### January 2010 1 EPA/600/R-09/019F 2 

# 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, NCJanuary 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 T ABLE OF 

## C ONTENTS 

## ______________________________________________________ III 

## L IST OF 

## T ABLES 

## ________________________________________________________ VIII 

## L IST OF 

## F IGURES 

## ________________________________________________________ XII 

## CO P ROJECT 

## T EAM 

## _____________________________________________________ XVIII 

## A UTHORS 

## , C ONTRIBUTORS 

## , AND 

## R EVIEWERS 

## ___________________________________ XX 

## C LEAN 

## A IR 

## S CIENTIFIC 

## A DVISORY 

## C OMMITTEE 

## CO NAAQS R EVIEW 

## P ANEL 

## ___________ XXIV 

## A CRONYMS AND 

## A BBREVIATIONS 

## ___________________________________________ XXVI 

## C HAPTER 

## 1. I NTRODUCTION 

## _______________________________________________ 1-1 1.1. Legislative Requirements _______________________________________________________ 1-2 1.2. History of the NAAQS for CO____________________________________________________

4538H 

### 1-3 1.3. ISA Development _____________________________________________________________

4539H 

### 1-4 1.4. Document Organization ________________________________________________________

450H 

### 1-6 1.5. Document Scope _____________________________________________________________

451H 

### 1-7 1.6. EPA Framework for Causal Determination__________________________________________

452H 

### 1-8 1.6.1. Scientific Evidence Used in Establishing Causality_____________________________

453H 

### 1-8 1.6.2. Association and Causation _______________________________________________

45H 

### 1-9 1.6.3. Evaluating Evidence for Inferring Causation __________________________________

45H 

### 1-9 1.6.4. Application of Framework for Causal Determination___________________________

456H 

### 1-12 1.6.5. Determination of Causality ______________________________________________

457H 

### 1-13 1.6.5.1. Effects on Human Populations ____________________________________

458H 

### 1-15 1.6.5.2. Effects on Ecosystems or Public Welfare____________________________

459H 

### 1-16 1.6.6. Concepts in Evaluating Adversity of Health Effects____________________________

450H 

### 1-16 1.7. Summary __________________________________________________________________

451H 

### 1-17 References ____________________________________________________________________

452H 

### 1-18 

## C HAPTER 

## 2. I NTEGRATIVE 

## O VERVIEW 

## ________________________________________ 453H 

## 2-1 2.1. Ambient CO Sources and Concentrations __________________________________________

45H 

### 2-1 2.2. Climate Forcing Effects ________________________________________________________

45H 

### 2-2 2.3. Exposure to Ambient CO _______________________________________________________

456H 

### 2-3 2.4. Dosimetry, Pharmacokinetic s, and Mode of Action ___________________________________

457H 

### 2-4 2.4.1. Dosimetry and Ph armacokinetics __________________________________________

458H 

### 2-4 2.4.2. Mode of Action_________________________________________________________

459H 

### 2-4 2.5. Health Effects ________________________________________________________________

4560H 

### 2-5 2.5.1. Cardiovascular Morbidity_________________________________________________

4561H 

### 2-5 2.5.2. Central Nervous System Effects ___________________________________________

4562H 

### 2-6January 2010 iv 

### 2.5.3. Birth Outcomes and Developmental Effects __________________________________ 2-7 2.5.4. Respiratory Morbidity____________________________________________________ 2-8 2.5.5. Mortality ______________________________________________________________

456H 

### 2-9 2.6. Policy-Relevant Considerations _________________________________________________

456H 

### 2-10 2.6.1. Susceptible Populations ________________________________________________

4567H 

### 2-10 2.6.2. Concentration- and Dose-Response Relationships ___________________________

4568H 

### 2-12 2.7. Integration of CO Health Effects_________________________________________________

4569H 

### 2-13 References ____________________________________________________________________

4570H 

### 2-18 

## C HAPTER 

## 3. S OURCE TO 

## E XPOSURE 

## _________________________________________ 4571H 

## 3-1 3.1. Introduction__________________________________________________________________

4572H 

### 3-1 3.2. CO Sources, Emissions, and Chemistry ___________________________________________

4573H 

### 3-1 3.2.1. Direct CO Emissions ____________________________________________________

457H 

### 3-1 3.2.2. Secondary CO Emissions and Associated Chemistry___________________________

457H 

### 3-9 3.3. CO Climate Forc ing Effects ____________________________________________________

4576H 

### 3-11 3.4. Ambient Measurements _______________________________________________________

457H 

### 3-16 3.4.1. Ambient Measurement Instruments _______________________________________

4578H 

### 3-16 3.4.2. Ambient Sampling Network Design________________________________________

4579H 

### 3-19 3.4.2.1. Monitor Siting Requirements _____________________________________

4580H 

### 3-19 3.4.2.2. Spatial and Tem poral Coverage___________________________________

4581H 

### 3-20 3.5. Environmental Concentrations __________________________________________________

4582H 

### 3-28 3.5.1. Spatial Variability ______________________________________________________

4583H 

### 3-28 3.5.1.1. National Scale ________________________________________________

458H 

### 3-28 3.5.1.2. Urban Scale __________________________________________________

458H 

### 3-37 3.5.1.3. Micro- to Neighborhood Scale and the Near-Road Environment__________

4586H 

### 3-53 3.5.2. Temporal Variability ____________________________________________________

4587H 

### 3-62 3.5.2.1. Multiyear Trends_______________________________________________

458H 

### 3-62 3.5.2.2. Hourly Variation _______________________________________________

4589H 

### 3-65 3.5.3. Associations with Copollutants ___________________________________________

4590H 

### 3-68 3.5.4. Policy-Relevant Background _____________________________________________

4591H 

### 3-72 3.5.4.1. Surface-Based Determinations ___________________________________

4592H 

### 3-72 3.5.4.2. Limitations of Othe r Possible Met hods ______________________________ 4593H 

### 3-74 3.6. Issues in Expos ure Assessment_________________________________________________

459H 

### 3-76 3.6.1. Summary of Findings from 2000 CO AQCD _________________________________

459H 

### 3-76 3.6.2. General Exposure Concepts _____________________________________________

4596H 

### 3-76 3.6.3. Exposure Modeling ____________________________________________________

4597H 

### 3-78 3.6.3.1. Stochastic Population-Based Time -Weighted Microenvironmental Exposure Models ______________________________________________

4598H 

### 3-78 3.6.3.2. Using Spatial Models to Estimate Exposure _________________________

459H 

### 3-79 3.6.4. Personal Exposure Monitors for CO _______________________________________

460H 

### 3-82 3.6.5. Indoor Exposure to CO _________________________________________________

4601H 

### 3-82 3.6.5.1. Infiltration of Ambient CO ________________________________________

4602H 

### 3-82 3.6.5.2. Exposure to Nonambient CO _____________________________________

4603H 

### 3-83 3.6.6. Exposure Assessment Studies at Different Spatial Scales ______________________

460H 

### 3-85 3.6.6.1. Neighborhood to Urban Scale Studies of Ambient CO Exposure _________

4605H 

### 3-85 3.6.6.2. Microscale Studies of Ambient CO Exposure: Near-Road and On-Road Exposures____________________________________________________

