Air Pollution

AIR POLLUTION
PAUL G. REINHART, PH.D., DABT, LORI WHITE, PH.D.,

JEE YOUNG KIM, SCD, LINDSAY WICHERS STANEK, PH.D., MSPH,
MARY ROSS, PH.D., AND BARBARA BUCKLEY, PH.D.
1 INTRODUCTION
The mere mention of air pollution conjures up visions of huge urban smokestacks
billowing voluminous clouds of brown, black, or gray and large city skyscrapers whose
spires disappear into the hazy clouds of smog that blanket large cities. However, air
pollution is a combination of both anthropogenic and natural origins. Air pollution has
been around for as long as we have had the forces of nature. Whether it be from dust or
sandstorms suspending particulate matter into the atmosphere, lightning strikes
causing fires which contribute combustion particles and gases, volcanic eruptions
spewing toxic particles and gases for miles, or meteorological inversions which trap
pollutants near the ground, preventing their dilution and dispersion into the atmosphere, nature plays a part in pollution. Nevertheless, the anthropogenic contributions
to air pollution have been significant and relentless. We have fouled the air to such an
extent that we can no longer see through it. What once were beautifully clear vistas,
enabling one to see many miles in any direction, have been reduced to a hazy few miles
in visibility. Our clean air has been replaced with an odorous substitute. One that not
only is aesthetically displeasing but also actually unhealthy to breathe for some
individuals.
It was during the height of the industrial revolution that the health effects of air
pollution in the cities became apparent. Many individuals became sick while others
Pattys Industrial Hygiene, Sixth Edition, Edited by Vernon E. Rose and Barbara Cohrssen
Copyright 2011 John Wiley & Sons, Inc.
2549
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AIR POLLUTION
died during very bad days of pollution. During the Great London Smog of 1952,
pollution levels in the city grew to such levels over several days that nearly 4,000
excess deaths were reported. As a result, the Clean Air Act of 1956 was enacted in the
United Kingdom.
In the United States, large cities took it upon themselves to institute air pollution
control measures. The first federal legislation involving air pollution was the Air
Pollution Control Act of 1955 and provided funds for federal research on air pollution.
This was followed by the Clean Air Act of 1963 that established a program within the
U.S. Public Health Service for research on air pollution monitoring and control
techniques. Later, the Air Quality Act of 1967 expanded the federal governments role
involving air pollution by enacting enforcement procedures concerning interstate
transport of pollutants. The Clean Air Act of 1970 brought about a number of
significant changes including the establishment of the National Ambient Air
Quality Standards (NAAQS) for air pollutants and the requirement for State
Implementation Plans to achieve these new standards. In addition, it authorized
the establishment of the National Emission Standards for Hazardous Air Pollutants
and required control of motor vehicle emissions. In 1971, the Environmental
Protection Agency was created to implement the requirements of the Clean Air
Act of 1970 and currently lists six air pollutants as criteria pollutants for which
NAAQS have been established. Criteria pollutants are air pollutants having numerous
or diverse sources that in the judgment of the U.S. EPA Administrator, cause or
contribute to air pollution, which may reasonably be anticipated to endanger public
health or welfare. The current criteria pollutants consist of carbon monoxide, lead,
ozone, nitrogen dioxide, sulfur dioxide, and particulate matter. Historically, the Clean
Air Act of 1970 has undergone two amendments (1977 and 1990), which have
further defined the federal governments efforts in air pollution monitoring and
control. As a result of these legislative acts, the air quality in the United States has
significantly improved.
2 CARBON MONOXIDE
2.1 Nature and Sources
Carbon monoxide (CO) is a colorless, odorless, and tasteless gas. It has a relative
density of 0.97 and therefore distributes within an enclosed space similarly to air.
Chemically, CO can bind to iron-containing moieties found in hemoglobin, myoglobin, and other cytochromes. The binding of CO to the iron-containing heme in
hemoglobin results in oxidation of the iron atom from Fe2 to Fe3 . This prevents the
binding of oxygen (O2) to the heme iron. The affinity of the heme iron for CO is
approximately 200 times greater than for O2. This preferential binding means that
small concentrations of CO can have profound effects on O2 binding and the formation
of carboxyhemoglobin versus oxyhemoglobin.
Sources of carbon monoxide encompass natural as well as man-made sources.
Natural sources include volcanic gases, forest and brush fires, generation during
electrical storms, endogenous production by animals and plants, and microbial release
CARBON MONOXIDE
2551
from soils. Anthropogenic sources include incomplete fuel combustion from transport
vehicles (cars, trucks, planes, trains, and ships), heating sources (furnaces, hot water
heaters, and kerosene heaters), cooking appliances (stoves, grills), industrial plant
exhausts, explosive detonations, and smoking.
2.2 Trends in Carbon Monoxide Levels

A major source of CO is vehicle emissions. In 1970, highway vehicles accounted for
80% of the CO emissions. Prompted by the Clean Air Act, significant improvements in
emissions controls were developed. As a result, CO emissions from vehicle exhaust
have dropped significantly (67% decrease from 1970 to 2006, Figs. 52.1 and 52.2) and
in 2006 accounted for 54% of the total CO emissions (Fig. 52.3). Considering the fact
that the number of miles traveled per year has also significantly increased over this
time period, the reduction in vehicle CO emissions seems all the more important
(Fig. 52.4).
As a result of the passing of the Clean Air Act, national ambient air levels for CO
have steadily declined (Fig. 52.5).
250,000
CO (thousands short tons)
Highway vehicles
200,000
Off-highway
150,000
100,000
Miscellaneous
50,000
Total
19
19 7 0
1975
1980
1985
1990
1991
1992
1993
1994
19 9 5
1996
1997
1998
2099
2000
2001
2002
2003
2004
200 5
06
0
Year
FIGURE 52.1 Major sources of estimated CO emissions. Figure was generated using data
from EPAs National Emissions Inventory (NEI) database. EPA maintains a national database
of air emissions information with input from numerous state and local air agencies, tribes, and
from industry. This database contains information on stationary and mobile sources that emit
criteria air pollutants and their precursors, as well as hazardous air pollutants. The database
includes estimates of annual emissions, by source, of air pollutants in each area of the country,
on an annual basis. The NEI includes emission estimates for all 50 States, the District of
Columbia, Puerto Rico, and the Virgin Islands. Source:http://www.epa.gov/ttn/chief/trends.
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AIR POLLUTION
8,000
CO (thousands short tons)
Fuel comb. elec. util.
7,000
Fuel comb. industrial
6,000
Fuel comb. other
Chemical & allied

product mfg
5,000
Metals processing
4,000
Petroleum & related
industries
3,000
Other industrial
processes
Solvent utilization
2,000
Storage & transport
1,000
Waste disposal &
recycling
19
70
19
75
19
80
19
85
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
0
Year
FIGURE 52.2 Minor sources of estimated CO emissions. Figure was generated using
data from EPAs NEI database. Source:http://www.epa.gov/ttn/chief/trends.
Fuel comb. elec.util.

0.30%
Fuel comb. other
0.53%
23.80%
1.09%
13.22%
0.31%
Chemical & allied product mfg
0.02%
0.14%
Metals processing
Petroleum & related industries
1.66%
9.17%
Other industrial processes

Solvent utilization
3.25%
0.67%
1.22%
53.81%
Storage & transport

Waste disposal & recycling
Highway vehicles
Off-highway
Miscellaneous
FIGURE 52.3 CO sources for 2006 (estimated). Figure was generated using data from EPAs
NEI database. Results are expressed as a percentage of the estimated total CO emissions for
2006. Source:http://www.epa.gov/ttn/chief/trends.
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CARBON MONOXIDE
3000
Travel (billions of miles)
200
2500
150
2000
1500
100
1000
50
500
CO emissions (millions of short tons)
250
3500
0
1970 1975 1980 1985 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
Annual vehicle miles
CO emissions
FIGURE 52.4 Comparison of annual vehicle miles traveled and CO emissions. Based on the
U.S. Department of Transportation, Federal Highway Administration estimations of annual
miles traveled and the NEI database estimations. Sources:http://www.epa.gov/ttn/chief/trends
and http://www.fhwa.dot.gov/environment/vmttext.htm.
National trend based on 144 sites
16
Concentration (ppm)
14
12
10
National standard
8
6
4
2
0
1
9
8
0
1
9
8
1
1
9
8
2
1
9
8
3
1
9
8
4
1
9
8
5
1
9
8
6
1
9
8
7
1
9
8
8
1
9
8
9
1
9
9
0
1
9
9
1
1
9
9
2
1
9
9
3
1
9
9
4
1
9
9
5
1
9
9
6
1
9
9
7
1
9
9
8
1
9
9
9
2
0
0
0
2
0
0
1
2
0
0
2
2
0
0
3
2
0
0
4
2
0
0
5
2
0
0
6
Year
19802006: 75% decrease in national average
FIGURE 52.5 CO air quality 19802006. Figure represents the second highest annual CO
concentration (based on an 8 h average) in parts per million. The blue band shows
the distribution of air pollution levels among the trend sites, displaying the middle 80%.
The white line represents the average among all the trend sites. Ninety percent of sites have
concentrations below the top line, while 10% of sites have concentrations below the bottom line.
The dashed line is the national ambient air quality standard for CO at the time of
writing. Source:http://www.epa.gov/air/airtrends/carbon.html.
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AIR POLLUTION
2.3 Health Effects

2.3.1 Introduction The deleterious effects of CO have been known for centuries.
As far back as the third century BC, the fumes from burning charcoal were used as a
method of execution for criminals and as a means for suicide. Once charcoal became a
popular method for home heating (fourteenth to fifteenth century), researchers and
physicians noted the toxicological effects from fumes and gases related to charcoal
mining and charcoal use. In 1688, it was discovered that coal could be distilled into a
gas (methane, hydrogen, and carbon monoxide) and coke. It was not until the late
1700s that the distilled coal gas found use as an illuminant. During the 1800s and into
the mid-1900s, coal gas found its way into factories, homes, offices, and street lights as
an illumination source. With the increased use of CO-containing fuels, increases in the
number of accidental as well as intentional exposures documented the toxicological
effects of CO exposure.
2.3.2 Symptoms of Exposure to CO The toxicological effects of CO exposure
have been well documented (122). The symptoms reported from CO exposure depend
on a number of factors including the gas concentration, length of exposure, age, current
health status, metabolic rate, and ventilation rate. Mild exposures produce headaches (2, 3, 2331), and dizziness (2, 25), while more serious exposures produce
nausea (2, 3, 24, 25, 32), vomiting (2, 25), weakness (25, 27), disorientation (25),
syncope (33), seizures (2, 3, 3440), confusion (25, 26), blurred vision (4150),
dysrhythmia (2, 51), cardiac ischemia (2, 52, 53), and coma (2, 3, 25, 5459). However,
these effects are from CO exposures much greater than what is typically found in the
ambient air.
2.3.3 Cardiovascular Effects The National Ambient Air Quality Standard for
CO (at the time of writing) is 9 ppm for an 8 h (averaged) exposure and 35 ppm for a 1 h
exposure. These values were derived based on research showing that cardiovascular
patients exposed to CO developed chest pain (angina) and/or electrocardiogram
changes earlier during exercise when compared to air exposed subjects (6064).
Measuring blood carboxyhemoglobin (COHb) levels, researchers were able to
show significant differences in those cardiovascular patients when COHb was as
low as 2.93.0%. Using the Coburn, Forster, and Kane differential equation (65)
(which allows one to predict COHb levels from known CO concentrations), the CO
concentrations could be predicted. Based on these results, it was thought that 2%
COHb would be the lower cut-off value providing an adequate margin of safety. While
exposure to CO may have a deleterious effect on people with cardiovascular disease,
research has shown that exposure to CO producing 520% COHb levels in healthy
adults both at rest and exercising, does not cause significant changes in cardiac rhythm
or conduction (66, 67).
2.3.4 Central Nervous System and Behavioral Effects Exposure to CO results in
the formation of COHb, which prevents the binding of oxygen and therefore reducing
the oxygen delivery to tissues. The brain compensates for this reduction by increasing
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2555
blood flow via vasodilation. A number of behavioral changes have been documented
with CO exposure but these effects have not been consistent and occur only at higher
COHb levels (generally >20%). These effects include alterations in vigilance, hand
eye coordination, and other forms of continuous performance.
2.3.5 Developmental Toxicity Another area of concern is developmental toxicity
from CO exposure. It is well documented that mothers who smoke during pregnancy
have an increased risk of developmental disorders including low birth weight. In
animal studies, maternal exposure to CO leading to 1525% COHb levels resulted in
low birth weight, cardiomegaly, delays in behavioral development, and disruption of
cognitive function (13, 6872). While these levels of CO are much greater than what
could be encountered in the ambient air, additional sources of CO such as smoking or
occupational exposure could produce a cumulative effect when combined.
3 LEAD
Lead (Pb) has been used for thousands of years in diverse applications such as paint,
ceramic glazes, water transport, and electrical components. It has useful chemical and
physical properties, including a low melting point (327.5 C), malleability, ease of
casting, and corrosion resistance. Lead is alloyed with a number of other elements
including calcium, tin, copper, silver, sulfur, bismuth, and cadmium and then used in
solder, ammunition, cables, and batteries. Other important properties of Pb are its
weight, number of electrons, and spatially diffuse valence orbitals, which determine its
behavior and toxicity in biological systems. Lead has been shown to form stable bonds
with sulfur and sulfur-containing compounds, but somewhat less so with carboxylic
acids (O-based ligands) and imidazoles (N-based ligands) (73). This allows Pb to
compete effectively with native or homeostatic metal ions (such as calcium) for
binding with the sulfhydryl, carboxyl, and imidazole side-chains comprising enzyme
active sites. This competition leads to inhibition of enzyme activity, as well as the
replacement of calcium in bone and, ultimately, to a substantial array of adverse human
health effects.
Lead is a multimedia pollutant, meaning that Pb emissions to the air contribute to Pb
concentrations in water, soil, and dusts, and further, that the Pb in soil and dust
contribute to Pb concentrations in ambient air (Fig. 52.6). Ingestion through food,
beverages, and dust is estimated to be 210 mg/day currently, compared to 50 mg/day
in 1990.
Automotive sources are no longer the major direct contributor of Pb emissions to
the atmosphere due to the phaseout of Pb from most domestic fuels. Mobile sourcerelated emissions, including brake wear, resuspension of road dust, and emissions
from piston-engine aircraft and racecars, still occur. However, the resuspension of
soil-bound Pb particles and contaminated road dust remains a significant source of
airborne Pb. The industrial sector is the major stationary source of Pb into the
environment. These industries include iron and steel foundries, coal and fuel oil
2556
AIR POLLUTION
Auto
emissions
Industrial
emissions
Crustal
weathering
Ambient
air
Surface and
ground water
Soil
Plants
Animals
Dusts
Food
Paint
Inhaled
air
Drinking
water
Man
FIGURE 52.6 Simplified diagram of environmental pathways contributing to multimedia Pb

