Hazards of heavy metal contamination

Lars Järup
Department of Epidemiology and Public Health, Imperial College, London, UK

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The main threats to human health from heavy metals are associated with
exposure to lead, cadmium, mercury and arsenic. These metals have been
extensively studied and their effects on human health regularly reviewed by
international bodies such as the WHO. Heavy metals have been used by
humans for thousands of years. Although several adverse health effects
of heavy metals have been known for a long time, exposure to heavy metals
continues, and is even increasing in some parts of the world, in particular in less
developed countries, though emissions have declined in most developed countries
over the last 100 years. Cadmium compounds are currently mainly used in
re-chargeable nickel–cadmium batteries. Cadmium emissions have increased
dramatically during the 20th century, one reason being that cadmium-containing
products are rarely re-cycled, but often dumped together with household waste.
Cigarette smoking is a major source of cadmium exposure. In non-smokers,
food is the most important source of cadmium exposure. Recent data indicate
that adverse health effects of cadmium exposure may occur at lower exposure
levels than previously anticipated, primarily in the form of kidney damage but
possibly also bone effects and fractures. Many individuals in Europe already
exceed these exposure levels and the margin is very narrow for large groups.
Therefore, measures should be taken to reduce cadmium exposure in the
general population in order to minimize the risk of adverse health effects. The
general population is primarily exposed to mercury via food, fish being a major
source of methyl mercury exposure, and dental amalgam. The general population
does not face a significant health risk from methyl mercury, although certain
groups with high fish consumption may attain blood levels associated with
a low risk of neurological damage to adults. Since there is a risk to the fetus in
particular, pregnant women should avoid a high intake of certain fish, such as
shark, swordfish and tuna; fish (such as pike, walleye and bass) taken from
polluted fresh waters should especially be avoided. There has been a debate
on the safety of dental amalgams and claims have been made that mercury from
amalgam may cause a variety of diseases. However, there are no studies so far
that have been able to show any associations between amalgam fillings and ill
Correspondence to: Lars health. The general population is exposed to lead from air and food in roughly
Järup, Department of equal proportions. During the last century, lead emissions to ambient air have
Epidemiology and Public
caused considerable pollution, mainly due to lead emissions from petrol. Children
Health, Imperial College,
London, UK. E-mail: are particularly susceptible to lead exposure due to high gastrointestinal uptake
[email protected] and the permeable blood–brain barrier. Blood levels in children should be

British Medical Bulletin 2003; 68: 167–182 British Medical Bulletin, Vol. 68 © The British Council 2003; all rights reserved
DOI: 10.1093/bmb/ldg032
Impact of environmental pollution on health: balancing risk

reduced below the levels so far considered acceptable, recent data indicating
that there may be neurotoxic effects of lead at lower levels of exposure than
previously anticipated. Although lead in petrol has dramatically decreased
over the last decades, thereby reducing environmental exposure, phasing
out any remaining uses of lead additives in motor fuels should be encouraged.
The use of lead-based paints should be abandoned, and lead should not
be used in food containers. In particular, the public should be aware of glazed

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food containers, which may leach lead into food. Exposure to arsenic is
mainly via intake of food and drinking water, food being the most important
source in most populations. Long-term exposure to arsenic in drinking-water is
mainly related to increased risks of skin cancer, but also some other cancers,
as well as other skin lesions such as hyperkeratosis and pigmentation changes.
Occupational exposure to arsenic, primarily by inhalation, is causally
associated with lung cancer. Clear exposure–response relationships and
high risks have been observed.

Introduction
Although there is no clear definition of what a heavy metal is, density is
in most cases taken to be the defining factor. Heavy metals are thus
commonly defined as those having a specific density of more than 5 g/cm3.
The main threats to human health from heavy metals are associated
with exposure to lead, cadmium, mercury and arsenic (arsenic is a met-
alloid, but is usually classified as a heavy metal).
Heavy metals have been used in many different areas for thousands of
years. Lead has been used for at least 5000 years, early applications including
building materials, pigments for glazing ceramics, and pipes for transporting
water. In ancient Rome, lead acetate was used to sweeten old wine, and
some Romans might have consumed as much as a gram of lead a day.
Mercury was allegedly used by the Romans as a salve to alleviate teething
pain in infants, and was later (from the 1300s to the late 1800s)
employed as a remedy for syphilis. Claude Monet used cadmium pig-
ments extensively in the mid 1800s, but the scarcity of the metal limited
the use in artists’ materials until the early 1900s.
Although adverse health effects of heavy metals have been known for
a long time, exposure to heavy metals continues and is even increasing
in some areas. For example, mercury is still used in gold mining in many
parts of Latin America. Arsenic is still common in wood preservatives, and
tetraethyl lead remains a common additive to petrol, although this use has
decreased dramatically in the developed countries. Since the middle of
the 19th century, production of heavy metals increased steeply for more
than 100 years, with concomitant emissions to the environment (Fig. 1).