460H 

### 3-87 3.6.7. Association between Personal CO Exposure and Copollutants __________________

4607H 

### 3-90 3.6.8. Implications for Epidemiology ____________________________________________

4608H 

### 3-90 3.6.8.1. Measurement Error_____________________________________________

4609H 

### 3-91 3.6.8.2. Exposure Issues Related to Nonambient CO ________________________

4610H 

### 3-92 3.6.8.3. Spatial Variability ______________________________________________

461H 

### 3-92 3.6.8.4. Temporal Variability ____________________________________________

4612H 

### 3-93January 2010 v 

### 3.6.8.5. CO Exposure in Copollutant Mixtures ______________________________

4613H 

### 3-94 3.6.8.6. Conclusions __________________________________________________

461H 

### 3-94 3.7. Summary and Conclusions ____________________________________________________

4615H 

### 3-95 3.7.1. CO Sources, Emissions, and Chemistry ____________________________________

461H 

### 3-95 3.7.2. Climate Forcing Effects Related to CO _____________________________________

4617H 

### 3-95 3.7.3. Ambient CO Measurements _____________________________________________

4618H 

### 3-96 3.7.4. Environmental CO Concentrations ________________________________________

4619H 

### 3-96 3.7.5. Exposure Assessment and Implications for Epidemiology ______________________

4620H 

### 3-97 References ____________________________________________________________________

4621H 

### 3-99 

## C HAPTER 

## 4. D OSIMETRY AND 

## P HARMACOKINETICS OF 

## C ARBON 

## M ONOXIDE 

## _____________ 462H 

## 4-1 4.1. Introduction__________________________________________________________________

4623H 

### 4-1 4.2. Carboxyhemoglo bin Modeling ___________________________________________________

462H 

### 4-1 4.2.1. The Coburn-Forster-Kane and Other Models _________________________________

4625H 

### 4-1 4.2.2. Multicompartment Models ________________________________________________

462H 

### 4-6 4.2.3. Model Comparison _____________________________________________________

4627H 

### 4-8 4.2.4. Mathematical Model Usage_______________________________________________

4628H 

### 4-8 4.3. Absorption, Distribution, and Elimination __________________________________________

4629H 

### 4-11 4.3.1. Pulmonary Ab sorption __________________________________________________

4630H 

### 4-11 4.3.1.1. Mass Transfer of Carbon Monoxide________________________________

4631H 

### 4-12 4.3.1.2. Lung Diffusion of Carbon Monoxide________________________________

4632H 

### 4-12 4.3.2. Tissue Uptake ________________________________________________________

463H 

### 4-13 4.3.2.1. Respirator y Tract ______________________________________________

463H 

### 4-13 4.3.2.2. Blood _______________________________________________________

4635H 

### 4-13 4.3.2.3. Heart and Skeletal Muscle _______________________________________

463H 

### 4-15 4.3.2.4. Other Tissues _________________________________________________

4637H 

### 4-16 4.3.3. Pulmonary and Tissue Elimin ation ________________________________________

4638H 

### 4-17 4.3.4. COHb Analysi s Met hods ________________________________________________ 4639H 

### 4-18 4.4. Conditions Affecting Uptake and Elimination _______________________________________

460H 

### 4-19 4.4.1. Physical Ac tivity _______________________________________________________

461H 

### 4-19 4.4.2. Altitude______________________________________________________________

462H 

### 4-19 4.4.3. Physical Characteristics ________________________________________________

463H 

### 4-20 4.4.3.1. Fetal Pharma cokinetics _________________________________________

46H 

### 4-20 4.4.4. Health Status _________________________________________________________

465H 

### 4-21 4.5. Endogenous CO Production and Metabolism ______________________________________

46H 

### 4-22 4.6. Summary and Conclusions ____________________________________________________

467H 

### 4-26 References ____________________________________________________________________

468H 

### 4-28 

## C HAPTER 

## 5. I NTEGRATED 

## H EALTH 

## E FFECTS 

## ___________________________________ 469H 

## 5-1 5.1. Mode of Action of CO Toxicity ___________________________________________________

4650H 

### 5-1 5.1.1. Introduction ___________________________________________________________

4651H 

### 5-1 5.1.2. Hypoxic Me chanisms____________________________________________________

4652H 

### 5-1 5.1.3. Nonhypoxic Mechanisms ________________________________________________

4653H 

### 5-2 5.1.3.1. Nonhypoxic Mechanisms Reviewed in the 2000 CO AQCD ______________

465H 

### 5-2 5.1.3.2. Recent Studies of N onhypoxic Me chanism s __________________________

465H 

### 5-3 5.1.3.3. Implications of N onhypoxic Me chanis ms _____________________________

465H 

### 5-9 5.1.3.4. Summary ____________________________________________________

4657H 

### 5-12 5.2. Cardiovascular Effects ________________________________________________________

4658H 

### 5-12 5.2.1. Epidemiologic Studies with Short-Term Exposure_____________________________

4659H 

### 5-12 5.2.1.1. Heart Rate and Heart Rate Variability ______________________________

460H 

### 5-13 5.2.1.2. ECG Abnormalities In dicating I schem ia_____________________________

461H 

### 5-16 5.2.1.3. Arrhythmia ___________________________________________________

462H 

### 5-17January 2010 vi 

### 5.2.1.4. Cardiac Arrest_________________________________________________

463H 

### 5-18 5.2.1.5. Myocardial Infarction ___________________________________________

46H 

### 5-19 5.2.1.6. Blood Pressure________________________________________________

465H 

### 5-19 5.2.1.7. Vasomotor Function ____________________________________________

46H 

### 5-19 5.2.1.8. Blood Markers of Coagulation and Inflammation ______________________

467H 

### 5-20 5.2.1.9. Hospital Admissions and Emergency Departm ent Vi sits ________________

468H 

### 5-23 5.2.2. Epidemiologic Studies with Long-Term Exposure _____________________________

469H 

### 5-40 5.2.3. Summary of Epidemiologic Studies of Exposure to CO and Cardiovascular Effects ______________________________________________________________

