Environmental Toxicology and Pharmacology 26 (2008) 263271

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Environmental Toxicology and Pharmacology

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Mini-review

Heavy metals: Implications associated to sh consumption

M.I. Castro-Gonzlez a , M. Mndez-Armenta b,
a
b

Depto. Nutricin Animal, Instituto Nacional de Ciencias Mdicas y Nutricin SZ, Mexico
Lab. Neuropatologa Experimental, Instituto Nacional de Neurologa y Neurociruga MVS, Insurgentes Sur 3877, La Fama, Tlalpan, C.P. 14269, Mexico

a r t i c l e

i n f o

Article history:
Received 15 February 2008
Received in revised form 30 May 2008
Accepted 10 June 2008
Available online 18 June 2008
Keywords:
Fish consumption
Mercury
Cadmium
Lead
Arsenic
Heavy metals

a b s t r a c t
Metals are being utilized of ways in industries and agriculture; particularly heavy metals such as mercury,
cadmium, lead and arsenic constitute a signicant potential threat to human health because they are
associated to many adverse effects on health. The consumption of sh is recommended because it is a good
source of omega-3 fatty acids, which have been associated with health benets due to its cardio-protective
effects. However, the content of heavy metals discovered in some sh makes it difcult to establish clearly
the role of sh consumption on a healthy diet. Therefore the present mini-review accounts for the recent
evidence of the effect of these toxic metals on the human health and their possible implications in sh
consumption.
2008 Elsevier B.V. All rights reserved.

Contents
1.
2.

3.
4.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Heavy metals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1.
Mercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.
Cadmium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.
Lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4.
Arsenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Health effects of sh consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Final commentary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction
Metals differ from other toxic substances in that they are neither
created nor destroyed by humans. Humans have used heavy metals
in many different areas for thousands of years; this use inuences
their potential for health effects in at least two major ways: rst, by
environmental transport, that is, by human or anthropogenic contributions to air, water, soil, and food, and second by altering the
speciation or biochemical form of the element (Beijer and Jernelov,
1986). Although several adverse health effects of heavy metals have

Corresponding author.
E-mail address: mmendezarmenta@hotmail.com (M. Mndez-Armenta).
1382-6689/$ see front matter 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.etap.2008.06.001

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been known for a long time, the exposure to these elements continues; moreover, it is even increasing in some parts of world, in
particular in the less developed countries, though emissions have
declined in most developed countries over the last 100 years (Jarup,
2003). Owing to their toxicity persistence and tendency to accumulate in water and sediment, heavy metals and metalloids, when
occurring in higher concentrations, become severe poisons for all
living organisms (Has-Schn et al., 2006).
Diet is the main route of exposure to heavy metals in the case of
population no-exposed to them. Although the basic role of nutritionally essential metals is to provide some components of a vital
biochemical or enzymatic reaction, a number of metabolic interactions between nutritionally essential and nonessential toxic metals
may reduce the health hazard of the toxic metal (Goyer, 1997).

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M.I. Castro-Gonzlez, M. Mndez-Armenta / Environmental Toxicology and Pharmacology 26 (2008) 263271

Increased concentrations of metals; mainly mercury, cadmium and

lead; have been observed in freshwater sh in open waters. This is
important because the water metal concentration correlates positively with concentrations in sh tissue (Svobodova et al., 1996). The
level of heavy metal bioaccumulation in sh tissues is inuenced by
biotic and abiotic factors, such as sh biological habitat, chemical
form of metal in the water, water temperature and pH value, dissolved oxygen concentration, water transparency, as well as by sh
age, gender, body mass, and physiologic conditions (Has-Schn et
al., 2006). After the catastrophe in Minamata, Japan, caused by sh
consumption containing methyl mercury, the study of the effects
of heavy metals present in fresh sh heavy metals in fresh sh as
part of human diet is of particular interest.
On the other hand, the nutritional benets of sh are mainly due
to the content of high-quality protein and high content of the two
kinds of omega-3 polyunsaturated fatty acids: eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA) in different comestible
species (Castro-Gonzlez, 2002; Clarkson, 2002; Domingo et al.,
2007). Omega-3 fatty acids (EPA) have probed to have protective
effects in preventing coronary heart disease, reducing arrhythmias
and thrombosis (Kinsella et al., 1990; Oomen et al., 2000; KrisEtherton et al., 2002) lowering plasma triglyceride levels (Harris,
1997; Ismail, 2005) and reducing blood clotting tendency (Agree
et al., 1997; Din et al., 2004; Ismail, 2005). However, the content
of toxic heavy metals in sh can counteract the positive effects of
the omega-3 fatty acids present in sh and their benecial effects
on heart disease risk (Chan and Egeland, 2004). The present minireview highlights some aspects of how mercury, cadmium, lead and
arsenic are implicated in sh consumption.

