1 January 2010 

2 EPA/600/R-09/019F 

Integrated Science Assessment for 

Carbon Monoxide 

National Center for Environmental Assessment-RTP Division 

Office of Research and Development 

U.S. Environmental Protection Agency 

Research Triangle Park, NC 
January 2010 ii 

Disclaimer 

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

policy and approved for publication. Mention of trade names or commercial products does not 

constitute endorsement or recommendation for use. 
January 2010 iii 

Table of Contents 

TABLE OF CONTENTS______________________________________________________ III

LIST OF TABLES ________________________________________________________ VIII

LIST OF FIGURES ________________________________________________________ XII

CO PROJECT TEAM_____________________________________________________ XVIII

AUTHORS, CONTRIBUTORS, AND REVIEWERS ___________________________________ XX

CLEAN AIR SCIENTIFIC ADVISORY COMMITTEE CO NAAQS REVIEW PANEL ___________ XXIV

ACRONYMS AND ABBREVIATIONS ___________________________________________ XXVI

CHAPTER 1. INTRODUCTION _______________________________________________ 1-1

1.1. Legislative Requirements _______________________________________________________1-2

1.2. History of the NAAQS for CO____________________________________________________4538H1-3

1.3. ISA Development _____________________________________________________________4539H1-4

1.4. Document Organization ________________________________________________________450H1-6

1.5. Document Scope _____________________________________________________________451H1-7

1.6. EPA Framework for Causal Determination__________________________________________452H1-8

1.6.1. Scientific Evidence Used in Establishing Causality_____________________________453H1-8

1.6.2. Association and Causation _______________________________________________45H1-9

1.6.3. Evaluating Evidence for Inferring Causation __________________________________45H1-9

1.6.4. Application of Framework for Causal Determination___________________________456H1-12

1.6.5. Determination of Causality ______________________________________________457H1-13

1.6.5.1. Effects on Human Populations ____________________________________458H1-15

1.6.5.2. Effects on Ecosystems or Public Welfare____________________________459H1-16

1.6.6. Concepts in Evaluating Adversity of Health Effects____________________________450H1-16

1.7. Summary __________________________________________________________________451H1-17

References ____________________________________________________________________452H1-18

CHAPTER 2. INTEGRATIVE OVERVIEW ________________________________________ 453H2-1

2.1. Ambient CO Sources and Concentrations __________________________________________45H2-1

2.2. Climate Forcing Effects ________________________________________________________45H2-2

2.3. Exposure to Ambient CO _______________________________________________________456H2-3

2.4. Dosimetry, Pharmacokinetics, and Mode of Action ___________________________________457H2-4

2.4.1. Dosimetry and Pharmacokinetics __________________________________________458H2-4

2.4.2. Mode of Action_________________________________________________________459H2-4

2.5. Health Effects ________________________________________________________________4560H2-5

2.5.1. Cardiovascular Morbidity_________________________________________________4561H2-5

2.5.2. Central Nervous System Effects ___________________________________________4562H2-6
January 2010 iv 

2.5.3. Birth Outcomes and Developmental Effects __________________________________2-7

2.5.4. Respiratory Morbidity____________________________________________________2-8

2.5.5. Mortality ______________________________________________________________456H2-9

2.6. Policy-Relevant Considerations _________________________________________________456H2-10

2.6.1. Susceptible Populations ________________________________________________4567H2-10

2.6.2. Concentration- and Dose-Response Relationships ___________________________4568H2-12

2.7. Integration of CO Health Effects_________________________________________________4569H2-13

References ____________________________________________________________________4570H2-18

CHAPTER 3. SOURCE TO EXPOSURE _________________________________________ 4571H3-1

3.1. Introduction__________________________________________________________________4572H3-1

3.2. CO Sources, Emissions, and Chemistry ___________________________________________4573H3-1

3.2.1. Direct CO Emissions ____________________________________________________457H3-1

3.2.2. Secondary CO Emissions and Associated Chemistry___________________________457H3-9

3.3. CO Climate Forcing Effects ____________________________________________________4576H3-11

3.4. Ambient Measurements _______________________________________________________457H3-16

3.4.1. Ambient Measurement Instruments _______________________________________4578H3-16

3.4.2. Ambient Sampling Network Design________________________________________4579H3-19

3.4.2.1. Monitor Siting Requirements _____________________________________4580H3-19

3.4.2.2. Spatial and Temporal Coverage___________________________________4581H3-20

3.5. Environmental Concentrations __________________________________________________4582H3-28

3.5.1. Spatial Variability ______________________________________________________4583H3-28

3.5.1.1. National Scale ________________________________________________458H3-28

3.5.1.2. Urban Scale __________________________________________________458H3-37

3.5.1.3. Micro- to Neighborhood Scale and the Near-Road Environment__________4586H3-53

3.5.2. Temporal Variability ____________________________________________________4587H3-62

3.5.2.1. Multiyear Trends_______________________________________________458H3-62

3.5.2.2. Hourly Variation _______________________________________________4589H3-65

3.5.3. Associations with Copollutants ___________________________________________4590H3-68

3.5.4. Policy-Relevant Background _____________________________________________4591H3-72

3.5.4.1. Surface-Based Determinations ___________________________________4592H3-72

3.5.4.2. Limitations of Other Possible Methods______________________________4593H3-74

3.6. Issues in Exposure Assessment_________________________________________________459H3-76

3.6.1. Summary of Findings from 2000 CO AQCD _________________________________459H3-76

3.6.2. General Exposure Concepts _____________________________________________4596H3-76

3.6.3. Exposure Modeling ____________________________________________________4597H3-78

3.6.3.1. Stochastic Population-Based Time-Weighted Microenvironmental 

Exposure Models ______________________________________________4598H3-78

3.6.3.2. Using Spatial Models to Estimate Exposure _________________________459H3-79

3.6.4. Personal Exposure Monitors for CO _______________________________________460H3-82

3.6.5. Indoor Exposure to CO _________________________________________________4601H3-82

3.6.5.1. Infiltration of Ambient CO ________________________________________4602H3-82

3.6.5.2. Exposure to Nonambient CO _____________________________________4603H3-83

3.6.6. Exposure Assessment Studies at Different Spatial Scales ______________________460H3-85

3.6.6.1. Neighborhood to Urban Scale Studies of Ambient CO Exposure _________4605H3-85

3.6.6.2. Microscale Studies of Ambient CO Exposure: Near-Road and On-Road 

Exposures____________________________________________________460H3-87

3.6.7. Association between Personal CO Exposure and Copollutants __________________4607H3-90

3.6.8. Implications for Epidemiology ____________________________________________4608H3-90

3.6.8.1. Measurement Error_____________________________________________4609H3-91

3.6.8.2. Exposure Issues Related to Nonambient CO ________________________4610H3-92

3.6.8.3. Spatial Variability ______________________________________________461H3-92

3.6.8.4. Temporal Variability ____________________________________________4612H3-93
January 2010 v 

3.6.8.5. CO Exposure in Copollutant Mixtures ______________________________4613H3-94

3.6.8.6. Conclusions __________________________________________________461H3-94

3.7. Summary and Conclusions ____________________________________________________4615H3-95

3.7.1. CO Sources, Emissions, and Chemistry ____________________________________461H3-95

3.7.2. Climate Forcing Effects Related to CO _____________________________________4617H3-95

3.7.3. Ambient CO Measurements _____________________________________________4618H3-96

3.7.4. Environmental CO Concentrations ________________________________________4619H3-96

3.7.5. Exposure Assessment and Implications for Epidemiology ______________________4620H3-97

References ____________________________________________________________________4621H3-99

CHAPTER 4. DOSIMETRY AND PHARMACOKINETICS OF CARBON MONOXIDE_____________ 462H4-1

4.1. Introduction__________________________________________________________________4623H4-1

4.2. Carboxyhemoglobin Modeling ___________________________________________________462H4-1

4.2.1. The Coburn-Forster-Kane and Other Models _________________________________4625H4-1

4.2.2. Multicompartment Models ________________________________________________462H4-6

4.2.3. Model Comparison _____________________________________________________4627H4-8

4.2.4. Mathematical Model Usage_______________________________________________4628H4-8

4.3. Absorption, Distribution, and Elimination __________________________________________4629H4-11

4.3.1. Pulmonary Absorption __________________________________________________4630H4-11

4.3.1.1. Mass Transfer of Carbon Monoxide________________________________4631H4-12

4.3.1.2. Lung Diffusion of Carbon Monoxide________________________________4632H4-12

4.3.2. Tissue Uptake ________________________________________________________463H4-13

4.3.2.1. Respiratory Tract ______________________________________________463H4-13

4.3.2.2. Blood _______________________________________________________4635H4-13

4.3.2.3. Heart and Skeletal Muscle _______________________________________463H4-15

4.3.2.4. Other Tissues _________________________________________________4637H4-16

4.3.3. Pulmonary and Tissue Elimination ________________________________________4638H4-17

4.3.4. COHb Analysis Methods ________________________________________________4639H4-18

4.4. Conditions Affecting Uptake and Elimination _______________________________________460H4-19

4.4.1. Physical Activity _______________________________________________________461H4-19

4.4.2. Altitude______________________________________________________________462H4-19

4.4.3. Physical Characteristics ________________________________________________463H4-20

4.4.3.1. Fetal Pharmacokinetics _________________________________________46H4-20

4.4.4. Health Status _________________________________________________________465H4-21

4.5. Endogenous CO Production and Metabolism ______________________________________46H4-22

4.6. Summary and Conclusions ____________________________________________________467H4-26

References ____________________________________________________________________468H4-28

