Ambient Air Toxics & Acute Human Health Effects

Air Toxics: What We Know, What We Don’t Know, and What We Need to Know University of Houston Hilton, Houston, Texas October 17-18, 2005

Winifred J. Hamilton, PhD, SM Assistant Professor and Director Environmental Health Section Chronic Disease Prevention and Control Research Center Baylor College of Medicine, Houston, Texas 713.798.1052; [email protected]

OUTLINE

1.

2.

AIR TOXICS…WHAT ARE THEY?

HOW DO WE MEASURE EXPOSURE?

3.

4.

5.

ACUTE VS CHRONIC DISEASE?

HOW DO WE STUDY HEALTH EFFECTS?

 

THE 3 WORKSHOP QUESTIONS

 Do better exposure estimates lead to stronger associations?

Is it preferable to focus on acute or chronic health effects?

Do diseases correlate with exposure?

6.

SELECTED AAT HEALTH STUDIES 7.

8.

BCM HC AP & ADMITS STUDY THE “AH, DUH” FACTOR

Ambient Air Toxics & Acute Human Health Effects

1. AIR TOXICS…WHAT ARE THEY?



Air Toxics (ATs)



Definition:

“Gaseous, aerosol or particulate pollutants (other than the six criteria pollutants) which are present in the air in low concentrations with characteristics such as toxicity or persistence so as to be a hazard to human, plant or animal life” (EPHC NEPM, Australia)  Lists of key ATs vary and change: - HAPs (~ ATs N = 188) - TRI (N = 650) - Calif TACs (N = 224) - NATA (N = 33) - NEPM-AT (N = 6) Calif “Hot Spot” Program (N = 18) - Manmade chemicals on the market (N ~ 60,000) 

Criteria Air Pollutants (CAPs)

  O3, NO2, SO2, CO, PM, Pb What differentiates the 6 CAPs from the ATs?

1. Acetaldehyde A C P 2. Acetamide P 3. Acetonitrile 4. Acetophenone 6.

9.

Acrolein A C P 7. Acrylamide 8. Acrylic acid Acrylonitril P P P 10. Alkyl chloride P P 5. 2-acetylaminofluorene 11. 4-aminobiphenyl C 12. Aniline C P 13. o-Anisidine 14. Antimony compounds P 15.

Arsenic compounds P 16. Asbestos P 17.

Benzene A C P 18. Benzidine 19. Benzotrichloride 20. Benzyl chloride P 21.

Beryllium compounds 22. Biphenyl P 23. Bis(2-ethylhexyl) phthalate (DEHP) 24. Bis(chloromethyl)ether P

The 188 HAPS

25. Bromoform 26.

1,3-butadiene 27.

C Cadmium compounds 28. Calcium cyanamide P 29. Caprolactam A 30. Captan P 31. Carbaryl A P 32. Carbon disulfide P 33.

Carbon tetrachloride 34. Carbonyl sulfide C P 35. Catechol C 36. Chloramben P 37. Chlordane P 38. Chlorine A P 39. Chloroacetic acid 41. Chlorobenzene 42. Chlorobenzilate 43.

46.

Chloroform ether A 45. Chloroprene P P P P 40. 2-chloroacetophenone 44. Chloromethyl methyl Chromium compounds 47. Cobalt compounds A P 48.

Coke oven emissions A A C P A C P 49. Cresols/Cresylic acid C P 50. o-Cresol C P 51. m-Cresol C P 52. p-Cresol C P 53. Cumene P 54. Cyanide Compounds P 55. 2,4-D, salts and esters P 56. DDE P 57. Diazomethane A 58. Dibenzofurans 59. 1,2-dibromo-3-chloropropane A 60. Dibutylphthalate A 61. 1,4-dichlorobenzene 62. 3,3-dichlorobenzidene 63. Dichloroethyl ether P 64.

1,3-dichloropropene 65. Dichlorvos P 66. Diethanolamine A P P 67. N,N-diethyl aniline 68. Diethyl sulfate P 69. 3,3-dimethoxybenzidine 70. Dimethyl aminoazobenzene 71. Dimethyl carbamoyl chloride 72. 1,1-dimethyl hydrazine 73. Dimethyl phthalate P 74. Dimethyl sulfate A 75. 4,6-dinitro-o-cresol, and salts P 76. 2,4-dinitrophenol P 77. 2,4-dinitrotoluene 78. 1,4-dioxane P 79. 1,2-diphenylhydrazine 80. Epichlorohydrin P 81. 1,2-epoxybutane 82. Ethyl acrylate P 83. Ethyl benzene 85. Ethyl chloride P 84. Ethyl carbamate P 86.

