Health Risks of Potentially Toxic Metals Contaminated Water

Groundwater which fulfills globally 50–80% need of drinking water, due to Anthropogenic and geologic activities, has been continuously contaminated by potentially toxic metals, causing a range of effects to animals and citizenry. In the developing countries, about 80% of diseases are waterborne diseases. Bio accumulation of these metals in citizenry due to intake of contaminated vegetables, fruits, fishes, seafood and drinking water and beverages causes a serious threat to citizenry. Toxicity of these metals is due to metabolic interference and mutagenesis, interference in the normal functioning of structural proteins, enzymes, and nucleic acids by binding them, adversely affecting the immune and hematopoietic systems in citizenry and animals. The toxic metals also enrich antibiotic resistant microbes particularly bacteria by Co-selection (occurring by Co-resistance and cross-resistance) as it promotes antibiotic resistance in bacteria even in absence of antibiotics. These metals in living cells cause cytotoxicity, oxidative stress resulting in the damages of antioxidants, enzyme inhibition, loss of DNA repair mechanism, protein dysfunction and damage to lipid per oxidase. Endocrine disruption, neuro-developmental toxicity, biosynthesis of hemoglobin, metabolism of vitamin D, renal toxicity, damage to central nervous system, hearing speech and visual disorders, hypertension, anemia, dementia, hematemesis, bladder, lung, nose, larynx, prostate cancer, and bone diseases are some other health’s risks to human.


Introduction
Water the "life-blood of the biosphere" may be an alcahest which dissolves different chemicals and environmental pollutants. Globally, groundwater is the main source of domestic drinking water both in rural and urban areas and fulfills approximately 80% need of drinking water in the rural areas and 50% of urban water need. As surface water infiltrates to unconfined aquifers easily, these aquifers are contaminated very easily. The pollution of groundwater causes significant alteration in the environment. The most sources of lakes, rivers, ponds, and streams are the groundwater. When contaminated groundwater is supplied to those sources, the surface water is additionally contaminated which causes harm to birds, animals, and plants. Because of population growth over the last 50 years, the abstraction of groundwater has increased leading to reduce natural discharge flows and groundwater quality. Groundwater quality is additionally suffering from recharge rate and recharge quality. Existence of human on earth without potentially toxic metals is not possible.

Sources of potentially toxic element contaminants within the water
Contamination of the environment by potentially toxic metals has increased after war II because of rapid industrialization and urbanization and increased rate of mobilization and transport [7]. The main sources of groundwater of contamination by heavy metals are:

Natural
Rock weathering, forest fires, volcanic eruptions, biogenic sources, and wind born soil particles are the natural sources of potentially toxic metals within the environment. Within the rocks, these metals are present as hydroxides, sulphides, oxides, silicates, phosphates, and chelated with organic compounds.

Anthropogenic activities
Industrial manufacturing of products to satisfy with the stress of the massive population like to cement production, iron industry, steam power plants, glass production, paint, and tanning industries is one among the causes of environmental pollution because of human activities. Agricultural activities (use of sewage sludge as manure), irrigation by sewage wastewater, mining, and metallurgical processes, garbage and waste mud incineration facilities, combustion of fuels, surface emission, and traffic and runoffs are other ways to release the pollutants within the different environmental compartments. The main route of the groundwater and aquatic contamination by potentially toxic metals are the leaching from toxic industrial waste dumps and municipal landfills and leaching of agricultural chemicals from soils into the upper aquifers [8].
As the concentration of potentially toxic metals within the environment is continuously increasing, and therefore, the soil retention capacity of those metals is decreasing and the resultant is the leaching of those metals within the groundwater [9]. Fertilizers and pesticides applied within the fields contain these potentially toxic metals (Cr, Cd, Cu, Zn, Ni, Mn, Pb, and As) as impurities [7]. Another source of groundwater contamination by potentially toxic metals is the urban runoffs which contain Pb, Cu, Zn, Fe, Cd, Cr, and Ni. The intrusion of seawater in aquifers also causes a rise in concentration levels of potentially toxic metals in the groundwater. Another anthropogenic source of the heavy metals in the environment is the burning of wastes at residential levels and dumpsites.

