracing from the apparatus for recording
     the movements of the body due to the heartbeat.
Biosphere:  The part of the world in which life can exist.
C3 type  plant:  A type of plant in which the first stable product of
     photosynthesis is a compound containing three carbon atoms, namely
     phosphoglyceric acid.
                                     A-2

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Cannabis sativa:  Hemp; contains cannabinol, an  hallucinogenic
     variously called bhang, ganja, hashish, or  marihuana.

Carboxyhemoglobin (COHb):  The compound formed by the combination of
     carbon monoxide with hemoglobin.

Carboxymyoglobin (COMb):  The compound formed by the combination of
     carbon monoxide with myoglobin.

Carcinogenesis:  The development of a carcinoma, a malignant new
     growth of epithelial cells.

Cardiac index:  The rate of blood pumping by the heart, divided by
     the surface area of the body; expressed in  units of liters per
     minute per square meter.

Cardiovascular:  Pertaining to heart and blood vessels.

Catecholamine:  One of a group of compounds having a sympathomimetic
     action such as norephinephrine, epinephrine, and dopamine.

Catheter:  a tubular, flexible surgical instrument for withdrawing
     fluids from, or introducing fluids into, a  cavity of the body.

Central nervous system (CNS):  Brain and spinal  cord together.

Cerebral blood flow (CBF):  Blood flow through the cerebrum or main
     portion of the brain.

Cerebral cortex:  Outer  layer of the brain.

Cerebrovascular:  Refers to blood vessels of the brain.

Chemical kinetics:  The  study of the rate or speed at which one
     chemical substance  is converted into another.

Chemiluminescence:  Light emitted during a chemical reaction.

Chemoreceptor:  Specialized cells adapted for excitation by chemical
     substances, such as found in the senses of  smell and of taste.

Chronaxie:  The minimum  time an electric current must flow at a voltage
     twice the minimal potential necessary for stimulation for the muscle
     to contract.

Claudication:  Limping or lameness; a complex of symptoms frequently
     associated with occlusive arterial diseases of the limbs.

Colorimetric:  A type of chemical analysis in which the amount of a
     chemical substance  present is found by measuring the light
     absorption due to its intrinsic color or the color of another
     substance into which it can be completely converted.

Contingent negative variation (CNV):  Slow-wave  brain potentials
     evoked by a stimulus.

Coronary:  Pertaining to the arteries and veins  of the heart.


                                 A-3

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Coulometric:   A type of chemical analysis in which the amount of a
     substance present is determined by causing it to undergo an
     electrochemical reaction and measuring the amount of electricity
     needed to carry the reaction to completion.

Critical flicker fusion frequency (CFEF):  The frequency at which
     intermittent flashes of light appear as a steady or continuous
     light.

Cynomolgus:  Monkeys of the genus Macaca, particularly the species
     M. irus, used in laboratory research.

Cytochrome:  Iron-containing respiratory pigment for intracellular
     oxidation.

Cytochrome oxidase:  A blood protein enzyme found in cells, usually
     attached to mitochondria (rod-shaped organelles), associated
     with copper.
                                             -18
Debye:  A unit of electric moment equal to 10    stat coulomb-
     centimeter; a measure of the electrical asymmetry of a molecule.

Diastole:  The dilatation of the heart, filling the ventricles with
     blood.

Diffusion:  The process by which particles of gases, liquids, or
     solids intermingle as a result of their spontaneous movement
     caused by thermal agitation, and move from a region of higher
     concentration to a region of lower concentration.

Diurnal:  Having a daily cycle.

Dyspnea:  Difficulty of breathing; labored breathing.

Electrocardiogram (EKG):  A tracing made by an electrocardiograph
     which measures changes of electrical potential occurring during
     the heartbeat.
                                     A-4

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Elution:  The release or removal of a substance by a solvent, from
     a material which had retained the substance for a time.

Endogenous:  Originating within the organism.

Epicotyl:  The upper portion of an plant embryo or seedling.

Epidemiology:  The study of the relationships of the various factors
     determining the frequency and distribution of diseases in a
     human community.

Epinasty:  The downward curling or curving of a foliage leaf.

Equivalent Method:  A method of sampling and analyzing air for a
     pollutant that has been officially designated as an equivalent
     method by the Environmental Protection Agency.  It must have a
     consistent relationship to a reference method when both methods
     are used to measure the concentration of the pollutant in a
     real atmosphere.