4670H 

### 5-40 5.2.4. Controlled Human Exposure Studies ______________________________________

4671H 

### 5-41 5.2.5. Toxicologica l Studies ___________________________________________________

4672H 

### 5-44 5.2.5.1. Endothelial Dysfunction _________________________________________

4673H 

### 5-44 5.2.5.2. Cardiac Remodeling Effects______________________________________

467H 

### 5-46 5.2.5.3. Electrocardiographic Effects______________________________________

4675H 

### 5-47 5.2.5.4. Summary of Cardiova scular Toxicology_____________________________

467H 

### 5-47 5.2.6. Summary of Cardiovascular Effects _______________________________________

467H 

### 5-47 5.2.6.1. Short-Term Exposure to CO______________________________________

4678H 

### 5-47 5.2.6.2. Long-Term Exposure to CO ______________________________________

4679H 

### 5-48 5.3. Central Nervous System Effects ________________________________________________

4680H 

### 5-49 5.3.1. Controlled Human Exposure Studies ______________________________________

4681H 

### 5-49 5.3.2. Toxicologica l Studies ___________________________________________________

4682H 

### 5-49 5.3.3. Summary of Central Nervous System Effects ________________________________

4683H 

### 5-49 5.4. Birth Outcomes and Developmental Effects________________________________________

468H 

### 5-50 5.4.1. Epidemiologic Studies __________________________________________________

4685H 

### 5-50 5.4.1.1. Preterm Birth _________________________________________________

468H 

### 5-50 5.4.1.2. Birth Weight, Low Birth Weight, and Intrauterine Growth Restriction/Small for Gestational Age_______________________________

4687H 

### 5-53 5.4.1.3. Congenital Anomalies __________________________________________

468H 

### 5-60 5.4.1.4. Neonatal and Postneonatal Mortality _______________________________

4689H 

### 5-61 5.4.1.5. Summary of Epidemiologic Studies of Birth Outcomes and Developmental Effects __________________________________________

4690H 

### 5-63 5.4.2. Toxicological Studies of Birth Outcomes and Developmental Effects ______________

4691H 

### 5-63 5.4.2.1. Birth Outcomes________________________________________________

4692H 

### 5-63 5.4.2.2. Developmental Effects __________________________________________

4693H 

### 5-68 5.4.3. Summary of Birth Outcomes and Developmental Effects _______________________

469H 

### 5-79 5.5. Respiratory Effects ___________________________________________________________

4695H 

### 5-81 5.5.1. Epidemiologic Studies with Short-Term Exposure_____________________________

469H 

### 5-81 5.5.1.1. Pulmonary Function, Respiratory Sy mptoms, and Medi cation Use________

4697H 

### 5-81 5.5.1.2. Respiratory Hospital Admissions, ED Visits and Physician Visits _________

4698H 

### 5-88 5.5.2. Epidemiologic Studies with Long-Term Exposure _____________________________

469H 

### 5-96 5.5.2.1. Pulmonary F uncti on ____________________________________________

470H 

### 5-96 5.5.2.2. Asthma and Asthma Symptoms ___________________________________

4701H 

### 5-97 5.5.2.3. Respiratory Allergy and Other Allergic Responses ____________________

4702H 

### 5-98 5.5.2.4. Summary of Associations between Long-Term Exposure to CO and Respiratory Morbidity ___________________________________________

4703H 

### 5-98 5.5.3. Controlled Human Exposure Studies ______________________________________

470H 

### 5-99 5.5.4. Toxicologica l Studies ___________________________________________________

4705H 

### 5-99 5.5.5. Summary of Respiratory Health Effects ___________________________________

4706H 

### 5-100 5.5.5.1. Short-Term Exposure to CO_____________________________________

470H 

### 5-100 5.5.5.2. Long-Term Exposure to CO _____________________________________

4708H 

### 5-101 5.6. Mortality __________________________________________________________________

4709H 

### 5-101 5.6.1. Epidemiologic Studies with Short-Term Exposure to CO ______________________

4710H 

### 5-101 5.6.1.1. Summary of Findings from 2000 CO AQCD ________________________

471H 

### 5-101 5.6.1.2. Multicity Studies ______________________________________________

4712H 

### 5-101 5.6.1.3. Meta-Analysis of All Criteria Pollutants ____________________________

4713H 

### 5-106 5.6.1.4. Single-City Studies ____________________________________________

471H 

### 5-107January 2010 vii 

### 5.6.1.5. Summary of Mortality and Short-Term Exposure to CO _______________

4715H 

### 5-109 5.6.2. Epidemiologic Studies with Long-Term Exposure to CO_______________________

4716H 

### 5-109 5.6.2.1. U.S. Cohort Studies ___________________________________________

471H 

### 5-110 5.6.2.2. U.S. Cross-Sectional Analysis ___________________________________

4718H 

### 5-113 5.6.2.3. Summary of Mortality and Long-Term Exposure to CO ________________

4719H 

### 5-114 5.7. Susceptible Populations______________________________________________________

4720H 

### 5-114 5.7.1. Preexisting Disease___________________________________________________

4721H 

### 5-116 5.7.1.1. Cardiovascular Disease ________________________________________

472H 

### 5-116 5.7.1.2. Obstructive Lung Disease ______________________________________

4723H 

### 5-117 5.7.1.3. Diabetes ____________________________________________________

472H 

### 5-118 5.7.1.4. Anemia _____________________________________________________

4725H 

### 5-118 5.7.2. Lifestage ___________________________________________________________

4726H 

### 5-119 5.7.2.1. Older Adults _________________________________________________

472H 

### 5-119 5.7.2.2. Gestational Development _______________________________________

4728H 

### 5-120 5.7.3. Gender _____________________________________________________________ 4729H 

### 5-121 5.7.4. Altitude_____________________________________________________________

4730H 

### 5-121 5.7.5. Exercise____________________________________________________________

4731H 

### 5-122 5.7.6. Proximity to Roadways ________________________________________________

4732H 

### 5-122 5.7.7. Medications and Other Substances ______________________________________

473H 

### 5-123 5.7.8. Summary of Susceptible Populations _____________________________________

473H 

### 5-123 5.8. Summary _________________________________________________________________

4735H 

### 5-124 References ___________________________________________________________________

4736H 

### 5-125 

## A NNEX 

## A. A TMOSPHERIC 

## S CIENCE 

## __________________________________________ 473H 

## A-1 A NNEX 

## B. D OSIMETRY 

## S TUDIES 

## ____________________________________________ 4738H 

## B-1 References ____________________________________________________________________

4739H 

### B-6 

## A NNEX 

## C. E PIDEMIOLOGY 

## S TUDIES 

## __________________________________________ 470H 

## C-1 References ___________________________________________________________________

471H 

### C-99 

## A NNEX 

## D. C ONTROLLED 

## H UMAN 

## E XPOSURE 

## S TUDIES 

## ____________________________ 472H 

## D-1 References ____________________________________________________________________

473H 

### D-4 

## A NNEX 

## E. T OXICOLOGICAL 

## S TUDIES 

## _________________________________________ 47H 

## E-1 References ___________________________________________________________________

475H 

### E-23January 2010 viii 

# List of Tables

0H Table 1-1. Aspects to aid in judging caus ality.__________________________________________________________

476H 1-13

1H Table 1-2. Weight of evidence for causal deter mination.__________________________________________________

47H 1-14

2H Table 2-1. Causal determinations for health effects categories. _____________________________________________

478H 2-5

3H Table 2-2. Range of mean and 99th percentile concentrati ons (ppm) in US and Canadian studies of short-term CO exposure and CVD hospita lizations._____________________________________________