Potentially toxic metals within the drinking, ground, and surface water
A review of the literature showed that globally number of groundwater, drinking water, and surface water samples contains the potentially toxic metals beyond their permissible limit which affects adversely the human and ecological health. The arsenic concentration in the groundwater samples ranged from 0.0005 to 1.15 mg/L [14-16]. Author himself [17, 18] studied the concentration of potentially toxic metals in the groundwater samples for 20 years (1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) and found that (i) concentration of those metals are increasing with time, (ii) concentration of those metals decreased with depth, and (iii) the concentration became beyond the permissible limit after the year 2000. The concentration of the toxic metals in the groundwater, drinking water, and surface water samples are recorded in Table 1.

Potentially toxic metals within the sediments
The accumulated amounts of the potentially toxic metals in the sediments are reported in Table 1.

Bioaccumulation of probably toxic metals in vegetables and fruits irrigated by contaminated ground and surface water
A long-term study made by the author himself [17,18] found that the concentration of potentially toxic metals in the soils of agricultural fields of Aligarh irrigated by sewage effluent is continuously increasing, and therefore, the concentration of those metals in edible parts of the crops grown such soils were beyond toxic limits, and maximum accumulation was within the potato followed by maize [53]. Bansal [53] during their studies on the concentrations of Pb, Cd, Ni, Cr, Zn, and Cu in the vegetables palak, cabbage, brinjal, lady's finger, tomato, bitter gourd, radish, and cauliflower grown in the soils of periurban areas of Aligarh irrigated by sewage effluent water found that the concentration of the metals Cd, Pb, and Ni in all the studied vegetables were beyond their permissible limits for human consumption. The Target Hazard Quotient (THQ) values also denote that consumption of those vegetables will cause a potential risk for human health risk. Kabir and Bhuyan [54] found that the concentration of Cu in the hen's egg yolk (1.85-3.65 mg/kg) and albumin (0.5-1.15 mg/kg) were beyond permissible limits. The concentrations of these metals in the vegetables grown globally are given in Table 1.

Bioaccumulation of potentially toxic metals in freshwater fish, marine fish aqueous flora and fauna
Bioaccumulation of the potentially toxic heavy metals within the ecosystem of the Riverine has a negative impact on the ecological health of aquatic animals and causes decrease in their populations [55,56]. Several researchers have reported fish deformities, decline of fish populations, and reduce in their growth rates if the concentration of potentially toxic metals increased beyond their tolerable limit [57,58]. The concentrations of those metals in freshwater fish are reported in Table 2. The info in Table 3 denotes the concentration of those metals in marine fish and other organisms.    2.1-8.7 Table 3.

Sample
The concentration of different potentially toxic metals in different tissues of marine organisms.

Potentially toxic metals-resistance
The potentially toxic metals (Cd, Cu, Pb, Zn, Cr (III), Cr (VI), and Hg) aren't only toxic to human health but also enrich antibiotic resistant microbes particularly bacteria. Co-selection of an antibiotic and metal resistance in bacteria is extremely important because it promotes antibiotic resistance in bacteria even in the absence of antibiotics. Co-selection occurs by two mechanisms: i. Co-resistance: when antibiotics and these metals co-exist within the same environment, these metals influence some antibiotic resistant bacteria to survive in more polluted environment. Co-resistance occurs when two or more different resistant genes are present on the same genetic elements (plasmid, transposon, Integron) or are present within the same bacterial strain which provides resistant to different compounds. The rise of antibiotic resistant genes is directly correlated with the concentration of those metals [87].
ii. Cross-resistance: cross resistance occurs when antibiotics and potentially toxic metals target the same microbes leading to generic detoxification of genes by reducing intracellular concentration of antibiotics and metals, and enhanced efflux occurs during cross-resistance [87].
Besides these two mechanisms, co-selection is additionally promoted by coregulatory mechanism which occurs when different resistant genes is controlled by one regulator gene [88]. The impact of the potentially toxic metals on the antibiotic resistant bacterial strain is a given in Table 4.