CHAPTER 5. INTEGRATED HEALTH EFFECTS ___________________________________ 469H5-1

5.1. Mode of Action of CO Toxicity ___________________________________________________4650H5-1

5.1.1. Introduction ___________________________________________________________4651H5-1

5.1.2. Hypoxic Mechanisms____________________________________________________4652H5-1

5.1.3. Nonhypoxic Mechanisms ________________________________________________4653H5-2

5.1.3.1. Nonhypoxic Mechanisms Reviewed in the 2000 CO AQCD ______________465H5-2

5.1.3.2. Recent Studies of Nonhypoxic Mechanisms __________________________465H5-3

5.1.3.3. Implications of Nonhypoxic Mechanisms _____________________________465H5-9

5.1.3.4. Summary ____________________________________________________4657H5-12

5.2. Cardiovascular Effects ________________________________________________________4658H5-12

5.2.1. Epidemiologic Studies with Short-Term Exposure_____________________________4659H5-12

5.2.1.1. Heart Rate and Heart Rate Variability ______________________________460H5-13

5.2.1.2. ECG Abnormalities Indicating Ischemia_____________________________461H5-16

5.2.1.3. Arrhythmia ___________________________________________________462H5-17
January 2010 vi 

5.2.1.4. Cardiac Arrest_________________________________________________463H5-18

5.2.1.5. Myocardial Infarction ___________________________________________46H5-19

5.2.1.6. Blood Pressure________________________________________________465H5-19

5.2.1.7. Vasomotor Function ____________________________________________46H5-19

5.2.1.8. Blood Markers of Coagulation and Inflammation ______________________467H5-20

5.2.1.9. Hospital Admissions and Emergency Department Visits ________________468H5-23

5.2.2. Epidemiologic Studies with Long-Term Exposure _____________________________469H5-40

5.2.3. Summary of Epidemiologic Studies of Exposure to CO and Cardiovascular 

Effects ______________________________________________________________4670H5-40

5.2.4. Controlled Human Exposure Studies ______________________________________4671H5-41

5.2.5. Toxicological Studies ___________________________________________________4672H5-44

5.2.5.1. Endothelial Dysfunction _________________________________________4673H5-44

5.2.5.2. Cardiac Remodeling Effects______________________________________467H5-46

5.2.5.3. Electrocardiographic Effects______________________________________4675H5-47

5.2.5.4. Summary of Cardiovascular Toxicology_____________________________467H5-47

5.2.6. Summary of Cardiovascular Effects _______________________________________467H5-47

5.2.6.1. Short-Term Exposure to CO______________________________________4678H5-47

5.2.6.2. Long-Term Exposure to CO ______________________________________4679H5-48

5.3. Central Nervous System Effects ________________________________________________4680H5-49

5.3.1. Controlled Human Exposure Studies ______________________________________4681H5-49

5.3.2. Toxicological Studies ___________________________________________________4682H5-49

5.3.3. Summary of Central Nervous System Effects ________________________________4683H5-49

5.4. Birth Outcomes and Developmental Effects________________________________________468H5-50

5.4.1. Epidemiologic Studies __________________________________________________4685H5-50

5.4.1.1. Preterm Birth _________________________________________________468H5-50

5.4.1.2. Birth Weight, Low Birth Weight, and Intrauterine Growth 

Restriction/Small for Gestational Age_______________________________4687H5-53

5.4.1.3. Congenital Anomalies __________________________________________468H5-60

5.4.1.4. Neonatal and Postneonatal Mortality _______________________________4689H5-61

5.4.1.5. Summary of Epidemiologic Studies of Birth Outcomes and 

Developmental Effects __________________________________________4690H5-63

5.4.2. Toxicological Studies of Birth Outcomes and Developmental Effects ______________4691H5-63

5.4.2.1. Birth Outcomes________________________________________________4692H5-63

5.4.2.2. Developmental Effects __________________________________________4693H5-68

5.4.3. Summary of Birth Outcomes and Developmental Effects _______________________469H5-79

5.5. Respiratory Effects ___________________________________________________________4695H5-81

5.5.1. Epidemiologic Studies with Short-Term Exposure_____________________________469H5-81

5.5.1.1. Pulmonary Function, Respiratory Symptoms, and Medication Use________4697H5-81

5.5.1.2. Respiratory Hospital Admissions, ED Visits and Physician Visits _________4698H5-88

5.5.2. Epidemiologic Studies with Long-Term Exposure _____________________________469H5-96

5.5.2.1. Pulmonary Function ____________________________________________470H5-96

5.5.2.2. Asthma and Asthma Symptoms ___________________________________4701H5-97

5.5.2.3. Respiratory Allergy and Other Allergic Responses ____________________4702H5-98

5.5.2.4. Summary of Associations between Long-Term Exposure to CO and 

Respiratory Morbidity ___________________________________________4703H5-98

5.5.3. Controlled Human Exposure Studies ______________________________________470H5-99

5.5.4. Toxicological Studies ___________________________________________________4705H5-99

5.5.5. Summary of Respiratory Health Effects ___________________________________4706H5-100

5.5.5.1. Short-Term Exposure to CO_____________________________________470H5-100

5.5.5.2. Long-Term Exposure to CO _____________________________________4708H5-101

5.6. Mortality __________________________________________________________________4709H5-101

5.6.1. Epidemiologic Studies with Short-Term Exposure to CO ______________________4710H5-101

5.6.1.1. Summary of Findings from 2000 CO AQCD ________________________471H5-101

5.6.1.2. Multicity Studies ______________________________________________4712H5-101

5.6.1.3. Meta-Analysis of All Criteria Pollutants ____________________________4713H5-106

5.6.1.4. Single-City Studies ____________________________________________471H5-107
January 2010 vii 

5.6.1.5. Summary of Mortality and Short-Term Exposure to CO _______________4715H5-109

5.6.2. Epidemiologic Studies with Long-Term Exposure to CO_______________________4716H5-109

5.6.2.1. U.S. Cohort Studies ___________________________________________471H5-110

5.6.2.2. U.S. Cross-Sectional Analysis ___________________________________4718H5-113

5.6.2.3. Summary of Mortality and Long-Term Exposure to CO ________________4719H5-114

5.7. Susceptible Populations______________________________________________________4720H5-114

5.7.1. Preexisting Disease___________________________________________________4721H5-116

5.7.1.1. Cardiovascular Disease ________________________________________472H5-116

5.7.1.2. Obstructive Lung Disease ______________________________________4723H5-117

5.7.1.3. Diabetes ____________________________________________________472H5-118

5.7.1.4. Anemia _____________________________________________________4725H5-118

5.7.2. Lifestage ___________________________________________________________4726H5-119

5.7.2.1. Older Adults _________________________________________________472H5-119

5.7.2.2. Gestational Development _______________________________________4728H5-120

5.7.3. Gender_____________________________________________________________4729H5-121

5.7.4. Altitude_____________________________________________________________4730H5-121

5.7.5. Exercise____________________________________________________________4731H5-122

5.7.6. Proximity to Roadways ________________________________________________4732H5-122

5.7.7. Medications and Other Substances ______________________________________473H5-123

5.7.8. Summary of Susceptible Populations _____________________________________473H5-123

5.8. Summary _________________________________________________________________4735H5-124

References ___________________________________________________________________4736H5-125

ANNEX A. ATMOSPHERIC SCIENCE __________________________________________ 473HA-1

ANNEX B. DOSIMETRY STUDIES ____________________________________________ 4738HB-1

References ____________________________________________________________________ 4739HB-6

ANNEX C. EPIDEMIOLOGY STUDIES __________________________________________ 470HC-1

References ___________________________________________________________________ 471HC-99

ANNEX D. CONTROLLED HUMAN EXPOSURE STUDIES ____________________________ 472HD-1

References ____________________________________________________________________ 473HD-4

ANNEX E. TOXICOLOGICAL STUDIES _________________________________________ 47HE-1

References ___________________________________________________________________ 475HE-23
January 2010 viii 

List of Tables 

0HTable 1-1. Aspects to aid in judging causality.__________________________________________________________476H1-13

1HTable 1-2. Weight of evidence for causal determination.__________________________________________________47H1-14

2HTable 2-1. Causal determinations for health effects categories. _____________________________________________478H2-5

3HTable 2-2. Range of mean and 99th percentile concentrations (ppm) in US and Canadian studies of 

short-term CO exposure and CVD hospitalizations._____________________________________________479H2-15

4HTable 3-1. Literature values for CO yields from hydrocarbons in per carbon units, except as noted. 

Specific hydrocarbons are noted in parentheses. ______________________________________________4750H3-10

5HTable 3-2. Performance specifications for analytical detection of CO, based on 40 CFR Part 53. __________________4751H3-18

6HTable 3-3. Counts of CO monitors by sampling scale meeting 75% completeness criteria for use in the 

U.S. during 2005-2007. __________________________________________________________________4752H3-21

7HTable 3-4. Proximity to CO monitors for the total population by city._________________________________________4753H3-27

8HTable 3-5. Proximity to CO monitors for adults aged 65 and older by city. ____________________________________475H3-28

9HTable 3-6. Distribution of 1-h avg CO concentration (ppm) derived from AQS data._____________________________475H3-31

10HTable 3-7. Distribution of 24-h avg CO concentration (ppm) derived from AQS data.____________________________4756H3-33

1HTable 3-8. Distribution of 1-h daily max CO concentration (ppm) derived from AQS data. ________________________475H3-34

12HTable 3-9. Distribution of 8-h daily max CO concentration (ppm) derived from AQS data. ________________________4758H3-35

13HTable 3-10. Table of intersampler comparison statistics, as defined in the text, including Pearson r, P90 

(ppm), COD and d (km) for each pair of hourly CO monitors reporting to AQS for 

2005-2007 in Denver, CO. ________________________________________________________________4759H3-40

14HTable 3-11. Table of intersampler comparison statistics, as defined in the text, including Pearson r, P90 

(ppm), COD and d (km) for each pair of hourly CO monitors reporting to AQS for 

2005-2007 in Los Angeles, CA. ____________________________________________________________4760H3-46

15HTable 3-12. National distribution of all hourly observations, 1-h daily max, 1-h daily average, and 8-h 

daily max concentration (ppm) derived from AQS data, based on monitor scale 

designations, 2005-2007. _________________________________________________________________4761H3-53

16HTable 3-13. Percentage of time exposed to ambient CO (adjusted to reflect the absence of nonambient 