479H 2-15

4H Table 3-1. Literature values for CO yields from hydr ocarbons in per carbon units, except as noted. Specific hydrocarbons ar e noted in parentheses. ______________________________________________

4750H 3-10

5H Table 3-2. Performance specifications for analytical detection of CO, based on 40 CFR Part 53. __________________

4751H 3-18

6H Table 3-3. Counts of CO monitors by sampling scale meet ing 75% completeness criteria for use in the U.S. during 2005-2007. __________________________________________________________________

4752H 3-21

7H Table 3-4. Proximity to CO monitors for the total populati on by city._________________________________________

4753H 3-27

8H Table 3-5. Proximity to CO monitors for adults aged 65 and older by city. ____________________________________

475H 3-28

9H Table 3-6. Distribution of 1-h avg CO concentr ation (ppm) derived from AQS data._____________________________

475H 3-31

10H Table 3-7. Distribution of 24-h avg CO concentr ation (ppm) derived from AQS data.____________________________

4756H 3-33

1H Table 3-8. Distribution of 1-h daily max CO c oncentration (ppm) derived from AQS data. ________________________

475H 3-34

12H Table 3-9. Distribution of 8-h daily max CO c oncentration (ppm) derived from AQS data. ________________________

4758H 3-35

13H Table 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. ________________________________________________________________

4759H 3-40

14H Table 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. ____________________________________________________________

4760H 3-46

15H Table 3-12. National distribution of all hourly observati ons, 1-h daily max, 1-h daily average, and 8-h daily max concentration (ppm) deriv ed from AQS data, based on monitor scale designations, 2005-2007. _________________________________________________________________

4761H 3-53

16H Table 3-13. Percentage of time exposed to ambient CO (adj usted to reflect the absence of nonambient CO from ETS and gas cooking), average CO exposures, and percentage of exposure estimated for t he population. ______________________________________________________________

4762H 3-86

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

4763H 4-9

18H Table 4-2. CO concentration in pmol/mg wet weight ti ssue and fold tissue CO concentration changes (normalized to background ti ssue concentrations) – human.______________________________________

476H 4-16

19H Table 5-1. Responses to CO exposures at low and moderate concentrations. _________________________________

4765H 5-8

20H Table 5-2. Tissue concentration of CO fo llowing inhalati on exposure. _______________________________________

476H 5-10

21H Table 5-3. Tissue concentration of CO fo llowing increased endogenous production.____________________________

476H 5-11

2H Table 5-4. Summary of studies investigating the effect of CO exposure on HRV parameters._____________________

4768H 5-16

23H Table 5-5. Summary of studies investigating the effect of CO exposure on cardiac arrhythmias. __________________

4769H 5-18January 2010 ix 24H Table 5-6. Summary of studies investigating the effe ct of CO exposure on blood markers of coagulation and inflammation. _____________________________________________________________

470H 5-23

25H Table 5-7. Summary of CHD hospita l admission studies. a ________________________________________________ 471H 5-28

26H Table 5-8. Summary of stroke hospital admission studies. a _______________________________________________ 472H 5-31

27H Table 5-9. Summary of CHF hospita l admission studies. _________________________________________________

473H 5-33

28H Table 5-10. Association of ambient air pollution levels and cardiovascular morbidity in visits with and without specific se condary conditions. _______________________________________________________

47H 5-34

29H Table 5-11. Summary of nonspecific CVD hos pital admissi on studies.________________________________________

475H 5-37

30H Table 5-12. Brief summary of PTB studies._____________________________________________________________

476H 5-53

31H Table 5-13. Brief summary of birt h weight studies. _______________________________________________________

47H 5-59

32H Table 5-14. Behavioral re sponses. ___________________________________________________________________

478H 5-69

3H Table 5-15. Neuronal responses. ____________________________________________________________________

479H 5-72

34H Table 5-16. Neurotransmitter changes. ________________________________________________________________

4780H 5-74

35H Table 5-17. Developing auditory system. ______________________________________________________________

4781H 5-76

36H Table 5-18. Cardiovascular and systemic developmental re sponses._________________________________________

4782H 5-78

37H Table 5-19. Range of CO concentrations reported in key respiratory morbidity studies that examined effects associated with s hort-term exposure to CO._____________________________________________

4783H 5-82

38H Table 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. _____________________________________

478H 5-89

39H Table 5-21. Range of CO concentrations reported in key respiratory morbidity studies that examined effects associated with l ong-term exposure to CO. _____________________________________________

4785H 5-96

40H Table 5-22. Range of CO concentrations reported in multi city studies that examine mortality effects associated with short-term exposure to CO. _________________________________________________

4786H 5-102

41H Table 5-23. Range of CO concentrations reported in single- city studies that examine mortality effects associated with short-term exposure to CO. _________________________________________________

478H 5-107

42H Table 5-24. Range of CO concentrations reported in U.S. -based studies that examine mortality effects associated with long-term exposure to CO. __________________________________________________

478H 5-110

43H Table 5-25. Range of definitions of “susceptible” and “vulnerable” in the CO literature. __________________________

4789H 5-115

4H Table 5-26. Adult U.S. population in 2007 with respirator y diseases and cardiovascular diseases._________________

4790H 5-117

45H Table A-1. Listing of all CO monitors currently in us e, along with their lim its of detection. ________________________

4791H A-8

46H Table A-2. Microscale monitors meeting 75% completeness criteria, 2005-2007. ______________________________

4792H A-9

47H Table A-3. Middle scale monitors meeting 75 % completeness crit eria, 2005-2007. ____________________________

4793H A-11

48H Table A-4. Neighborhood scale monitors meeting 75% completeness criteria, 2005-2007. ______________________

479H A-12

49H Table A-5. Urban scale monitors meeting 75% completeness criteria, 2005-2007. ____________________________

4795H A-15

50H Table A-6. Regional scale monitors meeting 75% completeness criteria, 2005-2007. __________________________

4796H A-15

51H Table A-7. Monitors meeting 75% completeness crit eria, 2005-2007 with no scale delared. _____________________

479H A-16

52H Table A-8. Numbers of high LOD and trace-level monitors in each state that met completeness criteria for 2005-2007. ________________________________________________________________________

4798H A-18January 2010 x 53H Table 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. _______________________________________________________________________

479H A-30

54H Table 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 hour ly CO monitors reporting to AQS in Atlanta, GA. _________________________________________________________________________________

480H A-33

5H Table 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. _________________________________________________________________________________

4801H A-36

56H Table 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.__________________________________________________________________________

4802H A-39

57H Table 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._________________________________________________________________________

4803H A-42

58H Table 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.__________________________________________________________________________

480H A-45

59H Table 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. ________________________________________________________________________

4805H A-48

60H Table 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. ___________________________________________________________________________

4806H A-53

61H Table 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. _____________________________________________

4807H A-55

62H Table 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. _____________________________________________

480H A-55

63H Table 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._____________________________________________

4809H A-56

64H Table 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. ____________________________________________

4810H A-56

65H Table 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. _________________________________________