Ergometer:  An apparatus measuring the work performed by a group of
     muscles.

Erythrocyte:  Red blood cell (corpuscle).

Erythropoiesis:  The formation of erythrocytes (red blood cells).

Erythropoietin:  Substances regulating the production of red blood
     cells.

Ethanol:  Ethyl alcohol.

Etiolation:  Paleness due to the exclusion of light.

Etiology:  Pertaining to the factors that cause disease and the method
     of  their introduction to the host; the sum of knowledge regarding
     causes.

Exogenous:  Originating from outside the organism.

Exothermic reaction:  A chemical transformation in which heat or other
     energy is liberated.

Fibrillation (cardiac):  Rapid, irregular contractions of the muscle
     fibers of the heart.

Fourier  transform spectroscopy:  An improved method for obtaining
     absorption spectra of high quality.  All of the available radiant
     energy is sent continuously through the sample (in contrast to
     conventional instruments in which only a very narrow band of
     wavelengths is used at any moment, the remainder being discarded)
     and the absorption spectrum is reconstructed by optical and
     mathematical processing.
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Gas chromatography:  A method of chemical analysis in which a mixture
     of gases or vapors is separated into its components by passage
     (in an inert carrier gas) through a column of material which
     interacts more or less strongly with the individual components,
     retaining them for longer or shorter times before release into
     the effluent gas stream.

Gaussian distribution:  Synonymous with normal distribution.

Globin:  The protein constituent of hemoglobin.

Glycolysis:  The breakdown of glycogen or glucose into lactic acid.

Haldane constant:  Ratio of the stability constant for carboxyhemoglobin
     to that for oxyhemoglobin; a measure of the relative affinity of
     hemoglobin for carbon monoxide as compared to its affinity for
     oxygen.

Half-time:  The time required for the concentration, or amount, of
     a substance to decrease to half its initial value.

Hectare:  A metric measure of area containing 10,000 square meters
     (2.471 acres).

Hematocrit:  The volume percentage of erythrocytes (red blood cells)
     in whole blood.

Hemoglobin (Hb):   Iron-containing protein respiratory pigments
     occurring in the red blood cells of vertebrates and transporting
     oxygen to the tissues and carbon dioxide from the tissues.

Hemopoiesis:  Hematopoiesis, the formation and development of
     blood cells.

Hexobarbital:  A sedative and an hypnotic.

Histopathology:  Pertaining to diseased tissues of the body.

Hopcalite:  A catalyst for converting carbon monoxide to carbon
     dioxide, which consists of a mixture of oxides of copper, cobalt,
     manganese, and silver.

Hydrocyanic acid (HCN):  An aqueous solution of hydrogen cyanide; a
     poisonous liquid used chiefly in fumigating and in organic syntheses

Hydroxyl radical:  Unstable, electrically neutral fragment of a
     molecule containing one oxygen atom and one hydrogen atom.  It
     is formed by disruption of a water (or other hydroxyl-containing)
     molecule, as a result of exposure to far ultraviolet light or
     other high-energy radiation such as Xrays.
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Hyperpnea:   Abnormal increase in the depth and rate of the respiratory
     movements; heavy or labored breathing.
Hypertrophy:  The enlargement or overgrowth of an organ or part due
     to an increase in size of its constituent cells.
Hypobaric hypoxia:  Deficiency of oxygen due to less than normal pressure.
Hyponasty:   The upward curling or curving of a foliage leaf.
Hypothalamus:  Part of the brain; has many functions, e.g., regulation
     of water balance, body temperature, sleep, food intake, and
     development of secondary sex characteristics.
Hypothermia:  Abnormally low temperature.
Hypoxemia:   Deficient oxygenation of the blood; hypoxia.
Hypoxia:  Low oxygen content or tension.  Anemic hypoxia is due to
     reduction of the oxygen-carrying capacity of the blood as a result
     of a decrease  in the total hemoglobin or an alteration of the
     hemoglobin constituents.
Hypoxic hypoxia:  A term used to denote hypoxia due to low oxygen tension
     to distinguish it from that due to carboxyhemoglobin in which CO
     replaces 02-
Intercalated disks:  Short lines or V-shaped stripes extending across
     the fibers of  heart muscle.
Intraperitoneal:  Within the body cavity.
In vitro:  Outside  the living organism.
Jn vivo:  Within the living organism.
Ischemia:  Deficiency of blood:  myocardial ischemia, deficiency of
     blood supply to the heart muscle.
Isopleth:  On a map, a line connecting points at which a particular
     variable has a specified constant value.
Lactate dehydrogenase (LDH):  An enzyme that catalyzes the dehydrogenation
     of alpha hydroxy acids to alpha keto acids;  in certain cases,
     specifically restricted to lactate.
Leghemoglobin:  A pigment found in leguminous root nodules.
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Leucine aminopeptidase:   A proteolytic enzyme that catalyzes the hydrolysis
     of peptide linkage involving the ami no acid, leucine.