Ethylene dibromide P 87.

Ethylene dichloride 88. Ethylene glycol P 89. Ethylene imine 90.

Ethylene oxide A A P 91. Ethylene thiourea 93.

Formaldehyde P 92. Ethylidene dichloride A C P 94. Glycol ethers P 95. Heptachlor P 96.

Hexachlorobenzene P

= 32/33 NATA HAPs (33 = diesel PM); A = Leikauf list of asthma HAPs; C = In cigarette smoke; P = Pesticide active ingredient (PAN)

The 188 HAPS

continued

97. Hexachlorobutadiene 98. Hexachlorocyclopentadiene P 99. Hexachloroethane P 100. Hexamethylene-1,6 103.

diisocyanate 101. Hexamethylphosphoramide 102. Hexane Hydrazine A C P 104. Hydrochloric acid A 105. Hydrogen fluoride A 106. Hydrogen sulfide A P 107. Hydroquinone C P 108. Isophorone P 109.

Lead compounds 110. Lindane P 111. Maleic anhydride P P 112.

113.

Manganese compounds Mercury compounds 114. Methanol P 115. Methoxychlor P 116. Methyl bromide P A P 117.

Methyl chloride C P 118. Methyl chloroform 119. Methyl ethyl ketone P 120. Methyl hydrazine A P 121. Methyl iodide P 122. Methyl isobutyl ketone P 123. Methyl isocyanate 126. 4,4-methylene bis 127.

132.

Methylene chloride diisocyanate 131. Naphthalene P 130. Mineral fibers, fine P Nickel compounds A P 124. Methyl methacrylate P 128. Methylene diphenyl P A 125. Methyl tert butyl ether 129. 4,4-methylenedianiline A C P 133. Nitrobenzene 135. 4-nitrophenol P 134. 4-nitrobiphenyl 136. 2-nitropropane 137. N-nitroso-n-methylurea 138. N-nitrosodimethylamine C 139. N-nitrosomorpholine 140. Parathion P 141. Pentachloronitrobenzene 142. Pentachlorophenol P 143. Phenol C 144. p-phenylenediamine 145. Phosgene A 146. Phosphine A P 147. Phosphorus P 148. Phthalic anhydride P 149.

150.

Polychlorinated biphenyls Polycyclic organic matter C 151. 1,3-propane sultone 152. beta-propiolactone 153. Propionaldehyde 155.

156. Propylene oxide 158.

Quinoline 159. Quinone 162. Styrene 165.

166.

P A C C P 160. Radionuclides C P C P 154. Propoxur (Baygon) 157. 1,2-propylenimine P Propylene dichloride 161. Selenium compounds P 163. Styrene oxide 164. 2,3,7,8-tetrachlorodibenzo -p-dioxin A C 1,1,2,2-tetrachloroethane Tetrachloroethylene (perc) 167. Titanium tetrachloride 168. Toluene C P P 169. 2,4-toluene diamine 170. 2,4-toluene diisocyanate A P 171. o-toluidine C 172. Toxaphene P 173. 1,2,4-trichlorobenzene P 174. 1,1,2-trichloroethane 175.

Trichloroethylene 176. 2,4,5-trichlorophenol A P 177. 2,4,6-trichlorophenol A P 178. Triethylamine P P 179. Trifluralin P 180. 2,2,4-trimethylpentane 181. Vinyl acetate P 182. Vinyl bromide 183. Vinyl chloride P 184. Vinylidene chloride 185. Xylenes (isomers and mixture) 186. o-xylenes 187. m-xylenes 188. p-xylenes

= 32/33 NATA HAPs (33 = diesel PM); A = Leikauf list of asthma HAPs; C = In cigarette smoke; P = Pesticide active ingredient (PAN)

2. HOW DO WE MEASURE EXPOSURE?

 

Survey (eg, use of pesticides) Microenvironments (eg, RIOPA)

 Personal monitors 

All outdoors (eg, Six City)

 Ambient monitoring network 

Geospatial

 Proximity, dispersion, CMAQ, TRI facilities, roadways… 

Variables that affect exposure

  “Events” (accidents, fireworks…) Activity, vehicle use, age, smoking… 

Which chemicals? What averaging schemas?...