2. Heavy metals
2.1. Mercury
Mercury (Hg) is one of the most toxic heavy metals in our environment including the lithosphere, hydrosphere, atmosphere and
biosphere. A series of complex chemical transformations allows the
three-oxidation states of Hg cycle in the environment (Barbosa et
al., 2001). In the zero oxidation state (Hg0 ), mercury exists in its
metallic form, vapor is the most abundant form (98%). The mercurous and mercuric states are the two higher oxidation states
where the mercury atom has lost one (Hg+ ) or two electrons (Hg2+ ),
respectively; methyl mercury is the most important form of mercury in terms of toxicity and health effects from environmental
exposures (Jackson, 1997; Goyer and Clarsksom, 2001; ATSDR,
2003c). Natural and anthropogenic and re-emitted sources are the
three major sources of Hg emissions, whereas the most important anthropogenic sources of Hg pollution in the environment are
urban discharges, agricultural materials, mining and combustion
and industrial discharges (Jackson, 1997; Zhang and Wong, 2007).
The contamination chain of Hg follows, closely, the cyclic order:
industry, atmosphere, soil, water, phytoplankton, zooplankton, sh
and human (Kadar et al., 2000). The general population is most
commonly exposed to mercury primarily from two sources: (1) eating sh and marine mammals (e.g., whales, seals) that may contain
some methyl mercury in their tissues or (2) from the release of elemental mercury from the dental amalgam because it may dissolve
in saliva and be ingested (Sallsten et al., 1996; ATSDR, 2003c); relative contribution of mercury from these two main sources will vary
considerably for different individuals (ATSDR, 2003c).
The main molecular mechanisms involved in methyl mercury
toxicity are inhibition of protein synthesis, microtubule disruption,
increase of intracellular Ca2+ with disturbance of neurotransmitter function due to mainly binding of methyl mercury to thiol or

sulfhydryl groups (CTE, 2000; Sanfeliu et al., 2003; Bridges and

Zalups, 2005). Intracellular mercury therefore attaches itself to
thiol residues of proteins resulting in activation of sulfur and blocks
related enzymes, cofactors and hormones (Mathieson, 1995) Also,
free radicals overproduction may result from indirect interactions
of methyl mercury at critical cellular sites or as a consequence of
protective mechanisms inhibition, the formation of reactive oxygen species in, kidney, liver and brain have been observed following
administration of methylmercuric chloride to rodents, sh and in
vitro cells (Ali et al., 1992; Berntssen et al., 2003; Mori et al., 2007;
Costa et al., 2007).
The gastrointestinal absorption of methyl mercury is on the
order of 9095%. Absorbed methyl mercury is transported bound
to red blood cells and it is widely distributed throughout the body;
then methyl mercury is excreted from the body in urine and feces.
All forms of mercury go through the bloodbrain barrier and placenta to the fetus. The biological half-life of methyl mercury in
humans is approximately 65 days (Clarkson, 2002; GwalteneyBrant, 2002).
Methyl mercury poisoning mostly affects the nervous system
and it is especially harmful to infants developing nervous system. Maternal exposure can threaten the fetus because chemicals
can be transferred to the developing fetus through the placenta
(Slikker, 1994; Gochfeld, 2003); in fact, fetal brain is more susceptible than adult brain to mercury-induced damage (Clarkson et al.,
2003). In adults, methyl mercury has a latency of 1 month or longer
after acute exposure and the main symptoms of methyl mercury
exposition related with intoxication to nervous system are parestesias and numbness in the hands and feet, coordination difculties
and concentric constriction of the visual eld, auditory symptoms,
ischemic stroke, dementia and depression (Jarup, 2003; He et al.,
2004; Morris et al., 2005); moreover the methyl mercury can cause,
nephrotoxicity and gastrointestinal toxicity with ulcerations and
hemorrhage (Stohs and Bagghi, 1995; Gwalteney-Brant, 2002).
Mercury is present in some sh and is of considerable interest because of its potential hazard to the health of people who
consume them and its toxicity increases as consequence of metals accumulated in aquatic organisms. Bioaccumulation of methyl
mercury in sh depends on the trophic level, age or length of sh
(Zhang and Wong, 2007) as walleye, pike swordsh, tuna and shark
can have high levels of methyl mercury due to bioaccumulation
and biomagnication (ATSDR, 2003c). Rivers, lakes and sea have
abundance of sh diversity; an important number of authors have
reported concentrations of mercury in some species such as tuna,
carp, tench, gray mullet, ell, sual, bagrus, snakehead, and bighead,
grass and common carp. Mercury levels in rivers Neretva, Croatia (Has-Schn et al., 2006), Catalonia, Spain (Falc et al., 2006),
Kahanawake, Canada (Chan et al., 1999), and Nile, Egypt (Sallam
et al., 1999), have been reported to be below permissible limits
according to the international standard concentrations and therefore it has been advised that the consumption of the species coming
from these places is safe for human health (Table 1). However,
sh coming from Lower Nitra River, Slovakia have showed methyl
mercury concentrations between 0.08 and 1.20 mg/kg wet weight
(Andreji et al., 2005, 2006), those coming from New Jersey, USA
had 0.65 0.10.05 0.001 ppm, wet weight (Burger and Gochfeld,
2005), the ones from Mojana, Colombia had 0.346 0.171 in carnivorous sh0.146 0.102 mg/g fresh wt (fw) in non-sh carnivorous
(Marrugo-Negrete et al., 2008) has been reported. Usero et al.
(2003) found that concentrations of mercury in three species (eel,
common sole and gray mullet) of sh muscle were considerably
lower than the maximum levels for human consumption in southern Atlantic coast of Spain (Table 1).
Due to the health hazards consequence of excess of mercury
exposure, ATSDR (2003c) 2003c estimated mean dietary exposure

M.I. Castro-Gonzlez, M. Mndez-Armenta / Environmental Toxicology and Pharmacology 26 (2008) 263271

265

Table 1
Comparison of some heavy metals present average values in sh
Country/region

Fish species

Range mg/kg wet weight (mg/kg or g/g) ppm

Hg

Cd

Pb

Nitra River Slovakia

Chub
Barbel
Roach
Perch

1.353.88
1.934.57
1.522.18
2.736.52

0.060.34
0.060.32
0.190.58
0.090.031

0.262.48
0.240.89
0.200.38
0.405.81

Andreji et al. (2005)

Lower Nitra River,

Slovak Republic.