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 Hazards of heavy metal contamination

90 4500

80 Production Emissions 4000

Cu
70

Production (million tonnes / year)

3500

Emissions (thousand tonnes / year)

Pb
Zn
60 3000

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50 2500

40 2000

30 1500

20 1000

10 500

0 0

00 10 0 0 0 0 0 0 0
20 93 94 95 96 97 98 99
- 19 - 19 - 19 -1 -1 -1 -1 -1 -1 -1
50 01 11 21 31 41 51 61 71 81
18 19 19 19 19 19 19 19 19 19

Fig. 1 Global production and consumption of selected toxic metals, 1850–1990.

Source: Ref. 43.

At the end of the 20th century, however, emissions of heavy metals started
to decrease in developed countries: in the UK, emissions of heavy metals
fell by over 50% between 1990 and 20001.
Emissions of heavy metals to the environment occur via a wide range
of processes and pathways, including to the air (e.g. during combustion,
extraction and processing), to surface waters (via runoff and releases
from storage and transport) and to the soil (and hence into groundwaters
and crops) (see Chapter 1). Atmospheric emissions tend to be of greatest
concern in terms of human health, both because of the quantities
involved and the widespread dispersion and potential for exposure that
often ensues. The spatial distributions of cadmium, lead and mercury
emissions to the atmosphere in Europe can be found in the Meteorologi-
cal Synthesizing Centre-East (MSC-E) website (http://www.msceast.org/
hms/emission.html#Spatial). Lead emissions are mainly related to road
transport and thus most uniformly distributed over space. Cadmium
emissions are primarily associated with non-ferrous metallurgy and fuel
combustion, whereas the spatial distribution of anthropogenic mercury
emissions reflects mainly the level of coal consumption in different
regions.
People may be exposed to potentially harmful chemical, physical and
biological agents in air, food, water or soil. However, exposure does not
result only from the presence of a harmful agent in the environment. The key

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Impact of environmental pollution on health: balancing risk

word in the definition of exposure is contact2. There must be contact

between the agent and the outer boundary of the human body, such as
the airways, the skin or the mouth. Exposure is often defined as a function
of concentration and time: “an event that occurs when there is contact at
a boundary between a human and the environment with a contaminant of
a specific concentration for an interval of time”3. For exposure to happen,
therefore, co-existence of heavy metals and people has to occur (see

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Chapter 1).

Cadmium
Occurrence, exposure and dose
Cadmium occurs naturally in ores together with zinc, lead and copper.
Cadmium compounds are used as stabilizers in PVC products, colour
pigment, several alloys and, now most commonly, in re-chargeable nickel–
cadmium batteries. Metallic cadmium has mostly been used as an anti-
corrosion agent (cadmiation). Cadmium is also present as a pollutant in
phosphate fertilizers. EU cadmium usage has decreased considerably
during the 1990s, mainly due to the gradual phase-out of cadmium products
other than Ni-Cd batteries and the implementation of more stringent EU
environmental legislation (Directive 91/338/ECC). Notwithstanding these
reductions in Europe, however, cadmium production, consumption and
emissions to the environment worldwide have increased dramatically
during the 20th century. Cadmium containing products are rarely re-cycled,
but frequently dumped together with household waste, thereby contam-
inating the environment, especially if the waste is incinerated.
Natural as well as anthropogenic sources of cadmium, including
industrial emissions and the application of fertilizer and sewage sludge
to farm land, may lead to contamination of soils, and to increased cadmium
uptake by crops and vegetables, grown for human consumption. The
uptake process of soil cadmium by plants is enhanced at low pH4.
Cigarette smoking is a major source of cadmium exposure. Biological
monitoring of cadmium in the general population has shown that ciga-
rette smoking may cause significant increases in blood cadmium (B-Cd)
levels, the concentrations in smokers being on average 4–5 times higher
than those in non-smokers4. Despite evidence of exposure from environ-
mental tobacco smoke5, however, this is probably contributing little to
total cadmium body burden.
Food is the most important source of cadmium exposure in the general
non-smoking population in most countries6. Cadmium is present in most
foodstuffs, but concentrations vary greatly, and individual intake also varies
considerably due to differences in dietary habits4. Women usually have