Benzene 6 am Benzene 3 pm

COUNTY

Austin Brazoria Chambers Colorado Fort Bend Galveston Harris Liberty Matagorda Montgomery Walker Waller Wharton

TOTAL CENSUS 2000 POPULATION

23,497 241,769 26,031 20,390 354,452 250,158 3,400,578 70,154 37,957 293,768 61,758 32,663 41,188

4,854,363 2003 TRI ON-SITE RELEASES (LB)

44,748 39,115,132 386,193 35,673 2,234,522 13,699,267 42,853,740 38,413 352,651 722,517 14,173 12,131 89,093

99,598,253 # FAC

2 35 9 4 15 16 334 4 2 14 2 3 4

444 PER CAPITA (LB)

1.90

161.79

14.84

1.75

6.30

54.76

12.60

0.55

9.29

2.46

0.23

0.37

2.16

20.52

Hardin Jefferson Orange

TOTAL

48,073 252,051 84,966

385,090

27,176 5 0.57

23,267,161 5,912,238 49 12 92.31

69.58

29,206,575 66 75.84

http://www.epa.gov/triexplorer Population density, TRI & NPL Sites

13.45 ug/m3 = 6.1 ppbV 1,3-butadiene

Monitored Concentrations of Outdoor HAPs

Ambient Air Toxics & Acute Human Health Effects

The Big Three… HC a strong contender…BUT lower PM levels…?

STANDARDS (ppbV) HAP AND COUNTY (# sites in 2004, hourly) BENZENE

Harris (13,4) Jefferson (7,1) Los Angeles (8,0)

TxESL 1-hr TxESL Ann EPA Bench WHO EU 25.0 1.0 ~.07 RB MAXIMUM 24-HOUR AVG AT ANY MONITOR (ppbV) 2000 2001 2002 2003 2004

Note: EPA DB in ppbC (divide by 6 carbon for ppbV) 52.2 44.3 41.0 70.9 73.5 9.6 6.9 8.6 3.8 9.1 4.0 19.4 5.4 49.4 2.9

1,3-BUTADIENE

Harris (13,4) Jefferson (7,1) Los Angeles (4,0)

50.0 5.0 0.0 RB

Note: EPA DB in ppbC (divide by 4 carbon for ppbV) 48.8 87.6 49.5 72.2 37.4 14.0 0.9 37.0 1.2 9.2 1.0 14.8 0.8 22.4 0.5

FORMALDEHYDE

Harris (3,0) Jefferson (0,0) Los Angeles (7,0)

12.0 1.2 0.1 80**

Note: EPA DB in ppbC (divide by 1 carbon for ppbV) 78.0 15.8 17.5 51.3 20.1 ND 38.1 ND 44.6 ND 41.2 ND 46.0 http://www.epa.gov/air/data/geosel.html; **=30 minutes; ESL=Effect Screening Level; ND=No Data; RB=Risk Based ND 15.5

Measuring Risk



U.S. Rating Systems

 EPA’s NAAQSs     OSHA/NIOSH LD50 EPA’s IRIS TCEQ’s ESLs 

International

 WHO (IARC)  Australia’s EPHC is developing NEPM standards for 5 ATs: benzene, formaldehyde, benzo(a)pyrene, toluene and xylenes 

Weak areas in our understanding

 Low exposure, long duration     Subtle effects (cognition, endocrine disruption...) Multipollutant and cumulative effects Windows of harm, latency, lag times Differences in susceptibility



Measuring Health Risk from Air Toxics

National Air Toxics Assessment (NATA)

 Assesses risk from 32 of the 188 HAPS, plus diesel PM     Air Toxics Emissions Inventory …?

Estimate ambient concentrations across US …?

Estimate population exposures across US …?

Characterize public health risk (cancer and noncancer) …?

Relationship of estimated cancer risk from air toxics with median household income among Maryland census tracts, 2000 (Apelberg 2005) http://www.epa.gov/ttn/atw/nata/

3. ACUTE VS CHRONIC DISEASE

 

Acute Disease / Health Effects

 An illness or clinical symptoms that have a rapid onset and short but often severe course (eg, asthma or heart attack) 

Chronic Disease / Health Effects

 An illness or clinical symptoms that are prolonged, do not resolve spontaneously, and are rarely cured completely (eg, diabetes, cancer, multiple sclerosis, hypertension)

What differentiates chronic from acute disease?