Chub
Common carp
Prussian carp
Roach
Wels catsh

0.351.41
0.460.95
0.341.10
0.151.02
0.443.64

0.242.37
0.231.81
0.062.55
0.180.92
0.392.76

0.3224.3
0.300.49
0.3610.98
0.3334.59
0.081.11

Andreji et al. (2006)

River Neretva, Croatia

Carp
Tench
Sval
Grey mullet
Eel

0.110.287
0.0940.167
0.030.109
0.1150.248
0.0950.124

0.0160.155
0.010.105
0.010.048
0.0140.1
0.0160.041

0.2110.432
0.0850.174
0.10.146
0.10.115
0.0310.142

Catalonia, Spain

Sardine
Tuna
Anchovy
Mackerel
Sworfsh
Salmon
Hake
Red mullet
Sole
Cuttle sh

0.070.09
0.380.58
0.080.09
0.060.15
1.592.22
0.040.05
0.120.29
0.140.36
0.040.13
0.040.08

0.0020.01
0.010.02
0.0010.02
0.0030.01
0.020.10
0.010.01
0.0050.01
0.0010.01
0.00040.01
0.010.09

0.010.08
0.010.02
0.010.02
0.010.02
0.010.02
0.010.25
0.010.13
0.0020.07
0.010.08
0.010.10

River Nile, Egypt

Bagrus

0.0260.391

0.280.053

0.0220.654

New Jersey, USA

Blue sh
Chilean sea bass
Cod
Croaker
Flounder
Porgie
Red snapper
Whiting
Yellow n tuna

0.26 0.02
0.38 0.06
0.11 0.01
0.14 0.02
0.05 0.001
0.10 0.01
0.24 0.01
0.04 0.004
0.65 0.1

0.006 0.002
0.004 0.001
0.0005 0.0003
0.001 0.0004
0.01 0.002
0.004 0.001
0.002 0.001
0.009 0.005
0.03 0.005

0.06 0.01
0.11 0.01
0.12 0.01
0.09 0.01
0.06 0.01
0.14 0.017
0.12 0.01
0.09 0.011
0.04 0.01

0.26 0.04
1.17 0.3
2.2 0.5
1.9 0.2
3.3 0.4
1.8 0.17
0.23 0.04
1.9 0.4
1.0 0.1

Grey mullet
Eel
Common sole

0.013
0.011
0.014

0.030
0.032
0.028

0.03
0.09
0.05

1.98
2.91
3.96

Liebre

Grey mullet
Eel
Common sole

0.013
0.023
0.012

0.021
0.050
0.028

0.03
0.05
0.05

2.00
2.37
3.56

San Carlos

Grey mullet
Eel
Common sole

0.010
0.018
0.017

0.013
0.015
0.010

0.04
0.05
0.04

1.36
0.52
2.62

San Juan

Grey mullet
Eel
Common sole

0.010
0.010
0.013

0.018
0.020
0.025

0.05
0.03
0.03

1.38
0.63
3.16

Spain regions
Bacuta

Reference
As

0.0160.07
0.0280.101
0.0340.121
0.2550.42
0.0840.124
3.533.94
0.991.25
3.935.42
1.737.47
1.782.44
1.602.37
3.224.55
15.3917.77
4.558.40
2.455.33

Has-Schn et al. (2006)

Falc et al. (2006)

Sallam et al. (1999)

Burger and Gochfeld
(2005)

Usero et al. (2003)

of 8.2 g/d (range, 0.37203.5 g/day) for females and 8.6 g/day
(range, 0.22165.7 g/day) for males. For an average body weight
(bw) of 65 kg for women and 70 kg for men, the daily intakes of
mercury would be 0.126 g/(kg day) (range, 5.73.131 ng/(kg day))
for women and 0.123 g/(kg day) (range, 3.12.367 ng/(kg day))
for men, respectively. Recently the Environmental Protection
Agency (EPA, 1999) created a reference dose (RfD) for mercury
of 0.1 g/(kg bw d), the RfD is a numerical estimate of the daily
oral exposure oh the human population, which includes sensitive
subgroups such as children. In the year 2003, the Joint FAO/WHO
Expert Committee on Food Additives (JECFA) revised its risk assessment on methylmercury in sh and adopted a lower Provisional

Weekly Intake (PTWI) of 1.6 g/(kg bw week) to replace the previous PTWI of 3.3 g/(kg bw week) of total mercury for the general
population. This risk assessment is based on two major epidemiology studies which researched about the relationship between
maternal exposure to mercury and impaired neurodevelopment
in their children from two regions where consumption of sh and
seafood is high and adverse effects on child neurodevelopment have
been reported (Grandjean et al., 1997; Murata et al., 2007). Actually, in contrast to the EPA, the Joint FAO/WHO Expert Committee on
Food Additives calculated the called provisional tolerable weekly
intake (PTWI) of 1.6 g/(kg weight week) (Smith and Sahyoun,
2005).