Lipids:  Various substances including fats, waxes, phosphatids,
     cerebrosides and related or derived compounds.

Lognormal:   A type of statistical distribution in which the logarithm
     of a variable has a normal distribution, in contrast to the
     familiar case in which the variable itself has a normal distribution.

Methylene chloride (Dichloromethane; CH^CK):  A compound which causes
     an elevation of carboxyhemoglobin; a commercial solvent.

Microflora:   Microscopic plant life; bacteria.

Microglial:   Pertaining to the microglia, small non-neural, interstitial
     cells that form part of the supporting structure of the central
     nervous system.

Microwave rotational spectroscopy:   A method for chemical analysis
     of gases by measuring the absorption of electromagnetic radiation
     in the centimeter wavelength region, which is based on the
     characteristic rotational frequency of the specific gas molecule.
                                o
Milligrams per cubic meter (mg/m ):   A measure of concentration of a
     substance.  In this instance,  the weight in milligrams of CO
     contained in one cubic meter of the ambient air, which may be
     converted to "parts per million" at one atmosphere by
     multiplication by the factor 0.873 at 25 C, or by the factor 0.800
     at 0 C.  At pressures other than one atmosphere (760 torr) such a
     factor should be multiplied by an additional factor of 760/p,
     where p is the ambient pressure in torr.

Mitochondria:  Small organelles found in the cytoplasm of the cell
     and which are concerned with cellular metabolism.

Mixing ratio:  The ratio of the mass of a substance (such as water
     vapor) in an air sample, to the total mass of all the other
     substances in the same air sample.

Mole:  Gram molecular weight.  The amount of a substance represented
     by writing "grams" after its molecular weight (the sum of the
     atomic weights of all the elements in its formula).  One mole
     of any substance contains 6.02 x 10   molecules.
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Mossbauer spectroscopy:  A method for chemical analysis and structure
     studies, based on small variations (due to chemical and physical
     factors) in the energy of gamma rays emitted by radioactive atoms.

Myelin:  A lipid substance forming a sheath around some nerves.

Myocardial infarction:  A necrotic (dead) area of the heart muscle.

Myocardium:  Muscle of the heart.

Myocardosis:  Disorder of the middle, thick muscle layer of the
     heart wal1.

Myoglobin:  A protein found in muscle fibers, which is similar to
     hemoglobin in its reversible binding of oxygen.

Necrosis:  Localized death of living tissue.

Neonate:  A new-born infant.

Normal distribution:  A type of  statistical distribution in which the
     set of values obtained in a large number of independent repetitions
     of a measurement can be represented by a symmetrical bell-shaped
     curve.

Nuclear magnetic resonance:  A type of radiofrequency spectroscopy
     used for chemical analysis  and molecular probes, based on small
     changes (caused by nearby electrons) in the magnetic energy levels
     shown by certain atomic nuclei.

Orsat:  An apparatus or method for chemical analysis of gas mixtures,
     in which each gas successively is removed from the sample by an
     appropriate chemical reagent, and the decrease in volume or
     pressure is measured after  each step.

Oxygen partial pressure (P02):   The amount of pressure exerted by

     oxygen as one component of  a mixture of gases, equal to the
     pressure it would exert if  it were alone in the same container.
     The total pressure of a gas mixture is the sum of the partial
     pressures of the individual gases.

Oxyhemoglobin:  The compound formed by the combination of oxygen with
     hemoglobin.

Oxymyoglobin:  The compound formed by the combination of oxygen with
     myoglobin.

