Environmental Toxicology and Pharmacology 20 (2005) 351360

Low dose mercury toxicity and human health

Farhana Zahir a, , Shamim J. Rizwi a , Soghra K. Haq b , Rizwan H. Khan b
a Interdisciplinary Brain Research Centre, JN Medical College, AMU, Aligarh, U.P., India
b Interdisciplinary Biotechnology Unit, AMU, Aligarh, U.P., India

Received 8 November 2004; accepted 20 March 2005

Available online 17 May 2005

Abstract

Post Minamata incident there has been awareness about mercury toxicity even among the general public. Previous researches contributed a
vast amount of data regarding acute mercury exposure, but gradually information about the low dose [Ninomiya, T., Ohmori, H., Hashimoto, K.,
Tsuruta, K., Ekino, S., 1995. Expansion of methylmercury poisoning outside minamata: an epidemiological study on chronic methylmercury
poisoninig outside of Minamata. Environ. Res. 70 (1) 4750; Lebel, J., Mergler, D., Lucotte, M., Amorim, M., Dolbec, J., Miranda, D.,
Arantes, G., Rheault, I., Pichet, P., 1996. Evidence of early nervous system dysfunction in Amazonian populations exposed to low-levels
of methylmercury. Neurotoxicology 17 (1) 157167] of mercury toxicity has been trickling in. With mercury contaminating rain-, ground-
and sea-water no one is safe. Polluted water leads to mercury laced fish, meat and vegetable. In aquatic environments, inorganic mercury
is microbiologically transformed into lipophilic organic compound methylmercury. This transformation makes mercury more prone to
biomagnification in food chains. Consequently, populations with traditionally high dietary intake of food originating from fresh or marine
environment have highest dietary exposure to mercury. Extensive research done on locals across the globe have already established this,
persons who routinely consume fish or a particular species of fish are at an increased risk of methylmercury poisoning. The easy access
of the toxicant to man through multiple pathways air, water, food, cosmetic products and even vaccines increase the exposure. Foetus and
children are more susceptible towards mercury toxicity. Mothers consuming diet containing mercury pass the toxicant to foetus and to infants
through breast milk. Decreased performance in areas of motor function and memory has been reported among children exposed to presumably
safe mercury levels. Similarly, disruption of attention, fine motor function and verbal memory was also found in adults on exposure to low
mercury levels. It is an occupational hazard for dental staff, chloralkali factory workers and goldminers, etc. Mercury has been found to be
a causative agent of various sorts of disorders, including neurological, nephrological, immunological, cardiac, motor, reproductive and even
genetic. Recently heavy metal mediated toxicity has been linked to diseases like Alzeihemers, Parkinsons, Autism, Lupus, Amyotrophic
lateral sclerosis, etc. Besides this, it poses danger to wildlife. Therefore, it becomes imperative to spread the information regarding the threat
of mercury exposure amongst the scientists and masses.
2005 Elsevier B.V. All rights reserved.

Keywords: Mercury pollution; Low dose toxicity; Biomagnification; Neurodegenerative disorders

1. Introduction lates in the food web. Amongst three forms of mercury,

the organic form is most toxic as it passes the blood brain
In 1950, Minamata bay tragedy caught the world un- barrier owing to its lipid solubility. The damage has vast
awares. It has been since recognized that the multiple path- implications with human beings at the top of food chain
ways of mercury contamination through air, water, food, getting worst of the deal owing to biomagnification. This
pharmaceuticals, cosmetic products, etc., pose serious con- review was written to focus on recent researches showing
cern because it persists in the environment and accumu- adverse health effects of low doses of mercury, to instigate
the requirement for a new era of pharmaceutical develop-
Corresponding author. ment and to create further awareness regarding environmental
E-mail address: farhanazahir@rediffmail.com (F. Zahir). remediation.

