• Rout of exposure of heavy metals in human body

Within the present period of growing technology, the density of heavy substance present in drinking
water is still not within the recommended limits as set by the governing authorities in different
countries of the world. Drinking water defiled with heavy metals as for instance ; arsenic, cadmium,
nickel, chromium, mercury, zinc and lead is getting alarming day by day for our health care and
professionals.

The rising source that resulting in measurable human exposure to heavy metals is the consumption
of contaminated drinking water. Utilization of heavy metal-contaminated water is turning out in high
morbidity and mortality rates all over the world.

• Sources of heavy metals

Heavy metals are detected naturally in earth’s lithosphere but technology related or research based
conditioning have caused severe changes in their geochemical cycles. These heavy metals also
accumulate in different segment of plants therefore causing several dangerous impact on human
health.

Heavy metals are a serious risk to soil quality due to their continuity after entering the soil. Heavy
metals negatively affect biological functions in soil.

In the previous research, it has pointed on the effects of heavy metals entering through sewage
sludge purposively added to soil for P and N fertilisation.

Yet, there are other important sources of heavy metal defilement, e.g. mining or industrial dumps,
where the density of heavy metals markedly exceed those of soils enriched with sewage sludge.

another important source of heavy metals is the sediments of rivers. Rivers deposited dump
remainders onto their plain part and flood affected areas. The relative contribution of Zn, Pb and Cu
to the heavy metal amount varies depending on the source.

Water is another vital source of heavy metals. These sources are often factual goods, e.g. runoff
from roofs, wear and tear of tires, food, or conditioning, e.g. large enterprises, auto wetlands. The
sources were linked by knowing the metals content in colourful goods and therefore the emigrations
from goods to sewage or storm water. The sources of sewage water and storm water were
distributed to enable comparison with other exploration and measures. The types were homes,
drainage water, businesses, pipe deposition( all transported in sewage water), atmospheric deposit,
business, erecting accoutrements and pipe deposition( transported in storm water).

Results show that it had been possible to track the sources of heavy metals for some metals similar
as Cu and Zn( 110 and 100%, independently) also as Ni and Hg( 70%).

Other metal sources are still inadequately understood or undervalued( Cd 60%, Pb 50%, Cr 20%
known). The most important sources of Cu were valve water and roofs. For Zn the most important
sources were galvanized material and auto wetlands. within the case of Ni, the most important
sources were chemicals used in the WTP and drinking water itself. And eventually, for Hg the
foremost dominant emigration source was the amalgam in teeth. For Pb, Cr and Cd, where sources
were more inadequately understood.
Continuous presence of pipe sediments within the plumbing system, which release Hg and Pb, might
be one explanation for the missing quantum of these metals. Large enterprises were founded to
make a veritably small contribution, 4% or lower for all metals studied.

Cadmium

Cadmium(Cd) is a heavy metal and is seen naturally in ores. Cd is used generally as stabilizer in
different products like colours, several alloys and in Polyvinyl chloride( PVC)- affiliated products.
Phosphate fertilizers is considered as another sources of Cd exposure. Also, during the twentieth
century, the yield of Cd, its operation and emigration to the atmosphere has been increased
throughout the world. Incineration of Cd containing waste can heavily contaminates the
atmosphere. For instance, soil contamination occurs when phosphate fertilizer and drainage residue
is used with crops where Cd is up taken by the crops and vegetables which are ultimately consumed
by humans( Järup et al., 1998). Another major source of Cd exposure could be cigarette smoking.
still, studies have established that this accounts for a little of total Cd concentration of body( Hossny
et al., 2001).

Mechanism of Cadmium exposure

When Cd penetrates into the blood, it's transported by proteins similar as albumin and
metallothionein(MT) in a Combined form. When Cd reaches in gastrointestinal tract, it enters liver
where it induced the production of metallothionein and Cd metallothionein is released into
sinusoidal blood. Cd may enter the enterohepatic cycle as cadmium- glutathione conjugates after
being released into the biliary tract. Whereas, in biliary tract, these Cd conjugates are broken into
cadmium- cysteine complexes and Cd can again penetrate into small intestine( Zalups and Ahmad,
2003). Also, it has been observed that Cd can be stored for a long time in kidney( Orlowski and
Piotrowski,) which can lead towards tubular necrosis. An estimation of blood Cd concentration
provides a more accurate estimate of recent exposures while amount of renal Cd concentration are
introduced to indicate past exposure and body burden of Cd( Jin et al., 2002).

