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
 Aerosols
– Particulates solid phase
• Dust
• Ash
• Fumes
– Solid and liquid
• Smoke (from combustion)
• Coastal aerosols
– Liquid
– Aggregate gases (sulfate, nitrate)
 Gases
COx
SOx
NOx
PAH

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
Mexico City
Santiago

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
• 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
- starting at 10ug/m3

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
• 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)
NAAQS: 0.03ppm, annual
0.14ppm, 24h

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 100µg/m3
: lower respiratory damage,
macrophage mediated

35. Gas pollutants -NO2
• 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
NAAQS: 0.05ppm, annual

36. Gas pollutants - CO
• 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
NAAQS: 9ppm, 8h
35ppm, 1h

37. Gas pollutants - O3
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
NAAQS: 0.12ppm, 1h
0.08ppm, 8h

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

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

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

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

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

43. Ambient O3, TSP and SO2

44. 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
O
Some nomenclature of oxidative species

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

46. 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
H2O
Hydroxyhydroperoxy compound
HO
.
H2O2
Lipid peroxidation cascade
aldehydes
Lipid fragmentation
Malondialdehyde (MDA)
8-isoprostane
LTB4 (PMN chemotractant)

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

51. The lung’s defenses:
Antioxidant molecules:
 ascorbic acid (vit. C)
 a-tocopherol (vit. E)
 uric acid
 glutathione (GSH)
Metabolic enzymes:
 SOD
 Catalase
 GPX
 GSTs

52. • Hazardous air pollutants
– Not included in the 6 criteria air pollutants
• Include
– Organic chemicals (acrolein, benzene)
– Minerals (asbestos)
– PAH (benzo[a]pyrene)
– Metals (Hg, Be)
– Pesticides (carbaryl, parathion)
• Some are carcinogenic
Other air pollutants - HAPs

53. Volatile Organic Pollutants
(VOCs)
• Sources: Petroleum emissions, fuel combustion,
incineration, biomass burning
• Account for ~14% of all air pollution
• Important factor of indoor air pollution
• Types
– Aliphatic
– Alcohols (ethylene glycol, MTBE)
– Aldehydes (formaldehyde)
– Aromatic (benzene, toluene, xylene)
– Halogenated (TCE, PERC, Methylene Chloride)
– Polycyclic (PAHs)
– Other (Carbon disulfide)

54. VOCs Health Effects
• Alkanes (solvents, varnishes, lacquers)
– Irritants, lung and skin
– CNS depressants, neuron degeneration,
paralysis
– Pulmonary edema
– React with OH radical in photochemical
pollution

55. • Alkenes (gasoline and aviation fuel) more
reactive than alkanes - chains, oxides,
halogenated HC
– CNS effects - cramps, tremor
– GI tract - nausea, vomiting
VOCs Health Effects

56. Aldehydes
• Formaldehyde H2C=O
– 50% of total aldehydes
– Water soluble
– Steep dose-effect:
0.5-1ppm: odor
2-3ppm: mild irritation
4-5ppm: intolerable
– Scrubbed in upper respiratory tract, but can also reach
deeper
– Nasal cancer? (rodents but not humans)
• Acrolein H2C=CHCH=O
– 5% of total but more irritating

57. Aromatic hydrocarbons (stable, persistent) - Low water
solubility, volatile, flammable - Priority pollutants (EPA)
• Benzene - most basic
– Carcinogen (epoxide, phenol metabolites)
– CNS toxicity - narcosis
– Irritation (skin, lung)
• Toluene (more lipophilic, but faster metabolism)
– CNS depressant (narcosis, impaired coordination,
headaches)
• Xylene (o-, p-, m-) (very lipophilic)
– CNS depressant (as above)
– Blood cell damage, anemia
– Irritant (skin)
VOCs Health Effects

58. Polycyclic aromatic hydrocarbons (PAH) incomplete
combustion of organic materials, incineration, industry, natural processes
– 16 of 126 priority pollutants
– Environmental transport, accumulation
– Photo - bio- degradation
• Carcinogens exposure* (metabolic activation) -
• Air exposure 0.02-3ug/day
• Cigarette smoke 0.1-0.25ug/cig
• Unfiltered cigarettes 2-5ug/day
• Vegetarian diet 3-9ug/day
• Drinking water 0.2-120ng/day
• Soil (urban) 0.003-0.4ug/day
VOCs Health Effects
* Menzie et.al. 1992, Env. Sci and Technol. Vol. 26: p.1278