exposure of human populations (from Ref. 118).
combustion, wood combustion, waste incineration, primary and secondary Pb smelters, copper and nickel smelters, Pb-acid battery plants, and Pb mining/processing.
Only one primary smelter remains operating in the United States, in Herculaneum, MI.
The most recent data for annual Pb production and use in the United States are shown in
Figure 52.7. Natural sources of Pb, such as volcanoes, sea-salt spray, biogenic sources,
forest fires, contribute about 19,000 metric tons of Pb to the air annually (74).
1,600,000
1,400,000
Other
Bearing metals
Metric tons
1,200,000
Brass and bronze

Casting metal
Type metal
1,000,000
Pipe and sheet lead

Caulking lead
800,000
Cable coverings
Solder
Ammunition
Pigments and paints
600,000
400,000
Gasoline additives
Batteries
200,000
0
1968 1972 1976 1980 1984 1989 1993 1997 2001 2003
Year
FIGURE 52.7 Annual lead production and use in the United States (19682003). Sources:
U.S. Bureau of Mines (19681995) and USGS (19962003).
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FIGURE 52.8
2557
Lead emissions in the United States from 1982 to 2002 (from Ref. 118).
3.2 Trends in Lead Levels

Lead levels in the United States have declined precipitously since the mid-1970s when
Pb was discontinued as an antiknock additive in gasoline (Fig. 52.8). Lead concentrations measured at 200 Federal Reference Methods monitors at U.S. sites ranged
from 0.10 to 0.22 mg/m3.
3.3 Health Effects
With the 98% decline in Pb emissions from 1970 through 2003, there was a
consequent parallel decline in blood Pb (PbB) levels in children (Fig. 52.9).
Although the geometric mean PbB levels have dropped to 12 mg/dL in the
20002004 period, compared to 15 mg/dL in 19761980, a large number of
children still have PbB levels above the current Center for Disease Control
(CDC) action level of 10 mg/dL (75).
The drop in ambient Pb levels, human exposures, and childrens PbB is a major
public health success, but significant exposures to Pb continue to occur in this country
due to the large environmental burden of Pb that still exists and to the fact that certain
populations are especially vulnerable and/or susceptible to Pb exposure. Deteriorating
paint in housing in low socioeconomic areas is a considerable source of exposure,
especially to young children who typically engage in hand-to-mouth activity.
Additionally, new research has demonstrated that PbB levels below 10 mg/dL, the
current CDC level of concern, can cause adverse health effects in both children and
adults. Lead affects every organ system in the body by a variety of mechanisms, mostly
linked to its ability to mimic calcium.
3.3.1 Effects of Pb on the Nervous System Of critical importance are the effects
of Pb on the developing nervous system. Neurobehavioral effects resulting from fetal,
2558
AIR POLLUTION
Micrograms of lead per deciliter of blood (g/dL)
Measure B1
30
25
90th percentile
(10% of children have
this blood lead level or greater)
20
15
10*
5
0
Median value
(50% of
children have this
blood lead level
or greater)
1976
1980
1988
1991
1992
1994
1999 2001
2000 2002
* 10 g of blood lead has been identified by CDC as elevated, which indicates need for intervention. There
is no demonstrated safe concentration of lead in blood. Adverse effects may occur at lower concentrations.
FIGURE 52.9 Concentrations of lead in blood of children ages 5 and under. Source: U.S.
EPA. Americas Children and the Environment (www.epa.gov/envirohealth/children). Data
from Centers for Disease Control and Prevention, National Center for Health Statistics,
National Health and Nutrition Examination Survey.
neonatal, and later postnatal Pb exposures have been consistently observed, even after
adjusting for potential confounding by care giving, parental intelligence, and socioeconomic status (SES). Neurocognitive decrements have been associated in young
children with PbB levels of 510 mg/dL, with some evidence of effects at lower
concentrations (7679). Effects on intellectual attainment of preschool and school age
children were observed at population mean concurrent PbB of 28 mg/dL (8082). A
large international pooled analysis of seven well-conducted prospective studies
showed a decline of 6.2 points in full scale IQ for an increase in concurrent PbB
levels from 1 to 10 mg/dL (83) (Fig. 52.10). Alterations in behavior, social conduct, and
attention are also associated with Pb exposures at low levels (84, 85).
There is inconclusive evidence for the effects of environmental Pb exposure on
adults. Associations were observed between bone Pb levels and neurobehavior, but not
between PbB and neurobehavior, suggesting that cumulative Pb exposure may be
more important in adults (86, 87).
The epidemiological findings of neurocognitive deficits in children are supported
by parallel findings in animal toxicological studies in which both rodents and
monkeys, exposed developmentally to Pb, resulting in steady-state PbB levels of
10 mg/dL, demonstrated behavioral impairments that persisted into adulthood (88,
89). Mechanisms associated with these deficits include response perseveration;
insensitivity to changes in reinforcement density or contingencies; deficits in
attention; reduced ability to inhibit inappropriate responding; impulsivity; and
distractibility. No evident threshold has yet been found for the neurocognitive effects
of Pb on the nervous system and the Pb-induced deficits, for the most part, have been
found to persist into adulthood. In both rodents and nonhuman primates, reactivity to
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FIGURE 52.10 Concentrationresponse relationship of IQ to PbB for the individual studies

and the pooled analysis by Lanphear et al. (from Ref. 83).
the environment and social behavior are affected at blood Pb levels of 1540 mg/
dL (90, 91). Visual function is impaired at PbB of 19 mg/dL (92) and auditory function
is impaired at PbB of 33 mg/dL (90, 91, 93).
Two genetic polymorphisms have been identified that possibly increase the
susceptibility to the neurodevelopmental consequences of Pb exposure in children.
Variants of the aminolevulinic acid dehydratase (ALAD) gene appear to influence the
absorption, retention, and toxicokinetics of Pb in humans (94) and variants of the
vitamin D receptor gene modify Pb concentrations in bone and the rate of resorption
and excretion of Pb over time (95).
Neurotoxicological studies in animals clearly demonstrated that Pb mimics calcium and affects neurotransmission and synaptic plasticity as shown in Figure 52.11.
3.3.2 Effects of Pb on the Immune System Recent epidemiological data demonstrate that Pb exposure may be associated with effects on cellular and humoral
immunity. Associations have been found between increasing PbB concentration and
increasing serum immunoglobins at PbB of <10 mg/dL in children (96) and at
somewhat higher levels in adults (>30 mg/dL). Associations have also been observed
between increasing PbB levels and decreases in T-cell abundance, with corresponding
increases in B-cell abundance. These effects have been observed in children whose
PbB concentrations ranged from 10 to 45 mg/dL (97). Toxicological studies have
shown that Pb targets immune cells, causing suppression of delayed type hypersensitivity response, elevation of IgE, and modulation of macrophages into a hyperinflammatory phenotype. These types of changes can cause increased risk of atopy,
asthma, and some forms of autoimmunity and reduced resistance to some infectious
diseases (98). Lead exposure of embryos resulting in PbB levels <10 mg/dL can
produce persistent later-life immunotoxicity (99). Figure 52.12 shows Pb-induced
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AIR POLLUTION
FIGURE 52.11 Demonstration of the mechanisms of action of Pb at a typical synapse. Lead

causes decrements in GABAergic, dopaminergic, and glutamatergic neurotransmission; interferes with Ca2 influx through voltage-sensitive channels; inhibits PKC at high concentrations;
and increases PKC activity at low concentrations. DA, dopamine; ER, endoplasmic reticulum;
GABA, g-aminobutyric acid; Glu, glutamate; PKC, protein kinase C; NMDA, N-methyl-Daspartate.
alterations to the immune system and to immunological pathways. Low to moderate

exposure to Pb induces functional shifts that are large compared to the relatively
modest changes among leukocytes.
3.3.3 Effects of Pb on the Cardiovascular and Renal Systems Both PbB and
bone Pb have been found to be associated with a longitudinal decline in renal function.
Toxicological studies show an initial accumulation of Pb primarily in the kidneys due
to glomerular filtration and subsequent tubular reabsorption, and, to a small extent,
through direct absorption from the blood (100). Lead exposure has consistently been
associated with enhanced risk of increased blood pressure and incidence of hypertension. A doubling of PbB (e.g., from 5 to 10 mg/dL) is associated with 1.0 mmHg
increase in systolic blood pressure (101), which at the population level can have a
profound impact on public health. Cumulative past Pb exposure (i.e., bone Pb) is an
important determinant in assessing cardiovascular effects. There is limited evidence
for an association of Pb with cardiovascular morbidity and mortality (102, 103).
Toxicological studies have shown that exposures creating PbB levels of 2030 mg/
dL for long periods result in arterial hypertension that persists long after cessation of
Pb exposure (104).
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2561
Key effects of lead on the immune system

Pb
Inflammatory tissue
T cells
Macrophages, macrophages and antigen

presenting cells
Membrane
arachidonic
acid
B cells
Host proteins
Modified neural antigens

Effects on antigen
processing
presentation
T0
Activation
Reduced response
to CSF-1
Th2
IL-4
IL-5
TNF-
Th1
Cell Surface
INF-
Class II
Auto-antibodies and
possible tissue
damage
Reduced cellmediated
immunity
IL-6
NO
ROI2
IL-12
PGE2
Skewed VB gene usage &

risk of autoimmunity
Increased tissue inflammation
IgE & increased risk of
Reduced cell-mediated immunity
atopy and asthma
FIGURE 52.12
Lead-induced alterations to the immune system.
3.3.4 Effects of Pb on Other Organ Systems Lead has long been known to disrupt
heme synthesis in children at 15 mg/dL (105) and in adults at 30 mg/dL (106). Studies in
animals have shown that Pb decreases red blood cell (RBC) survival and alters RBC
mobility (107). As mentioned above, Pb mimics calcium and thus, is readily taken up
and stored in bones and teeth (108). This disrupts mineralization of bone and can result
in growth suppression (109) and decreased bone density (110). During periods of bone
remodeling (e.g., pregnancy, lactation, aging), Pb can be mobilized and then transferred to the blood and other organs (111, 112). Lead exposure has been associated with
adverse dental outcomes including dental caries at PbB levels of <10 mg/dL (113).
Lead has been shown to produce both temporary and persisting effects on male and
female reproductive function and development and Pb disrupts endocrine function at
multiple points along the hypothalamicpituitarygonadal axis (114), elevating
corticosterone levels, and altering stress responsivity (115). This may be a potential
mechanism contributing to Pb-induced hypertension, with further possible roles in the
etiology of diabetes, obesity, and other disorders. Lead has been classified as a
probable carcinogen, according to the National Toxicology Program (116) and
International Agency for Research on Cancer (117). Associations between Pb exposure and DNA damage and micronuclei formation have been found, though associations with chromosomal aberrations, the more established indicator of cancer risk, are
inconsistent (118).
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AIR POLLUTION
4 OZONE
Ground-level ozone (O3) is a secondary pollutant formed by photochemical reactions
involving volatile organic compounds (VOCs), nitrogen oxides (NOx), and carbon
monoxide. Motor vehicles, chemical plants, refineries, factories, consumer and
commercial products, and other industries are all sources of these ambient precursors,
which react in the presence of heat and sunlight to form O3. Other sources of groundlevel O3 include intrusions of stratospheric O3 and transport by nocturnal low-level
jets. Figure 52.13 presents a diagram showing the major processes involved in O3
cycling in the atmosphere.
Stratosphere
Nonpolar
regions
H,
Cl,
Y
(X,
UV
Ozone
hole
O2
(in air)
OH
H2O
urf
ac
ew
at
e
H,
H
O3 + UV
HO2
RO2
ds
Ozone
NO
etat
io
Peroxides
NO2
to soi
l, veg
Volatile organic
compounds
NO
O+
n, a
n
O3
Y+
X or + YO
XO
+O
Depositi
on
2O 2
Polar
regions
Oxygen
Oxygen
Br)
=N
O,
+O
X
XO + O
+ O3
(X
Oxygen
+ O2
XO + O 2
X
h,
UV
XO r,)
X + or Y
Y+ O+
O O
O2 +
NO2 OH, RO
UV
Emissions
of NOx and
VDCs
Other organic
products
Troposphere
NO
2 +O
H
(m
a
Rainout
deposition
HNO3
Aerosol
uptake
FIGURE 52.13 Schematic overview of O3 photochemistry in the stratosphere and troposphere (from Ref. 119).
OZONE
2563
Temporal and spatial differences in O3 levels are dependent on the concentrations

of precursors, weather patterns, the intensity and spectral distribution of sunlight, and
long-range transport processes. Typically O3 concentrations peak in early- to midafternoon in the summertime and later in the day in areas where O3 abundance is
dependent upon transport from upwind sites.
4.2 Trends in Ozone Levels