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 Hazards of heavy metal contamination

lower daily cadmium intakes, because of lower energy consumption than

men. Gastrointestinal absorption of cadmium may be influenced by nutri-
tional factors, such as iron status7.
B-Cd generally reflects current exposure, but partly also lifetime body
burden8. The cadmium concentration in urine (U-Cd) is mainly influenced
by the body burden, U-Cd being proportional to the kidney concentration.
Smokers and people living in contaminated areas have higher urinary

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cadmium concentrations, smokers having about twice as high concen-
trations as non-smokers4.

Health effects
Inhalation of cadmium fumes or particles can be life threatening, and
although acute pulmonary effects and deaths are uncommon, sporadic
cases still occur9,10. Cadmium exposure may cause kidney damage. The
first sign of the renal lesion is usually a tubular dysfunction, evidenced
by an increased excretion of low molecular weight proteins [such as
β2-microglobulin and α1-microglobulin (protein HC)] or enzymes [such
as N-Acetyl-β-D-glucosaminidase (NAG)]4,6. It has been suggested that
the tubular damage is reversible11, but there is overwhelming evidence
that the cadmium induced tubular damage is indeed irreversible4.
WHO6 estimated that a urinary excretion of 10 nmol/mmol creatinine
(corresponding to circa 200 mg Cd/kg kidney cortex) would constitute a
‘critical limit’ below which kidney damage would not occur. However,
WHO calculated that circa 10% of individuals with this kidney concen-
tration would be affected by tubular damage. Several reports have since
shown that kidney damage and/or bone effects are likely to occur at lower
kidney cadmium levels. European studies have shown signs of cadmium
induced kidney damage in the general population at urinary cadmium
levels around 2–3 µg Cd/g creatinine12,13.
The initial tubular damage may progress to more severe kidney damage,
and already in 1950 it was reported that some cadmium exposed workers
had developed decreased glomerular filtration rate (GFR)14. This has been
confirmed in later studies of occupationally exposed workers15,16. An excess
risk of kidney stones, possibly related to an increased excretion of calcium
in urine following the tubular damage, has been shown in several studies4.
Recently, an association between cadmium exposure and chronic renal
failure [end stage renal disease (ESRD)] was shown17. Using a registry of
patients, who had been treated for uraemia, the investigators found a
double risk of ESRD in persons living close to (< 2 km) industrial cadmium
emitting plants as well as in occupationally exposed workers.
Long-term high cadmium exposure may cause skeletal damage, first
reported from Japan, where the itai-itai (ouch-ouch) disease (a combination

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Impact of environmental pollution on health: balancing risk

of osteomalacia and osteoporosis) was discovered in the 1950s. The

exposure was caused by cadmium-contaminated water used for irrigation of
local rice fields. A few studies outside Japan have reported similar findings4.
During recent years, new data have emerged suggesting that also relatively
low cadmium exposure may give rise to skeletal damage, evidenced by
low bone mineral density (osteoporosis) and fractures18–20.
Animal experiments have suggested that cadmium may be a risk factor

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for cardiovascular disease, but studies of humans have not been able to
confirm this4. However, a Japanese study showed an excess risk of car-
diovascular mortality in cadmium-exposed persons with signs of tubular
kidney damage compared to individuals without kidney damage21.