481H A-57

6H Table 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. _______________________________________

4812H A-58

67H Table 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. ____________________________________________

4813H A-59

68H Table 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.___________________________________________

481H A-60

69H Table A-25. Comparison of distributional data for hourly, 1-h daily max, 24-h avg, and 8-h daily max data for Seattle, WA. ___________________________________________________________________

4815H A-60

70H Table 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. __________________________________________________________________

4816H A-61

71H Table B-1. Recent studies related to CO dosimetry and pharmacokinetics. ___________________________________

4817H B-1January 2010 xi 72H Table C-1. Studies of CO exposure and cardiovascular morbidity. __________________________________________

481H C-1

73H Table C-2. Studies of CO exposure and cardiovascula r hospital admissions and ED visits.______________________

4819H C-17

74H Table C-3. Studies of CO exposure and neonat al and postneonat al outcomes. _______________________________

4820H C-26

75H Table C-4. Studies of short-term CO ex posure and respiratory morbidity ____________________________________

4821H C-35

76H Table C-5. Studies of short-term CO exposure and resp iratory hospital admissions and ED visits. ________________

482H C-42

7H Table C-6. Studies of long-term CO expos ure and respiratory morbidity. ____________________________________

4823H C-65

78H Table C-7. Studies of short-term CO exposure and mortality. _____________________________________________

482H C-70

79H Table C-8. Studies of long-term CO exposure and mortality.______________________________________________

4825H C-94

80H Table D-1. Controlled human exposure studies. ________________________________________________________

4826H D-1

81H Table E-1. Human and animal studies. _______________________________________________________________

4827H E-1January 2010 xii 

# List of Figures

82H Figure 1-1. Identification of studies fo r inclusion in the ISA. _________________________________________________

482H 1-5

83H Figure 2-1. Excess risk estimates from epidemiologic studi es of short-term CO exposure and CVD hospitalizations along with author-report ed mean and AQS-derived 99th percentile CO concentrations. _________________________________________________________________________

4829H 2-15

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

4830H 3-3

85H Figure 3-2. Trends in anthropogenic CO emissions (MT) in the U.S. by source category for 1990 and 1996-2002. _____________________________________________________________________________

4831H 3-4

86H Figure 3-3. Surface air CO concentrations at Chebogue Point during the ICARTT campaign. ______________________

4832H 3-5

87H Figure 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. _____________________________________________________________________________

483H 3-7

8H Figure 3-5. Trends in subnational CO emissions in t he 10 U.S. EPA Regions for 1990 and 1996-2002. ______________

483H 3-7

89H Figure 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._________________________________________

4835H 3-8

90H Figure 3-7. Components of RF in 2005 resulting from emissions since 1750. (S) and (T) indicate stratospheric and tropospheric changes, respectively.___________________________________________

4836H 3-14

91H Figure 3-8. Integrated RF of year 2000 emissions ov er 20-yr and 100-yr time horizons.__________________________

4837H 3-15

92H Figure 3-9. Scatterplot comparing data from co-located monitors in Charlotte, NC. _____________________________

483H 3-19

93H Figure 3-10. Map of CO monitor locations in the U.S. in 2007. ______________________________________________

4839H 3-22

94H Figure 3-11. Map of CO monitor locations with respect to population density in the Denver, CO CSA, total popul ation. ________________________________________________________________________

480H 3-23

95H Figure 3-12. Map of CO monitor locations with respect to population density in the Denver, CO CSA, age 65 and older. _______________________________________________________________________

481H 3-24

96H Figure 3-13. Map of CO monitor locations with respect to population density in the Los Angeles, CA CSA, total population.____________________________________________________________________

482H 3-25

97H Figure 3-14. Map of CO monitor locations with respect to population density in the Los Angeles, CA CSA, age 65 and older. __________________________________________________________________

483H 3-26

98H Figure 3-15. County-level map of second-highest 1-h avg CO concentrations in the U.S. in 2007.___________________

48H 3-29

9H Figure 3-16. County-level map of second-highest 8-h avg CO concentrations in the U.S. in 2007.___________________

485H 3-30

10H Figure 3-17. Seasonal plots showing the variability in co rrelations 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. __________________________________________________________

486H 3-36

10H Figure 3-18. Map of CO monitor locations and maj or highways for Denver, CO._________________________________

487H 3-38

102H Figure 3-19. Box plots illustrating the distribution of 2005-2007 hourly CO concentrations in Denver, CO. ____________

48H 3-39

103H Figure 3-20. Intersampler correlation versus distance for monitors located within the Denver CSA.__________________

489H 3-41

104H Figure 3-21. Map of CO monitor locations and major highways for Los Angeles, CA._____________________________

4850H 3-42

105H Figure 3-22. Box plots illustrating the distribution of 2005-2007 hourly CO concentrations in Los Angeles, CA.___________________________________________________________________________

4851H 3-43January 2010 xiii 106H Figure 3-23. Intersampler correlation versus distance for moni tors located within the Los Angeles CSA.______________

4852H 3-48

107H Figure 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.____________________________________________________

4853H 3-50

108H Figure 3-25. Aerial view of the location of CO monitor I (m arked by the red pin) in Azusa, CA (Los Angeles CSA), depicting its proximity to mixed use land. Sc ale: 1 cm = 145 m. ______________________

485H 3-51

109H Figure 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. ______________

485H 3-52

10H Figure 3-27. Distribution of hourly CO concentrati on data by city and monitoring scale. ___________________________

4856H 3-55

1H Figure 3-28. Distribution of 1-h daily max CO concent ration data by city and monitoring scale. _____________________

4857H 3-56

12H Figure 3-29. Relative concentrations of CO and copollutants at various distances from the I-710 freeway in Los Angeles._________________________________________________________________________

485H 3-57

13H Figure 3-30. CO concentration time series 20 m and 300 m from the I-440 highway in Raleigh, NC. _________________

4859H 3-58

14H Figure 3-31. CO concentration profile 10 m from I-440 in Raleigh, NC, behind a noise barrier and in open terrain. ___________________________________________________________________________

4860H 3-59

15H Figure 3-32. Dimensionless tracer gas conc entration on the windward and leeward sides of the canyon plotted against the elev ation of the measurement ______________________________________________

4861H 3-60

16H Figure 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).__________________________________________________________________________________

4862H 3-61

17H Figure 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. _____________________________

4863H 3-63

18H Figure 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. ________________________________________________________

486H 3-64

19H Figure 3-36. Diel plot generated from weekday hourly CO data (ppm) for the 11 CSAs and CBSAs, 2005-2007. ____________________________________________________________________________

4865H 3-66

120H Figure 3-37. Diel plot generated from weekend hourly CO data (ppm) for the 11 CSAs and CBSAs, 2005-2007. ____________________________________________________________________________

486H 3-67

12H Figure 3-38. Seasonal plots showing the variability in co rrelations between hourly CO concentration and co-located hourly SO 2 , NO 2 , O 3 , PM 10 and PM 2.5 concentrations. __________________________________

