Available online at www.sciencedirect.com

Environmental Pollution 151 (2008) 362e367
www.elsevier.com/locate/envpol

Human health effects of air pollution
Marilena Kampa, Elias Castanas*
Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, P.O. Box 2208, Heraklion, 71003, Greece
Received 4 June 2007; accepted 10 June 2007

The effect of air pollutants on human health and underlying mechanisms of cellular action are discussed.
Abstract
Hazardous chemicals escape to the environment by a number of natural and/or anthropogenic activities and may cause adverse effects onhuman health and the environment. Increased combustion of fossil fuels in the last century is responsible for the progressive change in the atmospheric composition. Air pollutants, such as carbon monoxide (CO), sulfur dioxide (SO2), nitrogen oxides (NOx), volatile organic compounds(VOCs), ozone (O3), heavy metals, and respirable particulate matter (PM2.5 and PM10), differ in their chemical composition, reaction properties, emission, time of disintegration and ability to diffuse in long or short distances. Air pollution has both acute and chronic effects on humanhealth, affecting a number of different systems and organs. It ranges from minor upper respiratory irritation to chronic respiratory and heartdisease, lung cancer, acute respiratory infections in children and chronic bronchitis in adults, aggravating pre-existing heart and lung disease,or asthmatic attacks. In addition, short- and long-term exposures have also been linked with premature mortality and reduced life expectancy.
These effects of air pollutants on human health and their mechanism of action are briefly discussed.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Air pollutant; Human health; Cellular actions; Detoxification

1. Introduction
Although a number of physical activities (volcanoes, fire,etc.) may release different pollutants in the environment,
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. By definition, an air pollutant is any substance which may harm
humans, animals, vegetation or material. As far as humans
are concerned an air pollutant may cause or contribute to anincrease in mortality or serious illness or may pose a present
or potential hazard to human health. The determination ofwhether or not a substance poses a health risk to humans is* Corresponding author. Tel.: þ30 28 1039 4580; fax: þ30 28 1039 4581.
E-mail addresses: kampa@med.uoc.gr (M. Kampa), castanas@med.uoc.gr(E. Castanas).
0269-7491/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.envpol.2007.06.012

based on clinical, epidemiological, and/or animal studies
which demonstrate that exposure to a substance is associatedwith health effects. In the context of human health, ‘‘risk’’ isthe probability that a noxious health effects may occur.
2. Pollutant categories
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 havebeen reported, differing in their chemical composition, reaction properties, emission, persistence in the environment, ability to be transported in long or short distances and theireventual impacts on human and/or animal health. However,they share some similarities and they can be grouped to four
categories:
1. Gaseous pollutants (e.g. SO2, NOx, CO, ozone, Volatile
Organic Compounds).