Cancer
The IARC has classified cadmium as a human carcinogen (group I) on the
basis of sufficient evidence in both humans and experimental animals22.
IARC, however, noted that the assessment was based on few studies of
lung cancer in occupationally exposed populations, often with imperfect
exposure data, and without the capability to consider possible con-
founding by smoking and other associated exposures (such as nickel and
arsenic). Cadmium has been associated with prostate cancer, but both
positive and negative studies have been published. Early data indicated
an association between cadmium exposure and kidney cancer23. Later
studies have not been able clearly to confirm this, but a large multi-centre
study showed a (borderline) significant over-all excess risk of renal-cell
cancer, although a negative dose–response relationship did not support
a causal relation24. Furthermore, a population-based multicentre-study of
renal cell carcinoma found an excess risk in occupationally exposed
persons25. In summary, the evidence for cadmium as a human carcinogen
is rather weak, in particular after oral exposure. Therefore, a classification
of cadmium as ‘probably carcinogenic to humans’ (IARC group 2A) would
be more appropriate. This conclusion also complies with the EC classifi-
cation of some cadmium compounds (Carcinogen Category 2; Annex 1
to the directive 67/548/EEC).

Mercury
Occurrence, exposure and dose
The mercury compound cinnabar (HgS), was used in pre-historic cave
paintings for red colours, and metallic mercury was known in ancient
Greece where it (as well as white lead) was used as a cosmetic to lighten
the skin. In medicine, apart from the previously mentioned use of mercury
as a cure for syphilis, mercury compounds have also been used as diuretics

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 Hazards of heavy metal contamination

[calomel (Hg2Cl2)], and mercury amalgam is still used for filling teeth in
many countries26.
Metallic mercury is used in thermometers, barometers and instruments
for measuring blood pressure. A major use of mercury is in the chlor-
alkali industry, in the electrochemical process of manufacturing chlorine,
where mercury is used as an electrode.
The largest occupational group exposed to mercury is dental care staff.

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During the 1970s, air concentrations in some dental surgeries reached
20 µg/m3, but since then levels have generally fallen to about one-tenth
of those concentrations.
Inorganic mercury is converted to organic compounds, such as methyl
mercury, which is very stable and accumulates in the food chain. Until the
1970s, methyl mercury was commonly used for control of fungi on seed
grain.
The general population is primarily exposed to mercury via food, fish
being a major source of methyl mercury exposure27, and dental amal-
gam. Several experimental studies have shown that mercury vapour is
released from amalgam fillings, and that the release rate may increase by
chewing28.
Mercury in urine is primarily related to (relatively recent) exposure to
inorganic compounds, whereas blood mercury may be used to identify expo-
sure to methyl mercury. A number of studies have correlated the number of
dental amalgam fillings or amalgam surfaces with the mercury content in
tissues from human autopsy, as well as in samples of blood, urine and
plasma26. Mercury in hair may be used to estimate long-term exposure, but
potential contamination may make interpretation difficult.

Health effects

Inorganic mercury
Acute mercury exposure may give rise to lung damage. Chronic poisoning is
characterized by neurological and psychological symptoms, such as tremor,
changes in personality, restlessness, anxiety, sleep disturbance and depres-
sion. The symptoms are reversible after cessation of exposure. Because of
the blood–brain barrier there is no central nervous involvement related to
inorganic mercury exposure. Metallic mercury may cause kidney damage,
which is reversible after exposure has stopped. It has also been possible to
detect proteinuria at relatively low levels of occupational exposure.
Metallic mercury is an allergen, which may cause contact eczema, and
mercury from amalgam fillings may give rise to oral lichen. It has been
feared that mercury in amalgam may cause a variety of symptoms. This
so-called ‘amalgam disease’ is, however, controversial, and although some

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Impact of environmental pollution on health: balancing risk

authors claim proof of symptom relief after removal of dental amalgam

fillings29, there is no scientific evidence of this30.

Organic mercury
Methyl mercury poisoning has a latency of 1 month or longer after acute
exposure, and the main symptoms relate to nervous system damage31. The
earliest symptoms are parestesias and numbness in the hands and feet.