4867H 3-68

12H Figure 3-39. Seasonal plots showing the variability in co rrelations between hourly CO concentration and co-located hourly SO 2 , NO 2 , O 3 , PM 10 and PM 2.5 concentrations for Denver, CO.______________________

486H 3-69

123H Figure 3-40. Seasonal plots showing the variability in co rrelations between hourly CO concentration and co-located hourly SO 2 , NO 2 , O 3 , PM 10 and PM 2.5 concentrations for Los Angeles, CA.__________________

4869H 3-70

124H Figure 3-41. Linear regression of n-butane and isopent ane concentration as a function of CO concentration, Riverside, CA.______________________________________________________________

4870H 3-71

125H Figure 3-42. Map of the baseline monitor sites used in this assessment to compute PRB concentrations._____________

4871H 3-73

126H Figure 3-43. Monthly (circles) and annual (squares) aver age CO concentrations (ppb), 2005-2007. _________________

4872H 3-74

127H Figure 3-44. Distribution of time that the sample populat ion spends in various environments, from the NHAPS. ______________________________________________________________________________

4873H 3-79

128H Figure 3-45. Hourly personal versus ambient CO conc entrations obtained in Baltimore, MD,_______________________

487H 3-84

129H Figure 3-46. Box plots of the ratio of personal to ambient concentrations obtained in Baltimore, MD, ________________

4875H 3-85January 2010 xiv 130H Figure 3-47. Comparison of in-vehicle (solid line) and outside-th e-vehicle (dotted line) results for (left) driving with windows closed and air conditioner in recirculat ing air mode, and (right) driving with windows closed and air c onditioner in fresh air mode. _______________________________________

4876H 3-89

13H Figure 4-1. Plot of fractional sensitivities of sele cted variables versus time of exposure. __________________________

487H 4-4

132H Figure 4-2. Simulated COHb formation fo r two 5-day workweeks.____________________________________________

487H 4-6

13H Figure 4-3. Overall structure of the Bruce and Br uce (2008, 193977) multi compartment model of storage and transport of CO. _______________________________________________________________

4879H 4-7

134H Figure 4-4. Predicted COHb levels in healthy commuters expo sed to various CO c oncentrations over a 60-min commute twice a day.______________________________________________________________

480H 4-10

135H Figure 4-5. Predicted COHb levels due to va rious endogenous CO production rates.____________________________

481H 4-11

136H Figure 4-6. Diagrammatic presentation of CO uptake and e limination pathways and CO body stores._______________

482H 4-12

137H Figure 4-7. O 2 Hb dissociation curve of normal human bl ood, of blood containing 50% COHb, and of blood with only 50% Hb because of anemia. __________________________________________________

483H 4-15

138H Figure 4-8. Changes in blood COHb after exposure to CO for a few minutes (A) or several hours (B), representing the biphasic nat ure of CO elimination._____________________________________________

48H 4-18

139H Figure 4-9. Predicted maternal and fetal COHb during per iodic exposure to CO (50 ppm for 16 h followed by 0 ppm for 8 h ). _______________________________________________________________

485H 4-21

140H Figure 4-10. Representative estimates of endogenous CO production rate s resulting from various conditions and diseases. _________________________________________________________________

486H 4-23

14H Figure 4-11. Representative COHb saturation resulting from various diseases and conditions. _____________________

487H 4-24

142H Figure 4-12. Representative exhaled CO conc entrations (ppm) resulting from various conditions plotted as fold increases over healthy human controls from each study.___________________________________

48H 4-25

143H Figure 5-1. Direct effect s of CO. _____________________________________________________________________

489H 5-12

14H Figure 5-2. Summary of effect estimates (95% confidence intervals) associated with hospital admissions for various forms of CHD. _______________________________________________________

4890H 5-27

145H Figure 5-3. Summary of effect estimates (95% confidence in tervals) associated with ED visits and hospital admissions for stroke. _____________________________________________________________

4891H 5-30

146H Figure 5-4. Summary of effect estimates (95% confidence intervals) associated with hospital admissions fo r CHF._____________________________________________________________________

4892H 5-32

147H Figure 5-5. Summary of effect estimates (95% confidence intervals) associated with hospital admissions fo r CVD._____________________________________________________________________

4893H 5-36

148H Figure 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 + PM 2.5 : red triangles; CO + PM 10 or TSP: purple triangles ) models. _________________________________

489H 5-38

149H Figure 5-7. Effect estimates from studies of ED visits and HAs for CVD outcomes other than stroke from single pollutant (CO only: black circ les) and gaseous copollutant models (CO + NO 2 , SO 2 and O 3 = green, blue, and orange tri angles, respectively). ____________________________________

4895H 5-39

150H Figure 5-8. Regression of the percent change in ti me to ST endpoint between the pre- and postexposure exercise tests ([postexpos ure–pre-exposure]/pre-exposure) and the measured blood COHb levels at the end of exercise for the 63 subjects combined. ____________________

4896H 5-42

15H Figure 5-9. Summary of effect estimates (95% confidence in tervals) for PTB associated with maternal exposure to ambient CO. _________________________________________________________________

4897H 5-52January 2010 xv 152H Figure 5-10. Summary of change in birth weight (95% conf idence intervals) associated with maternal exposure to ambient CO. _________________________________________________________________

489H 5-57

153H Figure 5-11. Summary of effect estimates ( 95% confidence intervals) for LBW associated with maternal exposure to ambient CO. _________________________________________________________________

489H 5-57

154H Figure 5-12. Summary of effect estimates (95% confidence in tervals) for SGA associated with maternal exposure to ambient CO. _________________________________________________________________

490H 5-58

15H Figure 5-13. Estimated effect (95% confidence interval s) on pulmonary function due to a 10th to 90th percentile increment change in pollutant concentration in single-pollutant models._____________________

4901H 5-84

156H Figure 5-14. Summary of associations for short-term exposure to CO and asthma symptoms, respiratory symptoms and medication use in asthmatic i ndividuals. _________________________________________

4902H 5-87

157H Figure 5-15. Summary of associations for short-term exposure to CO and respiratory hospital admissions. , ___________________________________________________________________________ 4903H 5-93

158H Figure 5-16. Summary of associations for short-term ex posure to CO and respiratory ED visits. ____________________

490H 5-95

159H Figure 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 pollu tant data. _________________________________________________________________

4905H 5-103

160H Figure 5-18. Summary of percent increase in total (nonaccidental) mortality for short-term exposure to CO from multici ty studies.________________________________________________________________

4906H 5-106

16H Figure 5-19. Summary of mortality risk estimates for long-term exposure to CO. _______________________________

4907H 5-113

162H Figure A-1. CO emissions density map and distribution for the state of Alaska and for Yukon-Koyukuk County in Alaska. _______________________________________________________________________

4908H A-1

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

490H A-2

164H Figure A-3. CO emissions density map and distribution for t he state of Massachusetts and for selected counties in Mas sachusetts. _______________________________________________________________

