EFFECTS AND CONTROL OF ENVIRONMENTAL POLLUTION FROM HEAVY METALS

KADUNA STATE UNIVERSITY, (KASU). DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE. A SEMINAR RESEARCH ON “EFFECTS AND CONTROL OF ENVIRONMENTAL POLLUTION FROM HEAVY METALS” BY SULEIMAN MUHAMMAD KASU/13/CHM/1044 ABSTRACT Heavy metals are naturally occurring elements that have a high atomic weight and a density at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the U.S. Environmental Protection Agency, and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potentials for human exposure, and molecular mechanisms of toxicity, carcinogenicity. CHAPTER ONE Introduction Pollution is the introduction of contaminants into the natural environment that cause adverse change. Pollution can take the form of chemical substances or energy, such as noise, heat or light. The components of pollution can be either foreign substances/energies or naturally occurring contaminants (reference). Pollution can be classified according to the part of environment affected, which are soil, air and water. Pollution may also be classified depending on the type of pollutants, for example heavy metal pollution where the pollutants are mainly heavy metals, where the pollutants are volatile organic compound it is known as volatile organic compound pollution (Ubwa et al., 2013). Discuss more on pollution TYPES OF POLLUTION 1.5 Air Pollution Air pollution is a type of environmental pollution in which the part of environment polluted is the air. Air pollution is the accumulation in the atmosphere of substances that, in sufficient concentrations, endanger human health or produce other measured effects on living matter and other materials. Air pollution is caused by emission of particulate matter and gases such as methane (CH4), sulfurdioxide (SO2) and oxides of nitrogen (NO)x as well as carbon monoxide (CO). Mining operations like drilling, blasting, hauling, collection and transportation are the major sources of air pollution (Oladoye and Adewuyi, 2014). Talk more 1.6 Water Pollution Water pollution is the introduction of chemical, biological and physical material into fresh or ocean that degrades the quality of the water and affects the organisms living in it. This process ranges from simple addition of dissolved or suspended solids to discharge of the most insidious and persistent toxic pollutants (such as pesticides, heavy metals, and nondegradable, bioaccumulative, chemical compounds (Ameh et al., 2014). Water pollution in coal mines occurs due to the coal content or impurities, rate of extraction, mining method, inflow rate of water and the amount of water used in mine. Once the mining activity begin, the hydrology of the area changes due to the addition of dissolved and suspended particles. The extent of water pollution is primarily due to the composition of ore deposits, structural features of the area and its surrounding and also the climate of the mining regions. It also depend on how the water enters into the mine and how it interacts with the rocks and ore in which way it is utilized in mining processes and the way it is pumped out of mines (Mahboob et al., 2014). 1.7 Soil Pollution Soil pollution is the degradation of the Earth's land surface through misuse of the soil by poor agricultural practice, mineral exploitation, industrial waste dumping, and indiscriminate disposal of urban wastes. It includes visible waste and litter as well as pollution of the soil itself (Kiran et al., 2012). Presence of heavy metals in soils has considerable impact on the environment causing severe damages thereby restricting soil use. Soil pollution caused by mining and mineral processes usually accumulate huge amount of heavy metals in waste dumps. Mining activity represent a high area of activity thus constituting a great hazard due to the presence of heavy metals related to functioning or abandoned mines (Marta et al, 2012). Discuss more Environmental Pollution Environmental pollution is the introduction of pollutants into the environment, which are generated through natural and anthropogenic activities that causes acute (short term) or chronic (long term) effects in living organisms (Bingol et al., 2010). Environmental pollution is the introduction of harmful substances into the environment which has many adverse effects on human health, agricultural productivity and natural ecosystem (Osuocha et al, 2013). Discuss more 1.4 Source of Environmental Pollution Environmental pollution caused by human activities such as industrial effluent discharge, vehicular emissions, waste incineration and mining operations have been the major sources of environmental pollution. Rapid growth of industries, population and transportation systems contribute to the increasing pollution levels. It is also known that mining, smelting and quarrying activities have created local environmental effects, these effects ranges from acute to chronic intoxications of living organisms that are exposed to the polluted environment (Ubwa et al., 2013). HEAVY METALS Heavy metals are naturally occurring elements that have a high atomic weight and a density at least 5 times greater than that of water, examples of heavy metals are Mercury (Hg), Cadmium (Cd), Arsenic (As), Chromium (Cr), Thallium (Tl), and Lead (Pb). Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment [2]. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals, due to their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health concern (reference). These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens according to the U.S. Environmental Protection Agency, and the International Agency for Research on Cancer (reference). Although heavy metals are naturally occurring elements that are found throughout the earth’s crust, most environmental contamination and human exposure result from anthropogenic activities such as mining and smelting operations, industrial production and use, and domestic and agricultural use of metals and metal-containing compounds [4–7]. Environmental contamination can also occur through metal corrosion, atmospheric deposition, soil erosion of metal ions and leaching of heavy metals, sediment re-suspension and metal evaporation from water resources to soil and ground water [8]. Heavy Metal Toxicity Heavy metal toxicity is the degree to which heavy metals can harm or affect humans or animals. Acute toxicity involves harmful effects through short-term exposure while chronic toxicity involves harmful effects over an extended period of time (Garba et al., 2013). Once heavy metals are ingested, numerous health problems occur. For example, Lead causes learning disabilities, impaired protein and haemoglobin synthesis and shorten the lifespan of red blood cells which leads to severe anaemia. Cadmium causes renal failure, accumulation in the bone which causes calcium loss and malfunctioning of peripheral and central nervous systems. Zinc causes slow growth in children, reduced fertility, headache and nausea (Mohammad et al., 2011). Arsenic toxicity causes diabetes, skin and bladder cancer (Roberge et al., 2009). Chromium toxicity is associated with allergies, skin irritation, perforation of the ear drum and respiratory track disorders (Silvia et al., 2013).Most accumulation of toxic metals is due to the ambient concentration of these metals through inhalation of dust and fumes ingestion of foods and drinks or absorption through the skin in most cases. However, most classical toxicities associated with metals have come through massive pollution of the environment through industrial activities (Tobias et al., 2013). 1.10 Sources of Heavy Metals. There are two main sources of heavy metals in the environment. These sources are natural or anthropogenic sources. Natural Sources: This is due to natural phenomenon such as weathering of rocks, volcanic activities, earth quake, forest fire and ocean sprays. The natural phenomenon releases heavy metals and other organic pollutants into the environment (Kennish, 1992). Anthropogenic Sources: This is due to human activities such as metal processing in refineries, domestic wastewater effluent, agricultural waste, transportation and combustion of fossil fuel and industrial sources include petroleum combustion, nuclear power stations and high tension lines, plastics, textiles, microelectronics, wood preservation and paper processing plants [9–11].. These activities release heavy metals and other pollutants which settle in the environment (Moore et al., 2011). CHAPTER TWO Heavy metals are generally defined as metals with relatively high densities, atomic weights, or atomic numbers. In metallurgy, for example, a heavy metal may be defined on the basis of density, whereas in physics the distinguishing criterion might be atomic number, while a chemist would likely be more concerned with chemical behaviour (reference). The earliest known metals—common metals such as iron, copper, and tin, and precious metals such as silver, gold, and platinum—are heavy metals. From 1809 onwards, light metals, such as magnesium, aluminium, and titanium, were discovered, as well as less well-known heavy metals including gallium, thallium, and hafnium (reference). Heavy metals are either essential nutrients (typically iron, cobalt, and zinc), or relatively harmless (such as ruthenium, silver, and indium), but can be toxic in larger amounts or certain forms. Other heavy metals, such as cadmium, mercury, and lead, are highly poisonous. Potential sources of heavy metal poisoning include mining and industrial wastes, agricultural runoff, occupational exposure, and paints and treated timber. (Reference) Physical and chemical characterizations of heavy metals need to be treated with caution, as the metals involved are not always consistently defined. As well as being relatively dense, heavy metals tend to be less reactive than lighter metals and have much less soluble sulfides and hydroxides (Reference). While it is relatively easy to distinguish a heavy metal such as tungsten from a lighter metal such as sodium, a few heavy metals such as zinc, mercury, and lead have some of the characteristics of lighter metals, and lighter metals such as beryllium, scandium, and titanium have some of the characteristics of heavier metals (reference). Heavy metal pollution is an inorganic