1382-6689/$ see front matter 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.etap.2005.03.007
352 F. Zahir et al. / Environmental Toxicology and Pharmacology 20 (2005) 351360

2. Sources of mercury 7.5 to 71.8 ng l (1), with a mean of 24.8 ng l (1). Liquid
water content explained about 60% of the variability in Hg
2.1. Mercury in air cloud concentrations (Malcolm et al., 2003). There are also
linkages between acidic deposition and fish mercury contam-
As a natural element mercury is ubiquitous in the en- ination and eutrophication of estuaries (Driscoll et al., 2003).
vironment (Fig. 1), approximately 10,000 tons originates Numerous factories that directly pump untreated effluents
from degassing of earths crust, to this amount approxi- pollute groundwater. The polluted water produces acidic rain
mately 20,000 tons/year is added by anthropogenic activity which ultimately contaminates all water bodies. Report pub-
(Hansen and Dasher, 1997). Mercury emissions from the lished in a reputed Indian daily, The Hindustan Times showed
coal smoke is the main source of anthropogenic discharge result of water samples analysed at IIT, Kanpur. Groundwa-
and mercury pollution in atmosphere. It is estimated that ter samples in India from eight places each from Punjab,
the mercury emissions will increase at a rate of 5% a year Haryana, Andhra Pradesh, Gujarat and Kanpur showed sur-
(Zhang et al., 2002). When medical devices like thermome- prisingly high levels of Hg in all samples. Water sample from
ter/sphygmomanometer or household items like fluorescent Panipat (Haryana) had highest level of Hg at concentration
night lamps or thermostats are discarded residual mercury 268 times that of safe limit, even the sample with least Hg
is emitted. The US Environmental Protection Agency (EPA) value had 58 times more mercury than the upper safe limit
National Emissions Inventory (NEI) had the most complete (Hindustan times, 1999). Algal bloom and leaf fall events can
coverage for all states. It found coal-fired electric utilities result in elevated methylmercury (MeHg) concentrations in
accounted for 52.7% of the regions Hg emissions. Other surface waters, potentially leading to increased MeHg accu-
important contributors to regional emissions included mu- mulation in fish (Balogh et al., 2002).
nicipal waste combustion (5.6%), mercury-cell chlor-alkali
plants and hazardous-waste incinerators (4% each), station- 2.3. Mercury contamination of food
ary internal combustion engines (ICEs) (3.5%), industrial,
commercial and institutional (ICI) boilers (3.3%) and lime 2.3.1. Food of animal origin
manufacturing (3.0%) and medical waste incineration (1%) The emitted mercury both natural and anthropogenic is in
(Murray and Holmes, 2004). Informal gold mining has used an inorganic form predominantly metallic vapour, which is
mercury since antiquity. High contamination of Brazilian carried off to great distances by winds and eventually falls in
Amazon (Brazil is worlds second largest producer of gold) water bodies. In aquatic environments, inorganic mercury is
is indicated by the strong presence of mercury in its biota microbiologically transformed into lipophilic organic com-
(Grandjean et al., 1999). It is an occupational hazard for den- pound, methylmercury. This transformation makes mercury
tal staff (Rowland and Baird, 1994), chloralkali factory work- more prone to biomagnification in food chains. Consequently,
ers (Barregard and Lindstedt, 1994) goldminers (Grandjean populations with traditionally high dietary intake of food
et al., 1999), etc. originating from fresh or marine environment have highest
dietary exposure to Hg. Extensive research done on locals
2.2. Mercury in water across the globe have already established this for instance po-
lar Eskimos. Persons who routinely consume fish or a partic-
Mercury in air eventually passes into rivers, lakes and ular species of fish are at an increased risk of methylmercury
oceans after travelling long distances together with wind. poisoning (Table 1) (Hansen and Dasher, 1997). Since mer-
With mercury contaminating rain (Domagalski et al., 2004; cury intake is expressed on a per kilogram body weight basis
Levine, 2004), ground and seawater (Beldowski and Pemp- exposure of children under age 14 is twothree times high be-
kowiak, 2003), no one is safe. Cloud water was collected cause of higher food intake per kilogram body weight. After
during nine non-precipitating cloud events on Mt. Mansfield, measuring total mercury in the edible portions of 244 selected
VT in the northeastern USA between 1 August and 31 Octo- fish and shellfish purchased in Canada at the retail level, the
ber, 1998. Mercury cloud water concentrations ranged from Canadian advisory to children and women of child-bearing

Fig. 1. Mercury and environment.