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M.I. Castro-Gonzlez, M. Mndez-Armenta / Environmental Toxicology and Pharmacology 26 (2008) 263271

2.2. Cadmium
Cadmium is an industrial and environmental pollutant that
affects adversely a number of organs in humans. Cadmium is a
metal from group II B that has an atomic weight of 112.41; the
ionic form of cadmium (Cd2+ ) is usually combined with ionic forms
of oxygen (cadmium oxide, CdO2 ), chlorine (cadmium chloride,
CdCl2 ), or sulfur (cadmium sulfate, CdSO4 ). There are estimates that
30,000 tons of cadmium are released into the environment each
year, with an estimated 400013,000 tons coming from human
activities (ATSDR, 2003b). Natural as well as anthropogenic sources
of cadmium, which include industrial emissions and the application
of fertilizer and sewage sludge to farm land, increased cadmium
environmental levels (ATSDR, 2003b). It has been established that,
although cadmium occurs in the aquatic organism and marine environment only in trace concentrations, the salinity can affect the
speciation of this metal, and bioaccumulation is affected both by
temperature and salinity (Ray, 1986). In the general human population, cadmium exposure occurs mainly through two sources.
The rst is the oral route through water and food contaminated
with cadmium, particularly leafy vegetables, grains, cereals, fruits,
organ meat, and sh. The second source is through inhalation of
cadmium particles during industrial or everyday activities, among
which the inhaled Cd2+ from cigarette smoke should be considered as highly hazardous because cadmium is easily absorbed
by the lungs (Goyer, 1997; Saldivar et al., 1991; Stohs et al.,
1997).
In humans and other mammals, the absorption of cadmium
occurs through a process similar to that of the absorption of essential metals such as iron. This absorption is enhanced by dietary
deciencies of calcium and iron and by low protein diets; the cadmium is transported by the blood and distributed primarily to liver
and kidney (Goyer and Clarsksom, 2001). The liver and kidney are
its principal sites of long-term storage in the body; cadmium has
a long biological half-life, from 17 to 30 years in humans. Cadmium affects adversely a number of organs and tissues such as:
kidney (induces renal tubular dysfunction, proteinuria and chronic
renal insufciency), heart (aortic and coronary artherosclerosis,
increases cholesterol and free fatty acids) (Houston, 2007), lung
(brosis), skeletal system, testes, placenta, brain and the central
nervous system (CNS) (ATSDR, 2003b). Cadmium affects the CNS
of children; thus neurological disorders, such as learning disabilities and hyperactivity may occur (Thatcher et al., 1982) however,
Wong and Klaassen (1982) reported that cadmium is more toxic
to newborn and young rats that adult rat and this age difference in
susceptibility might be due to differences in the bloodbrain barrier
integrity and immaturity.
The molecular mechanisms of cadmium toxicity are no well
understood yet. Cadmium is known to enhance lipid peroxidation by increasing the production of free radicals in several organs,
mainly lung and brain; likewise to interfere with the cellular mechanisms against oxidation (glutathione peroxidase and catalase) and
this should be considered as a potential signicant event in the
generation of free radicals which lead to tissue damage and cellular death (Manca et al., 1991; Shukla et al., 1987, 1996; Kumar
et al., 1996; Mndez-Armenta et al., 2003; Mndez-Armenta and
Ros, 2007; Casalino et al., 2002). Cadmiums ability to generate
free radicals also leads to the oxidation of nuclei acids and alteration of DNA repair mechanisms (Hartwig et al., 2002), alterations
of membrane structure/function (Kumar et al., 1996) and inhibition
of energy metabolism (Muller, 1986).
The levels of contamination by cadmium in sh are of considerable interest because sh consumption is an important source of
intake cadmium for the general population. Most of the cadmium
content in sh or other seafood is highly absorbable in CdCl2 form;