CO from ETS and gas cooking), average CO exposures, and percentage of exposure 

estimated for the population. ______________________________________________________________4762H3-86

17HTable 4-1. Predicted COHb levels resulting from 1, 8, and 24 h CO exposures in a modeled human at 

rest ___________________________________________________________________________________4763H4-9

18HTable 4-2. CO concentration in pmol/mg wet weight tissue and fold tissue CO concentration changes 

(normalized to background tissue concentrations) – human.______________________________________476H4-16

19HTable 5-1. Responses to CO exposures at low and moderate concentrations. _________________________________4765H5-8

20HTable 5-2. Tissue concentration of CO following inhalation exposure. _______________________________________476H5-10

21HTable 5-3. Tissue concentration of CO following increased endogenous production.____________________________476H5-11

2HTable 5-4. Summary of studies investigating the effect of CO exposure on HRV parameters._____________________4768H5-16

23HTable 5-5. Summary of studies investigating the effect of CO exposure on cardiac arrhythmias. __________________4769H5-18
January 2010 ix 

24HTable 5-6. Summary of studies investigating the effect of CO exposure on blood markers of 

coagulation and inflammation. _____________________________________________________________470H5-23

25HTable 5-7. Summary of CHD hospital admission studies.a ________________________________________________471H5-28

26HTable 5-8. Summary of stroke hospital admission studies.a _______________________________________________472H5-31

27HTable 5-9. Summary of CHF hospital admission studies. _________________________________________________473H5-33

28HTable 5-10. Association of ambient air pollution levels and cardiovascular morbidity in visits with and 

without specific secondary conditions. _______________________________________________________47H5-34

29HTable 5-11. Summary of nonspecific CVD hospital admission studies.________________________________________475H5-37

30HTable 5-12. Brief summary of PTB studies._____________________________________________________________476H5-53

31HTable 5-13. Brief summary of birth weight studies. _______________________________________________________47H5-59

32HTable 5-14. Behavioral responses. ___________________________________________________________________478H5-69

3HTable 5-15. Neuronal responses. ____________________________________________________________________479H5-72

34HTable 5-16. Neurotransmitter changes. ________________________________________________________________4780H5-74

35HTable 5-17. Developing auditory system. ______________________________________________________________4781H5-76

36HTable 5-18. Cardiovascular and systemic developmental responses._________________________________________4782H5-78

37HTable 5-19. Range of CO concentrations reported in key respiratory morbidity studies that examined 

effects associated with short-term exposure to CO._____________________________________________4783H5-82

38HTable 5-20. Range of CO concentrations reported in key respiratory HA and ED visit studies that 

examine effects associated with short-term exposure to CO. _____________________________________478H5-89

39HTable 5-21. Range of CO concentrations reported in key respiratory morbidity studies that examined 

effects associated with long-term exposure to CO. _____________________________________________4785H5-96

40HTable 5-22. Range of CO concentrations reported in multicity studies that examine mortality effects 

associated with short-term exposure to CO. _________________________________________________4786H5-102

41HTable 5-23. Range of CO concentrations reported in single-city studies that examine mortality effects 

associated with short-term exposure to CO. _________________________________________________478H5-107

42HTable 5-24. Range of CO concentrations reported in U.S.-based studies that examine mortality effects 

associated with long-term exposure to CO. __________________________________________________478H5-110

43HTable 5-25. Range of definitions of “susceptible” and “vulnerable” in the CO literature. __________________________4789H5-115

4HTable 5-26. Adult U.S. population in 2007 with respiratory diseases and cardiovascular diseases._________________4790H5-117

45HTable A-1. Listing of all CO monitors currently in use, along with their limits of detection. ________________________ 4791HA-8

46HTable A-2. Microscale monitors meeting 75% completeness criteria, 2005-2007. ______________________________ 4792HA-9

47HTable A-3. Middle scale monitors meeting 75% completeness criteria, 2005-2007. ____________________________ 4793HA-11

48HTable A-4. Neighborhood scale monitors meeting 75% completeness criteria, 2005-2007. ______________________ 479HA-12

49HTable A-5. Urban scale monitors meeting 75% completeness criteria, 2005-2007. ____________________________ 4795HA-15

50HTable A-6. Regional scale monitors meeting 75% completeness criteria, 2005-2007. __________________________ 4796HA-15

51HTable A-7. Monitors meeting 75% completeness criteria, 2005-2007 with no scale delared. _____________________ 479HA-16

52HTable A-8. Numbers of high LOD and trace-level monitors in each state that met completeness criteria 

for 2005-2007. ________________________________________________________________________ 4798HA-18
January 2010 x 

53HTable A-9. Table of inter-sampler comparison statistics, including Pearson r, P90 (ppm), COD, and d 

(km), as defined in the text, for each pair of hourly CO monitors reporting to AQS in 

Anchorage, AK. _______________________________________________________________________ 479HA-30

54HTable A-10. Table of inter-sampler comparison statistics, including Pearson r, P90 (ppm), COD, and d 

(km), as defined in the text, for each pair of hourly CO monitors reporting to AQS in Atlanta, 

GA. _________________________________________________________________________________ 480HA-33

5HTable A-11. Table of inter-sampler comparison statistics, including Pearson r, P90 (ppm), COD, and d 

(km), as defined in the text, for each pair of hourly CO monitors reporting to AQS in Boston, 

MA. _________________________________________________________________________________ 4801HA-36

56HTable A-12. Table of inter-sampler comparison statistics, including Pearson r, P90 (ppm), COD, and d 

(km), as defined in the text, for each pair of hourly CO monitors reporting to AQS in 

Houston, TX.__________________________________________________________________________ 4802HA-39

57HTable A-13. Table of inter-sampler comparison statistics, including Pearson r, P90 (ppm), COD, and d 

(km), as defined in the text, for each pair of hourly CO monitors reporting to AQS in New 

York City, NY._________________________________________________________________________ 4803HA-42

58HTable A-14. Table of inter-sampler comparison statistics, including Pearson r, P90 (ppm), COD, and d 

(km), as defined in the text, for each pair of hourly CO monitors reporting to AQS in 

Phoenix, AZ.__________________________________________________________________________ 480HA-45

59HTable A-15. Table of inter-sampler comparison statistics, including Pearson r, P90 (ppm), COD, and d 

(km), as defined in the text, for each pair of hourly CO monitors reporting to AQS in 

Pittsburgh, PA. ________________________________________________________________________ 4805HA-48

60HTable A-16. Table of inter-sampler comparison statistics, including Pearson r, P90 (ppm), COD, and d 

(km), as defined in the text, for each pair of hourly CO monitors reporting to AQS in St. 

Louis, MO. ___________________________________________________________________________ 4806HA-53

61HTable A-17. Comparison of distributional data at different monitoring scales for hourly, 1-h daily max, 

24-h avg, and 8-h daily max data for Atlanta, GA. _____________________________________________ 4807HA-55

62HTable A-18. Comparison of distributional data at different monitoring scales for hourly, 1-h daily max, 

24-h avg, and 8-h daily max data for Boston, MA. _____________________________________________ 480HA-55

63HTable A-19. Comparison of distributional data at different monitoring scales for hourly, 1-h daily max, 

24-h avg, and 8-h daily max data for Denver, CO._____________________________________________ 4809HA-56

64HTable A-20. Comparison of distributional data at different monitoring scales for hourly, 1-h daily max, 

24-h avg, and 8-h daily max data for Houston, TX. ____________________________________________ 4810HA-56

65HTable A-21. Comparison of distributional data at different monitoring scales for hourly, 1-h daily max, 

24-h avg, and 8-h daily max data for Los Angeles, CA. _________________________________________ 481HA-57

6HTable A-22. Comparison of distributional data at different monitoring scales for hourly, 1-h daily max, 

24-h avg, and 8-h daily max data for New York City, NY. _______________________________________ 4812HA-58

67HTable A-23. Comparison of distributional data at different monitoring scales for hourly, 1-h daily max, 

24-h avg, and 8-h daily max data for Phoenix, AZ. ____________________________________________ 4813HA-59

68HTable A-24. Comparison of distributional data at different monitoring scales for hourly, 1-h daily max, 

24-h avg, and 8-h daily max data for Pittsburgh, PA.___________________________________________ 481HA-60

69HTable A-25. Comparison of distributional data for hourly, 1-h daily max, 24-h avg, and 8-h daily max 

data for Seattle, WA. ___________________________________________________________________ 4815HA-60

70HTable A-26. Comparison of distributional data for hourly, 1-h daily max, 24-h avg, and 8-h daily max 

data for St. Louis, MO. __________________________________________________________________ 4816HA-61

71HTable B-1. Recent studies related to CO dosimetry and pharmacokinetics. ___________________________________ 4817HB-1
January 2010 xi 

72HTable C-1. Studies of CO exposure and cardiovascular morbidity. __________________________________________ 481HC-1

73HTable C-2. Studies of CO exposure and cardiovascular hospital admissions and ED visits.______________________ 4819HC-17

74HTable C-3. Studies of CO exposure and neonatal and postneonatal outcomes. _______________________________ 4820HC-26

75HTable C-4. Studies of short-term CO exposure and respiratory morbidity ____________________________________ 4821HC-35

76HTable C-5. Studies of short-term CO exposure and respiratory hospital admissions and ED visits. ________________ 482HC-42

7HTable C-6. Studies of long-term CO exposure and respiratory morbidity. ____________________________________ 4823HC-65

78HTable C-7. Studies of short-term CO exposure and mortality. _____________________________________________ 482HC-70

79HTable C-8. Studies of long-term CO exposure and mortality.______________________________________________ 4825HC-94

80HTable D-1. Controlled human exposure studies. ________________________________________________________ 4826HD-1

81HTable E-1. Human and animal studies. _______________________________________________________________ 4827HE-1
January 2010 xii 

List of Figures 

82HFigure 1-1. Identification of studies for inclusion in the ISA. _________________________________________________482H1-5

83HFigure 2-1. Excess risk estimates from epidemiologic studies of short-term CO exposure and CVD 

hospitalizations along with author-reported mean and AQS-derived 99th percentile CO 

concentrations. _________________________________________________________________________4829H2-15