chemical hazard, which is mainly caused by lead (Pb), chromium (Cr), arsenic (As), cadmium (Cd), mercury (Hg), zinc (Zn), copper (Cu), cobalt (Co), and nickel (Ni) [1]. Five metals among them, Pb, Cr, As, Cd, and Hg, are the key heavy metal pollutants. These heavy metals are classified as strong carcinogens by the International Agency for Research on Cancer [2]. High level of heavy metal exposure can also cause permanent intellectual and developmental disabilities, including reading and learning disabilities, behavioural problems, hearing loss, attention problems, and disruption in the development of visual and motor function [2]. Among various types of pollution, heavy metal pollution is a crucial environmental problem. Some traditional pollutants, such as sulfur dioxide and carbon dioxide, have been put under control, but heavy metal pollution, which poses even greater risks to public health, is yet to gain policy makers’ attention (reference). Effects of heavy metals contaminations The effects of heavy metal-induced toxicity and carcinogenicity involve many mechanistic aspects, some of which are not clearly elucidated or understood (reference). However, each heavy metal is known to have unique features and physio-chemical properties that confer to its specific toxicological mechanisms of action (reference). This review provides an analysis of the environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, and carcinogenicity of arsenic, cadmium, chromium, lead, and mercury. Arsenic Environmental Occurrence, Industrial Production and Use Arsenic (As) is a ubiquitous (widespread or very prevalent) element that is detected at low concentrations in virtually all environmental matrices [33]. The major inorganic forms of arsenic include the trivalent arsenite and the pentavalent arsenate. The organic forms are the methylated metabolites – monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and trimethylarsine oxide. Environmental pollution by arsenic occurs as a result of natural phenomena such as volcanic eruptions and soil erosion, and anthropogenic activities [33]. Several arsenic-containing compounds are produced industrially, and have been used to manufacture products with agricultural applications such as insecticides, herbicides, fungicides, algaecides, sheep dips, wood preservatives, and dye-stuffs. They have also been used in veterinary medicine for the eradication of tapeworms in sheep and cattle [34]. Arsenic compounds have also been used in the medical field for at least a century in the treatment of syphilis, yaws, amoebic dysentery, and trypanosomaiasis [34,35]. Arsenic-based drugs are still used in treating certain tropical diseases such as African sleeping sickness and amoebic dysentery, and in veterinary medicine to treat parasitic diseases, including filariasis in dogs and black head in turkeys and chickens [35]. Recently, arsenic trioxide has been approved by the Food and Drug Administration as an anticancer agent in the treatment of acute promeylocytic leukemia [36], its therapeutic action has been attributed to the induction of programmed cell death (apoptosis) in leukemia cells [24]. Arsenic Potential for Human Exposure It is estimated that several million people are exposed to arsenic chronically throughout the world, especially in countries like Bangladesh, India, Chile, Uruguay, Mexico, Taiwan, where the ground water is contaminated with high concentrations of arsenic (reference). Exposure to arsenic occurs through oral route (ingestion), inhalation, dermal contact, and the parenteral route to some extent [33,34,37]. Arsenic concentrations in air range from 1 to 3 ng/m3 in remote locations (away from human releases), and from 20 to 100 ng/m3 in cities, in water the concentration is usually less than 10µg/L, although higher levels can occur near natural mineral deposits or mining sites while arsenic concentration in various foods ranges from 20 to 140 ng/kg [38]. Natural levels of arsenic in soil usually range from 1 to 40 mg/kg, but pesticide application or waste disposal can produce much higher values [25]. Mechanisms of Arsenic Toxicity and Carcinogenicity Analyzing the toxic effects of arsenic is complicated because the toxicity is highly influenced by its oxidation state and solubility, as well as many other intrinsic and extrinsic factors [45]. Several studies have indicated that the toxicity of arsenic depends on the exposure dose, frequency and duration, the biological species, age, and gender, as well as on individual susceptibilities, genetic and nutritional factors [46]. Most cases of human toxicity from arsenic have been associated with exposure to inorganic arsenic. Inorganic trivalent arsenite (AsIII) is 2–10 times more toxic than pentavalent arsenate (AsV) [5]. By binding to thiol or sulfhydryl groups on proteins, As (III) can inactivate over 200 enzymes. This is the likely mechanism responsible for arsenic’s widespread effects on different organ systems. U did not talk abt d ability of arsenic to cause cancer Cadmium Environmental Occurrence, Industrial Production and Use Cadmium (Cd) is a heavy metal of considerable environmental and