Heavy metals are toxic agents. They are toxic to humans and animals. Heavy metals which establish toxic actions to humans include; cadmium (Stohs and Bagchi,1995), lead ( Ferner, 2001) and mercury (Hawkes, 1997). Each of these has been studied in isolation for toxicity (Huton and Symon, 1986; Nriagu and Pacyna, 1988; Nriagu, 1989).

1. THE EFFECT OF CALCIUM TAINTED WATER ON CADMIUM INDUCED LIVER
DAMAGE
INTRODUCTION AND LITERATURE REVIEW
Heavy metals are toxic agent. They are toxic to humans and animals. Heavy metals which
establishes toxic actions to humans include; cadmium (Stohs and Bagchi,1995), lead ( Ferner,
2001) and mercury (Hawkes, 1997). Each of these has been studied in isolation for toxicity
(Huton and Symon, 1986; Nriagu and Pacyna, 1988; Nriagu, 1989). But, in the eco-system, be it
air, atmosphere, land, and water where they occur, they do not exist in isolation. They occur in
close association with other metal and non-metallic elemental pollutants. Among the metallic
pollutant could be calcium, copper, zinc, magnesium, manganese, iron and others. Metals are
known to interact with one another. The interaction can bring two elements together in close
proximity or it could cause out right displacement of one another. When ingested together in
food and water, they antagonize each other. When it comes to intestinal and pulmonary
absorption, it is therefore conceivable that the presence of other elements can the toxic potential
of each of the heavy metals that have been studied in isolation.
Eborge (1994) reported that warri river has an unacceptable high cadmium level, 0.3 mg
cadmium per liter of water which was 60 folds above the maximum allowable level of 0.005 mg
per liter. This report prompted our earlier studies on the hepato, nephro and gonadial toxicity of
cadmium. In rats exposed to this high dose via water and diet, the diet was formulated with feed

2. exposed to 0.3 mg cadmium per water. In the ambient water as protein source and the toxic
effect investigated and reported (Asagba and obi 2000; Asagba and Obi 2001; Obi and Ilori
2002; Asagba and Obi 2004a; Asagba and Obi 2004b; Asagba and Obi 2005).The study focus on
cadmium without taking into consideration the fact that other metals were also present in the
river water, and as such were co-consumed by the communities using the river water for cooking
drinking and for other domestic purposes. Hence, it is desirable to know if the presence of other
metals would enhance or diminish the toxic potential of cadmium or indeed if any other heavy
metals such as lead that was mentioned above. Therefore, the aim of the present study was to re-
examine the toxic potential of cadmium in the presence of other metals such as calcium and
magnesium.
The objectives set out to achieve were;
1. Re-examination of toxicity of using established and those for liver toxicity namely; blood alanine
amino transferase and aspartate amino transferase,alkaline phosphatase, bilirubin, albumin and
total protein.
2. Re-examine the status parameter in the absence of cadmium but in the presence of calcium or
magnesium or both.
3. Re-examine this parameters in the presence of cadmium, calcium and magnesium.
1.1 CADMIUM
Cadmium is a chemical element with symbol Cd and atomic number 48. This soft, bluish-white
metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Like
zinc, it prefers oxidation state +2 in most of its compounds and like mercury it shows a low
melting point compared to transition metals. Cadmium and its congeners are not always
considered transition metals, in that they do not have partly filled d or f electron shells in the
elemental or common oxidation states. The average concentration of cadmium in Earth's crust is
between 0.1 and 0.5 parts per million (ppm). It was discovered in 1817 simultaneously by
Stromeyer and Hermann, both in Germany, as an impurity in zinc carbonate. Cadmium occurs as
a minor component in most zinc ores and therefore is a byproduct of zinc production. It was used
for a long time as a pigment and for corrosion-resistant plating on steel, whereas cadmium
compounds were used to stabilize plastic. The use of cadmium is generally decreasing due to its