 F. Zahir et al. / Environmental Toxicology and Pharmacology 20 (2005) 351360 353

Table 1 species, the highest average content of mercury was found

Mercury levels in commercial fish and shellfish in Boletus pinicola at 7.37 ppm DW (Alonso et al., 2000). In
Fish species Mean mercury southeast Asia, the aquatic macrophyte water spinach (Ipo-
concentration (ppm) moea aquatica Forsk) is a popular vegetable that is culti-
Very high risk group vated in freshwater courses, it was found that the vegetable
Mackerel king 0.73 accumulated various heavy metals like mercury, cadmium
Shark 0.99
Sword fish 0.97
and lead in a nutrient deficient medium (Gothberg et al.,
Tile fish 1.45 2004).
High risk group
Tuna (fresh/frozen) 0.38 2.4. Mercury in pharmaceuticals and utility products
Tuna (canned albacore) 0.35
Lobster 0.31 Mercury has always been a popular choice for dental
Orange roughy 0.54 amalgams. Thimerosol is a mercury containing compound
Spanish Mackerel 0.45
used as a preservative in Hepatitis B, Diptheria, Pertussis,
Marlin 0.49
Grouper 0.55 Acellular pertussis and Tetanus vaccines. Use of mercury
in vaccines have caused furore in concerned circles owing
Medium risk group
White croaker 0.29
to death of infants and speculations over long-term effects
Bass 0.27 (Westphal and Hallier, 2003). Infants are exposed to phenyl
Carp 0.14 mercury from treated diapers and young children ingesting
Tile fish 0.15 mercuric chloride in teething powders have been found to
Tuna (canned light) 0.12 develop acrodynia and kawasaki disease (Kazantzis, 2002).
Sablefish 0.22
Scorpion fish 0.29
Skin whitening creams and soaps from developing countries
Weakfish (sea trout) 0.25 is a recognized source of chronic mercury poisoning (Harada
et al., 1999, 2001). Mercury level of almost 2000 times above
the allowable limit was found in blood of an indonesian do-
age is to limit their consumption of fresh and frozen tuna, mestic worker (Soo et al., 2003).
swordfish and shark to no more than one meal per month
(Dabeka et al., 2004). When 21 fish species, cephalopods and 2.5. Mercury and wildlife
crustaceans were analyzed for mercury accumulation the for-
mer two ranked highest (Schumacher et al., 1994). In Yokon It is well known that heavy metals in larger amounts are
delta system, biomagnification factor of 12 was calculated toxic to animals as well as plants; and mercury is no exception
for methylmercury, out of 29% fish species, 62% contained to this, though some of these metals may actually be required
Hg exceeding wildlife critical value for piscivorous animals. in trace amounts to support life. The general signs of mercury
Overall 24% fish exceeded critical value for human consump- toxicity for sheep, cattle, pig, chicken and turkey include lack
tion and 58% wildlife critical value (Duffy et al., 1998). Cattle of appetite, loss of weight, muscular incoordination, unsta-
and pigs kept in area with contaminated river water had twice ble gait and lameness. Sea birds from mercury contaminated
concentration of blood and hair Hg than control ones (Palheta colony, metal dosed birds and metal dosed mice have demon-
and Taylor, 1995). strated nephrotoxic lesions of severe type (Nicholson et al.,
1983). The possible effects of heavy metal exposure on the
2.3.2. Food of plant origin condition and health of great tit nestlings (Parus major) at
Emissions of mercury from the province of Guizhou in four study sites along a pollution gradient near a large non-
Southwestern China to the global atmosphere have been ferrous smelter in Belgium during three consecutive breeding
estimated to be approximately 12% of the world total an- seasons was taken. When taking into account the number of
thropogenic emissions primarily due to mining, chemical young in the nest at the time of sampling, nestling body mass
discharge and elecricity production. Even though the ma- and condition were significantly reduced at the most polluted
jor source of mercury is inorganic, it was observed that ac- site (Janssens et al., 2003). Methylmercury was attributed
tive transformation of inorganic mercury to organic mercury for decrease in reproduction of adult fathead minnows at
species (MeHg) takes place in water, sediments and soils. dietary concentrations encountered by predatory fishes in
It has been reported that the concentration of mercury in aquatic systems with contaminated food webs, implying that
rice grains can reach up to 569 g/kg of total Hg of which exposed fish populations could be adversely affected by this
145 g/kg is in MeHg form (Horvat et al., 2003). While ana- widespread contaminant (Hammerschmidt et al., 2002). Inor-
lyzing in situ aquatic and terrestrial plants in vicinity of chlo- ganic mercury disturbs a part of respiration process in shrimp
ralkali plants growing at Hg conc. 8.9 mg/kg it was found larvae Pandalus borealis (St-Amand et al., 1999). Embry-
that Cabbage Bracica oleracea and amaranthus Amaranthus otoxicity and teratogenecity of organic mercury compounds
oleraceous accumulated mercury at significant levels (Lanka have been observed in fish, birds and even mammals (Leonard
et al., 1992). Amongst edible mushrooms representing eight and Jacquet, 1983).
354 F. Zahir et al. / Environmental Toxicology and Pharmacology 20 (2005) 351360