in humans, the efciency of gastrointestinal absorption of cadmium

has been reported to be approximately 38% of the ingested load.
Cadmium is particularly accumulated in kidney; in muscles the
concentrations are low (ATSDR, 2003b).
Several studies have demonstrated the variability in concentrations of cadmium in sh. In the Lower Niitra River in the Slovak
Republic elevated concentration of cadmium was found in muscle of ve sh species; which suggests that consumption of sh
from this river its not recommended (Andreji et al., 2005, 2006).
Concentrations of cadmium were determined in ve species of sh
from River Neretva, Croatia; the results showed that concentrations
of cadmium are very high in carp, sval and mullet kidney, which
indicate the kidney tendency to accumulate cadmium, whereas the
concentrations of cadmium in muscle were lower (Has-Schn et al.,
2006). In Egypt, 50 samples of Bagrus collected from various localities of River Nile were analyzed and the results reveled that the
concentrations of Cd in sh muscles were elevated in 24% and 6%
of the examined sh samples (Cd concentration ranged from 0.028
to 0.053) (Sallam et al., 1999). However, high metal concentrations
in samples of sh (Mugil cephalus and Mallus barbatus) from the
Mediterranean Sea showed that the highest levels of cadmium were
found in liver, gill and muscle of both species; moreover, seasonal
changes in metal concentration were also observed (Cogun et al.,
2006). On the other hand, in four seawater reservoirs coast of Spain
the cadmium concentrations in sh muscle of eel, common sole and
gray mullet were reported below the maximum levels permitted for
human consumption (Usero et al., 2003).
Falc et al. (2006) and Burger and Gochfeld (2005) reported
different levels of heavy metals such as cadmium, arsenic, lead,
mercury, selenium and manganese, in species of sh obtained from
local markets and supermarkets in Catalonia, Spain and New Jersey USA. The results showed that there are signicant interspecic
differences for all metals and no sh type had the highest levels
of more than two metals, which suggests that the differences are
due to geography, throphic levels, size foraging method/localization
and propensity of metals to undergo biomagnication in the food
chain (Burger and Gochfeld, 2005). According to the report from
Catalonia, the highest mean metal concentrations found were the
following: arsenic, in red muller; cadmium, in clam and mussel;
mercury, in swordsh; and nally, the highest lead concentrations
were found in mussel and salmon. These results indicate a remarkable contribution of these species to the intake of these metals
(Falc et al., 2006).
The European Community (EEC, 2001) established the maximum levels permitted of cadmium in seafood as follows
0.05 mg/kg fw in sh, 0.5 mg/kg fw in crustaceans (crab excluded),
1.0 mg/kg fw in molluscs and crab. Moreover, the Joint FAO/World
Health Organization has recommended the provisional tolerable weekly intake (PTWI) as 0.007 mg/kg bw for cadmium
(420 g/week for a 60-kg person); the committee evaluated the
impact of different maximum levels of cadmium on the overall
intake (FAO/WHO, 2005).
2.3. Lead
Lead (Pb) is one of the most ubiquitous and useful metals known
to humans and it is detectable in practically all phases of the inert
environment and in all biological systems. Environmental levels of
lead have increased more than 1000-fold over the past three centuries as a result of human activity; the greatest increase occurred
between the years 1950 and 2000 (ATSDR, 2005). Lead is a naturally
occurring element; it is a member of Group 14 (IVA) of the periodic table, has an atomic weight of 207.2 and exists in three states:
Pb (0), the metal; Pb (II); and Pb (IV). Lead is a blush-gray heavy
metal and it is usually found combined with two or more other

M.I. Castro-Gonzlez, M. Mndez-Armenta / Environmental Toxicology and Pharmacology 26 (2008) 263271

elements to form lead compounds (ATSDR, 2005). Lead reaches the

aquatic system because of supercial soil erosion and atmospheric
deposition. The concentration of lead in deep ocean waters is about
0.010.02 g/l, but in surface ocean waters is about 0.3 g/l (Sepe
et al., 2003).
The main route of exposure for general population is food and air.
Occupational exposure to lead occurs for workers in the lead smelting and rening industries, battery, manufacturing plants, plastics
and printing industries. Children are particularly sensitive to the
effects of lead, which is considered a primary environmental hazard. Metal intoxication in young children produces a critical effect
in the developing nervous system due to its susceptibility to lead
toxicity (Goyer, 1993; Goyer and Clarsksom, 2001; Jarup, 2003).
Lead may enter the body through intestines, ingestion; through
the lungs, inhalation; through the skin, adsorption; or by direct
swallowing and ingestion. The metal is absorbed into and transported by the bloodstream to other tissues. Once absorbed, lead
accumulates in high concentrations in bone, teeth, liver, lung, kidney, brain, and spleen, and it goes through the bloodbrain barrier
and the placenta (Goyer and Clarsksom, 2001; Gwalteney-Brant,
2002). The biological half-life of lead may be considerably longer in
children than in adults; lead in blood has an estimate half-life of 35
days, in soft tissue 40 days and in bones 2030 years (Papanikolaou
et al., 2005). The major route of excretion of absorbed lead is the
urinary tract, usually with glomerular ltrate in the kidney; it can
also be excreted with bile through the gastrointestinal tract (Goyer
and Clarsksom, 2001).
The most sensitive targets for lead toxicity are the developing
nervous system, the haematological and cardiovascular systems,
and the kidney. The symptoms of lead poisoning are headache,
irritability, abdominal pain and various symptoms related to the
nervous system (Jarup, 2003). Chronic lead toxicity in humans
often develop dullness, irritability, poor attention span, epigastric, constipation, vomiting, convulsions, coma and death. Children
may be affected by encephalopathy with lethargy, mental dullness,
vomiting, irritability, and anorexia; in severe cases, the prolonged
exposition of lead can decrease the cognitive function and increase
behavior disorders, specially aggression, psychosis, confusion and
mental decit (Bellinger et al., 1992; Gwalteney-Brant, 2002; Jarup,
2003; ATSDR, 2005). The relationship between lead exposure and
cognitive dysfunctions is similar cross-species, which indicates that
exposure to lead results in similar manifestations (Costa et al.,
2004). Chronic lead toxicity affects gastrointestinal, neuromuscular, renal and haematological systems (ATSDR, 2005). Blood lead
level indicates a recent exposure, whereas bone lead level, which
forms 9095% of lead burden in adults and 8095% of total lead in
children indicates a chronic exposure (Kakkar and Jaffery, 2005).
However, blood lead levels in children below 10 g/dl have so far
been considered acceptable.
The main mechanisms of lead toxicity are the activation of
cellular functions due to this metals calcium mimicking effect,
and the inhibition of the activity of different proteins through its
binding to sulfhydryl groups. Lead has high afnity for sulfhydryl
groups and can inactivate enzymes, especially those involved in
heme synthesis, such as -aminolevulinic acid dehydratsase and
ferrochelatase (Gwalteney-Brant, 2002.) On the other hand, lead
has a higher afnity than calcium for calmodulin and can activate
some calmodulin-dependent processes, inhibit the calcium bombs
(calciumATPase, sodiumpotassium) and channels and replace
calcium in several of its receptors (Simons, 1986; Goyer, 1997;
Bridges and Zalups, 2005). This interaction between lead and calcium has been identied in numerous papers, which show that lead
absorption is inversely related to dietary calcium; thus it seems that
a low dietary intake of calcium can lead to higher levels of lead in
blood (Bogden et al., 1992).

