ARSENIC IN DRINKING WATER IN PAKISTAN AND ASSOCIATED HEALTH RISKS

This paper first reviews the arsenic nature, and its mobilization in environment. Arsenic is a significant element of earth crust and also in a human body. General sources of arsenic are air, food, cigarette smoke and beverages. Being soluble in water it exists in ionic forms and affects the humans who consume arsenic contaminated water. Its effects are severe and long lasting. Pakistan is one of those countries where most of the ground water is contaminated with arsenic. Different organizations such as World Health Organization, International Agency for Research in Oncology & International Agency for Research in Cancer and the United States Environmental Protection Agency has set up the maximum permissible value of arsenic in drinking water for various countries. IARC has ranked arsenic a group 1 human carcinogen which causes lung, bladder and urinary cancers. In Punjab (Pakistan) 20% of population is exposed to over 10  g/L in drinking water and 3% of population is exposed to over 50  g/L and in Sindh 36% of population is exposed to arsenic via drinking water. In Punjab and Sindh drinking water is contaminated with arsenic above the permissible value defined by World Health Organization (WHO), while KPK is less affected. Baluchistan is almost safe


ISSN: 2320-5407
Int. J. Adv. Res. 6(10), 52-60 53 and lung, and it is attributed to cancer of digestive and urinary systems also (Chen;. Humans are exposed to arsenic via inhalation of dust particles and by ingestion through drinking water (Rich et al., 1996).
It is reported that arsenic concentration in well waters ranges from 0.01 to 1.82 mg/1, which is approximately 0.5mg/1 (Pershagen, 1981). It is reported that at some places in Punjab and Sindh province the level of arsenic in drinking water is beyond the acceptable limit defined by World health organization (WHO) which is (10μg/L) (Khattak et al., 2016). Arsenic is exposed to human population via ingestion of arsenic contaminated water, foods, drugs, smoking, it exerts serious and prolonged effects on health (Singh et al., 2006).
Endothelial cell dysfunction, inflammation and angiogenesis are associated with cognitive dysfunction and these are proposed mechanisms which cause Alzheimer's disease (Bryant et al ., 2011). Epidemiological studies are conducted in different areas of the world, which revealed that arsenic exposure influences human health severely it causes cancers of liver, lung, bladder, kidneys and also cause skin cancers include hyperkeratosis and hyper pigmentation and it is also associated with neurological disorders such as amnesia and peripheral neuropathy, diabetes and arteriosclerosis (Raschid-Sally, 2000).

Regional Status of Arsenic Exposure in Pakistan
It is difficult to quantify the people who are subjected to arsenic poisoning especially in those areas where geochemical resources are limited. Estimations are extensive and based on four principles; (1) Frequency of recently documented cases of arsenicosis (2) Probability of ingested concentrations surpassing 50 μ g/L (3) Number of people living in arsenic exposed areas (4) Liable aptitude of region to mitigate/remediate against arsenic contamination (Thakur et al., 2010).

Punjab Province
Most populated province of Pakistan is Punjab where drinking water sources have been reported to contain Arsenic concentration above the safe limit defined by WHO and 20% of population is exposed to Arsenic (

Sindh Province
Epidemiological investigations are conducted in Sindh to expose the severe health effects of arsenic. Their findings revealed that 61-73 % population is exposed to severe and prolonged effects of arsenic on human population residing on the bank of Manchar Lake (Kazi et al., 2009). The general population of 30 to 40 % living in Bobak village near Manchar Lake are exposed to high levels of arsenic, which cause several dermal diseases such as skin lesions and rough skin with black dots (Arain et al., 2009).  Table -4 Health Problems with Arsenic in Drinking Water Arsenic in drinking water is ranked as a known human carcinogen by International Agency for Research of Oncology (IARO) and it cause skin, bladder and lung cancer. (Memon et al., 2014). Most of the human population is exposed to arsenic through ingestion, inhalation and through skin contact. Chronic respiratory diseases are caused by most of the lung carcinogens but few studies revealed that the population exposed to arsenic has non-malignant respiratory effects, but few studies reported high-risk assessment (Ehrenstein et al., 2005). Lung tumors, which are caused by arsenic exposure, show different genetic and epigenetic modifications when compared with the studies on individuals, which were living in arsenic free environment. Only inorganic arsenic is not involved in molecular alterations in arsenic -induced tumors but the product which are produced in arsenic metabolism play major role in such alterations (Hubax et al., 2013). It is estimated that the rate of mortality from lung cancer by consuming arsenic contaminated water is higher than that of lung bladder and kidney cancers including cardiovascular diseases (Smith et al., 2009).
Exposure of Arsine (AsH3) causes anemia due to massive intravascular hemolysis. Changes in sodium and potassium levels act as earliest indicators of erythrocytes impairment (Chabowska et al., 2002). It is reported that arsenic-induced apoptosis is induced as a result of over expression of BCR-ABL gene in human lymphoblast cells. Arsenic as a tumor causing agent and it is selective in inducing apoptosis in promyelocytic leukemia cells. It is studied that arsenic induces modifications in other signaling pathways via apoptosis (Tchounwou et al., 2003). Arsenic was characterized as a first chemical agent, which cause liver disease in humans. Chronic exposures of arsenic over periods of months and years cause accumulation of arsenic in liver and badly affect the hepatic system (Clarkson et al., 1991). Hyperkeratosis, hyper pigmentation and respiratory complications due to ingestion of arsenic in drinking water stimulate changes in hormonal and mucosal immune response (Luqueno et al., 2013).
The chronic arsenic exposure cause skin de pigmentation which results in white spots that looks like rain drops, this condition is medically described as leukomelanosis (Singh and Kumar; 2012). It is estimated that high arsenic exposure via drinking water into young children aged less than 20 years (RR=10.6, 95% CI 2.9-39.2, p<0.001) suffered from liver cancer and become target of mortality (Tantry et al., 2015). When arsenic is present in arsenate and arsenite ionic form these ions replaces the phosphate ions and thiol group in cell and disrupt the normal functioning of cells (Shahid et al., 2015). High levels of arsenic ingested by pregnant women exerts serious effects on reproductive and developmental systems, arsenic can cross the placental barrier and cause miscarriages, low-birth weight deliveries, and neonatal and postnatal mortalities (Lubin et al., 2007). Arsenic may affect internal organs, impair their normal functioning without causing any visible external symptoms, and become difficult to recognize. Hair, nails, urine and blood can be indicators of arsenic exposure before the external appearances (Petrusevski et  al., 2007).Arsenic affects children at higher rates because the symptoms are difficult to recognize at early (Bhatia et  al., 2014).