3. Toxicity of mercury Turner, 1995). Mothers consuming diet containing mercury

pass the toxicant to foetus (Murata et al., 2004) and to infants
There have been numerous studies dedicated to the study through breast milk (Grandjean et al., 1995). Decreased per-
of mercury toxicity. We have shortlisted a few below for formance in areas of motor function and memory has been
the better understanding towards low dose mercury toxicity reported among children exposed to presumably safe mer-
(Table 2). cury levels with maternal hair concentrations at 1020 g/g
(Grandjean and Weihe, 1998). Detectable subtle effects on
3.1. Low dose mercury affects nervous system of foetus brain function in domains of language, memory and motor
and children appeared at prenatal methylmercury exposure particularly
during second trimester. Neurobehavioral dysfunction was
Vulnerable periods during the development of the nervous reported even if maternal hair Hg is 6 g/g, corresponding
system are sensitive to environmental insults because they are value for blood is approximately 24 g/l (Grandjean et al.,
dependent on the temporal and regional emergence of crit- 1994).
ical developmental processes (i.e. proliferation, migration, Autism is a disorder that can lead to life-long disability.
differentiation, synaptogenesis, myelination, and apoptosis). Though not proved there is potential link between mercury
Evidence from numerous sources demonstrates that neural toxicity and autism in children (Lee et al., 2003). Subtle neu-
development extends from the embryonic period through rological disorders in children over mercury exposure have
adolescence. Different behavioral domains (e.g. sensory, mo- been widely reported (Johnson, 2004; Counter and Buchanan,
tor and various cognitive functions) are subserved by dif- 2004). The neuropathological examination of brains of chil-
ferent brain areas. Of critical concern is the possibility that dren prenatally exposed to organic mercury reveals dysplasia
developmental exposure to neurotoxicants may result in an of cerebral and cerebellar cortexes, neuronal ectopia and sev-
acceleration of age-related decline in function. This concern eral other developmental disturbances (Geelen and Dormans,
is compounded by the fact that developmental neurotoxicity 1990).
that results in small effects can have a profound societal im-
pact when amortized across the entire population and across 3.2. Low dose mercury affects nervous system of adults
the life span of humans (Rice and Barone, 2000).
The difference in sensitivity between foetus and adult Low concentrations of some metals, including mercury
organism is between 2 and 5 with foetus being more sus- can directly induce -synuclein fibril formation which are the
ceptible to methylmercury toxicity (Snyder, 1971). Maternal major constituent of intracellular protein inclusions (Lewy
consumption during pregnancy of methylmercury contami- bodies and Lewy neurites) in dopaminergic neurons of the
nated fish in Japan and of methylmercury contaminated bread substantia nigra leading to parkinsons (Uversky et al., 2001).
in Iraq caused psychomotor retardation in the offspring. Stud- Moreover, low concentrations of cobalt and mercury are able
ies in Iraq suggested adverse fetal effects when maternal hair to induce oxidative stress, cell cytotoxicity and increase the
mercury concentrations were as low as 20 ppm (Marsh and secretion of -amyloid 140 and 142 which may lead to neu-
rodegenerative diseases, such as Alzheimers and Parkinsons
diseases (Olivieri et al., 2002). Mercury binds to sulfhydryl
Table 2 groups of proteins and disulfide groups in amino acids result-
Effect of low dose mercury toxicity on various organ systems ing in inactivation of sulfur and blocks related enzymes, co-
Nervous system factors hormones (Mathieson, 1995; Markovich and James,
Adults Memory loss, including Alzheimer like 1999). Besides this, it also alters permeability of cellular
dementia, deficit in attention, hypoesthesia,
ataxia, dysarthrea, subclinical finger tremor
membrane by binding to sulfhydryl ( SH) radical (Bapu et
impairment of hearing and vision, sensory al., 1994). Blocked or inhibited sulfur oxidation at cellular
disturbances, increased fatigue levels has been found in many chronic neurodegenerative dis-
Children/infants Deficit in language (late talking) and memory orders, including Parkinsons disease, Alzheimers disease,
deficit in attention, Autism ALS, Lupus, Rheumatoid arthritis, Autism, etc. (Wilkinson
Motor system and Waring, 2002). Long-term study of low dose of mercury
Adults Disruption of fine motor function, decreased demonstrated hypoesthesia, ataxia, dysarthrea and impair-
muscular strength, increeased tiredness
ment of hearing and visual change in the study group, 10
Children/infants Late walking
years later, after the end of methylmercury dispersion from
Renal system Increases plasma creatinine level Minamata on coast of Shiranui sea (Ninomiya et al., 1995).
Cardiovascular system Alters normal cardiovascular homoeostasis
Immune system Decreases overall immunity of the body,
In another survey of fish eating population with low hair Hg
exacerbates lupus like autoimmunity, levels <10 ppm it was found that neurological symptoms par-
multiple sclerosis, autoimmune thyroiditis or ticularly sensory disturbances such as glove and stocking type
atopic eczema occured at a very high rate. (Harada et al., 1994). The adult
Reproductive system Decreases rate of fertility in both males and population of Amazonian ecosystem with hair mercury be-
females, birth of abnormal offsprings
low 50 g/g deomonstrated near visual contrast sensitivity,
 F. Zahir et al. / Environmental Toxicology and Pharmacology 20 (2005) 351360 355

