. An air pollutant is any substance which may harm humans, animals,
vegetation or material. A number of physical activities (volcanoes, fire, etc.)
may release different pollutants in the environment although anthropogenic
activities are the major cause of environmental air pollution. Hazardous
chemicals can escape to the environment by accident, but a number of air
pollutants are released from industrial facilities and other activities and may
cause adverse effects on human health and the environment (CEE,2012).
Air pollutants include suspended particles and gases including carbon
monoxide, volatile organic compounds (VOCs), nitrous oxides, sulphur dioxide,
and ozone. Suspended particles are called particulate matter (PM), which is a mixture
of tiny particles and liquid droplets that includes acids, organic chemicals,
metals, and dust. PM is measured by size: PM2.5 is 2.5 micrometres (?m) in diameter.
For comparison, a human hair is 70?m in diameter.
As far as humans are concerned an air pollutant may cause or
contribute to an increase in mortality or serious illness or may pose a present
or potential hazard to human health. The determination of whether or not a
substance poses a health risk to humans is based on clinical, epidemiological,
and/or animal studies which demonstrate that exposure to a substance is
associated with health effects. In the context of human health, ”risk” is the
probability that a noxious health effects may occur.
The main change in the atmospheric composition is primarily due to
the combustion of fossil fuels, used for the generation of energy and
transportation. Variant air pollutants have been reported, differing in their
chemical composition, reaction properties, emission, persistence in the
environment, ability to be transported in long or short distances and their
eventual impacts on human and/or animal health. However, they share some
similarities and they can be grouped to four categories:
a. Gaseous pollutants (e.g. SO2, NOx,
CO, ozone, Volatile Organic Compounds)
b. Persistent organic pollutants (e.g. dioxins).
c. Heavy metals (e.g. lead, mercury).
d. Particulate Matter.
Gaseous pollutants contribute to a great extent in
composition variations of the atmosphere and are mainly due to combustion of
fossil fuels (Katsouyanni, 2003). nitrogen oxides are emitted from fossil
fuel burning and ammonia is emitted from agricultural activities. Nitrogen is a
nutrient and its increased deposition affects plant biodiversity. In addition,
nitrogen contributes to acidification of soils and waters. Nitrogen oxides are
emitted as NO which rapidly reacts with ozone or radicals in the atmosphere
forming NO2. The main anthropogenic sources are mobile and stationary
Moreover, ozone in the lower atmospheric layers is formed by a
series of reactions involving NO2 and volatile organic compounds, a process
initiated by sun light. CO, on the other hand, is a product of incomplete
combustion. Its major source is road transport too. While the anthropogenic SO2 emitted from fossil fuel burning
(industry, households, transport), sulphur dioxide causes acidification of
soils, streams and lakes and leads to erosion of building materials, including
cultural heritage. volcanoes and oceans are its major natural sources. The
latter contribute only ~2% of the total emissions.
Finally, a major class of compounds that fuel combustion and
especially combustion processes for energy production and road transport are
the major source of emission are the so called volatile organic compounds
(VOCs). Volatile organic compounds (VOCs) are emitted as gases from certain
solids or liquids. VOCs include a variety of chemicals, some of which may have
short- and long-term adverse health effects. They are compounds that have a
high vapor pressure and low water solubility. Many VOCs are human-made
chemicals that are used and produced in the manufacture of paints, pharmaceuticals,
VOCs typically are industrial solvents, such as trichloroethylene;
fuel oxygenates, such as methyl tert-butyl ether (MTBE); or by-products
produced by chlorination in water treatment, such as chloroform. VOCs are often
components of petroleum fuels, hydraulic fluids, paint thinners, and dry
cleaning agents. (EPA, 2006)
Persistent organic pollutants – Persistent organic
pollutants (POPs) are chemicals of global concern due to their potential for
long-range transport, persistence in the environment, ability to bio-magnify
and bio-accumulate in ecosystems, as well as their significant negative effects
on human health and the environment. Humans are exposed to these chemicals in a
variety of ways: mainly through the food we eat, but also through the air we breathe,
in the outdoors, indoors and at the workplace. Many products used in our daily
lives may contain POPs, which have been added to improve product
characteristics, such as as flame retardants or surfactants. As a result, POPs
can be found virtually everywhere on our planet in measurable concentrations.