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Later, coordination difficulties and concentric constriction of the visual
field may develop as well as auditory symptoms. High doses may lead to
death, usually 2–4 weeks after onset of symptoms. The Minamata catas-
trophe in Japan in the 1950s was caused by methyl mercury poisoning
from fish contaminated by mercury discharges to the surrounding sea. In
the early 1970s, more than 10,000 persons in Iraq were poisoned by eating
bread baked from mercury-polluted grain, and several thousand people
died as a consequence of the poisoning. However, the general population
does not face significant health risks from methyl mercury exposure with
the exception of certain groups with high fish consumption.
A high dietary intake of mercury from consumption of fish has been
hypothesized to increase the risk of coronary heart disease32. In a recent
case-control study, the joint association of mercury levels in toenail clip-
pings and docosahexaenoic acid levels in adipose tissue with the risk of a
first myocardial infarction in men was evaluated33. Mercury levels in the
patients were 15% higher than those in controls (95% CI, 5–25%), and
the adjusted odds ratio for myocardial infarction associated with the
highest compared with the lowest quintile of mercury was 2.16 (95% CI,
1.09–4.29; P for trend = 0.006).
Another recent case-control study investigated the association between
mercury levels in toenails and the risk of coronary heart disease among male
health professionals with no previous history of cardiovascular disease.
Mercury levels were significantly correlated with fish consumption, and the
mean mercury level was higher in dentists than in non-dentists. When other
risk factors for coronary heart disease had been controlled for, mercury
levels were not significantly associated with the risk of coronary heart
disease34.
These intriguing contradictory findings need to be followed up by
more studies of other similarly exposed populations.

Lead
Occurrence, exposure and dose
The general population is exposed to lead from air and food in roughly
equal proportions. Earlier, lead in foodstuff originated from pots used

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 Hazards of heavy metal contamination

110
16

Total lead used per 6-month period (thousand tonnes)

100
15

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90

Average blood lead (µg / dL)

14

80
13

70
12

60 11

Lead used in gasoline

50 Average blood lead 10

40 9
1976 1977 1978 1979 1980

Fig. 2 Lead concentrations in petrol and children’s blood (USA).

Source: redrawn from Annest (1983), as reproduced in National Academy of Sciences/National Research
Council. Measuring Lead Exposure in Infants, Children, and Other Sensitive Populations. Washington, DC,
USA: National Academy Press, 1993.

for cooking and storage, and lead acetate was previously used to sweeten
port wine. During the last century, lead emissions to ambient air have
further polluted our environment, over 50% of lead emissions originating
from petrol. Over the last few decades, however, lead emissions in developed
countries have decreased markedly due to the introduction of unleaded
petrol. Subsequently blood lead levels in the general population have
decreased (Fig. 2).
Occupational exposure to inorganic lead occurs in mines and smelters
as well as welding of lead painted metal, and in battery plants. Low or
moderate exposure may take place in the glass industry. High levels of air
emissions may pollute areas near lead mines and smelters. Airborne lead can
be deposited on soil and water, thus reaching humans via the food chain.

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Impact of environmental pollution on health: balancing risk

Up to 50% of inhaled inorganic lead may be absorbed in the lungs.

Adults take up 10–15% of lead in food, whereas children may absorb
up to 50% via the gastrointestinal tract. Lead in blood is bound to
erythrocytes, and elimination is slow and principally via urine. Lead is
accumulated in the skeleton, and is only slowly released from this body
compartment. Half-life of lead in blood is about 1 month and in the
skeleton 20–30 years35.

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In adults, inorganic lead does not penetrate the blood–brain barrier,
whereas this barrier is less developed in children. The high gastrointestinal
uptake and the permeable blood–brain barrier make children especially
susceptible to lead exposure and subsequent brain damage. Organic lead
compounds penetrate body and cell membranes. Tetramethyl lead and
tetraethyl lead penetrate the skin easily. These compounds may also cross
the blood–brain barrier in adults, and thus adults may suffer from lead
encephalopathy related to acute poisoning by organic lead compounds.

Health effects
The symptoms of acute lead poisoning are headache, irritability, abdominal
pain and various symptoms related to the nervous system. Lead enceph-
alopathy is characterized by sleeplessness and restlessness. Children may
be affected by behavioural disturbances, learning and concentration
difficulties. In severe cases of lead encephalopathy, the affected person
may suffer from acute psychosis, confusion and reduced consciousness.
People who have been exposed to lead for a long time may suffer from
memory deterioration, prolonged reaction time and reduced ability to
understand. Individuals with average blood lead levels under 3 µmol/l
may show signs of peripheral nerve symptoms with reduced nerve
conduction velocity and reduced dermal sensibility. If the neuropathy is
severe the lesion may be permanent. The classical picture includes a dark
blue lead sulphide line at the gingival margin. In less serious cases, the
most obvious sign of lead poisoning is disturbance of haemoglobin synthesis,
and long-term lead exposure may lead to anaemia.
Recent research has shown that long-term low-level lead exposure in chil-
dren may also lead to diminished intellectual capacity. Figure 3 shows
a meta-analysis of four prospective studies using mean blood lead level over
a number of years. The combined evidence suggests a weighted mean
decrease in IQ of 2 points for a 0.48 µmol/l (10 µg/dl) increase in blood lead
level (95% confidence interval from −0.3 points to −3.6 points)35.
Acute exposure to lead is known to cause proximal renal tubular
damage35. Long-term lead exposure may also give rise to kidney damage
and, in a recent study of Egyptian policemen, urinary excretion of NAG