84HFigure 3-1. CO emissions (tons) in the U.S. by source sector in 2002 from the NEI and the BEIS.___________________4830H3-3

85HFigure 3-2. Trends in anthropogenic CO emissions (MT) in the U.S. by source category for 1990 and 

1996-2002. _____________________________________________________________________________4831H3-4

86HFigure 3-3. Surface air CO concentrations at Chebogue Point during the ICARTT campaign. ______________________4832H3-5

87HFigure 3-4. CO concentrations centered at ~3,000 m above sea level measured by the MOPITT sensor 

on the Terra satellite for the period July 15-23, 2004, during intense wildfires in Alaska and 

the Yukon. _____________________________________________________________________________483H3-7

8HFigure 3-5. Trends in subnational CO emissions in the 10 U.S. EPA Regions for 1990 and 1996-2002. ______________483H3-7

89HFigure 3-6. CO emissions density map and distributions for the state of Colorado and for selected 

counties in Colorado in 2002, from the NEI and the BEIS._________________________________________4835H3-8

90HFigure 3-7. Components of RF in 2005 resulting from emissions since 1750. (S) and (T) indicate 

stratospheric and tropospheric changes, respectively.___________________________________________4836H3-14

91HFigure 3-8. Integrated RF of year 2000 emissions over 20-yr and 100-yr time horizons.__________________________4837H3-15

92HFigure 3-9. Scatterplot comparing data from co-located monitors in Charlotte, NC. _____________________________483H3-19

93HFigure 3-10. Map of CO monitor locations in the U.S. in 2007. ______________________________________________4839H3-22

94HFigure 3-11. Map of CO monitor locations with respect to population density in the Denver, CO CSA, 

total population. ________________________________________________________________________480H3-23

95HFigure 3-12. Map of CO monitor locations with respect to population density in the Denver, CO CSA, 

age 65 and older. _______________________________________________________________________481H3-24

96HFigure 3-13. Map of CO monitor locations with respect to population density in the Los Angeles, CA 

CSA, total population.____________________________________________________________________482H3-25

97HFigure 3-14. Map of CO monitor locations with respect to population density in the Los Angeles, CA 

CSA, age 65 and older. __________________________________________________________________483H3-26

98HFigure 3-15. County-level map of second-highest 1-h avg CO concentrations in the U.S. in 2007.___________________48H3-29

9HFigure 3-16. County-level map of second-highest 8-h avg CO concentrations in the U.S. in 2007.___________________485H3-30

10HFigure 3-17. Seasonal plots showing the variability in correlations between 24-h avg CO concentration 

with 1-h daily max and 8-h daily max CO concentrations and between 1-h daily max and 

8-h daily max CO concentrations. __________________________________________________________486H3-36

10HFigure 3-18. Map of CO monitor locations and major highways for Denver, CO._________________________________487H3-38

102HFigure 3-19. Box plots illustrating the distribution of 2005-2007 hourly CO concentrations in Denver, CO. ____________48H3-39

103HFigure 3-20. Intersampler correlation versus distance for monitors located within the Denver CSA.__________________489H3-41

104HFigure 3-21. Map of CO monitor locations and major highways for Los Angeles, CA._____________________________4850H3-42

105HFigure 3-22. Box plots illustrating the distribution of 2005-2007 hourly CO concentrations in Los 

Angeles, CA.___________________________________________________________________________4851H3-43
January 2010 xiii 

106HFigure 3-23. Intersampler correlation versus distance for monitors located within the Los Angeles CSA.______________4852H3-48

107HFigure 3-24. Aerial view of the location of CO monitors A and B (marked by the red pins) in Denver, CO, 

depicting their proximity to the urban core.____________________________________________________4853H3-50

108HFigure 3-25. Aerial view of the location of CO monitor I (marked by the red pin) in Azusa, CA (Los 

Angeles CSA), depicting its proximity to mixed use land. Scale: 1 cm = 145 m. ______________________485H3-51

109HFigure 3-26. Aerial view of the location of CO monitor Q (marked by the red pin) in Pasadena, CA (Los 

Angeles CSA), depicting its proximity to a residential neighborhood. Scale: 1 cm = 145 m. ______________485H3-52

10HFigure 3-27. Distribution of hourly CO concentration data by city and monitoring scale. ___________________________4856H3-55

1HFigure 3-28. Distribution of 1-h daily max CO concentration data by city and monitoring scale. _____________________4857H3-56

12HFigure 3-29. Relative concentrations of CO and copollutants at various distances from the I-710 freeway 

in Los Angeles._________________________________________________________________________485H3-57

13HFigure 3-30. CO concentration time series 20 m and 300 m from the I-440 highway in Raleigh, NC. _________________4859H3-58

14HFigure 3-31. CO concentration profile 10 m from I-440 in Raleigh, NC, behind a noise barrier and in 

open terrain. ___________________________________________________________________________4860H3-59

15HFigure 3-32. Dimensionless tracer gas concentration on the windward and leeward sides of the canyon 

plotted against the elevation of the measurement ______________________________________________4861H3-60

16HFigure 3-33. Normalized difference between CO measurements taken at ground level and from the 39th 

floor of a building in a Phoenix, AZ street canyon as a function of bulk Richardson number 

(Ri).__________________________________________________________________________________4862H3-61

17HFigure 3-34. (Top) Trends in ambient CO in the U.S., 1980-2006, reported as the annual second highest 

8-h concentrations (ppm) for the mean, median, 10% and 90% values. _____________________________4863H3-63

18HFigure 3-35. Trends in ambient CO in the U.S., 1980-2005, reported as the annual second highest 8-h 

concentrations (ppm) for the EPA Regions 1 through 10, along with a depiction of the 

geographic extent of those Regions. ________________________________________________________486H3-64

19HFigure 3-36. Diel plot generated from weekday hourly CO data (ppm) for the 11 CSAs and CBSAs, 

2005-2007. ____________________________________________________________________________4865H3-66

120HFigure 3-37. Diel plot generated from weekend hourly CO data (ppm) for the 11 CSAs and CBSAs, 

2005-2007. ____________________________________________________________________________486H3-67

12HFigure 3-38. Seasonal plots showing the variability in correlations between hourly CO concentration and 

co-located hourly SO2, NO2, O3, PM10 and PM2.5 concentrations. __________________________________4867H3-68

12HFigure 3-39. Seasonal plots showing the variability in correlations between hourly CO concentration and 

co-located hourly SO2, NO2, O3, PM10 and PM2.5 concentrations for Denver, CO.______________________486H3-69

123HFigure 3-40. Seasonal plots showing the variability in correlations between hourly CO concentration and 

co-located hourly SO2, NO2, O3, PM10 and PM2.5 concentrations for Los Angeles, CA.__________________4869H3-70

124HFigure 3-41. Linear regression of n-butane and isopentane concentration as a function of CO 

concentration, Riverside, CA.______________________________________________________________4870H3-71

125HFigure 3-42. Map of the baseline monitor sites used in this assessment to compute PRB concentrations._____________4871H3-73

126HFigure 3-43. Monthly (circles) and annual (squares) average CO concentrations (ppb), 2005-2007. _________________4872H3-74

127HFigure 3-44. Distribution of time that the sample population spends in various environments, from the 

NHAPS. ______________________________________________________________________________4873H3-79

128HFigure 3-45. Hourly personal versus ambient CO concentrations obtained in Baltimore, MD,_______________________487H3-84

129HFigure 3-46. Box plots of the ratio of personal to ambient concentrations obtained in Baltimore, MD, ________________4875H3-85
January 2010 xiv 

130HFigure 3-47. Comparison of in-vehicle (solid line) and outside-the-vehicle (dotted line) results for (left) 

driving with windows closed and air conditioner in recirculating air mode, and (right) driving 

with windows closed and air conditioner in fresh air mode. _______________________________________4876H3-89

13HFigure 4-1. Plot of fractional sensitivities of selected variables versus time of exposure. __________________________487H4-4

132HFigure 4-2. Simulated COHb formation for two 5-day workweeks.____________________________________________487H4-6

13HFigure 4-3. Overall structure of the Bruce and Bruce (2008, 193977) multicompartment model of 

storage and transport of CO. _______________________________________________________________4879H4-7

134HFigure 4-4. Predicted COHb levels in healthy commuters exposed to various CO concentrations over a 

60-min commute twice a day.______________________________________________________________480H4-10

135HFigure 4-5. Predicted COHb levels due to various endogenous CO production rates.____________________________481H4-11

136HFigure 4-6. Diagrammatic presentation of CO uptake and elimination pathways and CO body stores._______________482H4-12

137HFigure 4-7. O2Hb dissociation curve of normal human blood, of blood containing 50% COHb, and of 

blood with only 50% Hb because of anemia. __________________________________________________483H4-15

138HFigure 4-8. Changes in blood COHb after exposure to CO for a few minutes (A) or several hours (B), 

representing the biphasic nature of CO elimination._____________________________________________48H4-18

139HFigure 4-9. Predicted maternal and fetal COHb during periodic exposure to CO (50 ppm for 16 h 

followed by 0 ppm for 8 h ). _______________________________________________________________485H4-21

140HFigure 4-10. Representative estimates of endogenous CO production rates resulting from various 

conditions and diseases. _________________________________________________________________486H4-23

14HFigure 4-11. Representative COHb saturation resulting from various diseases and conditions. _____________________487H4-24

142HFigure 4-12. Representative exhaled CO concentrations (ppm) resulting from various conditions plotted 

as fold increases over healthy human controls from each study.___________________________________48H4-25

143HFigure 5-1. Direct effects of CO. _____________________________________________________________________489H5-12

14HFigure 5-2. Summary of effect estimates (95% confidence intervals) associated with hospital 

admissions for various forms of CHD. _______________________________________________________4890H5-27

145HFigure 5-3. Summary of effect estimates (95% confidence intervals) associated with ED visits and 

hospital admissions for stroke. _____________________________________________________________4891H5-30