267

Accumulation of lead in different sh species has been determined in several works, Table 1 resume results where the
concentrations of lead in sh varied until exceeded the permissible limit for consumption of humans. Has-Schn et al. (2006)
showed that lead concentration is similar in all sh species except
carp which evidently tends to accumulate this heavy metal in all
tissue apart from gonads; the muscle values are shown in Table 1.
Falc et al. (2006), reported lead concentrations in various edible
marine species which varied from 0.002 to 0.21 g/g fw; whereas
that from a study in commercial sh obtained from supermarkets
and specialty sh markets in New Jersey reported that average lead
concentrations in none sh exceeded the maximum recommended
levels of lead in seafood (Burger and Gochfeld, 2005). Andreji et
al. (2006) determined lead concentrations which exceeded the
limit for lead content in sh muscle, 0.2 mg/kg wet weight; otherwise a determination of lead in six sh species from the Adriatic
Sea showed that concentrations of lead in all species examined
were below the maximum levels recommended by the European
Community for this element in seafood, which would lead to exposure levels lower than the provisional tolerable daily intakes (Sepe
et al., 2003). Ashraf et al. (2006) found levels of lead in canned
sh (salmon, sardines and tuna) at range of 0.230.84 g/g, which
indicates that canned sh have concentrations within WHO/FAO
permissible limits. Likewise, the concentrations of lead in muscle of
tree species (grey mullet, eel and common sole) were considerably
lower that the permissible limits (Table 1).
The ingestion of sh is an obvious means of exposure to metals because they accumulate substantial amounts of metals in their
tissues, especially in the muscles, and thus they represent a major
dietary source of lead for general population. The Joint FAO/WHO
Expert Committee on Food Additives established a provisional tolerable weekly intake (PTWI) for lead as 0.025 mg/kg bw. Whereas
the European Community (EEC, 2001) established the maximum
levels of lead in seafood as 0.2 mg/kg fw in sh, 0.5 mg/kg fw in crustaceans (crab excluded), and 1.0 mg/kg fw in bivalves molluscs and
crab (Sepe et al., 2003).
2.4. Arsenic
Arsenic, a naturally occurring element, is a worldwide contaminant that is found in rock, soil, water, air and food. Arsenic has a
complex chemical structure and can be found in elemental, trivalent (+3 arsenite), and pentavalent (+5 arsenate) inorganic forms
and trivalent and pentavalent organic forms. Organic arsenic is
formed when arsenic ions are combined with carbon and hydrogen. Inorganic arsenic is present in groundwater, which is used for
drinking in several countries all over the world; whereas organic
arsenic compounds are primarily found in sh and shellsh (ATSDR,
2003a). Inorganic arsenic, the form found in soil and water, is classied by the Environmental Protection Agency (EPA) as a Group
A human carcinogen (EPA, 1999; ATSDR, 2003a). High doses of
organic arsenic can produce the same toxicological effects as a
lower dose of inorganic arsenic (ATSDR, 2003a). Inorganic arsenic
is released into the environment from a number of anthropogenic
sources, which include geothermal discharges, industrial products
and wastes, copper and lead smelters, and glass manufactures that
add arsenic to raw materials (Goyer and Clarsksom, 2001). The use
of arsenic compounds as herbicides, pesticides, and fungicides are
other sources of environmental arsenic contamination.
Occupational exposures have also been reported in several
industries such as electronics, non-ferrous metal smelting, glass
manufacturing, manufacture and use of arsenical pesticides and
wood preservatives. The major sources of exposition for general
population are from food and water; food contains both organic
and inorganic arsenic, whereas drinking water contains primarily

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M.I. Castro-Gonzlez, M. Mndez-Armenta / Environmental Toxicology and Pharmacology 26 (2008) 263271