Effect of cadmium exposure

Cadmium exposure to human is occurred by inhalation and ingestion although on the main health
impacts recorded in the literature are through nutritional exposure( kidney and bone damage) and
inhalation from smoking tobacco and occupational exposure( lung damage). nutritional input
accounts for 90 of all exposure in non-smokers. Cadmium in the atmosphere is poisonous to trees
and creatures and numerousmicro-organisms. Cadmium doesn't degrade in the atmosphere to less
poisonous products which contributes to its bioaccumulation in the kidneys and liver of vertebrates
and domestic animals. Cadmium enters the atmosphere from a diversity of anthropogenic sources.

Wastewater is crucial source of environmental cadmium impurity and verbose pollution occurs
through artificial air emigrations and wide use of fertilizers on farming soils. trees including rice and
tobacco) that are grown in polluted soils take up cadmium and lead to human nutritional( and
inhalation) exposures. Still, human exposure also occurs when cadmium defiled soils are disturbed
and the dust is inhaled. Dietary element rich in meat( especially liver and kidneys) or products from
oceanic mammals may affect in a particularly high intake of cadmium. Cadmium isn't considered
essential for natural function in humans. Mainly kidney is affected by cadmium in both the general
population and the occupationally exposed. People with iron deficiency are considered to be at
particular threat as are tobacco smokers. Another critical effect is skeletal damage as a secondary
response to kidney damage or direct effect on the bone cells by the cadmium.( Manju et al., 2015).
Arsenic

Arsenic( As) exposure to human may happen as a result of drinking water defiled by artificial waste
or agrochemical waste( Hughes etal., 2011). defiled smogs or mists of As may be another source of
water impurity. As poisoning may also happen by eating polluted food containing pesticides or by
food that may be grown using high ranges of As metal or through food grown in As rich- soil( Nriagu
and Azcue, 1990a; Nriagu and Azcue, b). Unexpectedly, milk has also become a source of As
poisoning after contamination of milk occurs through mixing of As containing water. Excluding these
sources, As enters into body with inhalational and dermal exposure( Lauwerys and Hoet, 2001).
Humans are facing. occupational health problems that may be the result of As containing element
available commercially. In some occupational circumstances exposure to arsine gas is of great threat
to human health because arsine exposure may affect in quick deterioration of red blood cells( RBC’s)
performing in kidney failure. also, use of acid and crude metals is another major source of As
poisoning( Squibb and Fowler, 1983). Energy production from fossil energies and metal smelting may
affect in air, soil and water impurity( Chilvers and Peterson, 1987). still, human exposure to organic
As composites similar as arsenobetaine may affect from fish eating which contain organic As.
Identification of As exposure can be done by measuring As concentration in urine and also in hair
and nails. As exposure in history may be indicated casually by As amount in hair and nails. Recent As
exposure may be stylish determined by amount of As in urine samples( WHO, ).

Mechanism of Arsenic exposure

Red Arsenic is that the complex of As and sulfur (As2S2) also referred to as Sandaraca. Another sort
of As is yellow As (As2S3) also known as Auripigment [Konkola, 1992]. As is rarely found in free state
because mostly it exists in trivalent and pentavalent oxidation states or within the state of calcium or
sodium salts [Tchounwou et al., 2012]. Sodium arsenite or arsenic trioxide which is a trivalent type of
As can react with many of biological ligands containing sulfur groups and since of those reactions
arsenicals prevent many enzymes. Pentavalent form of As is known for its uncoupling property of
mitochondrial oxidative phosphorylation [Verity et al., 1995].

Effect of Arsenic exposure

Largest amount of As that's ingested in inorganic form is removed via urine and a little amount of As
may be bio transformed in first stage after methylation of As it is turned into mono methyl arsonic
acid and in second stage it's converted into dimethyl arsinic acid. These processes generally detoxify
the organic As is detoxified by these kind of processes but some organic As metabolites may causes
As toxicity [Bernstam and Nriagu, 2000].