 Reversibility? Easier causal connection?  Considerable blurring   Exacerbations (acute) often require chronic disease substrate What of acute exposure (eg, Bhopal) that leads to subsequent chronic disease state (eg, emphysema and CHF)?

 Is premature death an acute or chronic effect?

Measuring Disease



What endpoint?

 Biomarkers  BLLs, cotinine, DNA damage, PSA…    Community health questionnaire / survey Medication usage Clinic Visit  Signs (measurable, eg, FEV, eosinophils)  Symptoms (questionnaire, medical history)  Diagnosis    Hospitalization Emergency room visit Death 

Who, What, When and Where?

Ambient Air Toxics & Acute Human Health Effects

4. THE E-D RELATIONSHIP

Example: 1,3-Butadiene

Differences in susceptibility, detoxification and repair

• Metabolites in blood or urine • BD in fat

Exposure (BD, EB, EBdiol, DEB)

• Survey • EH History • Ambient monitors • Proximity • Personal monitors • Chamber studies

Internal dose

• Alveolar uptake • Other pathways?

Biologically effective dose

?

Early response Altered structure function

• Inflammatory or immune response • DNA adducts • Hb adducts • Gene mutations • SCEs • Malformed sperm • Germ cell mutations Risk modeling Simulations (PBPK modeling)

Disease Progression

• Dyspnea • Neurologic manifestations • Tumors • Leukemias • Lymphomas • Congenital abnormalities • Death

4. THE E-D RELATIONSHIP

continued



Types of studies

  Experimental and clinical trials Population (epidemiologic) studies   Case-control (retrospective) Cohort (prospective)   Ecologic Mixed 

Study methodologies

 Randomization, matching, spatial patterns, time-series, surveillance, questionnaire, molecular changes, controlling for confounding…  Money, time and availability of data are major constraints 

Take an environmental health / exposure history! Use a standardized form.

Ambient Air Toxics & Acute Human Health Effects

5. THE 3 WORKSHOP QUESTIONS



Do better exposure estimates lead to stronger associations?

  Probably…if you’re measuring the right things, if you understand the causal pathway (if it exists), if you adjust for confounders, if you have sufficient numbers….

Guard against waiting for the definitive study… 

Is it preferable to focus on acute or chronic health effects?

 Intertwined. Chronic disease is of more public health importance, but acute effects easier and cheaper to measure and more likely to find useful associations for regulatory decisions.



Do mortality and morbidity correlate with exposure?

   Correlation with CAPs, esp PM, strong across studies.

CAPs may in part be surrogates for ATs.

AT risk analyses suggest yes, but epi studies conflicting

Ambient Air Toxics & Acute Human Health Effects

6. SELECTED HEALTH STUDIES



CAP Major Prospective Studies

  CAPs ~ ATTs?

Ongoing methodological refinement; confounder control Update of 6 Cities and ACS Studies  Harvard 6-Cities Study (Dockery 1992, Lippman 2003, Krewski 2004)  8,111 adults in 6 US cities  FU 14-16 yr initial (b 1974-77)   ~ 26% mortality PM, sulfates Re-analyses find ~ same  American Cancer Society Study (Pope 1994, Lippman 2003, Krewski 2004)  295,223 adults in 50 US cities    FU 6 yr initial (b 1982) ~ 17% mortality PM Re-analyses find ~ same Mean increase and 95% CI for annual mortality increases per 10 µ g.m3 increment of PM2.5 based on 16 yr of mortality data. PM2.5 and sulfates associated with increased mortality from cardiovascular and pulmonary causes, as well as lung cancer.



6. SELECTED HEALTH STUDIES

continued

Major Retrospective Studies

  CAPs ~ ATTs?; Large Ns; refinement of methodologies APHEA: Air Pollution and Health - European Approach   30 European cities, extensive shared db and methodologies Multiple studies, publications (> 40), re analyses…  Samoli 2003 Le Tertre 2003 (right) % hospital admissions for ischemic heart disease in persons >65 yr per 10 µg/m3 PM10 for 0 & 1 average lag NMMAPS: National Morbidity, Mortality, and Air Pollution Study   90 US cities chosen by size; ~ 14-yr period Multiple studies, publications, re-analyses   10-ppb O3 in previous week = 0.52% mortality (Bell 2004) 0.41% mortality per 10 µg/m3 in PM10 (old GAM); 0.27% (new GAM); 0.21% (GLM) (Dominici 2005)



6. SELECTED HEALTH STUDIES

continued

Ambient Air Toxics

  Paucity of studies…focus on clarifying exposure Oxygenated urban air toxics and asthma variability in middle school children: A panel study  (Delclos G, in review) 29 labile asthmatic children, age 10-13, in the Aldine school district. Examines measures of lung function with personal exposure to air toxics, especially aldehydes. Confounders measured included other indoor and outdoor pollutants, air exchange rate, temperature, humidity and activity level.