Toxicity of potentially toxic metals
World Health Organization has reported that globally in the year 2015 approximately 8.8 million deaths were due to cancer, presence of potentially toxic metals beyond permissible limits within the environment is one among the main factors of the death because the endocrine system is disrupted by these metals. When the food or drinking water containing potentially toxic metals beyond their maximum tolerance concentration is ingested, the metabolism of living cells in the body is negatively affected [122]. The immune and hematopoietic systems in human and animals also are adversely affected on exposure to the mixtures of those metals [122]. Li et al. [123] reported that the main cause for human bone diseases is the presence of the potentially toxic metals beyond their permissible limit within the aquatic environment. Potentially toxic metals Pb, Hg, Cd, As, and Cr in living cells causes cytotoxicity [124] and oxidative stress [124], leading to the damages of antioxidants, enzyme inhibition, apoptosis (programmed cell death), loss of DNA repair mechanism, protein dysfunction, and damage to lipid peroxidase and of the membrane.

Cadmium
Cadmium in human causes Itai-Itai disease, liver/kidney lesions, hepato-colic effects [125], carcinoma, prostatic adenocarcinoma, osteoporosis, hypertension, disorder, and kidney lesions including enlargement, nuclear, and mitochondrial damages, and histological changes; decreased antioxidant power of kidney also Resistance mechanism is due to adsorption of lead by extracellular polysaccharides, cell exclusion and ion efflux to the cell exterior.

P. aeruginosa [115]
Tetracycline Shigella spp. [116] Ni Ni replaces the essential metals from metalloprotein. The activity of the enzymes is retarded as Ni binds the catalytic site of the enzyme. Ni causes oxidative stress which results in the enhanced DNA damage, protein impairment, and lipid peroxidation.
The resistance mechanism is due to energy-dependent Ni efflux pump induced by cnr which is promoted by a chemo-osmotic proton-antiporter system.
Activation of efflux pumps due to cross resistance between arsenic and antibiotics is the main mechanism Penicillin E. coli [107] Sulfonamide Salmonella spp. [117] Tetracycline E. coli [118] Amphenicol Salmonella spp. [119] Co Produces non B 12 cobalt protein.
The gene Czc, affects the inner and outer membranes and removes the cobalt from the cytoplasm Aminoglycoside Citrobacter spp. [106] Macrolide Enterobacter spp. [120] Penicillin Salmonella spp. [102] Quinolone E. coli [111] Sulfamethoxazole P. aeruginosa [121] Vancomycin Enterobacter spp.; Klebsiella spp. [106]  disrupts mineral balance within the body, causing dysfunctions of sexual glands and skeltel diseases. A psychomotor function of the brain is bogged down in the presence of Cd. The toxicity of cadmium to cell is because Cd can displace vitamin C and E from their metabolically active sites, decrease in absorption of calcium by intestine and enhanced dissolution of bone calcium causing disorder in the normal bone metabolism processes. Cd an endocrine disrupter causes neuro-developmental toxicity. Toxicity of Cd in fishes includes immune suppression and immune dysfunction.

Lead
Out of about four million tons of lead used per annum globally about three million tons is discharged within the environment. In the physical body, 90-95% of the intruding lead is accumulated within the bones which combine with bone minerals and organic matter causes rise in the blood lead level. Accumulation of lead within the bones affects the acid-base equilibrium causing calcium deficiency. Pb within the body lowers the active vitamin D 3 level and parathyroid level within the plasma affecting somatic cell function viz., decrease in the secretion of γcarboxyglutamic acid containing protein. Clinical studies have shown that if the extent of Pb in the drinking water is 50 μg/L, the blood lead level within the human is going to be about 30 μg/L; if the extent increased further, the lead level within the breast fed babies are enhanced causing hindrance within the bone development. If the blood lead level in children exceeds 75 μg/L, it causes coma, convulsions, and eventually death. Pb also affects central systema nervosum, renal, cardiovascular, neurological, and musculoskeletal systems. Pb influences the heme synthesizing enzymes by replacing Zn within the heme synthesis. Lead disrupts biosynthesis of hemoglobin, metabolism of Fe, Zn, and Cu, and of vitamin D within the body, and also causes cognitive impairment. Pb in physical body also acts as nephrotoxicants. Lead in fish's body also affects immune system [122]. Long-term exposure to the low concentration of a mix of Cd, As, and Pb in human and other animal cause hepatotoxic (damage to the liver) effects [123].

Chromium
The annual output of Cr globally is approximately 7.5 million tons. The secretion of Collagen-Type I which helps in the bone fracture healing is suppressed in the presence of chromium ion. Chromium in human causes nose ulcers, asthma, DNA damage, hemolysis, damage to liver, kidney, and carcinoma.