occupational concern. It is widely distributed in the earth's crust at an average concentration of about 0.1 mg/kg. The highest level of cadmium compounds in the environment is accumulated in sedimentary rocks, and marine phosphates containing about 15 mg cadmium/kg [88]. Cadmium is frequently used in various industrial activities. The major industrial applications of cadmium include the production of alloys, pigments, and batteries [89]. Although the use of cadmium in batteries has shown considerable growth in recent years, its commercial use has declined in developed countries in response to environmental concerns. In the United States for example, the daily cadmium intake is about 0.4µg/kg/day, less than half of the U.S. EPA’s oral reference dose [90]. This decline has been linked to the introduction of stringent effluent limits from electroplating works and, more recently, to the introduction of general restrictions on cadmium consumption in certain countries (reference). Potential of Cadmium for Human Exposure The main routes of exposure to cadmium are through inhalation or cigarette smoke, and ingestion of food. Skin absorption is rare. Human exposure to cadmium is possible through a number of several sources including employment in primary metal industries, eating contaminated food, smoking cigarettes, and working in cadmium-contaminated work places, with smoking being a major contributor [91, 92]. Other sources of cadmium include emissions from industrial activities, including mining, smelting, and manufacturing of batteries, pigments, stabilizers, and alloys [93]. Cadmium is also present in trace amounts in certain foods such as leafy vegetables, potatoes, grains and seeds, liver and kidney, and crustaceans and mollusks [94]. In addition, foodstuffs that are rich in cadmium can greatly increase the cadmium concentration in human bodies examples are liver, mushrooms, shellfish, mussels, cocoa powder and dried seaweed. An important distribution route is the circulatory system whereas blood vessels are considered to be main stream organs of cadmium toxicity. Chronic inhalation exposure to cadmium particulates is generally associated with changes in pulmonary function and chest radiographs that are consistent with emphysema [95]. Workplace exposure to airborne cadmium particulates has been associated with decreases in olfactory function [96]. Several epidemiologic studies have documented an association of chronic low-level cadmium exposure with decreases in bone mineral density and osteoporosis [97–99]. Molecular Mechanisms of Cadmium Toxicity and Carcinogenicity Cadmium is a severe pulmonary and gastrointestinal irritant, which can be fatal if inhaled or ingested. After acute ingestion, symptoms such as abdominal pain, burning sensation, nausea, vomiting, salivation, muscle cramps, vertigo, shock, loss of consciousness and convulsions usually appear within 15 to 30 min [105]. Acute cadmium ingestion can also cause gastrointestinal tract erosion, pulmonary, hepatic or renal injury and coma, depending on the route of poisoning [105, 106]. Chronic exposure to cadmium has a depressive effect on levels of norepinephrine, serotonin, and acetylcholine [107]. Rodent studies have shown that chronic inhalation of cadmium causes pulmonary adenocarcinomas [108, 109]. It can also cause prostatic proliferative lesions including adenocarcinomas, after systemic or direct exposure [110]. Chromium Environmental Occurrence, Industrial Production and Use Chromium (Cr) is a naturally occurring element present in the earth’s crust, with oxidation states (or valence states) ranging from chromium (II) to chromium (VI) [129]. Chromium compounds are stable in the trivalent [Cr(III)] form and occur in nature in this state in ores, such as ferrochromite. The hexavalent [Cr(VI)] form is the second-most stable state [28]. Elemental chromium [Cr(0)] does not occur naturally. Chromium enters into various environmental matrices (air, water, and soil) from a wide variety of natural and anthropogenic sources with the largest release coming from industrial establishments (reference). Industries with the largest contribution to chromium release include metal processing, tannery facilities, chromate production, stainless steel welding, and ferrochrome and chrome pigment production (reference). The increase in the environmental concentrations of chromium has been linked to air and wastewater release of chromium, mainly from metallurgical, refractory, and chemical industries. Chromium released into the environment from anthropogenic activity occurs mainly in the hexavalent form [Cr(VI)] [130]. Hexavalent chromium [Cr(VI)] is a toxic industrial pollutant that is classified as human carcinogen by several regulatory and non-regulatory agencies [130–132]. The health hazard associated with exposure to chromium depends on its oxidation state, ranging from the low toxicity of the metal form to the high toxicity of the hexavalent form. All Cr(VI)-containing compounds were once thought to be man-made, with only Cr(III) naturally ubiquitous in air, water, soil and biological materials. Recently, naturally occurring Cr(VI) has