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 Hazards of heavy metal contamination

X Boston

X Cincinnati

X Port Pirie

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X Sydney

Combined evidence

-15 -10 -5 0
Mean changes in IQ and 85% confidence intervals

Fig. 3 Estimated mean change in IQ for an increase in blood lead level from 0.48 to
0.96 µmol/l (10–20 µg/dl) from a meta-analysis of four prospective studies35.

was positively correlated with duration of exposure to lead from auto-

mobile exhaust, blood lead and nail lead36.
Despite intensive efforts to define the relationship between body burden
of lead and blood pressure or other effects on the cardiovascular system,
no causal relationship has been demonstrated in humans35.
Using routinely collected data on mortality (1981–96), hospital episode
statistics data 1992–1995 and statutory returns to the Health and Safety
Executive (RIDDOR), one death and 83 hospital cases were identified37.
The authors found that mortality and hospital admission ascribed to
lead poisoning in England were rare, but that cases continue to occur
and that some seem to be associated with considerable morbidity.
Blood lead levels in children below 10 µg/dl have so far been consid-
ered acceptable, but recent data indicate that there may be toxicolo-
gical effects of lead at lower levels of exposure than previously
anticipated. There is also evidence that certain genetic and environ-
mental factors can increase the detrimental effects of lead on neural
development, thereby rendering certain children more vulnerable to lead
neurotoxicity38.
IARC classified lead as a ‘possible human carcinogen’ based on suffi-
cient animal data and insufficient human data in 1987. Since then a few
studies have been published, the overall evidence for lead as a carcinogen
being only weak, the most likely candidates are lung cancer, stomach
cancer and gliomas39.

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Impact of environmental pollution on health: balancing risk

Arsenic
Occurrence, exposure and dose
Arsenic is a widely distributed metalloid, occurring in rock, soil, water
and air. Inorganic arsenic is present in groundwater used for drinking in
several countries all over the world (e.g. Bangladesh, Chile and China),

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whereas organic arsenic compounds (such as arsenobetaine) are primarily
found in fish, which thus may give rise to human exposure40.
Smelting of non-ferrous metals and the production of energy from fossil
fuel are the two major industrial processes that lead to arsenic contamination
of air, water and soil, smelting activities being the largest single anthro-
pogenic source of atmospheric pollution41. Other sources of contamination
are the manufacture and use of arsenical pesticides and wood preservatives.
The working group of the EU DG Environment concluded that there
were large reductions in the emissions of arsenic to air in several member
countries of the European Union in the 1980s. In 1990, the total emissions
of arsenic to the air in the member states were estimated to be 575 tonnes.
In 1996, the estimated total releases of arsenic to the air in the UK were
50 tonnes42.
Concentrations in air in rural areas range from <1 to 4 ng/m3, whereas
concentrations in cities may be as high as 200 ng/m3. Much higher con-
centrations (>1000 ng/m3) have been measured near industrial sources.
Water concentrations are usually <10 µg/l, although higher concentrations
may occur near anthropogenic sources. Levels in soils usually range from
1 to 40 mg/kg, but pesticide application and waste disposal can result in
much higher concentrations40.
General population exposure to arsenic is mainly via intake of food
and drinking water. Food is the most important source, but in some areas,
arsenic in drinking water is a significant source of exposure to inorganic
arsenic. Contaminated soils such as mine-tailings are also a potential
source of arsenic exposure40.
Absorption of arsenic in inhaled airborne particles is highly dependent on
the solubility and the size of particles. Soluble arsenic compounds are easily
absorbed from the gastrointestinal tract. However, inorganic arsenic is
extensively methylated in humans and the metabolites are excreted in the
urine40.
Arsenic (or metabolites) concentrations in blood, hair, nails and urine
have been used as biomarkers of exposure. Arsenic in hair and nails can
be useful indicators of past arsenic exposure, if care is taken to avoid
external arsenic contamination of the samples. Speciated metabolites in
urine expressed as either inorganic arsenic or the sum of metabolites
(inorganic arsenic + MMA + DMA) is generally the best estimate of recent
arsenic dose. However, consumption of certain seafood may confound

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 Hazards of heavy metal contamination

estimation of inorganic arsenic exposure, and should thus be avoided

before urine sampling40.