The most commonly encountered POPs are organochlorine pesticides,
such as DDT, industrial chemicals, most notably polychlorinated biphenyls
(PCB), as well as unintentional by-products of many industrial processes,
especially polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF),
commonly known as ‘dioxins’.
POPs bio-magnify throughout the food chain and bio-accumulate in
organisms. The highest concentrations of POPs are thus found in organisms at
the top of the food chain. Consequently, background levels of POPs can be found
in the human body.
Human exposure – for some compounds and scenarios, even to low
levels of POPs – can lead, among others, to increased cancer risk, reproductive
disorders, alteration of the immune system, neurobehavioural impairment,
endocrine disruption, genotoxicity and increased birth defects.
Heavy metals The term heavy metal refers to any
metallic chemical element that has a relatively high density and is toxic or
poisonous at low concentrations. Examples of heavy metals include mercury (Hg),
cadmium (Cd), arsenic (As), chromium (Cr), thallium (Tl), and lead (Pb). Heavy
metals are natural components of the Earth’s crust. They cannot be degraded or
destroyed. To a small extent they enter our bodies via food, drinking water and
air. As trace elements, some heavy metals (e.g. copper, selenium, zinc) are
essential to maintain the metabolism of the human body. However, at higher
concentrations they can lead to poisoning. Heavy metal poisoning could result,
for instance, from drinking-water contamination (e.g. lead pipes), high ambient
air concentrations near emission sources, or intake via the food chain.
Heavy metals are dangerous because they tend to bio accumulate.
Bioaccumulation means an increase in the concentration of a chemical in a
biological organism over time, compared to the chemical’s concentration in the
environment. Compounds accumulate in living things any time they are taken up
and stored faster than they are broken down (metabolized) or excreted. Heavy
metals can enter a water supply by industrial and consumer waste, or even from
acidic rain breaking down soils and releasing heavy metals into streams, lakes,
rivers, and groundwater.
Particulate matter (PM) – Particulate Matter (PM) includes both solid particles and liquid
droplets found in air. Many man-made and natural sources emit PM directly or
emit other pollutants that react in the atmosphere to form PM. These solid and
liquid particles come in a wide range of sizes. Particles less than 10 micrometres
in diameter tend to pose the greatest health concern because they can be
inhaled into and accumulate in the respiratory system. Particles less than 2.5 micrometres
in diameter are referred to as “fine” particles. Sources of fine
particles include all types of combustion (motor vehicles, power plants, wood
burning, etc.) and some industrial processes. Particles with diameters between
2.5 and 10 micrometres are referred to as “coarse”. Sources of coarse
particles include crushing or grinding operations, and dust from paved or
The Environmental Protection Agency uses its Air Quality Index to
provide general information to the public about air quality and associated
health effects. An Air Quality Index (AQI) of 100 for any pollutant corresponds
to the level needed to violate the federal health standard for that pollutant.
For PM2.5, an AQI of 100 corresponds to 40 micrograms per cubic meter (averaged
over 24 hours) — the current federal standard. An AQI of 100 for PM10
corresponds to a PM10 level of 150 micrograms per cubic meter (averaged over 24
3. Routes of exposure
Humans enter in contact with different air pollutants primarily via
inhalation and ingestion, while dermal contact represents a minor route of
exposure. Air pollution contributes, to a great extent, to the contamination of
food and water, which makes ingestion in several cases the major route of
pollutant intake (Thron, 1996). Via the gastrointestinal and respiratory tract,
absorption of pollutants may occur, while a number of toxic substances can be
found in the general circulation and deposit to different tissues. Elimination
occurs to a certain degree by excretion (Madden and Fowler, 2000).