Paradigm:  An example or pattern.
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Parts per million (ppm):   A measure of concentration of a substance.  In
     this instance, the volume in liters of CO contained in 1,000,000
     liters of the ambient air, which may be converted to "milligrams
     per cubic meter" by multiplication by the factor 1.145 at 25 C,
     or by the factor 1.250 at 0 C.   At pressures other than one
     atmosphere (760 torr) such a factor should be multiplied by an
     additional factor of p/760, where p is the ambient pressure in
     torr.

Pathology:  Study of the structural  and functional changes produced
     by diseases, e.g., abnormalities.

Photic:  Pertaining to light.

Photochemistry:  Study of the effects of light, ultraviolet rays,
     or other radiant energy in causing conversion of one chemical
     substance into another.

Photolysis:  Disruption of a molecule caused by exposure to ultraviolet
     or other radiation energy.

Photometry:  Measurement of light intensity; can be used for chemical
     analysis by measuring the intensity change caused by characteristic
     absorption or emission of radiant energy due to a chemical compound.

Planck's Radiation Law (hv = E):  Planck's constant (h) times the
     frequency of radiated energy (v) equals quanta of energy (E).

Plume:  An elongated mobile column,  as of smoke or exhaust gases.

Porphyrin:  Iron-free pyrrole derivatives which form the basis for
     respiratory pigments.

Postpartum:  Following parturition or giving birth to offspring.

Primordia (flower):  Earliest stage in the development of the flower.

Protoporphyrin:  An iron-free derivative of hematin,
     which together with globin forms hemoglobin.

Psychomotor:  Pertaining to motor effects of cerebral or psychic
     activity.

Psychotropic:  Exerting an effect upon the mind; usually applied to
     drugs that affect the mental state.

Pyrrole:  A liquid, weakly basic, cyclic substance (CJH-NH) obtained
     in the destructive distillation of various animal substances.
                                     A-10

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Radicals:   Unstable fragments of molecules which have an unpaired
     electron and tend to react or change rapidly into more stable
     substances.

Rapid eye movement (REM):  An indication that the sleeping subject
     has entered one of several "stages" characteristic of normal
     sleep.

Reference method:  The method of sampling and chemical analysis for a
     pollutant substance which has been officially designated as
     acceptable by the Environmental Protection Agency; includes a
     specific instrument which must be used in such analysis.

Scavenger:  A chemical substance which removes radicals by a rapid
     reaction, converting them to more stable substances.

Second derivative spectrometer:  An instrument for detecting weak
     absorption peaks by electronic processing of spectral intensity
     measurements, to yield the rate of change of the slope of the
     absorption spectrum plotted as a function of wavelength.   This makes
     the peaks much more visible.

Sequela (ae):  A lesion or affection following or caused by an
     attack of disease.

Sickle-cell anemia:  A disease marked by anemia and by ulcers and
     characterized by the red blood cells of the patient acquiring
     a sickle-like or crescentic shape i_n vitro; the disease is
     apparently confined to the negro race and it is hereditary.

Sigmoid:  Shaped like the letter S.

Sink:  An absorber of a substance, or a process which acts as a
     removal or dissipation mechanism.

Soret:  Intense peaks of light absorption shown by hemoglobin and
     related compounds, in the spectral region of about 400 to 440
     nanometers; named for the discoverer.

Spectrophotometer:  An instrument for measuring the relative light
     intensities (or absorption of light) at different wavelengths
     in a spectrum; used for chemical analysis of substances which
     have characteristic colors or absorption spectra.

Stoichiometric:  The amount of a chemical substance theoretically
     needed to react with, or produced by a reaction from, a specified
     amount of another substance, as expressed quantitatively by the
     chemical equation for the reaction.
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Stratosphere:   An upper region of the earth's atmosphere, above about
     10 to 16 kilometers, in which clouds are rare and there is little
     change of temperature with altitude.

Superior colliculus:  A portion of the brain primarily concerned
     with visual responses.

Synergism:  The joint action of agents so that their combined effect
     is greater than the algebraic sum of their individual effects.

Systole:  Contraction of the heart, forcing the blood out through the
     arteries.

Teratology:  Science that deals with abnormal development of the fetus,
     and congenital malformations.

Terpene:  A type of hydrocarbon found in plant oils, resins, and balsams,
     such as those produced by pine or other conifers.

Torr:  A unit of pressure equal to 1/760 of an atmosphere, roughly equal
     to one millimeter of mercury in the Torr i eel li barometer, or 1333
     dynes per square centimeter.