4910H A-3

165H Figure A-4. CO emissions density map and distribution fo r the state of Georgia and for selected counties in Georgia (Figure 1 of 2). _________________________________________________________

491H A-4

16H Figure A-5. CO emissions distribution for selected c ounties in Georgia (Figure 2 of 2).___________________________

4912H A-5

167H Figure A-6. CO emissions density map and distribution for the state of California and for selected counties in California. ____________________________________________________________________

4913H A-6

168H Figure A-7. CO emissions density map and distribution fo r the state of Alabama and for Jefferson County in Alabama. _____________________________________________________________________

491H A-7

169H Figure A-8. Map of CO monitor locations with respect to population density in the Anchorage CBSA, total popul ation. _______________________________________________________________________

4915H A-20

170H Figure A-9. Map of CO monitor locations with respect to population density in the Anchorage CBSA, ages 65 yr and older. ___________________________________________________________________

4916H A-20

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

4917H A-21

172H Figure A-11. Map of CO monitor locations with respect to population density in the Atlanta CSA, ages 65 yr and older. __________________________________________________________________________

4918H A-21

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

491H A-22January 2010 xvi 174H Figure A-13. Map of CO monitor locations with respect to population density in the Boston CSA, ages 65 yr and older. __________________________________________________________________________

4920H A-22

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

4921H A-23

176H Figure A-15. Map of CO monitor locations with respect to population density in the Houston CSA, ages 65 yr and older.________________________________________________________________________

492H A-23

17H Figure A-16. Map of CO monitor locations with respect to population density in the New York City CSA, total popul ation. _______________________________________________________________________

4923H A-24

178H Figure A-17. Map of CO monitor locations with respect to population density in the New York City CSA, ages 65 yr and older. ___________________________________________________________________

492H A-24

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

4925H A-25

180H Figure A-19. Map of CO monitor locations with respect to population density in the Phoenix CSA, ages 65 yr and older.________________________________________________________________________

4926H A-25

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

4927H A-26

182H Figure A-21. Map of CO monitor locations with respect to population density in the Pittsburgh CSA, ages 65 yr and older.________________________________________________________________________

4928H A-26

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

492H A-27

184H Figure A-23. Map of CO monitor locations with respect to population density in the Seattle CSA, ages 65 yr and older. __________________________________________________________________________

4930H A-27

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

4931H A-28

186H Figure A-25. Map of CO monitor locations with respect to population density in the St. Louis CSA, ages 65 yr and older.________________________________________________________________________

4932H A-28

187H Figure A-26. Map of CO monitor locations with AQS Site IDs for Anchorage, AK._______________________________

493H A-29

18H Figure A-27. Box plots illustrating the seasonal distributi on of hourly CO concentrations in Anchorage, AK. Note: 1 = winter, 2 = spring, 3 = summer, and 4 = fall on the x-axis. ___________________________

493H A-31

189H Figure A-28. Map of CO monitor locations with AQ S Site IDs for Atlanta, GA.__________________________________

4935H A-32

190H Figure A-29. Box plots illustrating the seasonal distribution of hourly CO conc entrations in Atlanta, GA. _____________

4936H A-34

19H Figure A-30. Map of CO monitor locations with AQS Site IDs fo r Boston, MA.__________________________________

4937H A-35

192H Figure A-31. Box plots illustrating the seasonal distribution of hourly CO c oncentrations in Boston, MA. _____________

4938H A-37

193H Figure A-32. Map of CO monitor locations with AQ S Site IDs for Houston, TX. _________________________________

493H A-38

194H Figure A-33. Box plots illustrating the seasonal distribution of hourly CO conc entrations in Houston, TX. ____________

490H A-40

195H Figure A-34. Map of CO monitor locations with AQS Site IDs for New York City, NY. ____________________________

491H A-41

196H Figure A-35. Box plots illustrating the seasonal distributi on of hourly CO concentrations in New York City, NY. _____________________________________________________________________________

492H A-43

197H Figure A-36. Map of CO monitor locations with AQS Site IDs fo r Phoenix, AZ. _________________________________

493H A-44

198H Figure A-37. Box plots illustrating the seasonal distribution of hourly CO c oncentrations in Phoenix, AZ._____________

49H A-46

19H Figure A-38. Map of CO monitor locations with AQS Site IDs fo r Pittsburgh, PA. _______________________________

495H A-47January 2010 xvii 20H Figure A-39. Box plots illustrating the seas onal distribution of hourly CO concentrations in Pittsburgh, PA. _________________________________________________________________________________

496H A-49

201H Figure A-40. Map of CO monitor locations with AQ S Site IDs for Seattle, WA. _________________________________

497H A-50

20H Figure A-41. Box plots illustrating the seasonal distribution of hourly CO conc entrations in Seattle, WA. _____________

498H A-51

203H Figure A-42. Map of CO monitor locations with AQ S Site IDs for St. Louis, MO. ________________________________

49H A-52

204H Figure A-43. Box plots illustrating the seasonal distribution of hourly CO conc entrations in St. Louis, MO.____________

4950H A-54

205H Figure A-44. Seasonal plots of correlations between hour ly CO concentration with hourly (1) SO 2, (2) NO 2 , (3) O 3 , (4) PM 10 , and (5) PM 2.5 concentrations for Anchorage, AK. ____________________________

4951H A-62

206H Figure A-45. Seasonal plots of correlations between hour ly CO concentration with hourly (1) SO 2 , (2) NO 2 , (3) O 3 , (4) PM 10 , and (5) PM 2.5 concentrations for Atlanta, GA. _______________________________

4952H A-63

207H Figure A-46. Seasonal plots of correlations between hour ly CO concentration with hourly (1) SO 2 , (2) NO 2 , (3) O 3 , (4) PM 10 , and (5) PM 2.5 concentrations for Boston, MA. _______________________________

4953H A-64

208H Figure A-47. Seasonal plots of correlations between hour ly CO concentration with hourly (1) SO 2 , (2) NO 2 , (3) O 3 , (4) PM 10 , and (5) PM 2.5 concentrations for New York City, NY. _________________________

495H A-65

209H Figure A-48. Seasonal plots of correlations between hour ly CO concentration with hourly (1) SO 2 , (2) NO 2 , (3) O 3 , (4) PM 10 , and (5) PM 2.5 concentrations fo r Phoenix, AZ. ______________________________

495H A-66

210H Figure A-49. Seasonal plots of correlations between hour ly CO concentration with hourly (1) SO 2 , (2) NO 2 , (3) O 3 , (4) PM 10 , and (5) PM 2.5 concentrations for Seattle, WA._______________________________