Arsenic
Smith et al. [126] after their research studies reported that if the person get 50 μg/L of arsenic (daily) then 13 out of 1000 individuals will suffer with lung, liver, kidney or bladder cancer. Skin lesions are by the uptake of 0.0012 mg/kg/day of arsenic. Bhattacharya et al. [125] found that low concentration of arsenic for long period damages liver in human and other animals. Enlargement of kidney, nuclear, and mitochondrial damages, histological changes, and decreased antioxidant power of kidney is additionally caused by arsenic in human. Arsenic also causes neurotoxic effects in human with the assembly of the reactive oxygen species which incorporates death of neuronal cells, cognitive dysfunction, and Alzheimer's disease. Cognitive impairment, deafness, hypertension, anemia dementia, hematemesis, and bladder cancer also is caused by As. The prolonged exposure to arsenic also affects central systema nervosum.

Mercury
Mercury is the third top hazardous substance. Aquatic organisms convert inorganic mercury to methyl mercury which inactivates Na+/K+ ATPase. Hg with the production of reactive oxygen causes neurotoxic effects in human including death of neuronal cells, cognitive dysfunction, and Alzheimer's disease. As Hg is an endocrine disrupter, during pregnancy exposure to metal causes long-term damages to new born as mercury disrupts the influences the maternal-fetal balance. Minamata disease, renal toxicity, skin, nose irritation, damage to central systema nervosum, hearing speech, and visual disorders are another health risks to human.

Copper
Copper an integral part of several enzymes in small amount (0.9 mg daily uptake) is an essential metal for animals and plants. Deficiency of copper in human causes anemia, a low number of leucocytes, defects in animal tissue, and osteoporosis in infants. The copper within the body beyond its permissible limit causes hematemesis, jaundice, melena, damage to central nervous system, liver, and kidney problems. Wilson's disease a genetic disease is additionally caused by copper.

Nickel
Nickel, a natural occurring metal, exists in a number of mineral forms and is an ingredient of chocolate, steel, and other metal products, pigments, valves and of batteries. Excess uptake of nickel by human causes asthma, pneumonia, allergies, heart disorder, skin rashes, and miscarriage. Chances of development of carcinoma, nose cancer, larynx cancer, and prostatic adenocarcinoma also are enhanced.

Cobalt
Cobalt is an essential metal for the life as it is the integral part of vitamin B 12 (cobalamin). Human when exposed to the higher concentration of cobalt causes decreased pulmonary function, asthma, interstitial lung disease, wheezing, and dyspnoea and reduces pulmonary function. Respiratory tract hyperplasia, pulmonary fibrosis, increase in number of red blood cells, emphysema, paralysis of the systema nervosum, seizures, growth retardation, and thyroid deficiency are diseases occurs in human at a really high concentration of the metal.

Zinc
As zinc plays a crucial role in number of metallo enzymes viz., dehydrogenase, alkaline phosphatase, carbonic anhydrase, leucine amino peptidase, superoxide dismutase, and deoxyribosenucleic acid (DNA) and ribosenucleic acid (RNA) polymerase is an essential metal in humans and animals. Over exposures to zinc in human causes dry or pharyngitis, chest tightness, headache, increased indices of pulmonary inflammation, nausea, decrease in the activity of copper metallo enzyme, decreased HDL-cholesterol level, immuno toxicity, and gastrointestinal effects.

Conclusions
• Contamination of ground and surface water by potentially toxic metals is a worldwide problem.
• The major route of the groundwater and aquatic contamination by potentially toxic metals are the leaching from toxic industrial waste dumps, municipal landfills, and leaching of agricultural chemicals from soils into the upper aquifers.
• Potentially toxic metals contaminated vegetables and fruits; fishes, seafood, and drinking water are the most sources of the ingestion of those metals by the citizenry.
• A number of biological and biochemical processes are disrupted in the physical body by accumulation of those metals. These metals also cause developmental abnormalities in the children.
• These potentially toxic metals promote the spread of antibiotic resistant genes which causes the ineffectiveness of broad-spectrum antibiotics.

Declaration
No original data is utilized in this review; all information is accessed from published work.