M. Kampa, E. Castanas / Environmental Pollution 151 (2008) 362e367

2. Persistent organic pollutants (e.g. dioxins).
3. Heavy metals (e.g. lead, mercury).
4. 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 as NO which rapidly reacts with ozone or radicals
in the atmosphere forming NO2. The main anthropogenic sources are mobile and stationary combustion sources. Moreover,ozone in the lower atmospheric layers is formed by a seriesof reactions involving NO2 and volatile organic compounds,
a process initiated by sun light. CO, on the other hand, isa product of incomplete combustion. Its major source is roadtransport too. While the anthropogenic SO2 results from the
combustion of sulphur-containing fossil fuels (principallycoal and heavy oils) and the smelting of sulphur containing
ores, volcanoes and oceans are its major natural sources.
The latter contribute only ~2% of the total emissions. Finallya major class of compounds that fuel combustion and especially combustion processes for energy production and roadtransport are the major source of emission are the so called
volatile organic compounds (VOCs). This is a class of compounds, which includes chemical species of organic naturesuch as benzene. Even though the majority of gaseous pollutants are inhaled and mainly affect the respiratory system they
can also induce haematological problems (CO, benzene) andcancer.
Persistent organic pollutants form a toxic group of chemicals. They persist in the environment for long periods oftime, and their effects are magnified as they move up throughthe food chain (bio-magnification). They include pesticides, aswell as dioxins, furans and PCBs. Generally, the generic term‘‘dioxins’’ is used to cover polychlorinated dibenzo-dioxins(PCDDs) and polychlorinated dibenzo-furans (PCDFs) while
polychlorinated biphenyls (PCB) are called ‘‘dioxin likecompounds’’ and can act similarly in terms of dioxin-type
toxicity (Schecter et al., 2006). Dioxins are formed during incomplete combustion and whenever materials containing
chlorine (e.g. plastics) are burned. Emitted in the atmosphere,
dioxins tend to deposit on soil and water but, being waterinsoluble, they do not contaminate ground water sources.
Most dioxins in plants come from air and dust or pesticides
and enter the food chain where they bio-accumulate due totheir ability to be stably bound to lipids.
Heavy metals include basic metal elements such as lead,
mercury, cadmium silver nickel, vanadium, chromium andmanganese. They are natural components of the earth’s crust;they cannot be degraded or destroyed, and can be transported
by air, and enter water and human food supply. In addition,
they enter the environment through a wide variety of sources,
including combustion, waste water discharges and manufacturing facilities. To a small extent they enter human bodies
where, as trace elements, they are essential to maintain thenormal metabolic reactions. However, at higher (although relatively low) concentrations they can become toxic (Jarup,2003). Most heavy metals are dangerous because they tend363

to bio-accumulate in the human body. Bioaccumulationmeans 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 organisms any time they are taken in and stored fasterthan they are broken down (metabolized) or excreted.
Particulate matter (PM) is the generic term used for a typeof air pollutants, consisting of complex and varying mixturesof particles suspended in the breathing air, which vary insize and composition, and are produced by a wide variety ofnatural and anthropogenic activities (Poschl, 2005). Major
sources of particulate pollution are factories, power plants, refuse incinerators, motor vehicles, construction activity, fires,and natural windblown dust. The size of the particles varies(PM2.5 and PM10 for aerodynamic diameter smaller than
2.5 mm and 10 mm respectively) and different categories
have been defined: Ultrafine particles, smaller than 0.1 mm
in aerodynamic diameter, Fine particles, smaller than 1 mm,
and Coarse particles, larger than 1 mm. The size of the particles determines the site in the respiratory tract that they willdeposit: PM10 particles deposit mainly in the upper respiratory
tract while fine and ultra fine particles are able to reach lungalveoli. So far, no single component has been identified that
could explain most of the PM effects. Among the parametersthat play an important role for eliciting health effects are thesize and surface of particles, their number and their composition. The composition of PM varies, as they can absorb andtransfer a multitude of pollutants. However, their major components are metals, organic compounds, material of biologic
origin, ions, reactive gases, and the particle carbon core. Thereis strong evidence to support that ultra fine and fine particles
are more hazardous than larger ones (coarse particles), in
terms of mortality and cardiovascular and respiratory effects.
In addition, the metal content, the presence of PAHs and otherorganic components such as endotoxins, mainly contribute to
PM toxicity.
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, toa great extent, to the contamination of food and water, whichmakes 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 anddeposit 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 epidemiologicalstudies investigated the effects of air quality changes on human health. A constant finding is that air pollutants contributeto increased mortality and hospital admissions (Brunekreef

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M. Kampa, E. Castanas / Environmental Pollution 151 (2008) 362e367

