Environmental Health

1. Environmental Health Air pollution Week 8 C&D Chapters 15, 24 and 28

2. What is air pollution The result of emission into the air of hazardous substances at a rate that exceeds the capacity of natural processes in the atmosphere to convert, deposit, or dilute them…

3. Factors that affect air pollution • Emissions (traffic, industrial, domestic) • Geography (terrain) • Weather conditions (rain, winds, humidity) • Season • Time of day • Population density • Indoor vs outdoor

4. Types of air pollution • Gases • COx • SOx • NOx • PAH • Aerosols • Particulates solid phase • Dust • Ash • Fumes • Solid and liquid • Smoke (from combustion) • Coastal aerosols • Liquid • Aggregate gases (sulfate, nitrate)

5. Six primary or “criteria” air pollutants • Carbon monoxide (CO) • Ozone (O3) • Nitrogen dioxide (NO2) • Sulfur oxides (SOx) • PM2.5 and PM10 • Lead (Pb)

6. Types of air pollution • Individual pollutants • Reducing pollution (SO2) • Acid rain (fog) • Corrosive, eroding • Photochemical pollution • Aldehydes, electrophilic HCs • Oxidative, carcinogenic? • Mixtures and complex patterns

7. Types of Exposures: Continuous Repeated Low High (acute) Respiratory response (endpoints): Macroscopic (e.g. coughing, FEV) Histological Marked variability in responses - susceptibility

8. Combustion pollutants • VOCs • NOx • N-organics • Halo-organics • Metals • CO

9. Sources of combustion • Tobacco • Power plants • Incinerators • Automobiles • Industry

10. Diesel pollutants • Particulate matter • C + PAHs + N-aromatics • Gases • NOx, CO, SOx • VOCs • formaldehyde, acrolein, aldehydes • Respiratory inflammation • Cytotoxicity to airway cells

11. Outdoor air pollution Beijing Delhi

12. Outdoor air pollution Santiago Mexico City

14. Indoor pollutants • Non-specific symptoms • Household vs work space • Sick building syndrome (20% exposed) • Cigarette smoke, combustion products • Organic offgasing (glue, fabrics, furnishings) • Biological agents (infections, allergens) • Additional factors (stress, fatigue, diet, alcohol)

15. Indoor air pollution: Poor countries

17. In the lungs… • Site of deposition along tract • Solubility in respiratory fluids • Reactivity with membranes • Infiltration (alveolar gas exchange) • Level of exposure • Duration of exposure • Respiratory rate • Pre existing conditions (heart, lung)

18. Absorption in lungs • As gas, directly into blood stream • As particles, deposited onto bronchiolar and alveolar surface • Uptake by phagocytosis • Trigger of inflammatory response • Trigger of allergic response • Lung tissue scaring

20. Basic structure of respiratory tract

21. Measurements of lung volume

22. Typical lung volume measurements from normal lung, obstructive airway disease, and restrictive lung disease

23. Normal, Obstructive and Restrictive Patterns of Forced Expiration FVC = forced vital capacity FEV1 = forced expiratory volume at 1st second of active exhalation FEF25-75 = maximal mid-expiratory flow rate FEF75 = forced expiratory flow after 75% of expelled volume

24. Particulate matter pollution • Properties - varied Mixture of solid phase and absorbed materials (organic, inorganic and biological) Carbonaceous core 40-60%, C 7% • Sources • Combustion - oil and coal • Industry • Automobiles • Tobacco smoke • Biomass burning • Metal smelters NAAQS: PM10: 50ug/m3, annual 150ug/m3, 24h PM2.5 15ug/m3, annual 65ug/m3, 24h

25. Particulates - features • Physical size • Large • Small ~10um • Fine ~2.5um • Aerodynamic diameter (size equivalent of density=1) • Large - local irritation (>100um) • Inhalable (<100um) • Thoracic fraction (<20um) • Coarse PM10 (<10um) • Fine PM2.5 (<2.5um) • Ultrafine (<0.1um) • Chemical reactivity • Shape (fibers) • Water content respirable

26. Deposition of particles in humans

27. Parameters influencing particle deposition

28. Alveolar injury and responses

29. Urban Particulates • In the <2.5um range • Large water content, trace metals, acid gases, organic chemicals, biological • Rather uniform distribution • Include diesel

30. Health effects of particulate pollutants - starting at 10ug/m3 • Eye irritation • Respiratory tract infection • Exacerbation of asthma • Bronchial irritation • Heart disease • Possibly cancer (controversial) (diesel, TiO2, talc, carbon black, toner black) • Elevated hospital admissions, mortality • Causation(s) not fully understood

31. Gaseous pollutant features • Chemical reactivity (ozone) • Solubility in water • Soluble • Ambient (NOx, SOx) • Occupational (Hydrochloric acid, Ammonia) • Less soluble • H2S, ozone

32. Gas pollutants - SO2 NAAQS: 0.03ppm, annual 0.14ppm, 24h • Properties • Reacts with H2O and forms sulfurous acid (H2SO3), which oxidizes to sulfuric acid (H2SO4) • Chemical transformation of other pollutants • Responsible for acid rain effect • Sources • Biomass and fossil fuel combustion • Industrial emissions, smelters • Controls • Low-S fossil fuels (clean coal) • Emission control devices • London fog episode (acute)

33. SO2 …continued • Absorption at upper respiratory tract (sulfite, bisulfite) • Health effects (starting at <1ppm) • Respiratory tract irritation, bronchoconstriction • Pulmonary function impairment • Increased air flow resistance • Bronchitis • Exacerbation of heart diseases • Short acute: 2min 0.4-1ppm in asthmatics • Long term, low levels • Impairs immune pulmonary defenses • Susceptibility to infections