 Increased risk of preterm delivery among people living near the three oil refineries in Taiwan  (Yang 2004) Compared 7,095 first-parity singleton births to mothers living within 3 km (1.86 miles) of 3 refineries with 10% random sample of births in rest of Taiwan (N=50,388) between 1/1/1994 and 12/31/1997. Controlled for multiple confounders.   Outcome variable of interest = preterm delivery (< 37 weeks).

AOR = 1.14 (1.01-1.28)

Ambient Air Toxics & Acute Human Health Effects



6. SELECTED HEALTH STUDIES

continued

Ambient Air Toxics

continued

 The impact of polycyclic aromatic hydrocarbons and fine particles on pregnancy outcome  (Dejmek 2000) Compared birth outcomes (IUGR) in two communities  Teplice and Prachatice; N = 3378 and 1505  Similar levels of c-PAHs but Teplice has higher PM2.5

 Similar results: for each 10 ng c-PAH in first gestational month, AOR 1.22 (1.07 – 1.39) for IUGR  Suggests earlier association seen with PM due to PAH component AORs of IUGR by exposure to c-PAH in different months of gestation, adjusted for parity, maternal age and height, prepregnancy weight, education, marital status, month-specific maternal smoking, season, rhythm, and year of the study.



6. SELECTED HEALTH STUDIES

continued

Ambient Air Toxics

continued

 Asthma symptoms in Hispanic children and daily ambient exposures to toxic and criteria air pollutants  (Delfino 2003) Panel study of 22 Hispanic asthmatic adolescents in LA  Measured CAPs plus EC-OC, 10 ATs, asthma symptoms  Significant AORs of asthma exacerbation associated with interquartile increase in pollutant concentrations included 1.27 (1.05-1.54) for 8-hr NO2 1.23 (1.02-1.48) for benzene 1.37 (1.04-1.80) for formaldehyde 1.88 (1.12-3.17) for OC 1.85 (1.11-3.08) for EC



6. SELECTED HEALTH STUDIES

continued

Ambient Air Toxics

 Effect of motor vehicle emissions on respiratory health in an urban area (Buckeridge 2002)   SE Toronto. Ecologic study design Age- and gender-adjusted 1990-1992 hospital admission (respiratory vs genitourinary) rates by 334 EAs  GIS used to create 10-m street buffers to estimate EA PM2.5 exposure based on daily traffic counts   Adjusted for SES RR = 1.24 (1.05-1.45) for respiratory subset (asthma, bronchitis, COPD, pneumonia, URI) for log10 in PM2.5

7. BCM HC AP & ADMITS STUDY



Objective

  To analyze spatial relationships between hospital admissions and air pollution, with special attention to air toxics, in 337 4 x 4 km domains in Harris County, Texas.

Year 1 August 2000; year 2 August – October 2000

Coordinate System: NAD 1983, State Plane Texas, South Central, FIPS 4204, Feet Projection: Lambert Conformal Conic



337 4x4-km cells intersect Harris County Study Design

 Mixed-level ecologic correlation analysis

Ambient Air Toxics & Acute Human Health Effects

  

7. BCM HC AP & ADMITS STUDY

continued

Key collaborators

    Baylor College of Medicine (Hamilton WJ, Ningthoujam SS) University of Houston (Byun DW, Coarfa V, Kim S) UT School of Public Health (Chan W, Li Y) US Environmental Protection Agency (Ching JKS)

Data sources

  Hospital admissions from THCIC RUDF Pollutant concentrations   CMAQ-AT model hourly concentrations for each cell Concentrations from are monitors (TCEQ)  Census 2000 data  Median household income, % minority, housing…

IRB approvals from TDSHS and BCM

Ambient Air Toxics & Acute Human Health Effects



7. BCM HC AP & ADMITS STUDY

continued

Hospital Admissions

 Hospital coverage  95 hospitals (77.6% of hospitals, 96.0% of beds)  Two significant omissions: LBJ (324 beds) Quentin Meese (75 beds)  HC residents admitted = 44,078  Exclusions = 7,350   Newborns = 6,885 Accidents = 465    No discharge diagnosis = 40 Total for geocoding = 36,688 Total geocoded = 29,900 (81.5%) N = 36,688