decreased manual dexterity, tendency for increased muscular consumption advisories will remain the primary means of
fatigue, decreased muscular strength among women signifi- reducing human exposure to methylmercury (Anderson et
cantly in a dose dependent manner (Lebel et al., 1998). Sim- al., 2004). If concentration of methylmercury is very high in
ilarly disruption of attention, fine motor function and verbal mothers they do not conceive, if they do there is low rate of
memory was also found in adults of fish eating populations pregnancy the foetus is aborted or is stillborn. At even lower
on exposure to low mercury levels (Yokoo et al., 2003). The doses conception and live birth occurred but the child suffered
effects of mercury exposure at levels around 0.05 mg/m3 or from serious neurological symptoms (Harada, 1968).
lower have been of concern, include, increased complaints Women exposed to mercury vapour not exceeding the time
of tiredness, memory disturbance, subclinical finger tremor, weighted average air concentration of 0.01 mg/m3 declared
abnormal EEG by computerized analysis and impaired per- higher prevalence and incidence rates of menstrual disor-
formance in neurobehavioral or neuropsychological tests ders, primary subfecundity, and adverse pregnancy outcome
(Satoh, 2000). Neuropsychological effects in mercury vapor (De Rosis et al., 1985). According to WHO report 0.5 mg/kg
exposed male chloralkali workers with low concentrations Hg contaminated food should not be sold for human con-
of urinary mercury mean U-Hg 5.9 nmol/mmol creatinine sumption. Hg accounts for sub-fertility in Hong Kong males
(Cr) indicated lowering of visuomotor/psychomotor speed (Dickman and Leung, 1998). Organic as well as inorganic
and attention, and immediate visual memory (Ellingsen et mercury decreases the percentage of motile spermatozoa. Af-
al., 2001). Depression and impairment of short-term audi- ter 30 min incubation with 20 mol methylmercuric chloride
tory memory was found in workers exposed to low levels of less than 5% of human spermatozoa were found motile (Ernst
mercury (Soleo et al., 1990). and Lauritsen, 1991).