Health effects
Inorganic arsenic is acutely toxic and intake of large quantities leads to

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gastrointestinal symptoms, severe disturbances of the cardiovascular and
central nervous systems, and eventually death. In survivors, bone marrow
depression, haemolysis, hepatomegaly, melanosis, polyneuropathy and
encephalopathy may be observed. Ingestion of inorganic arsenic may
induce peripheral vascular disease, which in its extreme form leads to
gangrenous changes (black foot disease, only reported in Taiwan).
Populations exposed to arsenic via drinking water show excess risk of
mortality from lung, bladder and kidney cancer, the risk increasing with
increasing exposure. There is also an increased risk of skin cancer and
other skin lesions, such as hyperkeratosis and pigmentation changes.
Studies on various populations exposed to arsenic by inhalation, such
as smelter workers, pesticide manufacturers and miners in many different
countries consistently demonstrate an excess lung cancer. Although all
these groups are exposed to other chemicals in addition to arsenic, there
is no other common factor that could explain the findings. The lung cancer
risk increases with increasing arsenic exposure in all relevant studies,
and confounding by smoking does not explain the findings.
The latest WHO evaluation40 concludes that arsenic exposure via
drinking water is causally related to cancer in the lungs, kidney, bladder
and skin, the last of which is preceded by directly observable precancerous
lesions. Uncertainties in the estimation of past exposures are important
when assessing the exposure–response relationships, but it would seem
that drinking water arsenic concentrations of approximately 100 µg/l have
led to cancer at these sites, and that precursors of skin cancer have been
associated with levels of 50–100 µg/l.
The relationships between arsenic exposure and other health effects
are less clear. There is relatively strong evidence for hypertension and
cardiovascular disease, but the evidence is only suggestive for diabetes and
reproductive effects and weak for cerebrovascular disease, long-term neuro-
logical effects, and cancer at sites other than lung, bladder, kidney and skin40.

Conclusions
Recent data indicate that adverse health effects of cadmium exposure,
primarily in the form of renal tubular damage but possibly also effects on
bone and fractures, may occur at lower exposure levels than previously

British Medical Bulletin 2003;68 179

Impact of environmental pollution on health: balancing risk

anticipated. Many individuals in Europe already exceed these exposure

levels and the margin is very narrow for large groups. Therefore, measures
should be taken to reduce cadmium exposure in the general population
in order to minimize the risk of adverse health effects.
The general population does not face a significant health risk from
methylmercury, although certain groups with high fish consumption may
attain blood levels associated with a low risk of neurological damage to

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adults. Since there is a risk to the fetus in particular, pregnant women
should avoid a high intake of certain fish, such as shark, swordfish and
tuna. Fish, such as pike, walleye and bass, taken from polluted fresh
waters should especially be avoided.
There has been a debate on the safety of dental amalgams and claims
have been made that mercury from amalgam may cause a variety of diseases,
but to date no studies have been able to show any associations between
amalgam fillings and ill health.
Children are particularly vulnerable to lead exposure. Blood levels in
children should be reduced below the levels so far considered acceptable,
recent data indicating that there may be neurotoxic effects of lead at lower
levels of exposure than previously anticipated. Although lead in petrol has
dramatically declined over the last decades, thereby reducing environmental
exposure, there is a need to phase out any remaining uses of lead additives
in motor fuels. The use of lead-based paints should also be abandoned, and
lead should not be used in food containers. In particular, the public should
be aware of glazed food containers, which may leach lead into food.
Long-term exposure to arsenic in drinking water is mainly related to
increased risks of skin cancer, but also some other cancers, and other skin
lesions such as hyperkeratosis and pigmentation changes. Occupational expo-
sure to arsenic, primarily by inhalation, is causally associated with lung
cancer. Clear exposure–response relationships and high risks have been
observed.

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