4. Health effects
Sporadic air pollution events, like the historic London fog in 1952
and a number of short and long term epidemiological studies investigated the
effects of air quality changes on human health. A constant finding is that air
pollutants contribute to increased mortality and hospital admissions
(Brunekreef and Holgate, 2002). The different composition of air pollutants,
the dose and time of exposure and the fact that humans are usually exposed to
pollutant mixtures than to single substances, can lead to diverse impacts on
human health. Human health effects can range from nausea and difficulty in
breathing or skin irritation, to cancer. They also include birth defects,
serious developmental delays in children, and reduced activity of the immune
system, leading to a number of diseases. Moreover, there exist several
susceptibility factors such as age, nutritional status and predisposing
conditions. Health effects can be distinguished to acute, chronic not including
cancer and cancerous. Epidemiological and animal model data indicate that
primarily affected systems are the cardiovascular and the respiratory system. However,
the function of several other organs can be also influenced (Cohen et al.,
2005; Huang and Ghio, 2006; Kunzli and Tager, 2005; Sharma and Agrawal, 2005).
4.1. Effects of air pollutants on different organs and systems
4.1.1. Respiratory system
Numerous studies describe that all types of air pollution, at high
concentration, can affect the airways. Nevertheless, similar effects are also
observed with long-term exposure to lower pollutant concentrations. Symptoms
such as nose and throat irritation, followed by bronchoconstriction and
dyspnoea, especially in asthmatic individuals, are usually experienced after exposure
to increased levels of sulphur dioxide (Balmes et al., 1987), nitrogen oxides
(Kagawa, 1985), and certain heavy metals such as arsenic, nickel or vanadium.
In addition, particulate matter that penetrates the alveolar epithelium (Ghio and
Huang, 2004) and ozone initiate lung inflammation (Uysal and Schapira, 2003).
In patients with lung lesions or lung diseases, pollutant-initiated inflammation
will worsen their condition. Moreover, air pollutants such as nitrogen oxides increase
the susceptibility to respiratory infections (Chauhan et al., 1998). Finally,
chronic exposure to ozone and certain heavy metals reduces lung function
(Rastogi et al., 1991; Tager et al., 2005), while the later are also
responsible for asthma, emphysema, and even lung cancer (Kuo et al., 2006; Nawrot
et al., 2006). Emphysema-like lesions have also been observed in mice exposed
to nitrogen dioxide (Wegmann et al., 2005).
4.1.2. Cardiovascular system
Carbon monoxide binds to haemoglobin modifying its conformation and
reduces its capacity to transfer oxygen (Badman and Jaffe, 1996). This reduced
oxygen availability can affect the function of different organs (and especially
high oxygenconsuming organs such as the brain and the heart), resulting in
impaired concentration, slow reflexes, and confusion. Apart from lung
inflammation, systemic inflammatory changes are induced by particulate matter,
affecting equally blood coagulation (Riediker et al., 2004). Air pollution that
induces lung irritation and changes in blood clotting can obstruct (cardiac)
blood vessels, leading to angina or even to myocardial infraction Vermylen et
al., 2005). Symptoms such as tachycardia, increased blood pressure and anaemia
due to an inhibitory effect on haematopoiesis have been observed as a
consequence of heavy metal pollution (specifically mercury, nickel and arsenic) (Huang and Ghio, 2006). Finally,
epidemiologic studies have linked dioxin exposure to increased mortality caused
by ischemic heart disease, while in mice, it was shown that heavy metals can
also increase triglyceride levels (Dalton et al., 2001).
4.1.3. Nervous system
The nervous system is mainly affected by heavy metals (lead,
mercury and arsenic) and dioxins. Neurotoxicity leading to neuropathies,
with symptoms such as memory disturbances, sleep disorders, anger,
fatigue, hand tremors, blurred vision, and slurred speech, have been
observed after arsenic, lead and mercury exposure (Ewan and Pamphlett,
1996; Ratnaike, 2003). Especially, lead exposure causes injury to the
dopamine system, glutamate system, and N-methyl-D-Aspartate (NMDA) receptor
complex, which play an important role in memory functions (Lasley and
Gilbert, 2000; Lasley et al., 2001). Mercury is also responsible for
certain cases of neurological cancer. Dioxins decrease nerve conduction
velocity and impaired mental development of children (Thomke et al.,
1999; Walkowiak et al., 2001).