3.3. Low dose mercury toxicity affects renal system 3.5. Low dose mercury toxicity affects immune system

Kidneys accumulate highest levels of mercury compared The immune system plays an important regulatory role in
to brain and liver (Hussain et al., 1998). Renal toxicity of the host-defense mechanisms. Patients with certain autoim-
mercuric chloride is well documented in literature. Nuclear mune and allergic diseases, such as systemic lupus, multi-
factor B (NF-B) is a thiol-dependent transcriptional fac- ple sclerosis, autoimmune thyroiditis or atopic eczema, often
tor that promotes cell survival and protects cells from apop- show increased lymphocyte stimulation by low doses of in-
totic stimuli. Mercuric ion Hg (2+) is, one of the strongest organic mercury in vitro (Prochazkova et al., 2004). It has
thiol-binding agents known, impairs NF-B activation and been repeatedly shown that the heavy metal mercury can in-
DNA binding at low M concentrations in kidney epithe- duce or exacerbate lupus like autoimmunity in susceptible
lial cells leading to apoptosis (Dieguez-Acuna et al., 2004). strains of rats and mice. A hallmark of such autoimmune in-
Renal function and immunologic markers among chloralkali duction is the accompaniment of an immune shift, in which
workers with long-term low exposure to mercury vapor when there is usually an initial skewing toward a Th2-like immune
examined indicated an effect of exposure on the kidney prox- environment (Hudson et al., 2003).
imale tubule cells (Ellingsen et al., 2000). Exposure to methylmercury significantly enhanced lym-
Renal dysfunction increases plasma ceratinine level upon phocyte responsiveness in most of the exposed groups at the
methylmercury intoxication for 5 ppm mercury for 2 years low concentration of 5 g/l, with the highest proliferative
(Yasutake et al., 1997). Decrease in protein (brain and liver) response (four-fold increase) in the methylmercury chlorde
acid and alkaline phosphatase and glutathione S transferase group (Ortega et al., 1997). Prolonged exposure to low doses
was observed upon 0.5 mol/ml mercury for five consecutive of inorganic mercury, suggested an in vivo functional defect
days, while thiobarbituric acid reactive substances (TBARS) of the monocytemacrophage system (Soleo et al., 1997).
was found to be significantly increased in brain and liver The exposure to very low levels of metallic mercury led to
indicating free radical stress (El-Demerdash, 2001). subtle impairment of circulating monocyte and NK cells (as
percentages) in a particular group of workers, even though
3.4. Low dose mercury toxicity affects reproduction they remained clinically asymptomatic (Vimercati et al.,
2001).
Advisories to reduce consumption of contaminated fish
have been issued by states since the early 1970s. Most women 3.6. Low dose mercury toxicity affects cardiovascular
of child bearing age consume commercial fish and a sub- system
stantial number also consume sport-caught fish containing
mercury, linked to reproductive and developmental effects. Recent evidence suggests that mercury content in fish may
Despite this potential exposure to dietary mercury, most are diminish the cardioprotective effect of fish intake (Chan and
unfamiliar with their states mercury fish-consumption ad- Egeland, 2004). Prenatal exposure to methylmercury may af-
visory.Until source control and environmental remediation fect development of cardiovascular homoeostasis, in children
efforts can reduce the environmental burden of mercury be- with lower birth weight, systolic and diastolic blood pressure,
low levels of concern, combined sport and commercial fish increase 13.9 mm Hg when cord blood mercury concentration
356 F. Zahir et al. / Environmental Toxicology and Pharmacology 20 (2005) 351360