System Effects Ref Cardiovascular system
Myocardial depolarization and cardiac arrhythmias, hypertension and atherosclerosis.

McCarty et al., 2011
Blood forming System Intravascular hemolysis, Erythrocytes impairment and anemia.

Pakulska et al., 2006
Respiratory system Lung tumors and bronchial epithelial cell malignant transformation.

Wang et al., 2011
Nervous system Polyneuropathy, EEG abnormalities and, in extreme cases, hallucinations, disorientation and agitation.

Khan et al., 2003
Renal system Protein urea, oliguria, mitochondrial damage in tubular cells

Role of Metabolism of Arsenic in its Toxicity
Two main types of reactions take place in Arsenic metabolism: (a) Pentavalent arsenic goes reduction reactions and convert into trivalent arsenic and (b) In oxidation reaction. These trivalent forms of arsenic are successively methylated to form mono, di and trimethylated products by using S-adenosyl methionine which act as methyl donor and glutathione (GSH) act as a co-factor (Pritchard, 2007). After ingestion, transition from blood into tissues arsenate undergoes reduction reaction and reduced to arsenite. In Liver, arsenic undergoes methylation reaction and methylated to form mono-methylated arsenic acid (MMAV), which further reduced to form mono-methyl arsenous 56 acid (MMA III). This is converted into dimethyl-arsenic acid (DMA V) through a series of methylation reactions. In this process of methylation, some reactive oxygen species (ROS) are formed (Lee et al., 2010). Arsenic metabolism is followed by methylation process because methylated arsenic is excreted fast and easily than inorganic arsenic (Rossman, 2003).

Worldwide Extent of Arsenic Problems
The maximum acceptable levels of dissolved arsenic in drinking water are 0.01mg/l and 0.05mg/l according to the World Health Organization and the United States Environmental Protection Agency, respectively. Several countries in the world have identified excess amount arsenic in drinking water including Argentina, Bangladesh, Chile, China, Hungary, India, Japan, Mexico, Mongolia, Poland, Taiwan, and the United States (Khalequzzaman et al., 2005). Most of the countries have found that their waters are contaminated with arsenic due to mining wastes; countries included Korea, Poland and Brazil. It is estimated in 2001 that approximately 130 million people are exposed to arsenic concentrations beyond the 50 μ g L−1 (Halem et al., 2009). In 1988, the EPA documented that continuing ingestion of arsenic 50 μ g /L-1 results in skin cancer rate of 1 in 400 in US, in 1992 EPA assessed that mortality risk of internal cancer is approximately 1.3 in 100 at 50 μ g/L. In 1999, NRC reported that overall cancer mortality risk is approximately 1 in 100 at 50 g/L (Talibi et al). IARC have been classified arsenic as a group 1 human carcinogen and toxic agent which also cause a wide variety of other diseases except cancer and almost every part of internal system of human body is disturbed through arsenic (Naujokas et al.,  2012). Most of the ground and surface water of Pakistan has exceeded the level of heavy metals defined by WHO (Gilani et al., 2013). According to a British Geological Survey study in 1998 on shallow tube-wells in 61 of the 64 districts in Bangladesh, 46% of the samples were above 0.010 mg/L and 27% were above 0.050 mg/L. When combined with the estimated 1999 population, it was estimated that the number of people exposed to arsenic concentrations above 0.05 mg/l is 28-35 million and the number of those exposed to more than 0.01 mg/l is 46-57 million (BGS, 2000). The US EPA suggested that by lowering the arsenic standard from 50 to 10 μ g/L could reduce 57 the mortality rate which is due to skin, lung and bladder cancers and from heart diseases (Kapaj et al., 2006).

Conclusion:-
It is derived that Arsenic is an element, which is hazardous to health mainly in ionic form in water. It influences human health mainly by the consumption of water. There are many countries in the world where drinking water has exceeded the maximum permissible level of arsenic defined by World Health Organization (WHO). Arsenic is a toxicant as well as a potent carcinogen which causes the lungs, urinary and bladder cancers. Pakistan is affected with arsenicism specifically Punjab and Sindh provinces. Drinking water of Lyyah and Faislabad districts of Punjab is badly affected. Ground water of Khairpur and Thatta (Sindh) have maximum concentration of Arsenic. KPK is less affected and Baluchistan has shown no arsenic concentration in experimental water samples.