Ambient O3 trends are influenced by year-to-year changes in meteorological conditions,
population growth, loadings of VOCs and NOx in the atmosphere, and by changes in
emissions from ongoing control measures. EPA has a nationwide network of monitoring
sites, from which it can track ambient air quality trends for O3. Figure 52.14a, b, and c
shows trends from 1980 and from 1990 for both the 1 h and the 8 h O3 standards
(0.12 ppm and 0.80 ppm, respectively). For the period from 1980 to 2006 (Fig. 52.14a),
based on monitoring at 275 sites, 8 h averages (based on annual 4th maximum 8 h
average) have decreased 21%. As shown in Figure 52.14b, during that same period, 1 h
averages (based on annual 2nd maximum 1 h average) have decreased 29%. As shown in
Figure 52.14c, for the period of 19902006, based on monitoring at 588 sites, 8 h
averages (based on annual 4th maximum 8 h average) have decreased 9%. Thus,
nationally, average O3 levels are decreasing, but the rate of decrease for 8 h levels
slowed during the 1990s. Concurrent trends in O3 precursors VOC and NOx levels are
also dropping. Levels of VOCs were 30 millions of tons/year in 1980, 23 in 1990, and 15
in 2006. Levels of NOx were 27 millions of tons/year in 1980, 25 in 1990, and 18 in 2006.
Recent EPA regulations to reduce regional emissions of NOx should further lower O3
levels.
4.3 Health Effects

Short-term exposures to O3 have been linked to number of respiratory effects including
decrements in lung function, increased respiratory symptoms, airway inflammation,
and airway responsiveness. More recent data have shown associations between shortterm O3 exposure and both mortality and cardiovascular morbidity. Long-term
exposures to O3 have been linked to reduced lung function growth in children and
morphological changes in animal studies. Long-term O3 exposures have not been
associated with carcinogenesis or mortality. Ozone-induced alterations of specific
endpoints, integrating epidemiologic, human clinical and toxicologic data, are discussed below.
4.3.1 Respiratory Effects of Short-Term O3 Exposures Decrements in lung
function have been associated with ambient O3 levels in a number of summer field
camp studies (121, 122). A combined reanalysis of these data by Kinney et al. (123)
demonstrated an average relationship between afternoon forced expiratory volume in
1 s (FEV1) and concurrent-hour O3 concentration of 0.50 mL/ppb. The declines in
lung function were noted particularly in children and asthmatics. Use of antioxidant
2564
AIR POLLUTION
supplements was found to diminish the O3 effect on lung function in both outdoor
workers and asthmatics (124, 125).
Controlled human exposure studies of healthy adults exposed to 0.08 ppm O3 for
6.6 h with moderate exercise had a group mean decrement in FEV1 of 6% (126).
Concentration (ppm)
0.15
0.10
National standard
0.05
0.00
1
9
8
0
1
9
8
1
1
9
8
2
1
9
8
3
1
9
8
4
1
9
8
5
1
9
8
6
1
9
8
8
1
9
9
9
1
9
8
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9
1
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3
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6
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2
0
0
3
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0
0
4
2
0
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5
2
0
0
6
Year
(a)
0.20
Concentration (ppm)
1
9
8
7
0.15
National standard
0.10
0.05
0.00
1
9
8
0
(b)
1
9
8
1
1
9
8
2
1
9
8
3
1
9
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4
1
9
8
5
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2
0
0
0
2
0
0
1
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0
2
2
0
0
3
2
0
0
4
2
0
0
5
2
0
0
6
Year
FIGURE 52.14 (a) Ozone air quality trends from 1980 to 2006 based on annual fourth
maximum 8 h average. The blue band shows the distribution of air pollution levels among the
trend sites, displaying the middle 80%. The white line represents the average among all the trend
sites. Source:http://www.epa.gov/oar/airtrends/ozone.html. (b) Ozone air quality trends from
1980 to 2006 based on annual second maximum 1 h average. The blue band shows the
distribution of air pollution levels among the trend sites, displaying the middle 80%. The white
line represents the average among all the trend sites. The dashed line is the national ambient air
quality standard for ozone at the time of writing. This applies to each graph a-c.Source:http://
www.epa.gov/oar/airtrends/ozone.html. (c) Ozone air quality trends from 1990 to 2006 based
on annual fourth maximum 8 h average. The blue band shows the distribution of air pollution
levels among the trend sites, displaying the middle 80%. The white line represents the average
among all the trend sites. Source:http://www.epa.gov/oar/airtrends/ozone.html.
OZONE
0.15
Concentration (ppm)
2565
0.10
National standard
0.05
0.00
1990
(c)
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
2001 2002 2003
2004 2005 2006
Year
FIGURE 52.14
(continued)
Ozone exposures of 0.5 ppm are the lowest at which statistically significant reductions
in FVC and FEV1 have been demonstrated in sedentary subjects. On average, young
adults exposed at rest for 2 h to 0.5 ppm O3 had O3-induced decrements of 4% in
forced vital capacity (FVC) and 7% in FEV1 (127, 128). Controlled human exposure
studies (129) using repeated acute (16 h) O3 exposures at 0.120.45 ppm over several
days showed that FEV1 response to O3 is enhanced on the second of several days of
exposure, but spirometric responses become attenuated on subsequent days with these
repeated exposures. This tolerance is lost after about a week without exposure.
Biological plausibility for these effects is provided by animal toxicological studies
(at levels of 0.250.4 ppm O3 for several hours) showing O3-induced rapid shallow
breathing (i.e., increased frequency and decreased tidal volume) that attenuates after
several days of exposure.
Respiratory symptoms associated with O3 exposure include cough, wheeze,
shortness of breath, production of phlegm, and increased medication use. Many
studies have found associations between acute exposure to O3 and increased respiratory symptoms and as-needed medication use in asthmatic children (130, 131). In a
pooled analysis from eight U.S. cities (132), the odds ratio for the incidence of
symptoms (cough, chest tightness, and wheeze) was 1.35 (95% CI: 1.04, 1.69) per
30 ppb increase in 8-h average O3 concentration. Human clinical studies using acute
exposures of 12 h at concentrations 0.12 ppm O3 reported symptoms of cough, pain
on deep inspiration, rapid, shallow breathing patterns during exercise, throat irritation,
and wheezing. Clinical studies of young, healthy adults using exposures of 68 h at
0.08 ppm during moderate exercise demonstrated symptoms of cough and pain with
deep inspiration. As with pulmonary effects, symptoms become attenuated following
repeated O3 exposures over several days, but this tolerance is lost after about a week.
Additionally, O3-induced respiratory symptoms gradually decrease in adults with
increasing age (119).
2566
AIR POLLUTION
Limited epidemiological evidence demonstrates an association between acute

ambient O3 exposure and airway inflammation in children (133). However, other
studies found no association between upper airway inflammation and O3 concentrations in school children (134). A study of 12 southern California communities (135),
with O3 levels of 0.0350.055 ppm, found an association between increased O3 and
respiratory-related school absences, with larger effects for lower respiratory diseases
than for upper respiratory diseases. Another study (136) suggests that ambient O3
concentrations, accumulated over 24 weeks, may be associated with school absenteeism, particularly illness-related absences.
A human clinical study has demonstrated acute airway inflammation in healthy
adults exposed to 0.080 ppm O3 for 6.6 h with exercise in controlled chamber
studies (137). These responses have been shown to occur even in the absence of
O3-induced pulmonary function decrements in those subjects. Earlier work showed
increased levels of polymorphonuclear leukocytes (PMNs) in the nasal lavage fluid of
humans exposed to 0.5 ppm O3 at rest for 4 h (138). These inflammatory responses are
attenuated over several days of repeated O3 exposures, however, the O3-induced lung
injury and increased permeability do not show attenuation, suggesting that continued
lung damage occurs during repeated episodes of O3 exposure (139, 140).
Biological plausibility for the epidemiological and human clinical findings of
O3-induced inflammation is provided by myriad animal toxicological studies. These
studies demonstrate that O3 disrupts the barrier function in lung that controls
bidirectional flow of fluids and cells between the air and the blood compartments.
The results are two well-characterized effects of O3 exposure, lung inflammation,
and increased permeability, which are distinct events controlled by independent
mechanisms. Figure 52.15 demonstrates the inflammatory cascade that is initiated
by the interaction of O3 with lipids in the epithelial lining fluid and cell membranes of
the lung. Lipid ozonation products cause a downstream activation of phospholipases,
arachidonic acid, leukotrienes, and prostanoids, which alter lung function (141).
Nitric oxide, and the inflammatory cytokines L-6, and IL-8 continue the cascade by
recruiting and activating inflammatory cells such as alveolar macrophages (AMs),
PMNs, blood monocytes, and mast cells, which, in turn, can start an additional
cycle of inflammatory responses (142). Platelet activating factor (PAF) increases
epithelial permeability and may have potential cardiovascular effects (143).
Release of substance P by neurons causes bronchoconstriction and increases vascular
permeability (144). Production of NOS-1 by these neurons induces airway
hyperreactivity (145).
Acute (13 h) animal exposures to O3 as low as 0.10.5 ppm can cause lung
inflammatory responses characterized by increased reactive oxygen species, inflammatory cytokines, influx of PMNs, and activation of AMs (146, 147). Further damage
to the epithelial airway tissues occurs as well, causing an increase in permeability of
both lung endothelium and epithelium. This results in increased susceptibility to
infectious diseases due to modulation of lung host defenses. Many of these studies
were performed in rats, which appear to be more resistant to O3-induced inflammation
than humans, such that exercising humans receive fourfold to fivefold higher O3
concentrations than resting rats (148).
OZONE
2567
FIGURE 52.15 Mechanisms of ozone toxicity. The inflammatory cascade starts by interactions of O3 with lipids in the epithelial lining fluid and in cell membranes. Lipid ozonation
reaction products include aldehydes, hydroxyhydroperoxides, and H2O2. These initiate lipase
activation in epithelial cells resulting in the downstream production of phospholipases,
arachidonic acid, leukotrienes, and prostanoids. Leukotrienes and prostanoids alter
lung function. Phospholipases initiate the production of NO, inflammatory cytokines, and
PAF. NO, IL-6, and IL-8 then participate in the recruitment and activation of inflammatory
cells (AMs, PMNs, blood monocytes, and mast cells), which, in turn, can start a second
cycle of inflammatory responses. PAF increases epithelial permeability and may have thrombolytic effects. Release of substance P by neurons causes altered lung function and
increases vascular permeability. Production of NOS-1 by these neurons induces airway
hyperreactivity.
2568
AIR POLLUTION
4.3.2 Airway Responsiveness Evidence from human clinical and animal toxicological studies demonstrates that acute exposure to O3 can induce airway hyperresponsiveness (AHR). Asthmatic subjects, who typically have increased airway
responsiveness at baseline, have further increases in responsiveness with O3 exposure (149). Asthmatics also demonstrate an increase in specific (i.e., allergen-induced)
airway reactivity in response to O3 exposure (150). These changes in airway
responsiveness after O3 exposure resolve more slowly than changes in pulmonary
function or symptoms (129). Attenuation of AHR is less likely with consecutive O3
exposures than attenuation of FEV1 (151). Furthermore, increases in AHR are not
strongly linked to the above-mentioned O3-induced decrements in lung function or
increases in symptoms. Mechanisms responsible for O3-induced AHR are not
completely understood, but are thought to involve inflammatory cytokines, prostanoids, or neuropeptides (see Fig. 52.15). A number of cell types also become activated
with O3 exposure, including mast cells, macrophages, and eosinophils. Reflex
bronchoconstriction is thought to be due to O3-induced epithelial damage that
increases direct access of mediators to the smooth muscle or receptors in the airways.
Ozone-induced AHR occurs in human asthmatics at ambient levels and in a number
of laboratory species at O3 concentrations as low as 0.51.0 ppm. Animal studies have
shown that O3 preexposure can augment ovalbumin-induced AHR (147, 152).
Importantly, there is a temporal relationship between inflammatory cell influx and
O3-induced AHR, however, inflammation is not a prerequisite for AHR (153).
Repeated O3 exposures enhance AHR, possibly by modulating rapidly adapting
airway receptors or by altering the structure of conducting airways (154). The rapid,
shallow breathing pattern elicited by O3 causes a more evenly distributed injury
pattern rather than protection from injury (155). Some of the newer animal studies of
O3-induced AHR suggest that exercise-induced bronchoconstriction may be mediated
by changes in tonicity of the bronchial smooth muscles (156). Vagally mediated
mechanisms may affect tracheal epithelial function and increase central airway
reactivity (157). Ozone may induce direct vascular constriction and may destroy
neural endopeptidases in airway epithelial cells, thus preventing the inactivation of
SP (158). Repeated O3 exposures may diminish neutrophilic inflammation, depress
cell proliferation, and cause cumulative distal airway lesions (159). The findings of
O3-induced decrements in lung function, respiratory symptoms, inflammation, and
AHR provide support for the epidemiological associations between O3 exposure and
respiratory-related hospitalizations and asthma ED visits during the warm season (160163). The evidence generally supports the findings of significant and robust
effects of O3 on various respiratory disease hospitalization outcomes. Large multicity
studies (164), as well as many studies from individual cities (165, 166) have reported
positive O3 associations with total respiratory hospitalizations, asthma, and COPD,
particularly in studies analyzing the O3 effect during the summer or warm season.
4.3.3 Cardiovascular Effects of Short-Term O3 Exposures A limited body of
epidemiological evidence suggests that O3 directly and/or indirectly contributes to
cardiovascular-related morbidity. Some population studies of cardiovascular hospital
admissions reported positive O3 associations during the warm season between ambient
OZONE
2569
O3 concentrations and cardiovascular hospitalizations (167). However, other studies