been found in ground and surface waters at values exceeding the World Health Organization limit for drinking water of 50 µg of Cr(VI) per liter [133]. Chromium is widely used in numerous industrial processes and as a result, is a contaminant of many environmental systems [134]. Commercially chromium compounds are used in industrial welding, chrome plating, dyes and pigments, leather tanning and wood preservation. Chromium is also used as anticorrosive in cooking systems and boilers [135, 136]. Potentials of Chromium for Human Exposure It is estimated that more than 300,000 workers are exposed annually to chromium and chromium-containing compounds in the workplace. In humans and animals, [Cr(III)] is an essential nutrient that plays a role in glucose, fat and protein metabolism by potentiating the action of insulin [5]. However, occupational exposure has been a major concern because of the high risk of Cr-induced diseases in industrial workers occupationally exposed to Cr(VI) [137]. Also, the general human population and some wildlife may also be at risk. It is estimated that 33 tons of total Cr are released annually into the environment [130]. The U.S. Occupational Safety and Health Administration (OSHA) recently set a “safe” level of 5µg/m3, for an 8 hours time-weighted average, even though this revised level may still pose a carcinogenic risk [138]. For the general human population, atmospheric levels range from 1 to 100 ng/cm3, but can exceed this range in areas that are close to Cr manufacturing [139]. Mechanisms of Chromium Toxicity and Carcinogenicity Major factors governing the toxicity of chromium compounds are oxidation state and solubility. Cr(VI) compounds, which are powerful oxidizing agents and thus tend to be irritating and corrosive, appear to be much more toxic systemically than Cr(III) compounds, given similar amount and solubility [146, 147]. Although the mechanisms of biological interaction are uncertain, the variation in toxicity may be related to the ease with which Cr(VI) can pass through cell membranes and its subsequent intracellular reduction to reactive intermediates (reference). Since Cr(III) is poorly absorbed by any route, the toxicity of chromium is mainly attributable to the Cr(VI) form (reference). It can be absorbed by the lung and gastrointestinal tract, and even to a certain extent by intact skin. The reduction of Cr(VI) is considered as being a detoxification process when it occurs at a distance from the target site for toxic or genotoxic effect while reduction of Cr(VI) may serve to activate chromium toxicity if it takes place in or near the cell nucleus of target organs [148]. If Cr(VI) is reduced to Cr(III) extracellularly, this form of the metal is not readily transported into cells and so toxicity is not observed. The balance that exists between extracellular Cr(VI) and intracellular Cr(III) is what ultimately dictates the amount and rate at which Cr(VI) can enter cells and impart its toxic effects [134]. Lead Environmental Occurrence, Industrial Production and Use Lead (Pb) is a naturally occurring bluish-gray metal present in small amounts in the earth’s crust. Although lead occurs naturally in the environment, anthropogenic activities such as fossil fuel burning, mining, and manufacturing contribute to the release of high concentrations. Lead has many different industrial, agricultural and domestic applications. It is currently used in the production of lead-acid batteries, ammunitions, metal products (solder and pipes), and devices to shield X-rays. An estimated 1.52 million metric tons of lead were used for various industrial applications in the United Stated in 2004. Of that amount (reframe the sentence), lead-acid batteries production accounted for 83 percent, and the remaining usage covered a range of products such as ammunitions (3.5 percent), oxides for paint, glass, pigments and chemicals (2.6 percent), and sheet lead (1.7 percent) [165, 166]. Potentials of Lead for Human Exposure Exposure of lead occurs mainly through inhalation of lead-contaminated dust particles or aerosols, and ingestion of lead-contaminated food, water, and paints [173, 174]. Adults absorb 35 to 50% of lead through drinking water and the absorption rate for children may be greater than 50%. Lead absorption is influenced by factors such as age and physiological status. In the human body, the greatest percentage of lead is taken into the kidney, followed by the liver and the other soft tissues such as heart and brain, however, the lead in the skeleton represents the major body fraction [175]. The nervous system is the most vulnerable target of lead poisoning. Headache, poor attention spam, irritability, loss of memory and dullness are the early symptoms of the effects of lead exposure on the central nervous system [170, 173]. Molecular Mechanisms of Lead Toxicity and Carcinogenicity There are many published studies that have documented the adverse effects of lead in children and the adult population (reference). In children, these studies have shown an association between blood level poisoning and diminished intelligence, lower intelligence quotient-IQ, delayed or