Acute intoxication may happen by the ingestion of big quantities of As causing gastrointestinal
disturbances then it's visiting affect cardiovascular system that may cause toxicity to CNS and
ultimately death may occur. In people who survive, could even be seen suffering from other long
term conditions like melanosis, bone marrow depression, hepatomegaly and encephalopathy. It is
found in a study that peoples having inhalational As exposure generally in smelter and miner
workers shows high rates of lung cancers.

Increased As exposure by drinking water causes mortality rates from lung, kidney and bladder
cancer. High risk of cancer has been related with high As exposure via drinking water. In order to the
latest evaluation performed by WHO, kidney, skin and bladder cancers are caused mainly by drinking
water containing excessive amount of As exposure. (Table 2) [WHO, 2011].

Nikel
Nickel( Ni) is the 24th most abundant element in earth as this metal is indigenous element of 3% of
earth crust. (Clayton and Clayton, 1994; Coogan etal., 1989; Young, 1995). Industrialization in high
scale is the major source of enrichment in environmental contaminants including Ni and their
relative health hazards. Two sources are considered( Anthropogenic and natural release) for high
quantity of Ni in environment and its excessive exposure to human beings with toxicity. Various vital
body functions are consists of Ni. But its high exposure may increase the toxic situations in human
body( Diagomanolin etal., 2004; Haber etal., 2000; Scott- Fordsmand, 1997).

Water and food are two sources of oral exposure that defiled with Ni compounds( Clayton and
Clayton, 1994; Haber etal., 2000). Industrial and commercial applications of this metal are of
numerous kinds. Ni and its alloys is used in chemical and food processing industries as a result of
which Ni is exposed to workers working in that industries( Clarkson etal., 1988). Ni can be emitted
into atmosphere by some natural sources including forest fires, volcanic emissions and windblown
dust. Emission of Ni into air can be happened by Coal combustion and waste incineration.( Buchet
and Lison, 1998; Clarkson etal., 1988; Clayton and Clayton, 1994).

Tobacco smoke is another source of Ni exposure to human. In medical science, dental and
orthopedic implants are source for Ni toxicity in humans. Researchers have found that women are
exposed to Ni by using pristine sword kitchen utensils for long time and by wearing cheap and low
standard jewellery ( Yang and Ren, 2010).

Welding and battery manufacturing company with increased Ni concentration as a result of

occupational exposure may vary extensively from micrograms to milligrams of Ni( Bencko, 1982).
Filtering or corrosion processes are main causes by which Ni present in pipes and holders gets
dissolved in drinking water and beverages. By these processes one may lead to daily oral Ni input of
1mg/ day( Grandjean, a; Grandjean, 1984b). Electroplating, nickel- cadmium alkaline batteries and
electronic equipment are the application of using Ni compound. White gold, sterling silver and
German silver are examples of Ni containing alloys. Because of this excessive use of Ni and its blends
it's being released into atmosphere during manufacturing processes and cause toxicity in humans(
Denkhaus and Salnikow, 2002). Likewise, in industries during welding, cutting and grinding
operations Ni is exposed to workers either by ingestion or by inhalation of Ni or because of skin
contact with Ni( Kasprzak etal., 2003; Seilkop and Oller,).

Mechanism of Nikel exposure

Ni absorption and Inhalational exposure by oral system causes acute toxicity symptoms in human
body. In human body , Ni bounded with thiol promoting to the formation of Ni-Thiol complexes.
When these complexes attached with molecular oxygen it results in free radicals production that
ultimately causes Ni toxicity. And there is an identical reaction of Ni complexes with lipid
hydroperoxides [Das et al., 2006]. Ni combines with a bunch of proteins called sulfhydryl proteins
and cause reduction in glutathione levels of body which causes toxicity of Ni in body [Valko et al.,
2005]. It is found that due to Ni exposure to human body its physiological chemistry is altered due to
decreased excretion of calcium ions via urinary tract and also because of nitrogen retention is
reduced following Ni exposure [US-EPA, 1994].