Ambient Air Toxics & Acute Human Health Effects



7. BCM HC AP & ADMITS STUDY

continued

Geocoded hospital admissions (N = 29,900) Cardiovascular

6,284 (17.1%)

Respiratory

2,946 (8.0%)

Cardiorespiratory

7,467 (20.4%)

Other

22,433 (61.2%)

  

7. BCM HC AP & ADMITS STUDY

continued

EPA’s CMAQ-AT Eulerian nested photochemical model

 MM5 meteorology  NEI99, augmented by NTI99 and TEI2000   SMOKE SAPRC99

BCM receives text files for each pollutant with hourly concentrations Generate for each cell for August 2000

     Mean maximum Mean of 24-hr avg 12-hr AM (6 a – 6 p) 12-hr PM (6 p – 6 a) AT score from rankings



7. BCM HC AP & ADMITS STUDY

continued

Pollutant concentrations from area monitors



Use IDL to run correlations BENZENE

4 3.5

3 2.5

2 1.5

1 0.5

0 8/ 21 8/ 22 8/ 23 8/ 24 8/ 25 8/ 26 8/ 27 8/ 28 8/ 29 8/ 30 8/ 31 Clinton CMAQ-AT vs Obs simulation observational Clinton

7. BCM HC AP & ADMITS STUDY

continued

Mean 24-hour CMAQ-AT generated ozone concentrations on August 1, 2000, in 337 4 x 4-km cells in Harris County. Red denotes the highest concentrations (35-45 ppbv) and the dark green denotes the lowest (9-25 ppbv).

7. BCM HC AP & ADMITS STUDY

continued

Median household income by cell. Dark green = < 25,000; red = > 70,000.

 

THE “AH, DUH” FACTOR

Convincing research is helpful…

   Drives regulations Significantly increases compliance Great education tool

However…

 Research should not be used to delay implementation of commonsense regulations or education to reduce exposure  Incentives for conservation, decreased vehicle use, decreased emissions   Elimination of unnecessary toxic processes / practices Education about personal exposure 

$ and political leadership needed to implement the “Ah, Duh” Stuff, now, while continuing research

Selected Sources

              Apelberg BJ, Buckley TJ, White RH. Socioeconomic and racial disparities in cancer risk from air toxics in Maryland. Environ Health Perspect 113:693-9(2005) Australia’s EPHC NEPM-AT program http://www.ephc.gov.au/nepms/air/air_toxics.html

EPA’s HAPs Database http://www.epa.gov/air/data/ Buckeridge DL, Glazier R, Harvey BJ, et al. Effect of motor vehicle emissions on respiratory health in an urban area. Environ Health Perspect 110:293-300.(2002) Delfino RJ, Gong H, Jr., Linn WS, Pellizzari ED, Hu Y. Asthma symptoms in Hispanic children and daily ambient exposures to toxic and criteria air pollutants. Environ Health Perspect 111:647-56(2003) Dominici F, McDermott A, Daniels M, Zeger SL, Samet JM. Revised analyses of the National Morbidity, Mortality, and Air Pollution Study: mortality among residents of 90 cities. J Toxicol Environ Health A 68:1071-92(2005) EPA’s Integrated Risk Information System http://www.epa.gov/iris/ EPA’s TRI Explorer http://www.epa.gov/triexplorer/ Leikauf GD. Hazardous air pollutants and asthma. Environ Health Perspect 110 Suppl 4:505-26(2002) Le Tertre A, Medina S, Samoli E, et al. Short-term effects of particulate air pollution on cardiovascular diseases in eight European cities. J Epidemiol Community Health 56:773-9(2002) Lippmann M, Frampton M, Schwartz J, et al. The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: A midcourse report of status, progress, and plans. Environ Health Perspect 111:1074-92(2003) National Air Toxics Assessment (NATA) http://www.epa.gov/ttn/atw/nata/ Payne-Sturges DC, Burke TA, Breysse P, Diener-West M, Buckley TJ. Personal exposure meets risk assessment: a comparison of measured and modeled exposures and risks in an urban community. Environ Health Perspect 112:589-98(2004) Yang CY, Chang CC, Chuang HY, Ho CK, Wu TN, Chang PY. Increased risk of preterm delivery among people living near the three oil refineries in Taiwan. Environ Int 30:337-42(2004)