3. toxicity (it is specifically listed in the European Restriction of Hazardous Substances (Morrow,
2010)) and the replacement of nickel-cadmium batteries with nickel-metal hydride and lithium-
ion batteries. One of its few new uses is in cadmium telluride solar panels. Although cadmium
has no known biological function in higher organisms, a cadmium-dependent carbonic anhydrase
has been found in marine diatoms.
1.1.1 PHYSICAL PROPERTIES
Cadmium is a soft, malleable, ductile, bluish-white divalent metal. It is similar in many respects
to zinc but forms complex compounds (Holleman et al., 1985). Unlike other metals, cadmium is
resistant to corrosion and as a result it is used as a protective layer when deposited on other
metals. As a bulk metal, cadmium is insoluble in water and is not flammable; however, in its
powdered form it may burn and release toxic fumes (CSEM, 2011).
1.1.2 CHEMICAL PROPERTIES
Although cadmium usually has an oxidation state of +2, it also exists in the +1 state. Cadmium
and its congeners are not always considered transition metals, in that they do not have partly
filled d or f electron shells in the elemental or common oxidation states (Cotton, 1999).
Cadmium burns in air to form brown amorphous cadmium oxide (CdO); the crystalline form of
this compound is a dark red which changes color when heated, similar to zinc oxide.
Hydrochloric acid, sulfuric acid and nitric acid dissolve cadmium by forming cadmium chloride
(CdCl2), cadmium sulfate (CdSO4), or cadmium nitrate (Cd(NO3)2). The oxidation state +1 can
be reached by dissolving cadmium in a mixture of cadmium chloride and aluminum chloride,
forming the Cd2
2+ cation, which is similar to the Hg2
2+ cation in mercury(I) chloride (Holleman
et al., 1985).
Cd + CdCl2 + 2 AlCl3 → Cd2(AlCl4)2
The structures of many cadmium complexes with nucleobases, amino acids and vitamins have
been determined (Carballo et al., 2013).
1.1.3 OCCURRENCE

4. Cadmium metal
Cadmium makes up about 0.1 ppm of Earth's crust. Compared with the more abundant 65 ppm
zinc, cadmium is rare (Wedepohl, 1995). No significant deposits of cadmium-containing ores are
known. Greenockite (CdS), the only cadmium mineral of importance, is nearly always associated
with sphalerite (ZnS). This association is caused by the geochemical similarity between zinc and
cadmium which makes geological separation unlikely. As a consequence, cadmium is produced
mainly as a byproduct from mining, smelting, and refining sulfidic ores of zinc, and to a lesser
degree, lead and copper. Small amounts of cadmium, about 10% of consumption, are produced
from secondary sources, mainly from dust generated by recycling iron and steel scrap.
Production in the United States began in 1907, (Ayres et al., 2003) but it was not until after
World War I that cadmium came into wide use (Plachy, 1998). One place where metallic
cadmium can be found is the Vilyuy River basin in Siberia (Fthenakis, 2004).
Rocks mined to produce phosphate fertilizers contain varying amounts of cadmium, leading to a
cadmium concentration of up to 300 mg/kg in the produced phosphate fertilizers and thus in the
high cadmium content in agricultural soils (Grant and Shepperd , 2008). Coal can contain
significant amounts of cadmium, which ends up mostly in the flue dust (Bettinelli et al., 1988).
1.1.4 BIOLOGICAL ROLE
Cadmium has no known useful role in higher organisms, (Hogan, 2010) but a cadmium-
dependent carbonic anhydrase has been found in some marine diatoms (Lane et al., 2005). The
diatoms live in environments with very low zinc concentrations and cadmium performs the
function normally carried out by zinc in other anhydrases. The discovery was made using X-ray
absorption fluorescence spectroscopy (XAFS) (Lane et al., 2000).
The highest concentration of cadmium has been found to be absorbed in the kidneys of humans,
and up to about 30 mg of cadmium is commonly inhaled throughout childhood and adolescence
(Perry et al., 1976). Cadmium can be used to block calcium channels in chicken neurons