reported no association between O3 and cardiovascular hospitalizations when O3
levels were lower and all-year data were considered (168). A few studies (169171)
have shown an association between O3 and cardiac physiologic outcomes such as heart
rate variability, ventricular arrhythmias, and incidence of myocardial infarction. One
controlled human exposure study (172) of cardiovascular effects found no significant
O3-induced differences in ECG, heart rate, or blood pressure in healthy or hypertensive
subjects with exposures of 0.3 ppm O3 with intermittent exercise. They did observe
impaired alveolararterial O2 transfer that could potentially reduce O2 supply to the
heart. Ozone-induced cardiovascular effects have been observed in toxicological
studies (173, 174) at concentrations of 0.30.5 ppm. These effects include decreased
heart rate, body core temperature, and blood pressure, which have been termed as
hypothermic response. Concentrations of O3 0.5 ppm cause tissue edema, possibly
mediated by atrial natriuretic factor, which controls capillary permeability, vasodilation, and blood pressure (175).
4.3.4 Mortality and Short-Term O3 Exposures Associations have been observed
between various measures of daily O3 concentrations and increased risk of mortality.
Single-city study estimates range between 0.5% and 5% excess deaths per standardized increment of O3 (176). Large multicity study estimates range between 0.5% and
1%, following corrections for confounding by time, weather, and copollutants (177).
When data are stratified by season, O3 risk estimates are much larger in the warm
season, and negative in the cool season, possibly due to the negative correlation
between low-level O3 and PM in that season (178). Risk estimates are highest for a 7
day distributed lag model, suggesting that the effects of acute O3 exposure on mortality
persist over several days. A recent meta-analysis (179) indicated that there was a
slightly greater risk of cardiovascular mortality compared to total mortality.
4.3.5 Respiratory Effects of Long-Term O3 Exposures Decrements in lung
function growth in children and lung morphology changes in animals have been
observed following long-term exposure to O3. Children in southern California
demonstrated smaller increases in various lung function parameters as they aged
when compared to children living in areas with lower ambient O3 levels (180, 181).
College-age students had decrements in maximally attained lung function (182,
183), however, other studies of young children and college-age students found no
association between lung function growth and O3 exposure (184, 185). These longterm studies are difficult to interpret because of concurrent coexposures to other
ambient air pollutants. Thus, there is no strong evidence for impacts of long-term,
relatively low-level O3 exposures on lung function development in children.
Long-term O3 exposure has been associated with the development of asthma in
adult males (186, 187). In high-O3 communities, the asthma risk was greater for
children who played three or more sports as compared with children who played no
sports. However, some recent cross-sectional surveys (188) detected no associations
between long-term O3 exposures and asthma prevalence in children after controlling
for covariates.
2570
AIR POLLUTION
A large body of animal toxicological studies of long-term exposures to O3 shows

that Type I cell necrosis and inflammatory responses generally decrease to near
control values with continued exposure, while hyperplastic and fibrotic changes
remain elevated or become more severe with time. Persistent O3-induced mucous
cell metaplasia in rats exposed to 0.25 ppm O3 (189) suggests that O3 exposure may
have the potential to induce similar long-lasting alterations in the airways of
humans. Lesions of the nasal cavity and centriacinar (CAR) lung, effects similar
to those seen in chronic airway disease in humans, were observed in mice exposed to
as low as 0.51.0 ppm of O3 for 2 years (190). Remodeling of the distal airways and
CAR has been shown to occur after subchronic and chronic exposure to O3.
Bronchiolization and collagen formation were demonstrated in rats exposed to
0.4 ppm O3 for only 56 days (191). Centriacinar remodeling and thickening of
tracheal, bronchial, and bronchiolar epithelium were observed after 3 and 20 months
exposure to 1.0 ppm O3, but not to 0.12 ppm O3 (192). A more recent series of
chronic studies in monkeys used a simulated, seasonal O3-exposure pattern of
0.5 ppm O3 exposures (8 h/day for 5 days, every 14 days for a total of 11 O3 episodes)
to examine possible injuryrepair processes occurring with seasonal O3 exposures (193196). They found remodeling in the distal airways, abnormalities in
tracheal basement membrane, eosinophil accumulation in conducting airways, and
decrements in airway innervation.
4.3.6 Vulnerability and Susceptibility to Ozone Responses to O3 are determined
by various factors including vulnerability and susceptibility. Vulnerability refers to
O3-related effects due to factors such as elevated exposure levels due to outdoor
working or playing sports. Susceptibility refers to innate (e.g., genetic or developmental) or acquired (e.g., age or disease) factors that make individuals more likely to
experience effects with exposure to O3. Epidemiological studies have established that
outdoor workers, due to their increased exposure to ambient air pollution, are more
vulnerable to O3-related effects (124, 197). Other studies have identified children and
adolescents involved in moderate to high physical exertion as having increased
responsiveness to ambient O3 (198). Controlled human exposure studies have shown
that physical exertion is a determinant of the response to O3 (199).
Epidemiological studies of asthmatics have found associations between O3
exposure and hospitalizations (200), ED visits (201), and decrements in lung
function (202). Individuals with COPD have also been identified as a susceptible
group, due to increased ED visits, hospitalizations, and premature mortality (203,
204). Human clinical studies indicate that individuals with preexisting pulmonary
diseases have increased susceptibility to O3. Relative to healthy young adults,
asthmatics exposed to O3 have slightly increased spirometric responses (150),
increased responses with increased disease severity (205), and significantly greater
neutrophil responses (206). Individuals with preexisting allergic airway disease
have increased responsiveness to bronchial allergen challenge with repeated O3
exposure over several days (207).
Age is a factor determining susceptibility to O3. Epidemiological studies have
identified associations between O3 exposure in children and adverse respiratory
NITROGEN OXIDES
ACP2
oxidative stress
(Wattiez et al., 2003)
2571
6 h AHR
24 h inflammation
(Savov et al., 2004)
Tol-like receptor-4
(Kleeberger et al., 2000)
Mouse chromosomes
4
6 h inflammation
6 h protein
7
11
PMN influx
15
24 h AHR
17
Tnfa
19
CC16
oxidant stress
(Mango et al., 1998)
epithelial permeability
(Broeckaert et al., 2003)
FIGURE 52.16
ozone.
Genes or gene loci on mouse chromosomes, which modulate responses to
outcomes such as decrements in lung function and respiratory symptoms (202, 208).
Studies that examined associations between O3 exposure in older adults (> 65 years of
age), mortality and hospitalizations, have reported excess risks of mortality and
hospitalizations with elevated O3 concentrations (209, 210). Human clinical studies
show that older adults (211) have decreased respiratory symptoms with O3 exposure,
which may allow this population to receive increased O3 doses causing greater injury.
Genetic susceptibility to O3 has been shown in epidemiological, human clinical,
and toxicological studies. Genetic polymorphisms for both inflammatory mediators
(TNF-a) and antioxidant enzymes (GSTM1 and NQO1) have been identified in
humans (212, 213) that may modulate the effects of O3 exposure on pulmonary
function and airway inflammation. Animal toxicological studies provide corroborative evidence of innate genetic susceptibility to O3. Various strains of mice and rats
have been identified as sensitive or resistant to the effects of O3 for a number of
different endpoints (214, 215) as shown in Figure 52.16, which shows genes or gene
loci that have been characterized in mice.
5 NITROGEN OXIDES
Nitrogen oxides (NOx) are a group of compounds composed of varying amounts of
nitrogen and oxygen. The term NOx refers to the sum of nitrogen dioxide (NO2) and
2572
AIR POLLUTION
nitric oxide (NO). Historically, the compound of concern for air pollution is NO2.
Nitrogen dioxide exists as a reddish brown gas at room temperature and has a pungent
odor. It has a vapor pressure at 20 C of 720 mmHg and a vapor density of 1.58. It is
highly reactive and decomposes in water to nitric acid and NO.
Nitrogen oxides exist as products of natural as well as man-made processes. There
are a number of natural sources for NOx. One is the burning of biomass, which utilizes
the fixed nitrogen in the fuel source for the production of NOx. The higher the fixed
nitrogen content of the biomass, the greater the production of NOx (i.e., burning
grasslands and agricultural vegetation > forest fires > wood for fireplaces and woodstoves). Another natural source of NOx is from lightning. Electrical discharges
generate NOx by thermal dissociation of nitrogen molecules in the surrounding
air. It is estimated that the annual generation of NOx by lightning is 1 million metric
tons in North America and 13 million metric tons globally (216). Lastly, soil can
release NOx through nitrification and denitrification processes. It is estimated that the
NOx contribution from the soil is 2 million metric tons in North America and 36
million metric tons worldwide (216).
The majority of nitrogen oxides in the air are the result of combustion of fossil fuels.
Based on the National Emissions Inventory calculations, the extrapolated production
of NOx for 2006 is over 16,000 metric tons. Of that, 58% of the NOx emissions will be
from highway and off-highway vehicles/equipment. Besides vehicle emissions, fuel
combustion by electric utilities and other industries produce the remainder of the NOx
emissions (Fig. 52.17).
22.06%
0.60%
0.09%
36.22%
1.00%
0.03%
4.09%
1.52%
2.38%
0.42%
0.42%
19.67%
3.97%
11.62%
Fuel comb. other
Chemical & allied product mfg
Metals processing
Petroleum & related industries
Other industrial processes
Solvent utilization
Storage & transport
Waste disposal & recycling
Highway vehicles
Off-highway
Miscellaneous
FIGURE 52.17 NOx sources for 2006 (estimated). Figure was generated using data from
EPAs NEI database. Results are expressed as a percentage of the estimated total CO emissions
for 2006. Source:http://www.epa.gov/ttn/chief/trends.
NITROGEN OXIDES
2573
30,000
NOx (thousands short tons)
25,000
20,000
Highway vehicles
15,000
Off-highway
10,000
Total
5,000
19
7
19 0
7
19 5
80
19
8
19 5
9
19 0
9
19 1
9
19 2
9
19 3
9
19 4
9
19 5
96
19
9
19 7
98
19
9
20 9
00
20
0
20 1
02
20
0
20 3
04
20
0
20 5
06
Year
FIGURE 52.18 Major sources of estimated NOx emissions. Figure was generated using data
from EPAs NEI database. EPA maintains a national database of air emissions information with
input from numerous state and local air agencies, tribes, and from industry. This database
contains information on stationary and mobile sources that emit criteria air pollutants and their
precursors, as well as hazardous air pollutants. The database includes estimates of annual
emissions, by source, of air pollutants in each area of the country, on an annual basis. The NEI
includes emission estimates for all 50 States, the District of Columbia, Puerto Rico, and the
Virgin Islands. Source:http://www.epa.gov/ttn/chief/trends.
5.2 Trends in Nitrogen Oxides Levels