34. Gas pollutants - H2SO4 • Product of SO2 • With metals and water --> sulf. Fly ash and acid rain • Protonates biomolecules - membrane damage • Bronchoconstriction • Increased air flow resistance • Mucus secretion protects (buffer) - nose inhalation • Asthmatics are more sensitive • Acidity interferes with mucociliary clearance • Chronic exposure to 100g/m3 : lower respiratory damage, macrophage mediated

35. Gas pollutants -NO2 NAAQS: 0.05ppm, annual • Properties • Oxidant, less potent than O3 • Sources • NO oxidation • High To combustion (automobiles, power plants) • Indoor - kerosene, gas stoves, ETS • Silos in farming (75-100ppm) • Health effects - starting at 1.5-2ppm • Deep lung irritant - terminal bronchioles • Alveolar cells, ciliated epithelia, Clara cells • Similar to ozone but less inflammatory (if < 2-5ppm) • Enhanced infection, suppression of macrophage action • Peaks more

36. Gas pollutants - CO NAAQS: 9ppm, 8h 35ppm, 1h • Properties • Odorless, heavier than air, stronger binder to Hb than O2 • Sources • Incomplete combustion • Traffic (inside the car, parking garages, tunnels is highest) • Inside cars = 3x urban streets, and = 5x residential streets • Health effects • Asphyxiant • Fatigue, confusion, headaches, dizziness, cardiac function (arrhythmias, angina) • Start at 2.5% COHb (0.5% baseline) (air level 50ppm for 90min) 2ppm COHb, no effect >5ppm COHb, cardiovascular effects 40ppm COHb, is fatal

37. Gas pollutants - O3 NAAQS: 0.12ppm, 1h 0.08ppm, 8h Good O3 - stratosphere Bad O3 - troposphere • Properties • Short lived, highly reactive, water soluble • Scrubbed in nasopharynx • Reaches terminal bronchioles and alveoli • Sources • Photochemical reactions • Health effects • Degenerative lung disease • Loss of lung function

38. uv Twist: In absence of HC- the reaction reaches equilibrium Car emitted HC- (PAH) react with O. …. Photochemical pollution NO2 NO + O O2 + O O3 O3 + NO O2 + NO2

39. Hydrocarbons shift photochemical reaction… HC- + O. Oxidized free radicals NO NO2 + Aldehydes Balance of photochemical reaction shifts toward O3 build-up!! O3

40. uv NO2 O2 Hydrocarbons Photochemical pollution O3 The O3 molecule is highly reactive O2. O3 O . 2 (HO.) H2O • Ultimate toxicant: • No enzyme can detoxify it • Only protection: prevention of its formation

41. Effects of Ozone on lung function FEV 0.5ml (Kinney et.al, 1996) ppb 1 0.12 - 0.4 ppm for 2-3 h FVC and FEV1

42. 0.30 300 0.24 240 0.20 200 180 0.18 0.12 120 0.10 100 90 0.09 0.08 80 70 0.07 0.06 60 50 0.05 0.04 40 0.02 20 Ozone levels ppm ppb LA, until 1998 LA, 1h-ave EU 1h ave LA, 8h-ave US-EPA 1h ave Italy study (low exposure) Effects on lung function observed WHO 1h ave US-EPA 8h ave WHO 8h ave Baseline

43. Ambient O3, TSP and SO2

44. Some nomenclature of oxidative species O Aldehydes R C Alcoxyl radical RO . (RO.) Alkoperoxyl radical RO2. (ROO.) Nitrous acid HONO Nitric acid HONO2 Hydroxyl radical HO .(HO.) Hydroperoxy radical HO2. (HOO.) H

45. Effects of O3 on proteins: Oxidation of: Aminoacids targets: • cystein • methionine • tryptophan • tyrosine • sulphydryls • amines • alcohols • aldehydes Inactivation/inhibition of enzymes in cellular compartments

46. H2O Effects of O3 on lipids: • Polyunsaturated fatty acids (PUFA): • primary target of O3 peroxidation of membrane lipids • Most important mechanism of O3-induced injury • O3 + PUFA carbonyl oxide aldehydes Hydroxyhydroperoxy compound HO. H2O2 Lipid peroxidation cascade Malondialdehyde (MDA) 8-isoprostane LTB4 (PMN chemotractant) Lipid fragmentation

47. Lipid peroxidation cascade

48. Effects on nucleic acids Electrophiles react with strong nucleophilic atoms of nucleic acids DNA + HO. Imidazole ring-opened purines or ring-contracted pyrimidines Strand breaks Blocked DNA replication Formation of adducts depurination (apurinic sites: mutagenic)

49. Effects of O3 on lung function • Decrement of lung function (FEV1 and FVC1) • Increased airway responsiveness (non specific) • Increased epithelial permeability, injury and loss • May influence allergic sensitization and responsiveness • May increase sensitivity to infections • Induces inflammatory reactions following injury • Exercise increases air flow and penetration

50. H+ NO2. Inflammatory oxidative burst • Three pathways of HO. generation: • NAD(P)H oxidase • Nitric oxide synthase (NOS) • Myeloperoxidase (MPO) L-citruline NOS L-arginine + O2 NO. Fenton HO. Oxidase NAD(P)H + O2 O2. NAD(P)+ H+ H20 O2 Cl- MPO HOOH + H+ +Cl- HOCl