146HFigure 5-4. Summary of effect estimates (95% confidence intervals) associated with hospital 

admissions for CHF._____________________________________________________________________4892H5-32

147HFigure 5-5. Summary of effect estimates (95% confidence intervals) associated with hospital 

admissions for CVD._____________________________________________________________________4893H5-36

148HFigure 5-6. Effect estimates from studies of ED visits and hospital admissions for CVD outcomes other 

than stroke from single pollutant (CO only: black circles) and particulate copollutant (CO + 

PM2.5: red triangles; CO + PM10 or TSP: purple triangles) models. _________________________________489H5-38

149HFigure 5-7. Effect estimates from studies of ED visits and HAs for CVD outcomes other than stroke 

from single pollutant (CO only: black circles) and gaseous copollutant models (CO + NO2, 

SO2 and O3= green, blue, and orange triangles, respectively). ____________________________________4895H5-39

150HFigure 5-8. Regression of the percent change in time to ST endpoint between the pre- and 

postexposure exercise tests ([postexposure–pre-exposure]/pre-exposure) and the 

measured blood COHb levels at the end of exercise for the 63 subjects combined. ____________________4896H5-42

15HFigure 5-9. Summary of effect estimates (95% confidence intervals) for PTB associated with maternal 

exposure to ambient CO. _________________________________________________________________4897H5-52
January 2010 xv 

152HFigure 5-10. Summary of change in birth weight (95% confidence intervals) associated with maternal 

exposure to ambient CO. _________________________________________________________________489H5-57

153HFigure 5-11. Summary of effect estimates (95% confidence intervals) for LBW associated with maternal 

exposure to ambient CO. _________________________________________________________________489H5-57

154HFigure 5-12. Summary of effect estimates (95% confidence intervals) for SGA associated with maternal 

exposure to ambient CO. _________________________________________________________________490H5-58

15HFigure 5-13. Estimated effect (95% confidence intervals) on pulmonary function due to a 10th to 90th 

percentile increment change in pollutant concentration in single-pollutant models._____________________4901H5-84

156HFigure 5-14. Summary of associations for short-term exposure to CO and asthma symptoms, respiratory 

symptoms and medication use in asthmatic individuals. _________________________________________4902H5-87

157HFigure 5-15. Summary of associations for short-term exposure to CO and respiratory hospital 

admissions., ___________________________________________________________________________4903H5-93

158HFigure 5-16. Summary of associations for short-term exposure to CO and respiratory ED visits. ____________________490H5-95

159HFigure 5-17. Posterior means and 95% posterior intervals of national average estimates for CO effects 

on total (nonaccidental) mortality at lags 0, 1, and 2 within sets of the 90 U.S. cities with 

available pollutant data. _________________________________________________________________4905H5-103

160HFigure 5-18. Summary of percent increase in total (nonaccidental) mortality for short-term exposure to 

CO from multicity studies.________________________________________________________________4906H5-106

16HFigure 5-19. Summary of mortality risk estimates for long-term exposure to CO. _______________________________4907H5-113

162HFigure A-1. CO emissions density map and distribution for the state of Alaska and for Yukon-Koyukuk 

County in Alaska. _______________________________________________________________________ 4908HA-1

163HFigure A-2. CO emissions density map and distribution for the state of Utah and for selected counties in 

Utah. _________________________________________________________________________________ 490HA-2

164HFigure A-3. CO emissions density map and distribution for the state of Massachusetts and for selected 

counties in Massachusetts. _______________________________________________________________ 4910HA-3

165HFigure A-4. CO emissions density map and distribution for the state of Georgia and for selected 

counties in Georgia (Figure 1 of 2). _________________________________________________________ 491HA-4

16HFigure A-5. CO emissions distribution for selected counties in Georgia (Figure 2 of 2).___________________________ 4912HA-5

167HFigure A-6. CO emissions density map and distribution for the state of California and for selected 

counties in California. ____________________________________________________________________ 4913HA-6

168HFigure A-7. CO emissions density map and distribution for the state of Alabama and for Jefferson 

County in Alabama. _____________________________________________________________________ 491HA-7

169HFigure A-8. Map of CO monitor locations with respect to population density in the Anchorage CBSA, 

total population. _______________________________________________________________________ 4915HA-20

170HFigure A-9. Map of CO monitor locations with respect to population density in the Anchorage CBSA, 

ages 65 yr and older. ___________________________________________________________________ 4916HA-20

17HFigure A-10. Map of CO monitor locations with respect to population density in the Atlanta CSA, total 

population. ___________________________________________________________________________ 4917HA-21

172HFigure A-11. Map of CO monitor locations with respect to population density in the Atlanta CSA, ages 65 

yr and older. __________________________________________________________________________ 4918HA-21

173HFigure A-12. Map of CO monitor locations with respect to population density in the Boston CSA, total 

population. ___________________________________________________________________________ 491HA-22
January 2010 xvi 

174HFigure A-13. Map of CO monitor locations with respect to population density in the Boston CSA, ages 65 

yr and older. __________________________________________________________________________ 4920HA-22

175HFigure A-14. Map of CO monitor locations with respect to population density in the Houston CSA, total 

population. ___________________________________________________________________________ 4921HA-23

176HFigure A-15. Map of CO monitor locations with respect to population density in the Houston CSA, ages 

65 yr and older.________________________________________________________________________ 492HA-23

17HFigure A-16. Map of CO monitor locations with respect to population density in the New York City CSA, 

total population. _______________________________________________________________________ 4923HA-24

178HFigure A-17. Map of CO monitor locations with respect to population density in the New York City CSA, 

ages 65 yr and older. ___________________________________________________________________ 492HA-24

179HFigure A-18. Map of CO monitor locations with respect to population density in the Phoenix CSA, total 

population. ___________________________________________________________________________ 4925HA-25

180HFigure A-19. Map of CO monitor locations with respect to population density in the Phoenix CSA, ages 

65 yr and older.________________________________________________________________________ 4926HA-25

18HFigure A-20. Map of CO monitor locations with respect to population density in the Pittsburgh CSA, total 

population. ___________________________________________________________________________ 4927HA-26

182HFigure A-21. Map of CO monitor locations with respect to population density in the Pittsburgh CSA, ages 

65 yr and older.________________________________________________________________________ 4928HA-26

183HFigure A-22. Map of CO monitor locations with respect to population density in the Seattle CSA, total 

population. ___________________________________________________________________________ 492HA-27

184HFigure A-23. Map of CO monitor locations with respect to population density in the Seattle CSA, ages 65 

yr and older. __________________________________________________________________________ 4930HA-27

185HFigure A-24. Map of CO monitor locations with respect to population density in the St. Louis CSA, total 

population. ___________________________________________________________________________ 4931HA-28

186HFigure A-25. Map of CO monitor locations with respect to population density in the St. Louis CSA, ages 

65 yr and older.________________________________________________________________________ 4932HA-28

187HFigure A-26. Map of CO monitor locations with AQS Site IDs for Anchorage, AK._______________________________ 493HA-29

18HFigure A-27. Box plots illustrating the seasonal distribution of hourly CO concentrations in Anchorage, 

AK. Note: 1 = winter, 2 = spring, 3 = summer, and 4 = fall on the x-axis. ___________________________ 493HA-31

189HFigure A-28. Map of CO monitor locations with AQS Site IDs for Atlanta, GA.__________________________________ 4935HA-32

190HFigure A-29. Box plots illustrating the seasonal distribution of hourly CO concentrations in Atlanta, GA. _____________ 4936HA-34

19HFigure A-30. Map of CO monitor locations with AQS Site IDs for Boston, MA.__________________________________ 4937HA-35

192HFigure A-31. Box plots illustrating the seasonal distribution of hourly CO concentrations in Boston, MA. _____________ 4938HA-37

193HFigure A-32. Map of CO monitor locations with AQS Site IDs for Houston, TX. _________________________________ 493HA-38

194HFigure A-33. Box plots illustrating the seasonal distribution of hourly CO concentrations in Houston, TX. ____________ 490HA-40

195HFigure A-34. Map of CO monitor locations with AQS Site IDs for New York City, NY. ____________________________ 491HA-41

196HFigure A-35. Box plots illustrating the seasonal distribution of hourly CO concentrations in New York 

City, NY. _____________________________________________________________________________ 492HA-43

197HFigure A-36. Map of CO monitor locations with AQS Site IDs for Phoenix, AZ. _________________________________ 493HA-44

198HFigure A-37. Box plots illustrating the seasonal distribution of hourly CO concentrations in Phoenix, AZ._____________ 49HA-46

19HFigure A-38. Map of CO monitor locations with AQS Site IDs for Pittsburgh, PA. _______________________________ 495HA-47
January 2010 xvii 

20HFigure A-39. Box plots illustrating the seasonal distribution of hourly CO concentrations in Pittsburgh, 

PA. _________________________________________________________________________________ 496HA-49

201HFigure A-40. Map of CO monitor locations with AQS Site IDs for Seattle, WA. _________________________________ 497HA-50

20HFigure A-41. Box plots illustrating the seasonal distribution of hourly CO concentrations in Seattle, WA. _____________ 498HA-51

203HFigure A-42. Map of CO monitor locations with AQS Site IDs for St. Louis, MO. ________________________________ 49HA-52

204HFigure A-43. Box plots illustrating the seasonal distribution of hourly CO concentrations in St. Louis, MO.____________ 4950HA-54

205HFigure A-44. Seasonal plots of correlations between hourly CO concentration with hourly (1) SO2, (2) 

NO2, (3) O3, (4) PM10, and (5) PM2.5 concentrations for Anchorage, AK. ____________________________ 4951HA-62

206HFigure A-45. Seasonal plots of correlations between hourly CO concentration with hourly (1) SO2, (2) 

NO2, (3) O3, (4) PM10, and (5) PM2.5 concentrations for Atlanta, GA. _______________________________ 4952HA-63

207HFigure A-46. Seasonal plots of correlations between hourly CO concentration with hourly (1) SO2, (2) 

NO2, (3) O3, (4) PM10, and (5) PM2.5 concentrations for Boston, MA. _______________________________ 4953HA-64