4.1.4. Urinary system
Heavy metals can induce kidney damage such as an initial tubular
dysfunction evidenced by an increased excretion of low molecular weight
proteins, which progresses to decreased glomerular filtration rate (GFR). In addition,
they increase the risk of stone formation or nephrocalcinosis (Damek-Poprawa and
Sawicka-Kapusta, 2003; Jarup, 2003; Loghman-Adham, 1997) and renal cancer
(Boffetta et al., 1993; Vamvakas et al., 1993).
4.1.5. Digestive system
Dioxins induce liver cell damage (Kimbrough et al., 1977), as
indicated by an increase in levels of certain enzymes in the blood (see
following discussion on the underlying cellular mechanisms of action), as well
as gastrointestinal and liver cancer (Mandal, 2005).
4.2. Exposure during pregnancy
It is rather important to mention that air pollutants can also affect
the developing foetus (Schell et al., 2006). Maternal exposure to heavy metals
and especially to lead, increases the risks of spontaneous abortion and reduced
fetal growth (preterm delivery, low birth weight). There are also evidences suggesting
that parental lead exposure is also responsible for congenital malformations
(Bellinger, 2005), and lesions of the developing nervous system, causing
important impairment in new-born’s motor and cognitive abilities (Garza et al.,
Similarly, dioxins were found to be transferred from the mother to
the fetus via the placenta. They act as endocrine disruptors and affect growth
and development of the central nervous system of the foetus (Wang et al.,
2004). In this respect, TCDD is considered as a developmental toxin in all
5. Cellular mechanisms involved in air pollutants actions
Common cellular mechanism by which most air pollutants exert their
adverse effects is their ability to act directly as prooxidants of lipids and
proteins or as free radicals generators, promoting oxidative stress and the
induction of inflammatory responses (Menzel, 1994; Rahman and MacNee, 2000).
Free radicals (reactive oxygen and nitrogen species) are harmful to cellular
lipids, proteins, and nuclear- or mitochondrial- DNA, inhibiting their normal
function (Valko et al., 2006). In addition, they can interfere with signaling
pathways within cells (Valko et al., 2006). In eukaryotic aerobic organisms
including humans, free radicals are continuously generated during normal
metabolism and in response to exogenous environmental exposures (e.g.
irradiation, cigarette smoke, metals and ozone). When free radical
concentration increases, due to an overwhelming of organism’s defense, a state
of oxidative stress occurs. This oxidative state has been implicated in
a wide variety of degenerative diseases such as atherosclerosis, heart attacks,
stoke, chronic inflammatory diseases (rheumatoid arthritis), cataract, central
nervous system disorders (Parkinson’s, and Alzheimer’s disease), age related
disorders and finally cancer.
Furthermore, the toxic effects of heavy metals, apart from inducing
oxidative stress, can be also attributed to their ability to substitute diverse
polyvalent cations (calcium, zinc, and magnesium) that function as charge
carriers, intermediaries in catalysed reactions, or as structural elements in
the maintenance of protein conformation. Indeed, metals accumulate in cellular
organelles and interfere with their function. For example, it has been observed
that lead accumulation in mitochondria induces several changes such as
inhibition of Ca2þ uptake, reduction of the transmembrane potential, oxidation
of pyridine nucleotides, and a fast release of accumulated Ca2þ (Chavez et al.,
1987). Moreover, metals bind to proteins (Goering, 1993) and inhibit a large
number of enzymes, including the mitochondrial ones (Rossi et al., 1993).
Nucleic acid binding proteins are also involved, while it has been shown that
metals can also bind to DNA, affecting the expression of genes. For example,
nickel enters the nucleus, interacts with chromatin and silences the expression
of genes such as tumour suppressor genes, inducing carcinogenesis (Costa et al.,
2003). Finally, some metals interfere with various voltage- and ligand-gated
ionic channels exerting neurotoxic effects.
For instance, lead affects the N-methyl-D-aspartic acid (NMDA)
receptor, subtypes of voltage- and calcium-gated potassium channels,
cholinergic receptors and voltage-gated calcium channels (Garza et al., 2006;
Toscano and Guilarte, 2005).