Oxidative phosphorylation occurring path is damaged because of decreased level of Nicotinamide

followed by chronic Ni exposure [Nielsen, 1982]. Oxidative stress was produced in RBC cells of
humans as a result of Ni exposure [M’Bemba-Meka et al., 2006]. Hematotoxicity is induced by Ni.
(Salnikow et al) conducted a study in rats and mice by inducing inhalational Ni exposure. RBC’s in
blood, packed cell volume (PCV) %, and the concentration of hemoglobin could even be increased by
inhalational Ni exposure. Study found that each one these parameters were increased because of
increased synthesis of erythropoietin and this happened in response to tissue hypoxia produced by
Ni exposure [Denkhaus and Salnikow, 2002; Kasprzak et al., 2003].

Immune system toxicity is also an evident to be caused by Ni metal exposure. Immunotoxic effects
are being induced in humans due to Ni induced damage to immune system. Skin allergy like
dermatitis is thought to be caused by Ni exposure [Moennich et al., 2009]. Mechanism of one kind of
Ni toxicity is creating damage to DNA which occurs as a result of binding of Ni to nuclear proteins
and also because of its binding to DNA [Shen and Zhang, 1994]. Base excision repair property of DNA
property is being interrupted by Ni thus the reason of its toxicity. Repairing of DNA adducts is being
impaired by Ni [Hartwig and Schwerdtle, 2002]. Proto-oncogenes are activated as a result of
enhanced proliferation of cells because of altered expression of genes. and thus the reason behind
this altered expression is carcinogenic metals [Beyersmann and Hartwig, 2008]. Membrane of
placenta is disrupted due to peroxidation of lipids induced by prenatal Ni exposure. Because of this
peroxidation pathway permeability of placenta is elevated and toxic damage is induced in fetus
[Cortijo et al., 2010].

Effect of Nikel exposure

According to the duration health effects of Ni may be classified as exposure of one day to Ni may
named as acute toxic health effects on the other hand 100 days of exposure by a person or more
then the toxic health effects may be considered as chronic effects. The IARC has declared this metal
as a carcinogenic substance to human health on the basis of the studies conducted on workers
exposed to Ni by their occupation( IARC, 1990).

Acute effects are conducted in two stages after Ni inhalational exposure( Table 2). The name of
these stages are immediate and delayed effects. At first only after many hours of Ni accidental
inhalation instant effects including feeling of vomiting, irritation, headache and wakefulness may
appear. also patient may feel an interval of 1- 5 days. Then, the next phase that's delayed symptoms
similar as vertigo, cough, cyanosis, tightness of chest and lassitude may appear( Sunderman Jr etal.,
1975). The injury of kidney and chances of haematuria can be considered as signs of acute toxicity
after Ni exposure( Kasprzak etal., 1980). substantially the cause of chronic Ni toxicity is its exposure
by the service of person particularly for workers of welding industries. substantially respiratory
system disorders similar as pneumoconiosis and asthma are happened by chronic inhalational
exposure( Grandjean, 1984a).

Experimental toxicities were audited in workers exposed to Ni for a long time because of their
occupation.( Chashschin etal., 1994). Lately, products that consist of Ni named as nickel based
nanoparticles has been used considerably in various industries( Zhang etal., 2003). These
nanoparticles show different types of bioactivity and therefore give colorful challenges to health of
human( Maynard and Kuempel,). In the last thirty years, different toxicological test systems have
been used to assess the genotoxicity convinced by Ni( Zhao etal., 2009b). Park et al worked by
comparing the results from trial conducted on alveolar epithelial cells which were exposed to nickel
nanoparticles 100 nm) as well as to titanium oxide which a compound already is known to beget
genotoxicity.
 Two studies were conducted on these cells. Results revealed more damage of alveolar cells ( which
were exposed to nickel nanoparticle as compared to titanium oxide) convinced by apoptosis.
resembling pattern of results were observed for DNA fragmentation in the cells( Park et , 2007).
Experimenters observed that these goods were due to generation of ROS where DNA was observed
to be adhered intointer-nucleosomal fractions( Nagata, 2000). Other nanoparticles which
summarizes that the crucial part player is oxidative stress( Yang etal., 2009).