inorganic forms of arsenic (ATSDR, 2003a; Jarup, 2003). Exposure

of millions to arsenic contaminated waters coming from hand tube
wells is a major concern in many Asiatic countries such as Taiwan,
Inner Mongolia and China (Chatterjee et al., 1995; Abernathy et al.,
1999). In Bangladesh, where the population is exposed to arsenic
through drinking water, the arsenic contamination of groundwater
is considered a severe public health. The general population has had
long-term exposure to arsenic from groundwater; studies indicate
that one out of ten people who drink water containing 500 g of
arsenic per liter may ultimately die from cancer caused by arsenic
(Smith et al., 2000). The World Health Organization established the
guideline level of arsenic in drinking water as 0.01 mg/l, calculated
as total arsenic (WHO, 2004).
Absorption of arsenic in inhaled particles is highly dependent on
the solubility and the size of particles, which are deposited in the
respiratory tract, and the oral arsenic is well absorbed from the gastrointestinal tract (soluble arsenic compounds are easily absorbed
from the gastrointestinal tract). The biological half-life of ingested
inorganic arsenic is about 10 h, and 5080% is excreted in about 3
days whereas the methylated arsenic has a half-life of 30 h (Goyer
and Clarsksom, 2001; Gwalteney-Brant, 2002). Ingested arsenic
can go through the placenta and result in cord blood concentrations that resemble maternal blood concentrations (Patrick, 2003).
Arsenic is transported in blood by binding to red blood cells and
it is distributed throughout the body; once absorbed, arsenites are
oxidized to arsenates and methylated. The As(+3) form undergoes
enzymic methylation primarily in the liver to form monomethylarsinic acid (MMA) and dimethylarsinic acid (DMA); this process
may then be repeated to result in dimethylated arsenic metabolites. Most arsenic is promptly excreted in the urine as a mixture of
As(+3), As(+5), MMA, and DMA; DMA is usually the primary form
in the urine (Goyer and Clarsksom, 2001; ATSDR, 2003a; Abernathy
et al., 2003). Arsenic has a predilection for sulfhydryl-rich keratin (skin) and tends to concentrate in the skin, but it can also be
deposited in bones, teeth, hair and nails, mainly when exposure is
chronic (Goyer and Clarsksom, 2001; Gwalteney-Brant, 2002). The
most commonly used biomarkers for identication and quantication of arsenic exposure are urine, blood, hair and nails (Kakkar and
Jaffery, 2005).
Apparent signs of chronic arsenic toxicity are skin changes that
include generalized hyperkeratosis and formation of hyperkeratotic
warts or corns on the palms and soles, along with areas of hyperpigmentation interspersed with small areas of hypopigmentation
on the face, neck, and back (Kakkar and Jaffery, 2005). Chronic
exposure to inorganic arsenic compounds may lead to neurotoxicity of both the peripheral and central nervous system (Goyer
and Clarsksom, 2001); whereas the mainly signs of acute toxicity of arsenic are an acute onset of profused vomiting, diarrhea,
colic, salivation, fever, disturbances of the cardiovascular and central nervous system which may lead to death (Gwalteney-Brant,
2002; Jarup, 2003). Arsenic is considered to be carcinogenic and
is related mainly to cancer in the lung, kidney, bladder, and skin
(ATSDR, 2003a).
The mechanisms of arsenic toxicity involve a number of
sulfhydryl-containing proteins and enzyme systems which are
altered by exposure to arsenic (Thomas et al., 2001). The mitochondria accumulates arsenic mediated by inhibition of pyruvate
oxidases and phosphatases; arsenic also inhibits succinic dehydrogenase activity and uncocoupling of oxidative phosphorilation. The
resulting fall in ATP levels affects, virtually, all cellular functions
(Na+ /K+ balance, protein synthesis, etc.) that induce generation
of reactive oxygen species and impair tissue respiration (Goyer
and Clarsksom, 2001; Thomas et al., 2001; Gwalteney-Brant, 2002;
ATSDR, 2003a). Moreover, arsenic interferes with DNA repair processes (nucleotide excision repair) (Hartwig et al., 2002) and

products changes in DNA methylation patterns that could affect

gene expression (Abernathy et al., 2003).
Humans can be exposed to arsenic through the intake of food
and drinking water, but for most people, the major exposure source
is the diet, mainly sh and sea food. It is well known that sea food
contains larger amounts of arsenic than other foods (Uneyama et
al., 2007). However, the organic arsenic in food and seafood appears
to be much less toxic than the inorganic forms (Abernathy et al.,
2003). The presence of arsenic in sh has been determinated in
several species such as; blue sh, porgie, red sapper, carp, mullet
tuna, and salmon. Concentrations of arsenic were determined in
ve sh species of the river Neretva, Croatia. The results show that
arsenic concentration is low in most sh, being always its highest
concentration in muscle (Has-Schn et al., 2006). Falc et al. (2006),
Burger and Gochfeld (2005), reported high levels of arsenic in some
species of sh (Table 1). On the other hand, Usero et al. (2003) found
high concentrations of arsenic in muscle of grey mullet, eel and
common sole on tree regions of coast Spain (Table 1).
The joint FAO/WHO Expert committee on Food Additives (JECFA)
established a provisional tolerable weekly intake (PTWI) for inorganic arsenic as 0.015 mg/kg bw (FAO/WHO, 2005); organo-arsenic
intakes of about 0.05 mg/(kg bw day) seemed not to be associated
to hazardous effects (Uneyama et al., 2007).