increases from 1 to 10 g/l cord blood (Sorensen and Murata, vae of urodele Pleurodeles waltl. After 12 days of treat-
1999). ment, concentration factors (concentration in the amphib-
ian organism/concentration in the water) of approximately
3.7. Low dose mercury toxicity affects motor activity 1200 and approximately 600 were found for methylmer-
cury and mercuric chloride, respectively (Zoll et al.,
There are numerous studies demonstrating locomotory 1988).
dysfunction in laboratory animals on exposure to mercury
(Rocha et al., 2001). Neurobehavioral manifestations of sub- 3.9. Molecular mechanisms of low dose mercury toxicity
tle neurotoxic effects on motor functions, associated with
low-level methylmercury exposure in humans have also been It is difficult to classify the molecular basis of low dose
demonstrated (Dolbec et al., 2000). Women showed com- mercury toxicity to tissues and organ systems initially due
paratively reduced grip strength (Lebel et al., 1996) and in- to lack of data, finally because it is a complex cascade of
creased tendency for muscular fatigue associated with low interrelated events that may directly or indirectly translate
mercury levels as oberserved in amazonian population (Lebel into pathological state of a particular organ system. Its neu-
et al., 1998). Mercury with low content of selenium might be rotoxicity to cerebellum at higher doses has been related to
one of the environmental factors which are thought to be in- impairment of motor function (Marcelo et al., 2005) and its
volved in production of Ayotropic Lateral Sclerosis (Mano et genotoxicity to neuronal cells in foetal state may result in
al., 1990). abnormal offsprings or foetal deaths but its exact mode of
activity at low doses, particularly at environmentally rele-
3.8. Low dose mercury toxicity affects genome vant concentrations which lead to subtle delays in neurode-
velopment remain unexplored. Basically it blocks essential
The reports for mercury genotoxicity have been com- functional groups in biomolecules and also displaces essen-
ing since 1980. First report showing clear cytotoxic effects tial metal ions from them. Mercuric ion is known as one
of 20 years exposure to methylmercury on human popula- of the strongest thiol-binding agents. Intracellular mercury
tion with a wide range of mercury exposure, based on a therefore attaches itself to thiol residues of proteins par-
well-known biological marker, hair mercury a clear rela- ticularly glutathione and cysteine resulting in inactivation
tion between methylmercury contamination and cytogenetic of sulfur and blocks related enzymes, cofactors and hor-
damage in lymphocytes at levels well below 50 g/g was mones (Mathieson, 1995). Its molecular interactions with
found. Although their results strongly suggest that, under sulfhydryl groups in molecules of albumin, metallothionein,
the conditions examined, methylmercury is both a spindle glutathione, and cysteine have been implicated in mecha-
poison and a clastogen, the biological significance of these nisms involved in renal (Zalups, 2000) and neuronal toxic-
observations are as yet unknown (Amorim et al., 2000). ity (James et al., 2005 and Fonnum and Lock, 2004). The
A long-term follow-up of these subjects should be under- other functional groups besides SH for which mercury has
taken. Theoretically, methylmercury-induced chromosome high affinity include, CONH2 , NH2 , COOH and PO4
damage in germline cells could give rise to abnormal off- (Hayes, 1983). It also blocks immune function of Mn and
spring. Mercuric chloride exposure in short term blood cul- Zn leading to deficiency of principal antioxidant enzyme,
tures lead to high sister chromosome excahanges/cell and superoxide dismutase, CuZnSOD and MnSOD (Rajanna
induced C-anaphases (abnormal mitosis) (Rao et al., 2001). and Hobson, 1995) which has a role in various diseases, in-
The chromosomal genotoxicity of mercury has been at- cluding Alzheimers disease, Parkinsons disease, Cancer,
tributed to its interation with microtubule assembly mercury Downs syndrome, Dengue, etc. (Noor et al., 2002). More-
inhibits microtubule assembly at concentrations above 1 M, over, in cerebellar granule cells in culture, low concentration
and inhibition is complete at about 10 M (Bonacker et al., of mercury causes a rise in [Ca2+ ] which may trigger a cas-
2004). cade of events leading to impairment of mitochondrial en-
Mercury genotoxicity have been observed in animals as ergy metabolism and generation of reactive oxygen species
well as in plants. The cytogenetic analysis revealed the effects (Fonnum and Lock, 2004). Mercury by inhibiting glutamic
of mercury on the mitotic and meiotic chromosomes which acid uptake further sensitises neurones to excitotoxic injury
were significantly correlated with soil-mercury levels. The (Fonnum and Lock, 2004). The combination of these mer-
bioconcentration of mercury in aerial tissues including grain cury triggered events enhances free radical stress that has
was observed indicating possible contamination of the agri- been cited widely in literature (Hussain et al., 1998 and Ali
cultural food chain (Panda et al., 1992). Low concentrations et al., 1992).
of inorganic mercury (Hg2+ ) and methylmercury chloride Free radical stress has been frequently reported as key
(CH3 HgCl) added separately or together lead to induction player in disease progression of as many as 50 diseases
of micronuclei in the binucleated erythrocytes of Prussian (Halliwell, 1994 and Langseth, 1993), aging and degener-
carp (Al-Sabti, 1994). The bioaccumulation of methylmer- ative disorders (Nagy, 2001). Mercury obstructs neurotrans-
curic chloride and mercuric chloride at low dose exposure mission by acting as a strong competitive inhibitor of mus-
was evaluated by determination of mercury levels in the lar- carinic cholinergic receptors (Coccini et al., 2000), though
 F. Zahir et al. / Environmental Toxicology and Pharmacology 20 (2005) 351360 357