208HFigure A-47. Seasonal plots of correlations between hourly CO concentration with hourly (1) SO2, (2) 

NO2, (3) O3, (4) PM10, and (5) PM2.5 concentrations for New York City, NY. _________________________ 495HA-65

209HFigure A-48. Seasonal plots of correlations between hourly CO concentration with hourly (1) SO2, (2) 

NO2, (3) O3, (4) PM10, and (5) PM2.5 concentrations for Phoenix, AZ. ______________________________ 495HA-66

210HFigure A-49. Seasonal plots of correlations between hourly CO concentration with hourly (1) SO2, (2) 

NO2, (3) O3, (4) PM10, and (5) PM2.5 concentrations for Seattle, WA._______________________________ 4956HA-67
January 2010 xviii 

CO Project Team 

Executive Direction 

Dr. John Vandenberg (Director)—National Center for Environmental Assessment-RTP Division, 

Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle 

Park, NC 

Ms. Debra Walsh (Deputy Director)—National Center for Environmental Assessment-RTP Division, 

Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle 

Park, NC 

Dr. Mary Ross (Branch Chief)—National Center for Environmental Assessment, Office of Research 

and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Scientific Staff 

Dr. Thomas Long (CO Team Leader)—National Center for Environmental Assessment, Office of 

Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Dr. Jeffrey Arnold—National Center for Environmental Assessment, Office of Research and 

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

Dr. Christal Bowman—National Center for Environmental Assessment, Office of Research and 

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

Dr. Barbara Buckley—National Center for Environmental Assessment, Office of Research and 

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

Mr. Allen Davis—National Center for Environmental Assessment, Office of Research and 

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

Dr. Steven J. Dutton—National Center for Environmental Assessment, Office of Research and 

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

Dr. Craig Hansen—Oak Ridge Institute for Science and Education, Postdoctoral Research Fellow to 

National Center for Environmental Assessment, Office of Research and Development, 

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

Dr. Erin Hines—National Center for Environmental Assessment, Office of Research and 

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

Dr. Douglas Johns—National Center for Environmental Assessment, Office of Research and 

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

Dr. Thomas Luben—National Center for Environmental Assessment, Office of Research and 

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

Dr. Elizabeth Oesterling Owens—National Center for Environmental Assessment, Office of 

Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 
January 2010 xix 

Dr. Joseph Pinto—National Center for Environmental Assessment, Office of Research and 

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

Dr. Jennifer Richmond-Bryant—National Center for Environmental Assessment, Office of Research 

and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Mr. Jason Sacks—National Center for Environmental Assessment, Office of Research and 

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

Technical Support Staff 

Ms. Laeda Baston—Senior Environmental Employment Program, National Center for 

Environmental Assessment, Office of Research and Development, U.S. Environmental Protection 

Agency, Research Triangle Park, NC 

Ms. Ellen Lorang—National Center for Environmental Assessment, Office of Research and 

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

Ms. Deborah Wales—National Center for Environmental Assessment, Office of Research and 

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

Ms. Barbara Wright—Senior Environmental Employment Program, National Center for 

Environmental Assessment, Office of Research and Development, U.S. Environmental Protection 

Agency, Research Triangle Park, NC 
January 2010 xx 

Authors, Contributors, and Reviewers 

Authors 

Dr. Thomas Long (CO Team Leader)—National Center for Environmental Assessment, Office of 

Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Dr. Jeffrey Arnold—National Center for Environmental Assessment, Office of Research and 

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

Dr. Christal Bowman—National Center for Environmental Assessment, Office of Research and 

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

Dr. Barbara Buckley—National Center for Environmental Assessment, Office of Research and 

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

Mr. Allen Davis—National Center for Environmental Assessment, Office of Research and 

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

Dr. Steven J. Dutton—National Center for Environmental Assessment, Office of Research and 

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

Dr. Craig Hansen— Oak Ridge Institute for Science and Education, Postdoctoral Research Fellow to 

National Center for Environmental Assessment, Office of Research and Development, 

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

Dr. Erin Hines—National Center for Environmental Assessment, Office of Research and 

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

Dr. Douglas Johns—National Center for Environmental Assessment, Office of Research and 

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

Dr. Thomas Luben—National Center for Environmental Assessment, Office of Research and 

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

Dr. Elizabeth Oesterling Owens— National Center for Environmental Assessment, Office of 

Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Dr. Joseph Pinto— National Center for Environmental Assessment, Office of Research and 

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

Dr. Jennifer Richmond-Bryant—National Center for Environmental Assessment, Office of Research 

and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Dr. Mary Ross—National Center for Environmental Assessment, Office of Research and 

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

Mr. Jason Sacks—National Center for Environmental Assessment, Office of Research and 

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

Dr. Matthew Campen—Lovelace Respiratory Research Institute, Albuquerque, NM 
January 2010 xxi 

Dr. Kazuhiko Ito—Department of Environmental Medicine, New York University School of 

Medicine, Tuxedo, NY 

Dr. Jennifer Peel—Department of Environmental and Radiological Health Sciences, Colorado State 

University, Fort Collins, CO 

Contributors 

Dr. Richard Baldauf—National Risk Management Research Laboratory, Office of Research and 

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

Dr. Vernon Benignus—National Health and Environmental Effects Research Laboratory, Office of 

Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Mr. Antonio Fernandez—Office of Transportation and Air Quality, Office of Air and Radiation, 

U.S. Environmental Protection Agency, Ann Arbor, MI 

Mr. Lance McCluney—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Dr. Kris Novak—National Center for Environmental Assessment, Office of Research and 

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

Dr. Adam Reff—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Ms. Kathryn Sargeant—Office of Transportation and Air Quality, Office of Air and Radiation, 

U.S. Environmental Protection Agency, Ann Arbor, MI 

Mr. Mark Schmidt—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Dr. Joseph H. Somers—Office of Transportation and Air Quality, Office of Air and Radiation, 

U.S. Environmental Protection Agency, Ann Arbor, MI 

Ms. Rhonda Thompson—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Reviewers 

Dr. Richard Baldauf—National Risk Management Research Laboratory, Office of Research and 

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

Dr. Vernon Benignus—National Health and Environmental Effects Research Laboratory, Office of 

Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Dr. Souad Benromdhane—Office of Air Quality Planning and Standards, Office of Air and 

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

Dr. Philip Bromberg—School of Medicine, University of North Carolina, Chapel Hill, NC 

Dr. Matthew Campen—Lovelace Respiratory Research Institute, Albuquerque, NM 
January 2010 xxii 

Dr. Daniel Costa—National Program Director for Air, U.S. Environmental Protection Agency, 

Research Triangle Park, NC 

Dr. Andrew Ghio—National Health and Environmental Effects Research Laboratory, Office of 

Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 

Dr. Kazuhiko Ito—Department of Environmental Medicine, New York University School of 

Medicine, Tuxedo, NY 

Dr. Petros Koutrakis—Harvard School of Public Health, Harvard University, Cambridge, MA 

Mr. John Langstaff—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Dr. Barry Lefer—Department of Geosciences, University of Houston, Houston, TX 

Dr. Karen Martin—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Dr. Dave McKee—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Ms. Connie Meacham—National Center for Environmental Assessment, Office of Research and 

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

Dr. Deirdre Murphy—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Dr. Ines Pagan—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Dr. Jennifer Parker—National Center for Health Statistics, Centers for Disease Control, Atlanta, GA 

Dr. Jennifer Peel—Department of Environmental and Radiological Health Sciences, Colorado State 

University, Fort Collins, CO 

Dr. Pradeep Rajan—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Mr. Harvey Richmond—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Dr. Joseph H. Somers—Office of Transportation and Air Quality, Office of Air and Radiation, 

U.S. Environmental Protection Agency, Ann Arbor, MI 

Dr. John Vandenberg—National Center for Environmental Assessment, Office of Research and 

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

Dr. Alan Vette—National Exposure Research Laboratory, Office of Research and Development, 

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

Dr. William Vizuete—Department of Environmental Sciences and Engineering, University of North 

Carolina, Chapel Hill, NC 

Ms. Debra Walsh—National Center for Environmental Assessment, Office of Research and 

Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 
January 2010 xxiii 

Dr. Lin Weaver—Department of Internal Medicine, LDS Hospital, Salt Lake City, UT 

Dr. Lewis Weinstock—Office of Air Quality Planning and Standards, Office of Air and Radiation, 

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

Mr. Ron Williams—National Exposure Research Laboratory, Office of Research and Development, 

U.S. Environmental Protection Agency, Research Triangle Park, NC 
January 2010 xxiv 

Clean Air Scientific Advisory Committee 

CO NAAQS Review Panel 

Chair of the Environmental Protection Agency’s Clean Air Scientific Advisory Committee 

Dr. Jonathan M. Samet*, Department of Preventive Medicine at the Keck School of Medicine, and 

Director of the Institute for Global Health at the University of Southern California, Los Angeles, CA 

Chair of the Carbon Monoxide Review Panel 

Dr. Joseph Brain*, Department of Environmental Health, Harvard School of Public Health, Harvard 

University, Boston, MA 

Members 

Dr. Paul Blanc, Department of Occupational Medicine, University of California-San Francisco, San 

Francisco, CA

Dr. Thomas Dahms, Department of Anesthesiology Research and Critical Care, St. Louis University 

School of Medicine, St. Louis, MO 

Dr. Russell R. Dickerson, Department of Meteorology, University of Maryland, College Park, MD 

Dr. Laurence Fechter, Research Service, Department of Veterans Affairs, Loma Linda VA Medical 

Center, Loma Linda, CA 

Dr. H. Christopher Frey*, College of Engineering, Department of Civil, Construction, and 

Environmental Engineering, North Carolina State University, Raleigh, NC

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

Biology, University of North Carolina, Chapel Hill, NC 

Dr. Joel Kaufman, Department of Environmental & Occupational Health Sciences, University of 

Washington, Seattle, WA 

Dr. Michael T. Kleinman, Department of Community & Environmental Medicine, University of 