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 activityof 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 canbe distinguished to acute, chronic not including cancer andcancerous. Epidemiological and animal model data indicatethat primarily affected systems are the cardiovascular andthe respiratory system. However, the function of several otherorgans can be also influenced (Cohen et al., 2005; Huang andGhio, 2006; Kunzli and Tager, 2005; Sharma and Agrawal,2005).
4.1. Effects of air pollutants on different organs andsystems
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 (Ghioand 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 forasthma, 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 thefunction of different organs (and especially high oxygenconsuming organs such as the brain and the heart), resulting
in impaired concentration, slow reflexes, and confusion. Apartfrom lung inflammation, systemic inflammatory changes are induced by particulate matter, affecting equally blood coagulation(Riediker et al., 2004). Air pollution that induces lung irritationand changes in blood clotting can obstruct (cardiac) bloodvessels, 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 effecton haematopoiesis have been observed as a consequence ofheavy metal pollution (specifically mercury, nickel and arsenic)(Huang and Ghio, 2006). Finally, epidemiologic studies havelinked 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, leadand 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 therisk 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 cellularmechanisms of action), as well as gastrointestinal and livercancer (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 therisks of spontaneous abortion and reduced fetal growth (preterm delivery, low birth weight). There are also evidencessuggesting that parental lead exposure is also responsible forcongenital malformations (Bellinger, 2005), and lesions of thedeveloping nervous system, causing important impairment in
newborn’s motor and cognitive abilities (Garza et al., 2006).
Similarly, dioxins were found to be transferred from the motherto the fetus via the placenta. They act as endocrine disruptors
and affect growth and development of the central nervous

M. Kampa, E. Castanas / Environmental Pollution 151 (2008) 362e367

system of the foetus (Wang et al., 2004). In this respect, TCDD
is considered as a developmental toxin in all species examined.
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 mitochondrialDNA, inhibiting their normal function (Valko et al., 2006).
In addition, they can interfere with signaling pathways withincells (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 toan overwhelming of organism’s defense, a state of oxidative
stress occurs. This oxidative state has been implicated ina 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 frominducing oxidative stress, can be also attributed to their ability
to substitute diverse polyvalent cations (calcium, zinc, andmagnesium) that function as charge carriers, intermediaries
in catalyzed reactions, or as structural elements in the maintenance of protein conformation. Indeed, metals accumulate incellular 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, oxidationof 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 beenshown 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
tumor 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-gatedpotassium channels, cholinergic receptors and voltage-gatedcalcium 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 asa 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 theinitiation, promotion and progression of cancer cells (Fig. 1).
6. Natural protection
In our day-to-day life we are exposed in different kinds ofpollutants. Health impacts, as already described above, dependon the pollutant type, its concentration, length of exposure,other coexisting pollutants and individual susceptibility.
Organelle
dysfunction

EnzymeInhibition
Substitutionof ions

Acute or Chronic
Toxic effects

DNA/nucleoprotein
binding

Pollutants
Free radical
generation

365

Voltage-and ligand-gatedionic channels Interference
DNA damage
Lipid peroxidation
Potein oxidationr
Signal transduction interference

Fig. 1. Basic mechanisms of carcinogenesis.

Carcinogenesis

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M. Kampa, E. Castanas / Environmental Pollution 151 (2008) 362e367

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 thresholdlevels. In addition efforts should be intensified by taking theappropriate 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 withdrug 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 varietyof enzymes such as cytochrome P450 (P450 or CYP), epoxidehydrolase, glutathione transferase, UDP-glucuronosyltransferase, sulfotransferase, NAD(P)H quinone oxidoreductase 1, andaldo-keto reductase. These enzymes mainly participate in theconversion 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 thedetoxification 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 nutrientswith 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 contributeto 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 ofoxidative stress. Indeed, as it has been shown by our groupthat the antioxidant activity of plasma in humans following
a diet rich in vegetables, fruits and olive oil was increased incomparison 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 theirantioxidant 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.

7. Conclusion
This brief review presents the adverse effects of a numberof (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 inplant-derived foods, may protect or decrease their effects on
different organs. This conclusion is supported by a numberof epidemiological studies on the beneficial effect of a Mediterranean-type diet on human health.

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