The U.S. EPA has designated NOx as a criteria pollutant and has set a National
Ambient Air Quality Standard for NOx using NO2 as the indicator. The current
standard is 0.053 ppm measured as an arithmetic annual average. Since setting the
standard, significant reductions in ambient NO2 levels have been observed (Figs. 52.18
and 52.19). Thanks largely to new technological advances in emissions control
systems used by the automotive industry and point sources like power plants, the
annual NO2 average has decreased 30% since 1990 (Fig. 5.4). As a result of efforts at
the federal, state, and local level, the primary NAAQS for NO2 has not been exceeded
since 1990 (Fig. 52.21).
5.3 Health Effects
5.3.1 Introduction Short-term exposure to high concentrations of NOx can result
in the development of severe pulmonary edema. However, these high concentrations
are restricted to industrial/occupational scenarios and shed little light on the health
effects from exposure to ambient air pollution. The majority of the toxicological
2574
AIR POLLUTION
1,600
Fuel comb. other
1400
NOx (thousands short tons)
Chemical & allied

product mfg
1200
Metals processing
1000
Petroleum & related

industries
Other industrial
processes
800
Solvent utilization
600
Storage & transport
400
Waste disposal &
recycling
200
Miscellaneous
19
7
19 0
75
19
8
19 0
8
19 5
9
19 0
9
19 1
9
19 2
93
19
9
19 4
9
19 5
9
19 6
9
19 7
9
19 8
9
20 9
00
20
0
20 1
0
20 2
0
20 3
0
20 4
0
20 5
06
Year
FIGURE 52.19 Minor sources of estimated NOx emissions. Figure was generated using data
from EPAs NEI database. Source:http://www.epa.gov/ttn/chief/trends.
0.06
Concentration (ppm)
National standard
0.05
0.04
0.03
0.02
0.01
0.00
1
9
8
0
1
9
8
1
1
9
8
2
1
9
8
3
1
9
8
4
1
9
8
5
1
9
8
6
1
9
8
7
1
9
8
8
1
9
8
9
1
9
9
0
1
9
9
1
1
9
9
2
1
9
9
3
1
9
9
4
1
9
9
5
1
9
9
6
1
9
9
7
1
9
9
8
1
9
9
9
2
0
0
0
2
0
0
1
2
0
0
2
2
0
0
3
2
0
0
4
2
0
0
5
2
0
0
6
Year
FIGURE 52.20 NO2 air quality 19802006. Figure represents the annual arithmetic average
in parts per million. The blue band shows the distribution of air pollution levels among the trend
sites, displaying the middle 80%. The white line represents the average among all the trend sites.
Ninety percent of sites have concentrations below the top line, while 10% of sites have
concentrations below the bottom line. The dashed line is the national ambient air quality
standard for NO2 at the time of writing. Source:http://www.epa.gov/air/airtrends/nitrogen.
html.
NITROGEN OXIDES
2575

0.06
National standard
Concentration (ppm)
0.05
0.04
0.03
0.02
0.01
0.00
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
FIGURE 52.21 NO2 air quality 19902006. Figure represents the annual arithmetic average
in parts per million. The blue band shows the distribution of air pollution levels among the trend
sites, displaying the middle 80%. The white line represents the average among all the trend sites.
Ninety percent of sites have concentrations below the top line, while 10% of sites have
concentrations below the bottom line. Source:http://www.epa.gov/air/airtrends/nitrogen.html.
literature on NOx identifies the lung as the primary target organ. Typically, the effects
seen are subtle cellular or biochemical alterations. These include changes in lipids,
proteins, amino acids, and enzymes resulting in altered cell membranes and antioxidant homeostasis. A variety of toxicological effects are seen in both controlled human
and animal exposures and are discussed below.
5.3.2 Alterations in Host Defense Mechanisms Some of the more sensitive
endpoints in NOx exposure relate to its ability to affect the bodys defense mechanisms. Numerous studies have reported effects at concentrations below 1 ppm of NO2.
One such effect is the impairment of mucociliary clearance. The airway responds to
irritation by increasing mucus production. In laboratory animals, exposure to low
levels of NO2 results in either an increase in mucociliary clearance or has no
effect (217). However, at higher concentrations ciliary action was decreased in a
concentration dependent manner (218).
In addition to ciliary and mucosal alterations, clearance is also determined by
phagocytosis from resident lung cells such as alveolar macrophages as well as
recruited cells such as polymorphonuclear leukocytes. Exposures to supraambient
concentrations of NO2 result in structural, biochemical, and functional changes in
alveolar macrophages. Structural changes that have been reported include membrane
blebbing, the appearance of fenestrae, and loss of surface projections (219). While
these structural changes would be expected to effect cellular chemotaxis and/or
phagocytosis, their actual biological ramifications have yet to be determined. A
2576
AIR POLLUTION
number of studies have investigated macrophage function following NO2 exposure in

laboratory animals and the results are inconsistent. However, these inconsistencies
may be explained by differences in species susceptibility and the timing of the
measured endpoint. Short-term exposures of rabbits to 1 ppm NO2 resulted in
decreased phagocytic capacity. However, higher concentrations increased phagocytosis while longer durations had no effect (220). Mice, however, when exposed to
5 ppm NO2 for several days failed to show effects on phagocytosis (221). In general,
effects on macrophage clearance have been transient and tend to return to control
values with time.
Macrophages are capable of producing a large number of substances that assist in
host defense. These substances can act directly on the pathogen as well as signal other
cell types to aid in the defense. Superoxide anion is released from macrophages and
plays a significant role in host defense. Exposure to NO2 has been reported to decrease
the ability of macrophages to produce superoxide anion (222224).
5.3.3 Effects on Humoral and Cell-Mediated Immunity A variety of immunological effects have been demonstrated in laboratory animals exposed to NO2. These
effects include a reduction in the primary response to an antigen (sheep red blood
cells) (221, 225), and a reduction in serum immunoglobins (226). However, these
responses, as well as others are not consistently reported and vary considerably
depending on the experimental conditions used (concentration of NO2, duration of
exposure, species).
5.3.4 Effects on Pathogenic Resistance While exposure to NO2 has shown
numerous effects on host defense, the biological significance of these effects is often
unknown. However, animal infectivity experiments use mortality as an endpoint and
as a result, clearly demonstrate the biological significance of the hostdefense
changes. A number of studies have reported both acute and chronic NO2 exposure
to cause an increase in bacterial and viral susceptibility. Following an acute exposure,
the lowest concentration of NO2 that increased lung susceptibility to bacterial
infections was 2 ppm for a 3 h exposure in mice (227, 228). Long-term exposures
of NO2 at concentrations as low as 0.5 ppm have been reported to reduce the efficiency
of lung defense against infections (229231).
5.3.5 Effects on Lung Function and Airway Reactivity Exposure to NO2 at or
near ambient levels has been shown to produce various decrements in lung function (232240) and to enhance airway reactivity (241). The lung function changes
include decreases in forced expiratory volume after 1 s (FEV1), forced vital capacity,
total respiratory resistance, forced expiratory flow between 25% and 75% of FVC
(FEF2575) and peak expiratory flow (PEF). However, these changes (with the
exception of specific allergen challenges) are equivocal throughout the literature.
The possible reasons for the discrepancies are many and include the type of study, the
study design, species used, age of the subject, previous exposure, atmosphere
composition, subject health status, location of the study, length of exposure, and
endpoint timing and measurement.
SULFUR DIOXIDE
2577
While a number of studies have described effects from NO2 exposure on airway
responses (242256), the data for increased airway reactivity to specific allergen
challenges following NO2 exposure is more persuasive. Responses include increases
in eosinophil priming (as evidenced by an increase in eosinophil cationic protein),
inflammatory cells and immunoglobins, and enhanced airway responses to inhaled
allergens.
Both epidemiological and clinical studies have reported highly variable findings on
the effect of NO2 on lung function and airway reactivity. Based on this information, it is
possible that under the right conditions, certain individuals may be particularly
sensitive to NO2 exposures.
5.4 Potential Mechanisms of NO2-Induced Toxicity
A number of mechanisms have been proposed for NOx toxicity. One potential
mechanism is lipid peroxidation of unsaturated fatty acids in cell membranes (257).
Lipid peroxidation by reactive oxidant gases is an important mechanism of cellular
injury. NO2-induced lipid peroxidation has been demonstrated in studies measuring
exhaled ethane, as thiobarbituric acid reactive substances in tissues (258) and by
conjugated dienes in tissue homogenates. Increased ethane exhalation was reported in
rats exposed to 0.04 ppm NO2 for 9 or 18 months (259) while shorter durations
(1 week) increased exhaled ethane in rats exposed to 1.2 ppm (260).
Another proposed mechanism is the oxidation of critical proteins such as enzymes
leading to toxicological effects (261). Lastly, cellular injury may occur via interactions
with reactive metabolites of NOx. Clearly, much remains to be learned about the
complex chemistry of NOx and the resultant toxicological effects.
6 SULFUR DIOXIDE
Sulfur is prevalent in all raw materials, including crude oil, coal, and ore that contains
common metals such as aluminum, copper, zinc, lead, and iron. Sulfur oxide (SOx)
gases are formed when fuel containing sulfur is burned, gasoline is extracted from oil,
or metals are extracted from ore. The only forms of monomeric SOx of interest in
tropospheric chemistry are sulfur dioxide (SO2) and sulfur trioxide (SO3). SO3 can be
emitted from the stacks of power plants and factories; however, it reacts extremely
rapidly with H2O in the stacks or immediately after release into the atmosphere to form
sulfuric acid (H2SO4), which then partitions into the aqueous phase of particles. Thus,
only SO2 is present in the tropospheric boundary layer at concentrations significant for
atmospheric chemistry and human exposures.
SO2 is oxidized either in the gas phase or in the aqueous phase in cloud drops due to
its high water solubility. A comparison of the relative rates of oxidation by gas and
aqueous phase reactions indicates that only about 20% of SO2 is oxidized by gas phase
reactions; thus, SO2 is oxidized mainly by aqueous phase reactions (262). The rate of
2578
AIR POLLUTION
oxidation of SO2 to sulfate (SO42) ranges from 0.5% to 2% h1 as measured in
power plant plumes (263), resulting in an atmospheric lifetime ranging from about 2
days to about a week, with respect to this process. SO2 is removed from the atmosphere
by dry deposition to moist surfaces, resulting in an atmospheric lifetime with respect to
deposition on the order of 1 week, depending on humidity. These two processes,
oxidation and deposition, lead to an overall lifetime of SO2 in the atmosphere of a few
days.
Anthropogenic emissions of SO2 are mainly from combustion of fossil fuels by
electrical utilities (66%) and industry (29%), with transportation-related sources
making only a minor contribution (5%) in 2002 (264). Thus, most SO2 emissions
originate from point sources. However, these estimates are nationwide averages and
may not accurately reflect the contribution of specific local sources determining a
persons exposure to SO2 at any given location and time. For example, shipping and
associated in-port activities may be a significant source of SO2 in some coastal
cities (265).
The largest natural sources of SO2 are volcanoes and biomass burning. Even so, SO2
constitutes a relatively minor fraction (0.005% by volume) of total volcanic emissions (266). Volcanic sources of SO2 in the United States are limited to the Pacific
Northwest, Alaska, and Hawaii. Emissions of SO2 from burning vegetation are
generally in the range of 12% of the biomass burned (267). Sulfur is bound in
amino acids in vegetation and is released during combustion. Gaseous sulfur emissions
from this source are mainly in the form of SO2.
In addition to its role as an emitted primary pollutant, SO2 is also produced by the
photochemical oxidation of reduced sulfur compounds, for example, dimethyl sulfide,
hydrogen sulfide, and carbonyl sulfide. Emissions of reduced sulfur species are
associated typically with marine organisms living either in pelagic or coastal zones
and with anaerobic bacteria in marshes and estuaries. Except for carbonyl sulfide,
which is lost mainly by photolysis (atmospheric lifetime of 6 months), all the other
species are relatively short-lived, having lifetimes of the order of a few hours to a few
days. Emissions of sulfur from natural sources are small compared to anthropogenic
emissions within the United States. However, important exceptions occur locally as
the result of volcanic activity, wildfires and in certain coastal zones.
6.2 Trends in Sulfur Dioxide Levels
SO2 data collected from the State and Local Air Monitoring Stations and National Air
Monitoring Stations networks show that the decline in SO2 emissions from electric
generating utilities has improved air quality. These reductions are due, in large part, to
controls implemented under the U.S. EPA Acid Rain Program. U.S. EPAs trends data
(www.epa.gov/airtrends) reveal that the national composite average SO2 annual mean
ambient concentration decreased by 53% from 1990 to 2006, with the largest singleyear reduction coming in 19941995, the U.S. EPA Acid Rain Programs first
operating year (Fig. 52.22). For the years 20032005, the mean 24 h average and
annual average SO2 concentrations in the United States were 4 ppb, with maximum
values of >120 ppb for the 24 h average and 1415 ppb for the annual average. For
SULFUR DIOXIDE
2579
Concentration (ppm)
0.03
0.02
0.01
0.00
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year
FIGURE 52.22 SO2 air quality trends from 1990 to 2006 (based on annual arithmetic
average). Source:http://www.epa.gov/oar/airtrends/sulfur.html (from Ref. 316).
the monitors reporting a 1 h maximum in these years, the mean concentration was
13 ppb, with a maximum value of >600 ppb.
6.3 Health Effects
Controlled human exposure studies and epidemiological studies have observed
associations of short-term exposures to SO2, both peak 515 min exposures and
24 h average exposures, with effects on the respiratory system, ranging from increases
in respiratory symptoms and lung function decrements, and increasing in severity to
emergency department (ED) visits and hospitalizations for respiratory causes. These
effects were observed particularly in individuals with preexisting respiratory diseases,
children, and older adults (65 years). Epidemiological evidence is suggestive of
associations between SO2 and nonaccidental all-cause and cardiopulmonary-related
mortality, but additional research is needed to more fully establish underlying
mechanisms by which such effects occur. Health effects of long-term exposure to
SO2 have not yet been clearly established.
6.3.1 Morbidity Effects from Short-Term Exposure to SO2 Due to its high
solubility, SO2 is readily removed in the moist surfaces of the nose and other
respiratory passages. With quiescent nasal breathing, almost all inhaled SO2 is
removed in the extrathoracic (head) region. This limits the potential for direct effects
on the more sensitive thoracic regions of the respiratory tract. Factors that can increase
penetration of SO2 to these regions include oral and oronasal breathing, increased
ventilation rates and the presence of particles or fog droplets that may act as carriers for
SO2. In exercising humans, the pattern of SO2 absorption is expected to shift from the
upper airways to the tracheobronchial airways in conjunction with a shift from nasal to
oronasal breathing and associated increased ventilatory rates.
The predominant health response following peak exposure (515 min) to SO2 is
bronchoconstriction in asthmatics, which is associated with symptoms of wheezing,
2580
AIR POLLUTION
chest tightness, and shortness of breath. Studies of controlled SO2 exposures have
reported increased respiratory symptoms with SO2 concentrations of as low as 0.4
0.6 ppm in exercising asthmatic subjects (268270). One study with SO2-sensitive
asthmatics reported that respiratory symptoms (i.e., shortness of breath, wheeze, and
chest tightness) increased with increasing SO2 concentrations (0, 0.5, and 1.0 ppm
SO2) following exposures of 10 min with varying levels of exercise (269). It was also
observed that exposure to 0.5 ppm SO2 during light exercise evoked a more severe
symptomatic response than heavy exercise in clean air.
Studies have also consistently demonstrated decreases in lung function (e.g.,
decreased forced expiratory volume in 1 s (FEV1) and increased specific airways
resistance (sRaw)) following peak exposures to SO2. These effects have clearly and
consistently been shown to be exacerbated among individuals with asthma, with
asthmatics exhibiting significant decrements in lung function following 515 min
exposures to SO2 concentrations of as low as 0.40.6 ppm while performing moderate
levels of exercise (269, 271273). Increasing SO2 levels from 0 to 0.5 ppm has been
shown to have a greater effect on sRaw and FEV1 than increasing the level of
exercise (269). Studies have further observed significant decrements in lung function
in some sensitive asthmatics following 515 min exposures to SO2 concentrations of
as low as 0.25 ppm while performing moderate levels of exercise (271, 273).
Moderate-to-severe asthmatics have greater exercise-induced sRaw increases and
FEV1 decrements compared to mild asthmatics; however, respiratory response with
increasing SO2 concentration has not been shown to differ significantly between mild
and moderate/severe asthmatics (272).
Consistent associations have been observed between ambient SO2 concentrations
(generally 24 h average) and various respiratory health outcomes in recent epidemiological studies. Two important new multicity studies (132, 274) and several other
studies (208, 275) have shown an association between short-term ambient SO2
concentrations and respiratory symptoms in children. Several new studies (276
278) found no association between SO2 levels and respiratory symptoms in adults.
These findings suggest supportive evidence for an association between short-term
exposure to ambient SO2 exposure and respiratory symptoms in children, particularly
those with asthma, but not in adults. While controlled human exposure studies reported
decrements in lung function following peak 515 min exposures to SO2 at near
ambient levels 90.5 in exercising asthmatic adults, epidemiological studies did not
provide strong evidence of an association between short-term, 24 h average ambient
SO2 exposures and changes in lung function in either children (132) or adults (279).
Bronchoconstriction following SO2 is mediated by chemosensitive receptors in the
tracheobronchial tree. Rapidly adapting receptors (RARs) and sensory C-fiber receptors found at all levels of the respiratory tract are sensitive to irritant gases such as
SO2 (280, 281). Activation of these vagal afferents cause central nervous system
reflexes resulting in bronchoconstriction, mucus secretion, mucosal vasodilation,
cough, apnea followed by rapid shallow breathing and effects on the cardiovascular
system such as bradycardia and hypotension or hypertension (280283).
Early experiments demonstrated that SO2-induced reflexes were mediated by
cholinergic parasympathetic pathways involving the vagus nerve and inhibited by
SULFUR DIOXIDE
2581
atropine (284, 285). In addition, bronchoconstriction was found to involve smooth