Tropopause:  The region of the earth's atmosphere which marks the
     transition from the troposphere below to the stratosphere above,
     at an altitude of about 10 to 16 kilometers, depending on latitude,
     season, and weather.

Troposphere:  The portion of the earth's atmosphere which extends from
     the surface out to an altitude of about 7 to 10 miles or 10 to 16
     kilometers.

Valence electrons:  The electrons in the outmost shell  of the atom
     which determine the extent to which an atom may combine with
     other atoms.

Vascular:  Of or pertaining to the blood vessels.

Vasodilation:  Dilation of a blood vessel, increasing the blood flow.
Vigilance:  A stage of alertness requiring continuous attention over
     long periods of time.
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Virtual Source:  A point from which divergent beams seem to emanate
     but do not actually do so.

Visual evoked response (VER):  Reaction to a visual stimulus.

White noise:  A heterogeneous mixture of sound waves extending over
     a wide frequency range.

Zoxazolamine:  Skeletal muscle relaxant; promotes excretion of uric
     acid in the urine.
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                                   TECHNICAL REPORT DATA
                            (Please read Instructions on the reverse before completing)
1. REPORT NO.
 EPA-600/8-79-022
             3. RECIPIENT'S ACCESSION NO.
4. TITLE ANDSUBTITLE
  AIR  QUALITY CRITERIA FOR CARBON  MONOXIDE
             5. REPORT DATE
               October 1979
             6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
   Informatics, Inc. and others  listed in the
   document as "Contributors and Reviewers"
             8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
   Informatics, Inc.
   6011  Executive Blvd.
   Rockville, MD. 20852
             10. PROGRAM ELEMENT NO.
             11. CONTRACT/GRANT NO.
                                                              68-02-2799
12. SPONSORING AGENCY NAME AND ADDRESS
             13. TYPE OF REPORT AND PERIOD COVERED
   Environmental Criteria and Assessment Office
   Office of Research and Development
   U.S.  Environmental Protection Agency
   Research Triangle Park, N.C. 27711	
             14. SPONSORING AGENCY CODE
                EPA/600/00
 15. SUPPLEMENTARY NOTES
 16. ABSTRACT
        This document summarizes  current scientific information regarding  carbon
 monoxide (CO) as a component of  the  ambient atmosphere and the effects  of CO upon man
 and  the environment. The observed  effects,  as presented herein, constitute the basis
 for  the criteria upon which the  U.S.  Environmental Protection Agency  (EPA) will review
 the  National  Ambient Air Quality Standard (NAAQS) for CO. In the CO criteria document
 the  following questions have been  addressed:   At what level of CO  in  the  ambient air
 do detectable adverse health effects  occur? What are these adverse health effects?
 What are the  major sources of CO?  Are there synergistic effects from  CO exposure in
 combination with other pollutants  and drugs?  How do ambient concentrations of CO affect
 humans  living at high altitudes? Are  present  monitoring methods adequate  to determine
 human exposure to CO? What are the global effects of increased CO emission into the
 atmosphere? It is in response to these and  related questions that this  document has
 been prepared.
17.
                                KEY WORDS AND DOCUMENT ANALYSIS
a.
                  DESCRIPTORS
b.IDENTIFIERS/OPEN ENDED TERMS
altitude       centra I  nervous system
carbon monoxide   internal combustion engines
air pollution     embryos
human health effects    angina pectoris
atmospheric composition  nitrogen fixation
cardiovascular diseases  plant metabolism
               sickle  cell  anemia
carboxyhemoglobin
nonhypoxic  effects
Denver,  Colorado
New York, New York
Baltimore,  Maryland
Washington, D.C.
CNS effects
claudication
c. COS AT I Field/Group
02A  06T
04B  07C
06A  08A
06C  13B
06E
06F
06P
Q6S
lypoxia
18. DISTRIBUTION STATEMENT
  RELEASE TO  PUBLIC
19. SECURITY CLASS (This Report)
  UNCLASSIFIED
21. NO. OF PAGES
                                              20. SECURITY CLASS (This page)

                                                UNCLASSIFIED
                           22. PRICE
EPA Form 2220-1 (Rev. 4-77)   PREVIOUS EDITION is OBSOLETE
                                             A-14
                    . GOVERNMENT PRINTING OFFICE: 1979 -640 - 0 1 3/ 3931 REGION NO. 4

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