4956H A-67January 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. Envi ronmental 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. Envi ronmental 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 Envi ronmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC Dr. Barbara Buckley—National Center for Enviro nmental 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 Enviro nmental 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 Environm ental 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 Enviro nmental 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, NCJanuary 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 Em ployment 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 Environm ental 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, NCJanuary 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 Envi ronmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC Dr. Barbara Buckley—National Center for Enviro nmental 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 Enviro nmental 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 Environm ental 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 Enviro nmental 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 Environm ental 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, NMJanuary 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 Re search Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC Dr. Vernon Benignus—National Health and Environm ental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC Mr. Antonio Fernandez—Office of Transportation a nd 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 Re search Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC Dr. Vernon Benignus—National Health and Environm ental 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 Protecti on Agency, Research Triangle Park, NC Dr. Philip Bromberg—School of Medicine, Univ ersity of North Carolina, Chapel Hill, NC Dr. Matthew Campen—Lovelace Respiratory Research Institute, Albuquerque, NMJanuary 2010 xxii 

### Dr. Daniel Costa—National Program Director fo r 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 Enviro nmental 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 Planni ng 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 Environm ental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC Dr. Alan Vette—National Exposure Research Laborat ory, 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, NCJanuary 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, NCJanuary 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 H ealth, 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 Meteorol ogy, University of Maryland, College Park, MD Dr. Laurence Fechter, Research Service, Departme nt 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, Cent er 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 Environmen tal 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, CAJanuary 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:

21H 

### barry.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 20004January 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 prosthesisJanuary 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 BK Ca voltage and Ca 2+ -activated K + channel(s) BP blood pressure BQ-123 endothelin A (ET A ) receptor antagonist BS black smoke BSP black smoke particles C a ambient concentration CA cardiac arrhythmia Ca 2+ 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 CdCl 2 cadmium chloride CFK Coburn-Forster-Kane CFR Code of Federal Regulations cGMP cyclic GMP CH 2 O formaldehydeJanuary 2010 xxviii CH 2 O 2 formic acid CH 3 methyl groups CH 3 CHO acetaldehyde CH 3 CO acetyl radical(s) CH 3 CO 3 NO 2 PAN, peroxyacetyl nitrate CH 3 O 2 methyl peroxy radical CH 3 OOH methyl hydroperoxide CH 4 methane ChAT choline acetyl-transferase CHD coronary heart disease CHF congestive heart failure CI confidence interval(s) CIS cerebral ischemic stroke C

j airborne concentration at location j CL/P cleft lip with or without palate CNS central nervous system CO carbon monoxide CO 2 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 D L lung diffusing capacity D L CO lung diffusing capacity of COJanuary 2010 xxix D m CO 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/dt LV left ventricular maximal and minimal first derived pressure (+dP/dt LV , -dP/dt LV ) dP/dt RV right ventricular maximal and minimal first derived pressure (+dP/dt RV , -dP/dt RV ) DSA deletion/substitution/addition E exposure over some duration E a exposure to pollutant of ambient origin EC elemental carbon ED emergency department EKG, ECG electrocardiogram E na 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 ET A endothelin A (ET A ) 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) FEF 25-75 forced expiratory flow between the times at which 25% and 75% of the vital capacity is reached FEM Federal equivalent method FEV 1 forced expiratory volume in 1 second f i fraction of time spent indoors F I CO fractional concentration of CO in ambient air F inf infiltration factorJanuary 2010 xxx f o 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 H 2 O 2 hydrogen peroxide H9c2 rat embryonic cardiomyocytes Hb hemoglobin HC(s) hydrocarbon(s) HCFC(s) hydrochlor ofluorocarbon(s) HCO formyl radical HEAPSS Health Effects of Air Pollution among Susceptible Subpopulations HEK293 human embryonic kidney cells (expe rimentally 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-1 α hypoxia-inducible factor HO heme oxygenase HO 2 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) h

ν 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 I to transient outward current IUGR intrauterine growth restriction K + potassium ion k dissociation rate k CO dissociation rate of carbon monoxide from hemoglobin K

m Michaelis Constant; Michaelis-Menten equation of enzyme kinetics k O2 Dissociation rate of oxygen from hemoglobinJanuary 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 th e 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 em ission factor model MODIS Moderate Resolution Imaging SpectroradiometerJanuary 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 MVO 2 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- κ B 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 NO 2 nitrogen dioxide NOAA National Oceanic and Atmospheric Administration NOAEL no observed adverse effect level NO • -Hb nitrosyl bound HbJanuary 2010 xxxiv NO • -Mb nitrosyl bound Mb NO X nitrogen oxides, oxides of nitrogen NRC National Research Council NTS nucleus of the solitar y tract (in brainstem) O 3 ozone O 2 Hb oxyhemoglobin (% concentration in mL O 2 / mL blood) O 2 Mb 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 absolu te difference in concentrations P A alveolar pressure PA pulmonary artery (myocytes) PACF partial auto-correlation functions P A CO alveolar pressure for carbon monoxide PAF platelet activating factor PAH polycyclic aromatic hydrocarbon PAHT pulmonary artery hypertension PAN peroxyacetyl nitrate (CH 3 CO 3 NO 2 ) P A O 2 alveolar pressure for oxygen P a O 2 arterial oxygen pressure PARP poly(ADP-ribose) polymerase P B barometric pressure (in mmHg) PBN N-tert-butyl-alpha-phenylnitrone P C average partial pressure in lung capillaries pCO partial pressure of CO P C O 2 average partial pressure of O 2 in lung capillaries PDGF platelet derived growth factor PEE prediction equation estimatesJanuary 2010 xxxv PEF peak expiratory flow PEFD(s) Personal Exposures Frequency Distributions PEM(s) personal exposure monitor(s) P H2O saturation pressure of water vapor PHD pulmonary heart disease P I partial pressure of inhaled air Pi inorganic phosphate PI3K phosphoinositide 3-kinase P I CO CO partial pressure in inhaled air PIH primary intracerebral hemorrhage PKB protein kinases B PM particulate matter PM 2.5 particulate matter with a nom inal mean aerodynamic diameter less than or equal to 2.5 μ m (referred to as fine PM) PM 10 particulate matter with a nominal mean aerodynamic diameter less than or equal to 10 μ m PM 10-2.5 particulate matter with a nomin al mean aerodynamic diameter greater than 2.5 μ m and less than or equal to 10 μ m (referred to as thoracic coarse particulate matter or the course fraction of PM 10 ). Concentration may be measured or calculated as the difference between measured PM 10 and measured PM 2.5 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 PNN 50 proportion of interval differences of successive normal-beat intervals greater than 50 ms in EKG PNS peripheral nervous system pO 2 partial pressure of oxygen in lung capillaries pPRB policy-relevant background PT prothrombin time PTB preterm birth PVCD peripheral vascular and cerebrovascular disease PvO 2 venous oxygen tension PVO 2 peak oxygen consumption Q cardiac output QCP Quantitative Circulatory PhysiologyJanuary 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 interv als 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 SF 6 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 strainJanuary 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 SO 2 sulfur dioxide SO 4 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 infectionJanuary 2010 xxxviii USC U.S. Code V A alveolar ventilation Vb blood volume V CO endogenous CO production rate V D Dead space volume V E ventilation rate VEGF vascular endothelial growth factor VLF very low energy frequency (HRV parameter) V max maximum velocity VO 2 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