muscle contraction since b2-adrenergic agonists such as isoproterenol reversed the
effects (285, 286).
More recent experiments in animal models demonstrated that both cholinergic and
noncholinergic mechanisms may be involved in SO2-induced effects. In two studies
utilizing bilateral vagotomy, vagal afferents were found to mediate the immediate
ventilatory responses to SO2 (287) but not the prolonged bronchoconstrictor response (288). Other studies showed that atropine failed to block SO2-induced
bronchoconstriction and that a local axon reflex resulting in C-fiber secretion of
neuropeptides (i.e., neurogenic inflammation) was responsible for the effect (289,
290). Neurogenic inflammation has been shown to play a key role in other animal
models of airway inflammatory disease (291).
In humans, the mechanisms responsible for SO2-induced bronchoconstriction are
not fully understood. Furthermore, they may differ between nonasthmatics and
asthmatics. In nonasthmatics, near complete attenuation of bronchoconstriction
has been demonstrated using the anticholinergic agents atropine and ipratripium
bromide (285, 292294). However in asthmatics, these same anticholinergic
agents (295, 296) as well as short- and long-acting b2-adrenergic agonists (297,
298), theophylline (299), cromolyn sodium (296), nedocromil sodium (300), and
leukotriene receptor antagonists (297, 301) only partially blocked SO2-induced
bronchoconstriction. None of these therapies have been shown to completely attenuate
the effects of SO2 implying the involvement of both parasympathetic pathways and
inflammatory mediators in asthmatics. Furthermore, it has been proposed that
alterations in autonomic responses (302), enhanced mediator release (294), and
sensitization of C-fibers and RARs due to airway inflammation (303) contribute to
the enhanced sensitivity to SO2 seen in asthmatics. Whether local axon reflexes play a
role in SO2-induced bronchoconstriction in asthmatics is not known (282, 283, 291).
However, differences in respiratory tract innervation between rodents and humans
suggest that C-fiber mediated neurogenic inflammation may be unimportant in
humans (282, 283, 291).
Epidemiological studies provide evidence for an association between ambient SO2
levels and ED visits and hospitalizations for all respiratory diseases, particularly
among children and older adults (65 years of age) (304308). A modest association
between ambient SO2 and ED visits and hospitalizations for asthma particularly
among children <14 years old is also suggested (305307). No relationship is apparent
in the limited number of studies evaluating ED visits and hospitalizations for COPD or
other respiratory diseases (204, 309). Biological plausibility for these findings of
increased ED visits and hospitalizations is found in the epidemiological and toxicological studies that observed SO2-related increases in respiratory symptoms and
decreases in lung function parameters. Additional evidence from animal toxicological
studies, generally at higher SO2 concentrations, suggests that pulmonary host defense
mechanisms are also affected by SO2 exposure. At SO2 concentrations of 1 ppm, an
initial acceleration of clearance of particles from the lower respiratory tract was
observed at 10 days, followed by a slowing at 25 days in rats (310). Another study in
dogs observed that at 1 ppm SO2 tracheal mucous flow was reduced (311). Two recent
2582
AIR POLLUTION
studies using a 10 ppm SO2 exposure regimen in mice found no effect on bactericidal
activity toward Staphylococcus aureus following acute (4 h) exposure (312, 313).
However, increased mortality rate and decreased survival time were observed in mice
that were exposed to the same dose for 1 day or 1, 2, or 3 weeks and then challenged
with an aerosol of Klebsiella pneumoniae (314).
6.3.2 Mortality Associated with Short-Term Exposure to SO2 Epidemiological
evidence is suggestive of associations between SO2 and nonaccidental all-cause
and cardiopulmonary-related mortality, but additional research is needed to more
fully establish underlying mechanisms by which such effects occur. Earlier studies,
including those using historical data from London and New York City air pollution
episodes, observed associations between SO2 and mortality; however, high levels
of SO2 were frequently accompanied by high levels of particulate matter, making it
difficult to resolve the relative roles of these two pollutants. The clearest mortality
associations were seen when both pollutants were at high levels (24 h average
values of both black smoke and SO2 exceeding 1000 mg/m3 (400 ppb for SO2)).
Recent epidemiological studies have reported associations between mortality and
SO2, often at mean 24 h average levels below 10 ppb. However, in the large
multicity time-series studies, the SO2 risk estimates were generally reduced
when copollutants, either particulate matter indices and/or NO2, were added in
the regression model. Thus, some extent of confounding among these pollutants is
suggested.
An intervention study from Hong Kong (315) supports the notion that a reduction in
SO2 levels results in a reduction in deaths, but this does not preclude the possibility that
the causal agent is not SO2 but rather something else that is emitted along with SO2,
such as the trace metals vanadium and nickel.
7 PARTICULATE MATTER
Particulate matter (PM) is a complex mixture of solid particles and liquid droplets that
range in shape and size. Particles are comprised of a number of components, including
acids, nitrates and sulfates, organic chemicals, metals, carbon, and biological material.
Some particles, known as primary particles are emitted directly from a source, such as
construction sites, unpaved roads, vehicles, smokestacks or fires. Others form via
complicated atmospheric reactions involving gases such as sulfur oxides and nitrogen
oxides that are emitted from power plants, industries, and automobiles. These
particles, known as secondary particles, are generally smaller in diameter than
mechanically derived particles.
As illustrated in Figure 52.23, particles typically measured in ambient air in the
United States are found to be in four general size modes, with overlapping tails of
distribution. The greatest mass of particles is in the two largest size modes, fine and
coarse particles, with an intermodal range between 1 and 3 mm. The distribution of
PARTICULATE MATTER
2583
8
Vapor
V/log Dp (m3/cm3)
Mechanically
generated
Condensation
6
Nucleation
5
4
ion
ion
lat
u
ag
lat
u
ag
Co
Co
1
0
0.001
0.01
0.1
1
Particle diameter, Dp (m)
Nucleation mode
10
100
Accumulation mode
Aitken mode
Coarse mode
Fine particles
Ultrafine particles
Coarse particles
FIGURE 52.23 An idealized size distribution showing fine and coarse particles and the
nucleation, Aitken and accumulation modes comprise fine particles. Also shown the major
formation and growth mechanisms of atmospheric particles.
particles that are above this range make up the coarse mode and the distribution of
particles that are below this range are fine particles. Fine particles can be subcategorized into three smaller size denominations: nucleation mode, Aitken mode, and
accumulation mode. Nucleation- and Aitken-mode particles comprise the ultrafine
PM size fraction. Ultrafine particles have the highest number distribution and the
greatest surface area compared to the larger particle size modes. Nucleation- and
Aitken-mode particles have relatively low mass and grow rapidly into accumulationmode particles, so they are not commonly observed or reported as separate modes in
volume or mass distributions.
Regulatory standards for fine particles often focus on particles with mass
median aerodynamic diameters (MMAD) less than 2.5 mm, or PM2.5. Numerous
agencies also monitor and regulate PM10, which refers to particles with MMAD less
than or equal to 10 mm; these particles are more likely to be inhaled past the
upper portions of the respiratory tract. The subset of coarse particles that are inhalable
(i.e., those able to penetrate the upper regions of the human respiratory system) is
thoracic coarse particles (PM102.5) and includes particles with MMAD between 2.5
and 10 mm.
2584
AIR POLLUTION
7.2 Trends in PM Levels