59. NAAQS - CAA 1990
• National Ambient Air Quality Standards
• ug/m3
or ppm
• National Air Quality and Emissions Trends
Report

60. NAAQ Standards for
six “criteria” pollutants
http://www.epa.gov/air/criteria.html
Pollutant Primary Stds. Averaging Times Secondary Stds.
9 ppm
(10 mg/m3)
35 ppm
(40 mg/m3)
Lead 1.5 µg/m3 Quarterly Average Same as Primary
0.053 ppm
(100 µg/m3)
Revoked(2) Annual(2) (Arith. Mean)
150 µg/m3 24-hour(3)
15.0 µg/m3 Annual(4) (Arith. Mean)
35 µg/m3 24-hour(5)
Ozone 0.08 ppm 8-hour(6) Same as Primary
0.12 ppm * 1-hour(7) Same as Primary
0.03 ppm Annual (Arith. Mean) -------
0.14 ppm 24-hour(1) -------
------- 3-hour(1) 0.5 ppm
(1300 µg/m3)
Particulate Matter
(PM10)
Sulfur Oxides
Particulate Matter
(PM2.5)
None
None
Same as Primary
Same as Primary
Nitrogen Dioxide
Carbon Monoxide
1-hour(1)
8-hour(1)
Annual (Arithmetic Mean)
*Applies only in limited areas

61. US Regulation history
• 1947 CA - Air pollution control Act
• 1955 - Truman’s Air pollution control Act
• 1963 Federal - Clean Air Act (1967 am)
• 1965 Federal - Motor vehicle Air pollution control Act
• 1970 The Clean Air Act: national level (EPA)
– O3, SO2, NO2, CO, PM, Pb, total hydrocarbons (dropped)
• 1970 Lead is banned as fuel additive
• 1990 CCA amendment: 118 chemicals, some carcinogenic
– Maximum achievable control technology
– Additional risk assessment if health effects beyond the MACT level
– Emission standards for motor vehicles (CO solution - MTBE new
problem)
• 1997 New standard for PM2.5

62. Clean Air Mercury and Interstate rules
• On March 15, 2005, EPA issued the Clean Air Mercury Rule to permanently
cap and reduce mercury emissions from coal-fired power plants for the first
time ever. This rule makes the United States the first country in the world to
regulate mercury emissions from utilities.
• On March 10, 2005, in a separate but related action, EPA issued the Clean Air
Interstate Rule (CAIR), a rule that will dramatically reduce air pollution that
moves across state boundaries.
• Together the Clean Air Mercury Rule and the Clean Air Interstate Rule create
a multi-pollutant strategy to reduce emissions throughout the United States.
http://www.epa.gov/air/mercuryrule/

63. Epi studies of air pollution
Outdoor studies predominantly
– Cohort studies (Harvard six cities; American Cancer Society;
Adventist Health Study of Smog)
– Biomarkers (breath, BAL, blood)
– Lung function (FEV1, FVC, FEF25-75)
– Symptoms (coughing wheezing, shortness of breath, cardiac
function)
– Long-term/chronic (confounders)
• Retrospective
• Prospective
– Time series
• National Morbidity, Mortality and Air Pollution Study (NMMAPS)
• Air Pollution and Health, a European Approach (APHEA)

64. Chronic effects of air pollution
• Los Angeles basin: “aging-like” effect on lung function
• Netherlands: 12y, SO2 and PM
• Rural PA: higher incidence of respiratory symptoms
• Harvard Six Cities Study: >15y, 20,000 people SO2 and
PM
• Overall reduced lung function, bronchitis
• Cancer risk: 2000/year vs 100,000/year from smoking -
associated with PM/VOC combinations

65. Relative contribution of individual air pollutants to
lung cancer rates after removing tobacco smoke
cancer (~85%)
PIC: products of
incomplete combustion

66. US emissions trend for VOCs, NOx, SO2,
and PM10, 1900-1990