California-Irvine, Irvine, CA 

Dr. Francine Laden, Department of Environmental Health, Harvard School of Public Health, 

Harvard University, Boston, MA 

Dr. Arthur Penn, Department of Comparative Biomedical Sciences, Louisiana State University 

School of Veterinary Medicine, Baton Rouge, LA 

Dr. Beate Ritz, School of Public Health, Epidemiology, University of California at Los Angeles, Los 

Angeles, CA 

Dr. Paul Roberts, Sonoma Technology, Inc., Petaluma, CA 
January 2010 xxv 

Dr. Armistead (Ted) Russell*, Department of Civil and Environmental Engineering, Georgia Institute 

of Technology, Atlanta, GA 

Dr. Anne Sweeney, Department of Epidemiology & Biostatistics, School of Rural Public Health, 

Texas A&M Health Science Center, College Station, TX 

Dr. Stephen R. Thom, Institute for Environmental Medicine, University of Pennsylvania, 

Philadelphia, PA 

* Members of the statutory Clean Air Scientific Advisory Committee (CASAC) appointed by the 

EPA Administrator 

Science Advisory Board Staff 

Ms. Kyndall Barry, Designated Federal Officer, 1200 Pennsylvania Avenue, N.W., Washington, DC, 

20460, Phone: 202-343-9868, Fax: 202-233-0643, Email:21Hbarry.kyndall@epa.gov

Physical/Courier/FedEx Address: 

Ms. Kyndall Barry, U.S. EPA Science Advisory Board Staff Office, Mail Code 1400F, Ariel Rios 

Building, Room 3610A, 1025 F Street, N.W., Washington, DC 20004 
January 2010 xxvi 

Acronyms and Abbreviations 

α alpha, ambient exposure factor 

a air exchange rate of the microenvironment 

AA abdominal aorta(s) 

AADT annual average daily traffic 

ABR auditory brainstem response 

ACS American Cancer Society 

ACS-CPS-II ACS Cancer Prevention Study II 

ADP adenosine diphosphate 

AEFV area under the expiratory flow-volume curve 

AGL above ground level 

Akt Akt cell signaling pathway 

AMI acute myocardial infarction 

AMP adenosine monophosphate 

ANOVA analysis of variance 

APO E apolipoprotein E 

ARI acute respiratory infection 

AP action potential 

APD action potential duration 

APEX Air Pollution Exposure 

APHEA Air Pollution and Health: A European Approach 

APTT activated partial thromboplastin time 

AQ air quality 

AQCD Air Quality Criteria Document 

AQS Air Quality System 

AR gastronomy reared 

ARCO gastronomy reared + CO exposure 

ARIC Atherosclerosis Risk in Communities 

ARID gastronomy reared with iron deficient diet 

ARIDCO gastronomy reared with iron deficient diet + CO exposure 

ATP adenosine triphosphate 

ATS American Thoracic Society 

AVP aortic valve prosthesis 
January 2010 xxvii 

β beta, beta coefficient, slope 

B lymphocytes bursa-dependent lymphocytes 

BALF bronchoalveolar lavage fluid 

BC black carbon 

BEAS-2B human bronchial epithelial cell line 

BEIS Biogenic Emissions Inventory System 

BELD Biogenic Emissions Landcover Database 

BHR bronchial hyper-responsiveness 

BKCa voltage and Ca2+-activated K+

 channel(s) 

BP blood pressure 

BQ-123 endothelin A (ETA) receptor antagonist 

BS black smoke 

BSP black smoke particles 

Ca ambient concentration 

CA cardiac arrhythmia 

Ca2+ calcium ion 

CAA Clean Air Act 

CAD coronary artery disease 

CALINE California Line Source Dispersion Model 

CAMP Childhood Asthma Management Program 

cAMP cyclic AMP 

CAP(s) concentrated ambient particles, compound action potential(s) 

CASAC Clean Air Scientific Advisory Committee 

CASN Cooperative Air Sampling Network 

CAth cardiac atherosclerosis 

CBSA Core-Based Statistical Area 

CCGG Carbon Cycle Greenhouse Gases Group 

CD cardiac dysrhthmias 

CD-1 mouse strain 

CDC Centers for Disease Control and Prevention 

CdCl2 cadmium chloride 

CFK Coburn-Forster-Kane 

CFR Code of Federal Regulations 

cGMP cyclic GMP 

CH2O formaldehyde 
January 2010 xxviii 

CH2O2 formic acid 

CH3 methyl groups 

CH3CHO acetaldehyde 

CH3CO acetyl radical(s) 

CH3CO3NO2 PAN, peroxyacetyl nitrate 

CH3O2 methyl peroxy radical 

CH3OOH methyl hydroperoxide 

CH4 methane 

ChAT choline acetyl-transferase 

CHD coronary heart disease 

CHF congestive heart failure 

CI confidence interval(s) 

CIS cerebral ischemic stroke 

Cj airborne concentration at location j

CL/P cleft lip with or without palate 

CNS central nervous system 

CO carbon monoxide 

CO2 carbon dioxide 

COD coefficient of divergence 

CoH, COH coefficient of haze 

COHb carboxyhemoglobin (% concentration measured in (mL CO/mL 

blood)) 

COMb carboxymyoglobin 

CONUS contiguous U.S. 

COPD chronic obstructive pulmonary disease 

CPS II Cancer Prevention Study II 

C-R concentration-response 

CRC Coordinating Research Council 

CrMP collapsin response mediator protein 

CRP C-reactive protein 

CSA Combined Statistical Area 

CVD cardiovascular disease 

d straight-line distance between monitor pairs 

df degrees of freedom 

DL lung diffusing capacity 

DLCO lung diffusing capacity of CO 
January 2010 xxix 

DmCO capacity for diffusion of CO into the muscle 

DMT-1 divalent metal transporter-1 

DMV dorsal motor nucleus of the vagus nerve 

DNA deoxyribonucleic acid 

DOCA Deoxycorticosterone acetate 

dP/dtLV left ventricular maximal and minimal first derived pressure (+dP/dtLV, 

-dP/dtLV) 

dP/dtRV right ventricular maximal and minimal first derived pressure 

(+dP/dtRV, -dP/dtRV) 

DSA deletion/substitution/addition 

E exposure over some duration 

Ea exposure to pollutant of ambient origin 

EC elemental carbon 

ED emergency department 

EKG, ECG electrocardiogram 

Ena exposure to pollutant of non-ambient origin 

eNOS endothelial nitric oxide synthase 

EPA U.S. Environmental Protection Agency 

EPO erythropoietin 

EPR Electron Paramagnetic Resonance 

EPRI Electric Power Research Institute 

ESRL Earth System Research Laboratory 

ET-1 endothelin-1 

ETA endothelin A (ETA) receptor 

ETS environmental tobacco smoke 

EXPOLIS six-city European air pollution study 

FAS apoptosis stimulating fragment 

FC interference filter 

FEF forced expiratory flow (L/s) 

FEF25-75 forced expiratory flow between the times at which 25% and 75% of 

the vital capacity is reached 

FEM Federal equivalent method 

FEV1 forced expiratory volume in 1 second 

fi fraction of time spent indoors 

FICO fractional concentration of CO in ambient air 

Finf infiltration factor 
January 2010 xxx 

fo fraction of time spent outdoors 

FR Federal Register 

FGR fetal growth restriction(s) 

FRM Federal reference method 

FSH follicle stimulating hormone 

FVC forced vital capacity 

FVII Factor VII 

FW fresh weight 

GAM generalized additive model(s) 

GD gestational day 

GEE generalized estimating equations 

GEM gas extraction monitor 

GFAP glial fibrillary acidic protein 

GFC gas filter correlation 

GLM generalized linear models 

GLMM generalized linear mixed models 

GMD Global Monitoring Division 

GMP guanosine monophosphate 

GSH glutathione 

GSSG oxidized glutathione 

GTP guanosine triphosphate 

GWP(s) global warming potential(s) 

H atomic hydrogen, hydrogen radical, height 

h hour 

H2O2 hydrogen peroxide 

H9c2 rat embryonic cardiomyocytes 

Hb hemoglobin 

HC(s) hydrocarbon(s) 

HCFC(s) hydrochlorofluorocarbon(s) 

HCO formyl radical 

HEAPSS Health Effects of Air Pollution among Susceptible Subpopulations 

HEK293 human embryonic kidney cells (experimentally transformed cell line) 

Hep3B Human hepatocarcinoma cell line 

HF heart failure, high frequency (HRV parameter) 

HFLFR high frequency to low frequency ratio (HRV parameter) 
January 2010 xxxi 

HH hypobaric hypoxia 

HIF-1α hypoxia-inducible factor 

HO heme oxygenase 

HO2 hydroperoxy radical 

HO-1 inducible isoform of heme oxygenase 

HO-2 constitutively expressed isoform of heme-oxygenase 

HO/CO heme oxygenase/carbon monoxide system 

HR heart rate, hazard ratio 

H/R hypoxia followed by reoxygenation 

HRV heart rate variability 

HS hemorrhagic stroke 

HUVEC(s) human umbilical vein endothelial cell(s) 

hν photon 

IARC International Agency for Research on Cancer 

IC inferior colliculus 

ICAM-1 intercellular adhesion molecule 

ICD implantable cardioverter defibrillator(s) 

ICR Institute for Cancer Research 

IDW inverse-distance-weighted 

IHD ischemic heart disease 

IL-x interleukin-6, 8, etc. 