impaired neurobehavioral development, decreased hearing acuity, speech and language handicaps, growth retardation, poor attention span, and anti social and diligent behaviors [178, 179, 184, 185]. In the adult population, reproductive effects, such as decreased sperm count in men and spontaneous abortions in women have been associated with high lead exposure [186, 187]. Acute exposure to lead induces brain damage, kidney damage, and gastrointestinal diseases, while chronic exposure may cause adverse effects on the blood, central nervous system, blood pressure, kidneys, and vitamin D metabolism [173, 174, 178, 179, 184–187]. How does it cause cancer? Mercury Environmental Occurrence, Industrial Production and Use Mercury (Hg) is a heavy metal belonging to the transition element series of the periodic table. It is unique in that it exists or is found in nature in three forms (elemental, inorganic, and organic), with each having its own profile of toxicity [207]. At room temperature elemental mercury exists as a liquid which has a high vapour pressure and is released into the environment as mercury vapour. Mercury also exists as a cation with oxidation states of +1 (mercurous) or +2 (mercuric) [208]. Methylmercury is the most frequently encountered compound of the organic form found in the environment, and is formed as a result of the methylation of inorganic (mercuric) forms of mercury by microorganisms found in soil and water [209]. Mercury is a widespread environmental toxicant and pollutant which induces severe alterations in the body tissues and causes a wide range of adverse health effects [210]. Both humans and animals are exposed to various chemical forms of mercury in the environment, these include elemental mercury vapour (Hg0), inorganic mercurous (Hg+1), mercuric (Hg+2), and the organic mercury compounds [211], this is because mercury is ubiquitous in the environment therefore humans, plants and animals cannot avoid the exposure of some form of mercury [212]. Hw does mercury cause cancer? Potentials of Mercury for Human Exposure Humans are exposed to all forms of mercury through accidents, environmental pollution, food contamination, dental care, preventive medical practices, industrial and agricultural operations, and occupational operations [215]. The major sources of chronic, low level mercury exposure are dental amalgams and fish consumption. Mercury enters water as a natural process of off-gassing from the earth’s crust and also through industrial pollution [216]. Algae and bacteria methylate the mercury entering the waterways. Methyl mercury then makes its way through the food chain into fish, shellfish, and eventually into humans [217]. Molecular Mechanisms of Mercury Toxicity and Carcingenicity The molecular mechanisms of toxicity of mercury are based on its chemical activity and biological features which suggest that oxidative stress is involved in its toxicity [220]. Through oxidative stress mercury has shown mechanisms of sulfhydryl reactivity. Once in the cell both Hg2+ and MeHg form covalent bonds with cysteine residues of proteins and deplete cellular antioxidants. Antioxidant enzymes serve as a line of cellular defence against mercury compounds [221]. The interaction of mercury compounds suggests the production of oxidative damage through the accumulation of reactive oxygen species (ROS) which would normally be eliminated by cellular antioxidants (reference). Hw does Hg cause cancer ENVIRONMENTAL REGULATION AND CONTROL OF HEAVY METAL POLLUTION CHAPTER THREE Conclusion A comprehensive analysis of published data indicates that heavy metals such as arsenic cadmium, chromium, lead, and mercury, occur naturally. However, anthropogenic activities contribute significantly to environmental contamination. These metals are systemic toxicants known to induce adverse health effects in humans, including cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, hematologic and immunologic disorders, and various types of cancer. The main pathways of exposure include ingestion, inhalation, and dermal contact. The severity of adverse health effects is related to the type of heavy metal and its chemical form, and is also time- and dose-dependent. Among many other factors, speciation plays a key role in metal toxicokinetics and toxicodynamics, and is highly influenced by factors such as valence state, particle size, solubility, biotransformation, and chemical form. Several studies have shown that toxic metals exposure causes long term health problems in human populations. Although the acute and chronic effects are known for some metals, little is known about the health impact of mixtures of toxic elements. Recent reports have pointed out that these toxic elements may interfere metabolically with nutritionally essential metals such as iron, calcium, copper, and zinc [245, 246]. In many areas of metal pollution, chronic low dose exposure to multiple elements is a major public health concern. Elucidating the mechanistic basis of heavy metal interactions is essential for health risk assessment and management of chemical mixtures. 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