National monitoring of PM10 concentrations in the United States began in 1987, with
PM2.5 measurements starting in 1999. Based on 391 sites and using seasonally
weighted annual averages, the levels of PM10 decreased an average of 30% between
1990 and 2006 (316) (Fig. 52.24a). A 14% decrease in PM2.5 seasonally weighted
annual average concentration was reported from 2000 to 2006, using 721 sites across
the United States (Fig. 52.24b). Reductions in emissions are largely attributable to
local and national air quality programs, such as the Acid Rain Program, which limits
SO2 emissions from power plants in the eastern United States and in turn, contributes to
lower PM levels (317).
7.3 Health Effects
The study of health effects associated with exposure to PM has been a major focus of
research in the last 15 years. Numerous reviews have been published on the
epidemiological and experimental evidence supporting health effects associated
with PM exposure (318324), and a more detailed discussion can be found in the
Air Quality Criteria for Particulate Matter (325) and a subsequent provisional
assessment (326). Various indicators of PM have been employed in health studies
and this discussion will focus primarily on studies using PM10 and smaller particle
size classes. A brief overview of the health evidence with a focus on what has
been learned regarding pathways or mechanisms for effects of PM exposure is
provided below.
7.3.1 Dosimetry The amount of PM inhaled from the atmosphere that is deposited
and subsequently retained at the target tissue is considered the dose. Dosimetry has
played a central role in the evaluation of PM health effects, and has been a primary
factor in regulatory decisions to focus on PM10 and smaller particle sizes. Briefly, as
depicted in Figure 52.25, the human respiratory tract can be divided into three main
regions: (1) extrathoracic, (2) tracheobronchial, and (3) alveolar. The regions differ
markedly in structure, function, surface area, mechanisms of deposition and removal,
and sensitivity or reactivity to deposited particles. Deposition patterns for coarse and
nucleation-mode ultrafine particles are similar, with significant fractional deposition
in all three regions (325). The accumulation mode size fraction deposits to a lesser
extent in the three respiratory system regions.
A number of factors affect particle deposition patterns including exposure concentration and duration, respiratory tract anatomy, ventilatory parameters, and particle
characteristics. Individuals with respiratory diseases (e.g., chronic obstructive pulmonary disease) can have greater total lung deposition (327, 328) and increased local
deposition (hot spots) due to uneven airflow (329). Similarly, clearance mechanisms
are dependent upon a number of environmental, anatomical, and physiological
factors (330) and can also be altered with disease state (325). In such cases, the
respiratory condition can result in enhanced susceptibility to inhaled particles by
increasing the delivered dose and slowing clearance rates and processes.
PARTICULATE MATTER
160
2585
National standard
Concentration (g/m3)
140
120
100
80
60
40
20
0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
(a)
Year
30
Concentration (g/m3)
25
20
National monitoring for PM2.5 began in 1999
National standard
15
10
0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
(b)
Year
FIGURE 52.24 (a) PM10 air quality from 1990 to 2006 based on annual second maximum
24 h average. The blue band represents the middle 80%, with the upper limit representing 90%
of sites with concentrations below that line, and 10% of sites having concentrations below the
bottom line. The white line represents the average among all sites. (b) PM2.5 air quality from
1999 to 2006 based on seasonally weighted annual average. The blue band represents the
middle 80%, with the upper limit representing 90% of sites with concentrations below that line,
and 10% of sites having concentrations below the bottom line. The white line represents the
average among all sites. The dashed line represents the national ambient air quality standard for
PM as of this writing.
7.3.2 Short-Term Exposure to PM There is a large body of epidemiological

evidence on associations between short-term exposure to PM and a range of health
outcomes. The observed health outcomes range from increased risk of mortality to
more subtle effects on the respiratory and cardiovascular systems (325). Since the
2586
AIR POLLUTION
ET.
Extrathoracic
region Pharynx
Posterior
Nasal passage
Nasal part
Oral part
Larynx
Trachea
Main bronchi
Tracheobronchial
region
BB
Bronchi
Bronchioles
Bronchiolar region
Ai
Alveolar interstitial
Bronchioles
Terminal bronchioles
bb
Alveolar
region
tb
Ai
Respiratory bronchioles
Alveolar duct +
Alveoli
FIGURE 52.25 Diagrammatic representation of respiratory tract regions in humans.

Sources: Adapted from International Commission on Radiological Protection, 1994 (ICRP
publication 66; Annals of the ICRP) and the U.S. EPA, Air Quality Criteria for Particulate
Matter (from Ref. 325).
early 1990s, numerous publications have reported associations between increased

daily mortality and various measurements of PM at much lower ambient PM
concentrations. These associations have been reported in numerous geographical
regions with differing climates, PM composition and sources, and levels of gaseous
copollutants (325).
Taken together, these studies collectively demonstrate positive associations between total nonaccidental mortality and short-term PM exposure, with stronger
evidence of associations for PM2.5. Focusing on the results of multicity studies
and the larger single-city studies, effect estimates for total mortality are generally
in the range of a 1% increased relative risk of mortality per 10 mg/m3 increase in
ambient PM2.5 or PM10 concentration. In general, relative risk estimates are larger for
PARTICULATE MATTER
2587
cause-specific mortality than total mortality, but the confidence intervals may also
increase due to lack of available data for the less frequent causes of death (322, 325).
Fewer studies have evaluated associations with short-term exposure to PM102.5.
These associations are generally similar in magnitude to those for PM2.5,
although frequently statistically insignificant, possibly due to increased measurement
error in estimating PM102.5 exposure (319, 325). Limited research indicates that
there may be a relationship between short-term exposure to ultrafine particles and
mortality (331, 332).
7.3.3 Long-Term Exposure to PM
7.3.3.1 Mortality Associations between long-term (i.e., over months to years)
exposure to PM and mortality have been evaluated in several prospective cohort
studies, as summarized in EPA (325) and Pope and Dockery (322). Two large cohort
studies have provided key evidence for cardiopulmonary mortality effects, as both
have undergone extensive, independent reanalysis and are based on cohorts that were
broadly representative of the U.S. population (333, 334). The effect estimates
for deaths from all causes range from 5% to 25% increased risk per 10 mg/m3
PM2.5, while effect estimates for deaths from cardiopulmonary causes are somewhat
higher, 1040% per 10 mg/m3 PM2.5.
7.3.3.2 Respiratory Morbidity Several studies have reported associations
between long-term (e.g., averaged over months to years) PM2.5 exposure with increased
incidence of respiratory symptoms and decreased lung function growth (238, 335337).
A recent epidemiological study has also reported an association between long-term
PM2.5 exposure and a measure of atherosclerosis development (338) and progression,
which is consistent with that observed in animal toxicological studies (339, 340).
7.3.3.3 Cancer A few epidemiological studies have also reported associations
between long-term exposure to PM and incidence of lung cancer (341, 342). Lung
cancer mortality is also associated with PM2.5 exposure, as evidenced by results that
demonstrate a 1015% increase per 10 mg/m3 PM2.5 for people living in more
polluted cities compared to cleaner cities (334). As discussed later, some PM
components, particularly PAHs, have mutagenic or genotoxic properties that
provides biological plausibility for the observed PM associations with cancer
incidence and mortality.
7.3.4 Fetal and Infant Development/Mortality Recent reviews of the literature
have concluded that there is some evidence linking exposure to PM and respiratory
deaths in the postneonatal period (343, 344). Exposure to several air pollutants has
been associated with increased risk of preterm births and intrauterine growth
retardation, although the evidence is insufficient to infer causality (344, 345).
Suggestive evidence for associations with low birth weight has also been reported,
although the findings were less consistent. The associations reported for adverse
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birth outcomes are generally rather small, and there are challenges in interpreting
this body of evidence (325). Toxicological studies employing PM to examine birth
outcomes are scarce.
7.4 Mechanisms
As discussed above, epidemiological evidence has played a key role in identifying the
effects associated with ambient PM, as well as in policy and regulatory decisions to
control PM. More recently, studies have focused on potential pathways for the
observed cardiopulmonary effects of PM. Generally these studies have employed
PM2.5 or PM10; the evidence discussed in this section is largely derived from PM2.5
studies. Recent toxicological studies have provided important insights that support the
effects observed in community health studies. Despite the progress made in this area,
specific mechanisms have yet to be elucidated.
The available evidence supports numerous hypotheses regarding induction of PM
effects. It appears unlikely that the complex particle mixture in ambient air would act
alone through any single pathway of response. Accordingly, it is plausible that several
physiological responses might occur in concert to produce reported health endpoints.
It should be recognized that, for the most part, the evidence from toxicological and
controlled human exposure studies discussed below reflects the effects of PM2.5 or
PM2.5 constituents, with substantially less data available on the potential mechanisms
of action for larger particles, such as thoracic coarse PM.
Toxicological studies have used a variety of particle types or surrogates of ambient
particles to evaluate potential mechanisms of PM toxicity. These include acid aerosols,
fly ash from coal- or oil-fired power plants (such as residual oil fly ash), diesel, and
crustal materials (e.g., Mt. St. Helens volcanic ash and road dust). More recently,
concentrated ambient particles (CAPs) have been employed, as well as ambient PM
collected on filters from monitoring stations. The CAPs exposure systems take outdoor
PM and enhance the concentration using virtual impactor or centrifugal technology;
this enables real-time exposure of human volunteers or animals to atmospheric PM and
gases (although the gases are not concentrated).
7.4.1 Effects on the Cardiovascular System Both acute and chronic PM exposures have been implicated in the observed cardiovascular morbidity and mortality
effects. These effects are linked to systemic inflammation, oxidative stress, and
mediation by the autonomic nervous system. The development and progression of
atherosclerosis is a relatively new research focus in the PM field and may partially
explain some of the epidemiological findings. Particle properties (e.g., soluble metals,
endotoxin, organic compounds, and surface composition) play a role in the physiological response, although the exact role(s) for these characteristics is yet to be fully
determined. In addition, ultrafine PM may cross the alveolarblood barrier and
translocate into the circulation, but evidence supporting this is inconclusive and quite
controversial in the PM research field. Figure 52.26 schematically illustrates hypothesized mechanisms thought to be involved in cardiovascular responses to PM
PARTICULATE MATTER
2589
CNS
Brainstem
Trachea
air
y
wa
Nonmyelinated
C-fibers
Sympathetic
ANS
Parasympathefic
ANS
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SP
,N
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Br
on
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ia
ch
PM
sm
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pacit
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Vasoc
on
BP
ation
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s tr
n
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ery
Pulmon n
tio
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PM
rd
ut
tp
ou
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ut
o
iac
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Inflammation
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ac
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ar
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disease states:
cardiac arrythmias.
COPD, etc.
Blockage of
coronary
artery
C-reactive protens
Cytokines
HR
Contractile force
Atherosclerosis
Platelet
activation
Clots
Fibrin
o
gen forma
tion
FIGURE 52.26 Schematic illustration of hypothesized pathways/mechanisms potentially

underlying the observed cardiovascular effects of PM. Source: U.S. EPA, Air Quality Criteria
for Particulate Matter (from Ref. 325).
exposure. Such effects may be especially deleterious to individuals compromised by

disease states such as ischemic heart disease, cardiac arrythmias, and COPD.
The modes of action that lead to systemic inflammation include (1) activation
of lung cells that release mediators that trigger a cascade of inflammatory reactions in
the circulation (346, 347) and (2) direct translocation of ultrafine PM or PM
constituents to extrapulmonary sites. Acute systemic inflammation (and the ensuing
oxidative stress) can lead to secondary vasoactive signals (348350) that could result
in endothelial dysfunction (351), platelet activation (346, 351, 352), and plaque
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AIR POLLUTION
destabilization (346, 351, 353). As one part of this pathway, inflammatory cytokines
induce tissue factor, which may cause endothelial cells to change from an antithrombitic to a procoagulant, clot-promoting state (354). Endothelial activation results
in the upregulation of adhesion molecules, which initiates local vascular inflammation with the recruitment of circulating leukocytes and monocytes (351, 354).
Furthermore, it has been hypothesized that stimulation of the bone marrow results
in increased release of monocytes that can participate in atherogenesis (355, 356). In
this manner, cells can enter the inflamed tissue and induce plaque formation.
PM exposure could promote hypercoagulation and hemostasis, possibly through
endothelial injury that results in platelet activation and subsequent platelet aggregation (352). Plaques may become prone to rupture with continued systemic inflammation via (1) upregulation of matrix metalloproteinases that break down collagen in
fibrous caps and/or (2) increases in CRP (346). Investigators have demonstrated that
animals exposed to PM can have increased plaque size in the aorta (340, 357) and
advanced atherosclerotic lesion phenotypes in coronary arteries (357), which may
lead to plaque instability.
The endothelium is an important regulator of vascular function, including blood
flow, coagulation, fibrinolysis, and inflammation. Vascular tone is primarily controlled
by production of nitric oxide, prostaglandins, and endothelins (ET). Endotheliumdependent alterations in vasodilation and vasoconstriction have been observed
following PM exposure, which have been linked to inhibition or decreased production
of NO and elevated levels of ET-1, respectively (346, 349, 354). It appears that
pulmonary inflammation is not a prerequisite for these vasomotor changes (348, 349).
Atherosclerosis development, acute coronary syndromes, and myocardial infarction
could all be consequences of endothelial dysfunction.
Thus, potentially dangerous alterations in systemic responses due to PM exposures
could be signaled by even small PM-related (a) changes in blood coagulation cascade
indicators, for example, increased blood platelet, fibrinogen, or Factor VII, or
decreased tissue plasminogen activator levels; (b) increased CRP or circulating
cytokines involved in the acute phase response; (c) upregulation of adhesion
molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intracellular
adhesion molecule-1 (ICAM-1), and E-selectin; and/or (d) impairment or enhancement of vasomotor activity.
Neurological mechanisms have also been proposed to explain PM effects on the
cardiovascular system (325, 354). It has been suggested that inhaled particles
stimulate pulmonary vagal afferents, which induce changes in autonomic control
of heart rate. Heart rate and blood pressure changes have been detected following
exposure to PM in humans and animals, but overall, the findings are inconclusive (325).
Pathophysiological changes in cardiac function can be detected by electrocardiographic recordings, with certain ECG parameters (e.g., heart rate variability or
HRV) recently gaining widening use as indicators of PM-induced cardiac effects.
When appropriately designed and carefully interpreted, studies utilizing measures of
HRV provide insight into the relationship between the perturbation of the internal or
external environment and subsequent changes in the modulation of autonomic neural
input to the heart. Generally, decreases in HRV measurements are observed following
PARTICULATE MATTER
2591
PM exposure, although it is unclear whether acute changes in HRV have deleterious