5. (Swandulla and Armstrong, 1989). Analytical methods for the determination of cadmium in
biological samples have been reviewed (klorz et al., 2013).
1.1.5 ENVIRONMENT
The biogeochemistry of cadmium and its release to the environment has been the subject of
review, as has the speciation of cadmium in the environment (Cullen et al., 2013).
1.1.6 CADMIUM POISONING
The bioinorganic aspects of cadmium toxicity have been reviewed (Maret et al., 2013).The most
dangerous form of occupational exposure to cadmium is inhalation of fine dust and fumes, or
ingestion of highly soluble cadmium compounds. Inhalation of cadmium-containing fumes can
result initially in metal fume fever but may progress to chemical pneumonitis, pulmonary edema,
and death (Hayes, 2007). Cadmium is also an environmental hazard. Human exposures to
environmental cadmium are primarily the result of fossil fuel combustion, phosphate fertilizers,
natural sources, iron and steel production, cement production and related activities, nonferrous
metals production, and municipal solid waste incineration. Bread, root crops, and vegetables
also contribute to the cadmium in modern populations (Mann, 2012). There have been a few
instances of general population toxicity as the result of long-term exposure to cadmium in
contaminated food and water, and research is ongoing regarding the estrogen mimicry that may
induce breast cancer (Mann, 2012). In the decades leading up to World War II, mining
operations contaminated the Jinzū River in Japan with cadmium and traces of other toxic metals.
As a consequence, cadmium accumulated in the rice crops growing along the riverbanks
downstream of the mines. Some members of the local agricultural communities consuming the
contaminated rice developed itai-itai disease and renal abnormalities, including proteinuria and
glucosuria (Nogawa et al., 2004).
Jinzū River area, which was contaminated with cadmium
The victims of this poisoning were almost exclusively post-menopausal women with low iron
and other mineral body stores. Similar general population cadmium exposures in other parts of
the world have not resulted in the same health problems because the populations maintained

6. sufficient iron and other mineral levels. Thus, although cadmium is a major factor in the itai-itai
disease in Japan, most researchers have concluded that it was one of several factors. Cadmium is
one of six substances banned by the European Union's Restriction on Hazardous Substances
(RoHS) directive, which bans certain hazardous substances in electrical and electronic equipment
but allows for certain exemptions and exclusions from the scope of the law. The International
Agency for Research on Cancer has classified cadmium and cadmium compounds as
carcinogenic to humans. Although occupational exposure to cadmium is linked to lung and
prostate cancer, there is still a substantial controversy about the carcinogenicity of cadmium in
low, environmental exposure. Recent data from epidemiological studies suggest that intake of
cadmium through diet associates to higher risk of endometrial, breast and prostate cancer as well
as to osteoporosis in humans (Julin et al., 2012). A recent study has demonstrated that
endometrial tissue is characterized by higher levels of cadmium in current and former smoking
females (Rzymski et al., 2014). Although some epidemiological studies show a significant
correlation between cadmium exposure and occurrence of disease conditions in human
populations, a causative role for cadmium as the factor behind these effects remains yet to be
shown. In order to prove a causative role, it will be important to define the molecular
mechanisms through which cadmium in low exposure can cause adverse health effects. One
hypothesis is that cadmium works as an endocrine disruptor because some experimental studies
have shown that it can interact with different hormonal signaling pathways. For example,
cadmium can bind to the estrogen receptor alpha, (Fechner et al., 2011) and affect signal
transduction along the estrogen and MAPK signaling pathways at low doses (Ali et al., 2010).
Tobacco smoking is the most important single source of cadmium exposure in the general
population. It has been estimated that about 10% of the cadmium content of a cigarette is inhaled
through smoking. The absorption of cadmium from the lungs is much more effective than that
from the gut, and as much as 50% of the cadmium inhaled via cigarette smoke may be absorbed
(Friberg, 1983). On average, smokers have 4–5 times higher blood cadmium concentrations and
2–3 times higher kidney cadmium concentrations than non-smokers. Despite the high cadmium
content in cigarette smoke, there seems to be little exposure to cadmium from passive smoking.
No significant effect on blood cadmium concentrations has been detected in children exposed to
environmental tobacco smoke. In the non-smoking part of the population food is the biggest

7. source of exposure to cadmium. High quantities of cadmium can be found for example in
crustaceans, molluscs, offals, and algal products. However, due to the higher consumption the
most significant contributors to the dietary cadmium exposure are grains, vegetables, and starchy
roots and tubers. Cadmium exposure is a risk factor associated with early atherosclerosis and
hypertension, which can both lead to cardiovascular disease (Jarup, 1998).
EDITOR SOURCE: The Effect Of Calcium Tainted Water On Cadmium Induced Liver Damage