3. Health effects of sh consumption

The benecial health effects of sh are based on several studies
from the last 25 years, most of which have linked sh consumption
to several health benets (Kinsella et al., 1990; Oomen et al., 2000;
Kris-Etherton et al., 2002). Nevertheless, several areas of uncertainty remain as the optimal intake of n 3 fatty acids (EPA and
DHA) is not clearly established. Some studies have reported contradictory results, since exist an increases levels of heavy metals
that can affected the health of consumers however, sh consumption is recommend due to all its nutritional benets not only
by n 3 fatty acids (Foran et al., 2006; Domingo et al., 2007).
The benecial effects of sh oil are attributed to their eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which
are polyunsaturated omega-3 fatty acids (omega-3 PUFAs) formed
from alpha-linolenic acid. These fatty acids are produced by monocellular algae or phytoplankton, which represent the beginning of
food chain, and accumulate in the fresh of marine sh (Jud et al.,
2006). The omega-3 PUFAS can act at very different levels of the cellular physiology, and the mainly mechanisms of actions proposed
include effect on sensitivity of some ionic channels and/or modify
intracellular calcium homeostasis (Jud et al., 2006). Other pathways involved in cellular signaling mechanisms are activation of
phospholipases, synthesis of eicosanoids, regulation of receptorassociated enzymes and protein kinases (Siddiqui et al., 2008).
Some studies support the idea that the intake of DHA and
EPA reduce high blood pressure, and signicantly reduce blood
triglyceride levels (Harris, 1997); well-conducted randomized controlled trials report that for people with a history of heart attack,
the regular consumption of (oily sh or sh oil/omega-3 supplements reduces the risk of non-fatal heart attack, fatal heart
attack and sudden death (Oomen et al., 2000; Kris-Etherton et
al., 2002; Din et al., 2004; Harris, 2004; Mozaffarian et al., 2005;
Jarvinen et al., 2006). The action mechanisms for these effects still
are not fully dened; but involve changes in membrane uidity,
receptor response and binding to intracellular receptors regulating gene transcription (Torrejon et al., 2007); Das (2000) suggested
an explain of the cardio-protective effects of n 3 fatty acids,
showed that the mainly mechanisms can be due to the suppressions of the tumor necrosis factor (TNF) and interleukinin-1

M.I. Castro-Gonzlez, M. Mndez-Armenta / Environmental Toxicology and Pharmacology 26 (2008) 263271

(IL-1) and the release and modulation of hypothalamic-piyuitaryadrenal anti-inammatory responses. On the other hand, Din et al.
(2008) suggested that reduced platelet monocyte aggregation can
be provides probably mechanism through which sh oils exert the
cardio-protective effects. Moreover, the intake of sh has shown
benets in other diseases such as rheumatoid arthritis (Cleland et
al., 2003; Goldberg and Katz, 2007; Rahman et al., 2008); psychiatric disorders (Cherubini et al., 2007; Song and Zhao, 2007; Peet
and Strokes, 2005) and lung disease (Cerchietti et al., 2007; Romieu
and Trenga, 2001). Recently, preliminary evidence regarding the
role of dietary omega-3 polyunsaturated fatty acids in modulating
each of the components of the triad of adiposity, inammation, and
fatty acid metabolism in the metabolic syndrome has been studied
(Robinson et al., 2007; Douglas, 2007; Lombardo et al., 2007).
However, one potential risk of dietary sh intake is its content of heavy metals, methylmercury mainly, recent evidence
suggests that high mercury content in sh may diminish the cardioprotective effect of sh intake (Salonen et al., 2000; Guallar et al.,
2002; Yoshizawa et al., 2002). In humans, cadmium, lead and/or
arsenic, have also been associated to serious health effects on adults
and children and one source of exposition is the intake of sh with
high content of either of these metals. This has been demonstrated
by several authors; Abernathy et al. (2003); Burger and Gochfeld
(2005); Andreji et al. (2006); Falc et al. (2006); Has-Schn et al.
(2006) have determined the levels of these metals in different sh
species which may be out of permissible limits. PTWI for adults or
children increased due to sh accumulation of substantial amounts
of metals in the sh tissue and thus, risk is also dependent on the
different metals residing in different sh. The American Heart Association suggests eating sh at least two times per week in order
to reach the daily intake of omega-3 fatty acids recommended for
healthy adults with no history of heart disease (Kris-Etherton et
al., 2002). In particular fatty sh such as anchovies, bluesh, carp,
catsh, halibut, herring, lake trout, mackerel, pompano, salmon,
striped sea bass, tuna (albacore), and whitesh, or an equivalent of
0.30.5 g/d e PUFAs are also recommended.
Therefore the intake of sh should be regulated; information
regarding the specie of sh consumed and its possible levels of
content of heavy metals can be of benet to diminish the hazard to
public health (Domingo et al., 2007). The potential harm from other
metals suggests that not only should people eat smaller quantities
of sh known to accumulate mercury but they also should eat a
diversity of sh in order to avoid consuming unhealthy quantities of
heavy metals; however, public should bear in mind that standards
have a margin of safety (Burger and Gochfeld, 2005).
4. Final commentary
In summary, we consume a large number of sea food mainly
sh that can be detectable amounts of heavy metals, however the
potential benet of sh consumption is very important and your
consumption is suggested by the rich nutrimental value but is
necessary that the levels of heavy metal do not exceed the permissible limits for intake of sh. Health institutions, public and private
organizations must have a continuous communication about riskbenet of sh consumption, this conrms the interest to analyze of
bases on which a public policy is elaborated, as well as, the responsibility for regulating the quality and improve the balance between
benet and risk of the sh human consumption.
Acknowledgment
This work was supported by Consejo Nacional de Ciencia y Tecnologa (CONACyT), Mxico grant 52811-Q.

269

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