Dioxin causes a broad range of adverse effects (Birnbaum, 1994):
they alter metabolism by inducing a number of metabolic enzymes (e.g. CYPs,
glutathione-transferase, tyrosine kinase etc.), homeostasis, through hormone
modulation (e.g. estrogens, androgens glucocorticoids, insulin, thyroid
hormones) and their receptors, and growth and differentiation by interfering
with growth factors (e.g. EGF, TGFa, TNFa) and their receptors. At the cellular
level, dioxins interact with the aryl hydrocarbon receptor (AhR) (Schwarz et
al., 2000) which has a basic helix-loop-helix domain, acting as a transcription
factor after nuclear translocation, allowing interaction of dioxins with DNA.
The receptor-ligand complex binds to specific sites on DNA, altering the
expression of a number of genes.
As far as cancer is concerned from the data presented above it
becomes clear that most pollutants play an important role in the initiation,
promotion and progression of cancer cells (Fig. 1).
6. Natural protection
In our day-to-day life we are exposed in different kinds of pollutants.
Health impacts, as already described above, depend on the pollutant type, its
concentration, length of exposure, other coexisting pollutants and individual
susceptibility. People living in cities are exposed to a greater extent, as a
consequence of increased industrialization and demands for energy and motor
vehicles. Occupational exposure is also an important factor that should be
taken into consideration. During the last decade, health effects of air
pollution are studied more in developed countries, while more and better
environmental monitoring data are required in order to setup threshold levels.
In addition, efforts should be intensified by taking the appropriate measures,
in order to reduce the possibility of human pollutant exposure. The human body,
in order to protect itself against the potential harmful insults from the
environment, is equipped with drug or xenobiotic metabolising enzymes (DMEs or
XMEs) that play a central role in the biotransformation, metabolism and/or
detoxification of xenobiotics or foreign compounds, including different kinds
of pollutants. XMEs include a variety of enzymes such as cytochrome P450 (P450
or CYP), epoxide hydrolase, glutathione transferase,
UDP-glucuronosyltransferase, sulfotransferase, NAD(P)H quinone oxidoreductase
1, and aldo-keto reductase. These enzymes mainly participate in the conversion
of xenobiotics to more polar and water-soluble metabolites, which are readily
excreted from the body. Finally, it should be noted that, in many cases, the
chemically reactive metabolites produced during metabolism, are equally harmful
and therefore undergo additional metabolism to inactive products.
Hence, the final outcome of a compound modulating the
detoxification enzyme systems is the result the effects on the different
metabolic pathways. A number of substances of dietary nature are beneficial,
protective, and supportive of good health and the body’s own natural chelation
mechanisms. They include nutrients with natural chelating properties, which may
help to detoxify the body, such as antioxidants, herbs, minerals, essential
amino acids, other detoxifying or protective agents, and fiber (Kelly, 2004).
Among them dietary antioxidants contribute to the organism’s antioxidant
defence system, that includes a series of antioxidant enzymatic (e.g.
peroxidase) and nonenzymatic compounds (such as glutathione, or food-derived
like vitamin E, or polyphenols), as well as damage removal / repair enzymes.
Several natural compounds, such as vitamins C, E, and A and
polyphenols, found in the majority of plant foods, interfere with or scavenge
ROS concentration within cells and subsequently protect the organism from the
adverse effects of oxidative stress. Indeed, as it has been shown by our group
that the antioxidant activity of plasma in humans following a diet rich in
vegetables, fruits and olive oil was increased in comparison to a normal diet
(Kampa et al., 2002). This increase can be mainly attributed to polyphenols
which exhibit a wide range of biological activities, including
anti-tumorigenic, anti-mutagenic, anti-inflammatory, and antiviral actions
(Bravo, 1998; Hertog and Hollman, 1996) mainly due to their antioxidant
properties and their ability to exert inhibitory effects by affecting basic
cellular functions. Indeed, the beneficial role of polyphenols in preventing
cancer can be in part attributed to their ability to modify enzymes that
activate or detoxify environmental carcinogens.
This brief review presents the adverse effects of a number of (air)
pollutants in human health. As shown, major impairments of different organs can
be observed. The main conclusion drawn is that, in view of increased exposure
of humans in a diversity of pollutants, dietary interventions, rich in
plant-derived foods, may protect or decrease their effects on different organs.
This conclusion is supported by a number of epidemiological studies on the
beneficial effect of a Mediterranean- type diet on human health.