Ambient Air Toxics & Acute Human Health Effects

1. 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; hamilton@bcm.tmc.edu

2. OUTLINE • AIR TOXICS…WHAT ARE THEY? • HOW DO WE MEASURE EXPOSURE? • 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? • SELECTED AAT HEALTH STUDIES • BCM HC AP & ADMITS STUDY • THE “AH, DUH” FACTOR

3. 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) - NATA (N = 33) - TRI (N = 650) - NEPM-AT (N = 6) - Calif TACs (N = 224) - 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?

4. 1. AcetaldehydeACP 2. Acetamide P 3. Acetonitrile 4. Acetophenone P 5. 2-acetylaminofluorene 6. AcroleinACP 7. Acrylamide P 8. Acrylic acid P 9. AcrylonitrilP 10. Alkyl chloride P 11. 4-aminobiphenyl C 12. Aniline CP 13. o-Anisidine 14. Antimony compounds P 15. Arsenic compoundsP 16. Asbestos P 17. BenzeneACP 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 25. Bromoform 26. 1,3-butadieneC 27. Cadmium compoundsACP 28. Calcium cyanamide P 29. CaprolactamA 30. Captan P 31. Carbaryl AP 32. Carbon disulfide P 33. Carbon tetrachlorideP 34. Carbonyl sulfide C 35. Catechol C 36. Chloramben P 37. Chlordane P 38. Chlorine AP 39. Chloroacetic acid P 40. 2-chloroacetophenone 41. Chlorobenzene P 42. Chlorobenzilate P 43. ChloroformP 44. Chloromethyl methyl etherA 45. Chloroprene 46. Chromium compoundsACP 47. Cobalt compounds AP 48. Coke oven emissionsA 49. Cresols/Cresylic acid CP 50. o-Cresol CP 51. m-Cresol CP 52. p-Cresol CP 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-dichloropropeneP 65. Dichlorvos P 66. DiethanolamineAP 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 sulfateA 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 P 84. Ethyl carbamate 85. Ethyl chloride P 86. Ethylene dibromideP 87. Ethylene dichlorideP 88. Ethylene glycol P 89. Ethylene imineA 90. Ethylene oxideA 91. Ethylene thiourea P 92. Ethylidene dichloride 93. FormaldehydeACP 94. Glycol ethers P 95. Heptachlor P 96. HexachlorobenzeneP = 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

5. The 188 HAPS continued 97. Hexachlorobutadiene 98. Hexachlorocyclopentadiene P 99. Hexachloroethane P 100. Hexamethylene-1,6-diisocyanate 101. Hexamethylphosphoramide 102. Hexane 103. HydrazineACP 104. Hydrochloric acid A 105. Hydrogen fluoride A 106. Hydrogen sulfide AP 107. Hydroquinone CP 108. Isophorone P 109. Lead compoundsP 110. Lindane P 111. Maleic anhydride P 112. Manganese compoundsAP 113. Mercury compoundsAP 114. Methanol P 115. Methoxychlor P 116. Methyl bromide P 117. Methyl chlorideCP 118. Methyl chloroform 119. Methyl ethyl ketone P 120. Methyl hydrazine 121. Methyl iodide P 122. Methyl isobutyl ketone P 123. Methyl isocyanate AP 124. Methyl methacrylate A 125. Methyl tert butyl ether 126. 4,4-methylene bis P 127. Methylene chlorideP 128. Methylene diphenyl diisocyanate P 129. 4,4-methylenedianiline 130. Mineral fibers, fine 131. Naphthalene P 132. Nickel compoundsACP 133. Nitrobenzene P 134. 4-nitrobiphenyl 135. 4-nitrophenol 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 AP 147. Phosphorus P 148. Phthalic anhydride P 149. Polychlorinated biphenyls 150. Polycyclic organic matterC 151. 1,3-propane sultone 152. beta-propiolactone 153. Propionaldehyde CP 154. Propoxur (Baygon) P 155. Propylene dichloride 156. Propylene oxide P 157. 1,2-propylenimine 158. QuinolineCP 159. Quinone P 160. Radionuclides C 161. Selenium compounds P 162. StyreneAC 163. Styrene oxide 164. 2,3,7,8-tetrachlorodibenzo-p-dioxinAC 165. 1,1,2,2-tetrachloroethaneP 166. Tetrachloroethylene (perc)P 167. Titanium tetrachloride 168. Toluene CP 169. 2,4-toluene diamine 170. 2,4-toluene diisocyanateAP 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 AP 177. 2,4,6-trichlorophenol AP 178. Triethylamine 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)

6. Benzene 6 am Benzene 3 pm 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?...

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

8. 13.45 ug/m3 = 6.1 ppbV 1,3-butadiene

9. Monitored Concentrations of Outdoor HAPs

10. The Big Three…HC a strong contender…BUT lower PM levels…? http://www.epa.gov/air/data/geosel.html; **=30 minutes; ESL=Effect Screening Level; ND=No Data; RB=Risk Based

11. 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 developingNEPM 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

12. 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/

13. 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?

14. 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?

15. Differences in susceptibility, detoxification and repair • Metabolites in blood or urine • BD in fat Exposure (BD, EB, EBdiol, DEB) Internal dose Biologically effective dose Early response Altered structure-function Disease Progression • Dyspnea • Neurologic manifestations • Tumors • Leukemias • Lymphomas • Congenital abnormalities • Death • Alveolar uptake • Other pathways? • Inflammatory or immune response • DNA adducts • Hb adducts • Gene mutations • SCEs ? • Malformed sperm • Germ cell mutations • Survey • EH History • Ambient monitors • Proximity • Personal monitors • Chamber studies Risk modeling Simulations (PBPK modeling) 4. THE E-D RELATIONSHIP Example: 1,3-Butadiene

16. 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.

17. 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

18. Update of 6 Cities and ACS Studies • Mean increase and 95% CI for annual mortality increases per 10 µg.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 • CAP Major Prospective Studies • CAPs ~ ATTs? • Ongoing methodological refinement; confounder control • 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

19. 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… • 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) (right) % ­ hospital admissions for ischemic heart disease in persons >65 yr per 10 µg/m3 ­ PM10 for 0 & 1 average lag Samoli 2003 Le Tertre 2003

20. 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)

21. 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 • 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

22. 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 included1.27 (1.05-1.54) for 8-hr NO2 1.23 (1.02-1.48) for benzene1.37 (1.04-1.80) for formaldehyde 1.85 (1.11-3.08) for EC1.88 (1.12-3.17) for OC

23. 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

24. Coordinate System: NAD 1983, State Plane Texas,South Central, FIPS 4204, Feet Projection: Lambert Conformal Conic 337 4x4-km cells intersect Harris County 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 • Study Design • Mixed-level ecologic correlation analysis

25. 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

26. 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

27. 7. BCM HC AP & ADMITS STUDY continued • Geocoded hospital admissions (N = 29,900) Cardiovascular6,284 (17.1%) Respiratory2,946 (8.0%) Cardiorespiratory7,467 (20.4%) Other22,433 (61.2%)

28. 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

29. Clinton CMAQ-AT vs Obs 7. BCM HC AP & ADMITS STUDY continued • Pollutant concentrations from area monitors • Use IDL to run correlations

30. 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).

31. 7. BCM HC AP & ADMITS STUDYcontinued Median household income by cell. Dark green = < 25,000; red = > 70,000.

32. 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

33. 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)