effects in this context (358).
Myocardial vulnerability, such as arrhythmia occurrence and ECG waveforms, has
also been examined with PM exposure. A number of studies have demonstrated
tachycardic and bradycardic arrhythmias in animals shortly after PM exposure, but
these studies were largely conducted at very high doses or concentrations (325).
Similarly, ST-segment elevations and depressions have been observed, as well as
T-wave alternans and morphological changes, which may indicate myocardial
ischemia and ion channel modifications, respectively (354).
7.4.2 Effects on the Respiratory System There are three hypothesized mechanisms for PM induction of direct respiratory system effects: (1) lung inflammation
and injury, (2) increased airway reactivity and exacerbation of asthma, and (3) impaired lung defense mechanisms and increased susceptibility to respiratory
infections (325).
Numerous toxicological studies demonstrate lung injury and inflammation following exposure to various particles. Strong evidence that provides coherence with
early epidemiological findings in the Utah Valley is documented in a study that used
ambient PM (PM10 and total suspended particulates) from filter extracts collected
from community air (359). A local steel mill, a major source of PM emissions in the
area, was closed for a 13 month period in the late 1980s. Epidemiological studies
reported that respiratory hospital admissions for children were reduced during the
period when the mill was not operating (360, 361). Intratracheal instillation of particle
extracts in both human volunteers and animals resulted in greater lung inflammatory
responses (as measured by increased levels of neutrophils, protein, and inflammatory
cytokines) for materials obtained while the plant was operational (362, 363).
Dosimetric analyses (see EPA, Ref. 325, Appendix 7A) indicate that the bolus
instillation doses of PM used in these experiments resulted in a one-time exposure
comparable to the cumulative dose that would result from a 6 to 9 week continuous
exposure to the upper range of ambient concentrations of PM10 that the community
might have experienced during winter weather inversions in the Utah Valley. In vitro
studies using a human airway epithelial cell line and primary rat airway epithelial cells
also showed evidence for inflammatory responses, such as increases in cytokine levels,
indicators of oxidative response in alveolar macrophages and some evidence of
cytotoxicity (364, 365). Additional evaluations indicate that the observed inflammatory responses were attributable to elevated metal content present in the particle
extracts during the periods when the steel mill was operating. Further studies
employing a combustion PM with high metals content (residual oil fly ash; ROFA)
also supports the above finding that metals may be a significant contributor to
toxicity (366, 367); these metals include soluble Fe, Ni, and V.
It is well documented that pulmonary inflammation is induced by PM2.5 exposure
(commonly via ROFA particles), although at lower exposure levels (comparable to
ambient concentrations), inflammation is not always observed (368, 369). Recent
studies indicate that ultrafine PM does not appear to cause as much cellular influx as the
other size fractions (370372), although older studies have demonstrated greater
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inflammation for ultrafine PM than fine PM of the same chemical composition at

similar mass doses (325). These conflicting results may be partially attributable to PM
composition.
Toxicological studies suggest that exacerbation of respiratory disease by ambient
PM may be caused in part by lung injury and inflammation. Rats with SO2-induced
bronchitis and monocrotaline-treated rats (as a model of pulmonary hypertension)
have greater inflammatory responses to CAPs (373375) and ROFA (376, 377) than
normal rats. This may result in larger, more detrimental health effects for susceptible
populations.
Toxicological studies have also demonstrated that pulmonary defense responses to
microbial agents can be affected with PM exposure. Studies using combustion related
particles, albeit at high doses, have shown effects such as increased inflammatory
responses (378) or mortality rate (379) from respiratory infections, compared with
animals exposed to infectious agents without PM exposure.
Finally, PM exposure may result in increased airway reactivity and exacerbation of
asthma. Acid aerosols may play a role in this response, as greater pulmonary function
changes in asthmatics compared to healthy individuals have been observed (325).
Increased airway resistance has been measured in healthy and asthmatic persons
exposed to diesel exhaust (380382). The strongest evidence supporting this hypothesis is from studies on diesel PM, as it has been shown to increase production of
antigen-specific IgE in mice (383) and humans (384387). Both the organic and the
carbon fractions have been implicated in the induction of allergic responses.
Upregulation of IgE may cause enhanced responsiveness to inhaled antigen in
PM-exposed individuals (325).
7.4.3 Mutagenicity and Genotoxicity Effects Toxicological studies have shown
extensive evidence that certain types of particles are mutagenic or otherwise genotoxic
in various types of bioassays (388, 389), and several recent in vivo and in vitro studies
have suggested that ambient particles are mutagenic (390). Only a few rodent
carcinogenicity studies using ambient air have been reported, however of those tested,
most demonstrated carcinogenic effects (389). Also, evidence of mutagenicity has
been reported in studies using exposures to emissions from wood/biomass burning,
coal combustion, and gasoline and diesel engine exhaust. Some of these studies
identified polyaromatic hydrocarbons (PAHs) and nitro-PAHs, as well as aromatic
amines and ketones as being more mutagenic than other components (388, 390). Such
results appear to provide experimental evidence that adds some degree of plausibility
for the reported epidemiological findings of ambient PM associations with increased
risk of lung cancer. However, some of the bioassay results were not indicative of
particularly strong mutagenic responses to the PM sample extracts or components
tested, nor was a high degree of association observed between in vitro genotoxic
effects and tumorigenic/cancer-causing potential across many different types of gases
and particles.
7.4.4 Oxidative Stress Effects A common proposed pathway leading to a range
of effects (discussed in the preceding sections) is PM-induced generation of
PARTICULATE MATTER
2593
reactive oxygen species (ROS). It has been hypothesized that specific PM

components may contribute to oxidative stress, including metals, organics (i.e.,
polycyclic aromatic hydrocarbons), and endotoxin. The production of ROS (and
possibly reactive nitrogen species) may result (1) directly from the interaction of
particle surfaces or components with lung tissue, (2) following activation and
recruitment of inflammatory cells, or (3) altered function of mitochondria or
NADPH-oxidase (391). These oxidative stress responses can lead to further downstream effects. For example, excess superoxide may be generated in the endothelium
by PM components, which can combine with NO to form peroxynitrite and limits
the amount of NO available to induce smooth muscle relaxation (351). Oxidative
DNA damage has been demonstrated in vivo following diesel exposure and in vitro
with diesel and urban PM types (391); however, the contribution of DNA damage
due to ROS to cancer and other PM-related health outcomes has yet to be
determined (391).
7.5 Effects Associated with Sources and Components of PM
The investigation of effects from different PM types is extremely complex, since there
is likely more than one potential mechanism or pathway underlying associations
reported with various health outcomes. In addition, particles may accumulate mass
and different components that vary over time due to atmospheric transformations and
chemical reactions.
Associations have been reported between mortality and short-term exposure to a
number of PM2.5 components. Some recent studies have used PM2.5 speciation data to
evaluate the effects of air pollutant combinations or mixtures using factor analysis or
source apportionment methods to evaluate health outcomes with different PM2.5
source types (392398). These studies reported that fine PM from combustion sources,
including motor vehicle emissions, coal combustion, oil burning and vegetative
burning, were associated with increased total nonaccidental or cardiovascular mortality. The findings of these studies, while providing some insight into the sources of
PM2.5 that might be associated with mortality, are likely not applicable to PM102.5
derived from different sources.
Toxicological studies indicate that various components, including metals, sulfates,
and elemental carbon and organic carbon, are linked with health outcomes, albeit at
generally high concentrations. Other recent epidemiological studies also report
associations between sulfates and mortality and morbidity, and provide new evidence
that organic or elemental carbon may be linked with effects (326). In addition,
biological constituents of particles (e.g., fungal spores, plant and insect fragments,
airborne bacteria) have been clearly linked with allergic, pulmonary, or inflammatory
responses in toxicological studies, and with respiratory symptoms or lung function
changes in epidemiological studies (325).
Studies comparing the effects of PM from different sources or locations have
generally shown that exposure to the various types of PM can result in different
responses, as illustrated in several intercomparison analyses. For example, in one
review of results from a series of in vitro exposures to different types of particles (399),
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certain responses, such as increases in pulmonary inflammation, may be greater with

smaller particles that have increased surface area. However, in vitro studies with
mineral or stone particles showed cytokine release to be affected by differences in PM
composition, not size (400). Other animal studies employing ambient PM from
different locations with varying source profiles have pointed to a number of PM
components or sources that may be partially responsible for the induced effects
(i.e., cytotoxicity, inflammation, and blood viscosity) (370, 371, 401, 402). Responses
correlated with individual markers (such as K, Cu, and Ba) for traffic and resuspended
soil, although the results do not appear consistent across locations or size fractions.
Similarly, in vitro studies have demonstrated a range of effects associated with
different PM components and sizes, including Br, Cr, Cu, Si, Fe, Mn, Ni, and organic
and elemental carbon (403407).
For the most part, information regarding components of particles has come
from PM2.5 studies. Some of these components, particularly biogenic material and
metals, can also be important components of PM102.5. More research involving the
systematic conduct of studies of potential effects of major components of PM
commonly found in each size fractions is needed, in recognition that PM of various
compositions from different sources can contrast markedly in its potency for producing toxicity.
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Air Pollution

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AIR POLLUTION

PAUL G. REINHART, PH.D., DABT, LORI WHITE, PH.D.,

2.2 Trends in Carbon Monoxide Levels

CO (thousands short tons)

CO (thousands short tons)

Fuel comb. elec. util.

Fuel comb. industrial

Fuel comb. other

Chemical & allied

Storage & transport

Fuel comb. elec.util.

Fuel comb. other

Chemical & allied product mfg

Other industrial processes

Storage & transport

Travel (billions of miles)

CO emissions (millions of short tons)

2.3 Health Effects

FIGURE 52.6 Simplified diagram of environmental pathways contributing to multimedia Pb

Brass and bronze

Pipe and sheet lead

3.2 Trends in Lead Levels

Micrograms of lead per deciliter of blood (g/dL)

FIGURE 52.10 Concentrationresponse relationship of IQ to PbB for the individual studies

FIGURE 52.11 Demonstration of the mechanisms of action of Pb at a typical synapse. Lead

alterations to the immune system and to immunological pathways. Low to moderate

Key effects of lead on the immune system

Macrophages, macrophages and antigen

Modified neural antigens

Skewed VB gene usage &

Increased tissue inflammation

IgE & increased risk of

Reduced cell-mediated immunity

atopy and asthma

Lead-induced alterations to the immune system.

Temporal and spatial differences in O3 levels are dependent on the concentrations

4.2 Trends in Ozone Levels

4.3 Health Effects

National trend based on 275 sites

2001 2002 2003

2004 2005 2006

Limited epidemiological evidence demonstrates an association between acute

O3 concentrations and cardiovascular hospitalizations (167). However, other studies

A large body of animal toxicological studies of long-term exposures to O3 shows

Genes or gene loci on mouse chromosomes, which modulate responses to

Fuel comb. elec. util.

Fuel comb. industrial

Fuel comb. other

Chemical & allied product mfg

Petroleum & related industries

Other industrial processes

Storage & transport

Waste disposal & recycling

NOx (thousands short tons)

Fuel comb. industrial

5.2 Trends in Nitrogen Oxides Levels

NOx (thousands short tons)

Chemical & allied

Petroleum & related

National trend based on 87 sites

National trend based on 170 sites

number of studies have investigated macrophage function following NO2 exposure in

atropine (284, 285). In addition, bronchoconstriction was found to involve smooth

7.2 Trends in PM Levels