INDAIR Indoor Air Model 

IOM Institute of Medicine 

IQR interquartile range 

IR immunoreactivity 

IS ischemic stroke 

ISA Integrated Science Assessment 

ITA internal thoracic artery of the heart 

Ito transient outward current 

IUGR intrauterine growth restriction 

K+

 potassium ion 

k dissociation rate 

kCO dissociation rate of carbon monoxide from hemoglobin 

Km Michaelis Constant; Michaelis-Menten equation of enzyme kinetics 

kO2 Dissociation rate of oxygen from hemoglobin 
January 2010 xxxii 

LBW low birth weight (<2,500 grams, (≈5lbs, 8 oz)) 

LCA+ leucocyte common antigen cells 

LD lactational day 

LDH lactate dehydrogenase 

LDL low-density lipoprotein 

LF low frequency (HRV parameter) 

LH luetenizing hormone 

LOAEL lowest observed adverse effect level 

LOD limit of detection 

LOESS locally weighted scatterplot smoothing 

LPS lipopolysaccharide 

LTP long-term potentiation 

LUR land use regression 

LV left ventricle 

LV+S left ventricular plus septum 

LVDP left ventricular developed pressure 

LVESP left ventricular end diastolic pressure 

LVSF left ventricular shortening fraction 

LVW left ventricular work 

M Haldane coefficient representing the CO chemical affinity for Hb [or 

Mb]), Reaction mediator. 

MAPK mitogen-activated protein kinase 

MAO-A monoamine oxidase A 

Mb myoglobin 

MC ultrafine particle mass concentration 

METs metabolic equivalent unit(s) 

MHC major histocompatibility complex 

MI myocardial infarction, “heart attack” 

min minute(s) 

MIP-2 macrophage inflammatory protein-2 

mitral E to A ratio mitral ratio of peak early to late diastolic filling velocity 

MMEF maximal midexpiratory flow 

MMP matrix metalloproteinase 

MOA(s) mode(s) of Action 

MOBILE6 Mobile source emission factor model 

MODIS Moderate Resolution Imaging Spectroradiometer 
January 2010 xxxiii 

MONICA Monitoring of Trends and Determinants in Cardiovascular Disease 

MOPITT Measurement of Pollution in the Troposphere 

MPO myeloperoxidase 

MPT mitochondrial permeability transition 

MR maternally reared 

mRNA messenger RNA 

MSA Metropolitan Statistical Area 

MSNA muscle sympathetic nerve activity 

MT million tons 

MVO2 myocardial oxygen consumption 

NAAQS National Ambient Air Quality Standards 

NADPH nicotinamide adenine dinucleotide phosphate 

NADH-TR nicotinamide adenine dinucleotide - tetrazolium reductase 

NAPAP National Acid Precipitation Assessment Program 

NARSTO North American Research Strategy for Tropospheric Ozone 

NAS National Academy of Sciences 

NASA National Aeronautics and Space Administration 

Nb neuroglobin 

NC ultrafine particle number concentration 

NDIR nondispersive infrared 

NE norepinephrine 

NEI National Emissions Inventory 

NF-κB nuclear factor kappa B 

NIHL noise-induced hearing loss 

NMDA N-methyl-D-aspartate 

NMHC(s) nonmethane hydrocarbon(s) 

NMMAPS National Morbidity, Mortality, and Air Pollution Study 

NN normal-to-normal (NN or RR) time interval between each QRS 

complex in the EKG 

nNOS neuronal nitric oxide synthase (NOS) 

NO nitric oxide 

NO• nitric oxide free radical 

NO2 nitrogen dioxide 

NOAA National Oceanic and Atmospheric Administration 

NOAEL no observed adverse effect level 

NO•

-Hb nitrosyl bound Hb 
January 2010 xxxiv 

NO•-Mb nitrosyl bound Mb 

NOX nitrogen oxides, oxides of nitrogen 

NRC National Research Council 

NTS nucleus of the solitary tract (in brainstem) 

O3 ozone 

O2Hb oxyhemoglobin (% concentration in mL O2 / mL blood) 

O2Mb oxymyoglobin 

OAE otoacoustic emissions 

OAQPS Office of Air Quality Planning and Standards 

OC organic carbon 

OH, OH• hydroxyl group, hydroxyl radical 

OR odds ratio 

OS occlusive stroke 

OSPM Operational Street Pollution Model 

P penetration factor 

P, p probability 

P90 90th percentile of the absolute difference in concentrations 

PA alveolar pressure 

PA pulmonary artery (myocytes) 

PACF partial auto-correlation functions 

PACO alveolar pressure for carbon monoxide 

PAF platelet activating factor 

PAH polycyclic aromatic hydrocarbon 

PAHT pulmonary artery hypertension 

PAN peroxyacetyl nitrate (CH3CO3NO2) 

PAO2 alveolar pressure for oxygen 

PaO2 arterial oxygen pressure 

PARP poly(ADP-ribose) polymerase 

PB barometric pressure (in mmHg) 

PBN N-tert-butyl-alpha-phenylnitrone 

PC average partial pressure in lung capillaries 

pCO partial pressure of CO 

PCO2 average partial pressure of O2 in lung capillaries 

PDGF platelet derived growth factor 

PEE prediction equation estimates 
January 2010 xxxv 

PEF peak expiratory flow 

PEFD(s) Personal Exposures Frequency Distributions 

PEM(s) personal exposure monitor(s) 

PH2O saturation pressure of water vapor 

PHD pulmonary heart disease 

PI partial pressure of inhaled air 

Pi inorganic phosphate 

PI3K phosphoinositide 3-kinase 

PICO CO partial pressure in inhaled air 

PIH primary intracerebral hemorrhage 

PKB protein kinases B 

PM particulate matter 

PM2.5 particulate matter with a nominal mean aerodynamic diameter less 

than or equal to 2.5 μm (referred to as fine PM) 

PM10 particulate matter with a nominal mean aerodynamic diameter less 

than or equal to 10 μm 

PM10-2.5 particulate matter with a nominal mean aerodynamic diameter greater 

than 2.5 μm and less than or equal to 10 μm (referred to as thoracic 

coarse particulate matter or the course fraction of PM10). 

Concentration may be measured or calculated as the difference 

between measured PM10 and measured PM2.5 concentrations. 

PMN polymorphonuclear leukocytes 

PNC particle number concentration / count 

PND post natal day 

pNEM/CO probabilistic NAAQS Exposure Model for CO 

PNN proportion of interval differences of successive normal-beat intervals 

in EKG 

PNN50 proportion of interval differences of successive normal-beat intervals 

greater than 50 ms in EKG 

PNS peripheral nervous system 

pO2 partial pressure of oxygen in lung capillaries 

pPRB policy-relevant background 

PT prothrombin time 

PTB preterm birth 

PVCD peripheral vascular and cerebrovascular disease 

PvO2 venous oxygen tension 

PVO2 peak oxygen consumption 

Q cardiac output 

QCP Quantitative Circulatory Physiology 
January 2010 xxxvi 

blood flow to other tissues 

RA radial artery of the heart 

RAW 264.7 mouse macrophage cell line 

RBC red blood cell 

RF radiative forcing 

rho(0) rho(0) cells (cells lacking mitochondrial DNA) 

Ri Richardson number 

rMSSD mean squared differences of successive difference normal-beat to 

normal-beat (NN or RR) time intervals between each QRS complex in 

the EKG 

RNA ribonucleic acid 

ROE Report on the Environment 

ROFA residual oil fly ash (particles) 

ROS reactive oxygen species 

RR normal-to-normal (NN or RR) time interval between each QRS 

complex in the EKG 

RR risk ratio(s) 

RUPERT Reducing Urban Pollution Exposure from Road Transport 

RV right ventricle (of heart) 

RVEDP right ventricular end diastolic pressure 

RVESP right ventricular end-systolic pressure 

RVSF right ventricular shortening fraction 

RVW right ventricular work 

SA sphinganine 

SAA serum amyloid A 

SAB Science Advisory Board 

SBP systolic blood pressure, spontaneous bacterial peritonitis 

SDNN standard deviation normal-to-normal (NN or RR) time interval 

between each QRS complex in the EKG 

sEng soluble endoglin 

SES socioeconomic status 

SF6 sulfur hexafluoride (tracer gas) 

sFlt soluble Fms-like tyrosine kinase-1 

SGA small for gestational age 

sGC soluble guanylate cyclase 

SHEDS Stochastic Human Exposure and Dose Simulation 

SHR Spontaneously hypertensive rat strain 
January 2010 xxxvii 

SIDS sudden infant death syndrome 

SIPs State Implementation Plan(s) 

siRNA small inhibitory RNA 

SLAMS State and Local Air Monitoring Stations 

SMC smooth muscle cell(s) 

SnMP tin-(IV)-mesoporphyrin 

SNP single-nucleotide polymorphism 

SnPP-IX tin protoporphyrin IX 

SO sphingosine 

SO2 sulfur dioxide 

SO4

2- sulfate 

SOD superoxide dismutase 

SOPHIA Study of Particles and Health in Atlanta 

STEMS Space-Time Exposure Modeling System 

STN Speciation Trends Network 

STPD standard temperature and pressure, dry 

SV stroke volume 

SVEB supraventricular (atrium or atrioventricular node) ectopic beats 

τ tau, photochemical lifetime 

T lymphocytes thymus-dependent lymphocytes 

TBARS thiobarbituric acid reactive substances 

TC total carbon 

TFAM mitochondrial transcription factor A 

Tg teragram(s) 

TH tyrosine hydroxylase 

THP-1 human monocyte-derived cell line, (can differentiate into 

macrophages) 

TIA transient ischemic attack 

TNF-α tissue necrosis factor alpha 

TPM total particulate matter 

TSP total suspended particles 

UFP ultrafine particle(s) 

ULTRA Exposure and Risk Assessment for Fine and Ultrafine Particles in 

Ambient Air (Study) 

URI upper respiratory infection 

URTI upper respiratory tract infection 
January 2010 xxxviii 

USC U.S. Code 

VA alveolar ventilation 

Vb blood volume 

VCO endogenous CO production rate 

VD Dead space volume 

VE ventilation rate 

VEGF vascular endothelial growth factor 

VLF very low energy frequency (HRV parameter) 

Vmax maximum velocity 

VO2 max maximum volume per time, of oxygen (maximal oxygen 

consumption, maximal oxygen uptake or aerobic capacity) 

VOC(s) volatile organic compound(s) 

VPB ventricular premature beat 

vWF von Willebrand factor 

W width 

WBC white blood cell 

WHI Women’s Health Initiative 

WKY Wistar-Kyoto rat strain 

ZnPP IX Zn protoporphyrin IX