this aspect awaits further study. The renal changes in work- 4. Conclusion
ers with chronic low level exposure to mercury indicated
increased tubular antigens and enzymes, altered levels of Multiple pathways of mercury through air, food, water,
biochemical enzymes, such as decreased urinary output of pharmaceuticals, cosmetics, etc., account for its easy accessi-
eicosanoids and glycosaminoglycans, and a more acidic pH. bility to man, factors like biomagnification of mercury along
However since urinary function was normal, the clinical sig- the food chain complicate the problem. Fish eating popula-
nificance of these findings is yet to be determined (Cardenas tions are at an increased risk. There are numerous studies es-
et al., 1993). tablishing mercury toxicity as occupational health hazard for
The observed reduced lymphocyte proliferation associ- goldminers, chloralkali workers and dental personnel. Since
ated with low levels of mercury (Soleo et al., 1997; Vimer- awareness regarding low-dose mercury toxicity is less; safety
cati et al., 2001) may translate into reduced resistance to dis- precautions are generally not taken even sometimes at per-
ease. Low-level, nontoxic inorganic mercury pre-exposure sonal level, e.g. children play with liquid metal of a broken
may interact with other risk factors, genetic or acquired, to thermometer.
promote subsequent autoimmune disease development (Via In view of numerous recent reports regarding low-dose
et al., 2003). Though molecular basis of immunotoxicity of mercury toxicity, its environmental contamination should be
mercury is relatively less studied, recent researches show that checked. A few countries have awareness campaigns, in some
low dose mercury suppresses immune response by reducing cases they are successful for instance. The Netherlands has
nitric oxide (NO) synthesis by inhibition of the nuclear factor reduced thimerosol (merthiolate) exposure through pharma-
B (NF-B) pathway and modulating cytokine expression by ceuticals (Vant Veen, 2001). Recent literature reports that
p38 mitogen-activated protein kinase (p38 MAPK) activation thimerosol has been removed from most of the childrens vac-
as observed in J774A.1, murine macrophage cell line (Kim et cines, but it is still present in flu vaccines given to pregnant
al., 2002). Mercury salts cause allergy by inducing IgE syn- women, the elderly, and to children in developing countries
thesis and promoting Th2-cytokine profile (Strenzke et al., (James et al., 2005). The governments of respective countries
2001). should ensure mercury free air, water and food by making
The fetus is especially vulnerable to methylmercury since strict laws regarding contaminating industrial units, ensuring
developing fetal brain processes, such as cellular division, proper disposal of mercury garbage and encouraging pro-
differentiation, and migration are disrupted by binding of cedures without use of mercury. Media and NGOs should
mercury to thiol groups of tubulin, the principal protein raise a voice against any negligence on part of government
constituent of neuronal microtubules (Clarkson, 1992). The besides educating the masses about mercury hygiene. There
chromosomal genotoxicity of mercury salts could be due to should be awareness among general public from abstaining
interaction of Hg2+ with the motor protein kinesin medi- mercury laced cosmetic products. Scientists should work to-
ating cellular transport processes (Bonacker et al., 2004). wards making vaccines in which mercury is not a preserva-
Genotoxicity of mercurials could have far reaching con- tive.
sequences ranging from birth of abnormal offsprings to
neuroegenerative disorders. Recently in a major break-
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