Transcript
IntroductiON There are 35 metals that concern us because of occupational or residential exposure; 23 of these are the heavy elements or "heavy metals": antimony, arsenic, bismuth, cadmium, cerium, chromium, cobalt, copper, gallium, gold, iron, lead, manganese, mercury, nickel, platinum, silver, tellurium, thallium, tin, uranium, vanadium, and zinc . Interestingly, small amounts of these elements are common in our environment and diet and are actually necessary for good health, but large amounts of any of them may cause acute or chronic toxicity (poisoning). Heavy metal toxicity can result in damaged or reduced mental and central nervous function, lower energy levels, and damage to blood composition, lungs, kidneys, liver, and other vital organs. Long-term exposure may result in slowly progressing physical, muscular, and neurological degenerative processes that mimic Alzheimer's disease, Parkinson's disease, muscular dystrophy, and multiple sclerosis. For some heavy metals, toxic levels can be just above the background concentrations naturally found in nature. Therefore, it is important for us to take protective measures against excessive exposure. The association of symptoms indicative of acute toxicity are usually severe, rapid in onset, and associated with a known exposure or ingestion cramping, nausea, and vomiting; pain; sweating; headaches; difficulty breathing; impaired cognitive, motor, and language skills; mania; and convulsions. The symptoms of toxicity resulting from chronic exposure (impaired cognitive, motor, and language skills; learning difficulties; nervousness and emotional instability; and insomnia, nausea, lethargy, and feeling ill) are also easily recognized; however, they are much more difficult to associate with their cause. Symptoms of chronic exposure are very similar to symptoms of other health conditions and often develop slowly over months or even years. Sometimes the symptoms of chronic exposure actually abate from time to time, leading the person to postpone seeking treatment, thinking the symptoms are related to something else. Heavy Metal Heavy metals are chemical elements with a specific gravity that is at least 5 times the specific gravity of water. The specific gravity of water is 1 at 4°C (39°F). Simply stated, specific gravity is a measure of density of a given amount of a solid substance when it is compared to an equal amount of water. Some well-known toxic metallic elements with a specific gravity that is 5 or more times that of water such as lead, 11.34. Beneficial Heavy Metals In small quantities, certain heavy metals are nutritionally essential for a healthy life. Some of these are referred to as the trace elements (e.g., copper, and zinc). These elements, or some form of them, are commonly found naturally in foodstuffs, in fruits and vegetables, and in commercially available multivitamin products. Heavy metals are also common in industrial applications such as in the manufacture of pesticides, batteries, alloys, electroplated metal parts, textile dyes, steel, and so forth. Many of these products are in our homes and actually add to our quality of life when properly used. Toxic Heavy Metals Heavy metals become toxic when they are not metabolized by the body and accumulate in the soft tissues. Heavy metals may enter the human body through food, water, air, or absorption through the skin when they come in contact with humans in agriculture and in manufacturing, pharmaceutical, industrial, or residential settings. Industrial exposure accounts for a common route of exposure for adults. Children may develop toxic levels from the normal hand-to-mouth activity of small children who come in contact with contaminated soil or by actually eating objects that are not food (dirt or paint chips). As a rule, acute poisoning is more likely to result from inhalation or skin contact of dust, fumes or vapours, or materials in the workplace. The Agency for Toxic Substances and Disease Registry (ATSDR) in Atlanta, Georgia, (a part of the U.S. Department of Health and Human Services) was established by congressional mandate to perform specific functions concerning adverse human health effects and diminished quality of life associated with exposure to hazardous substances. The ATSDR is responsible for assessment of waste sites and providing health information concerning hazardous substances, response to emergency release situations, and education and training concerning hazardous substances In cooperation with the U.S. Environmental Protection Agency, the ATSDR has compiled a Priority List for 2001 called the "Top 20 Hazardous Substances." The heavy metals zinc, lead, mercury and copper. Enviroment Issues The heavy metals, which include copper (Cu), zinc (Zn), lead (Pb), mercury (Hg), nickel (Ni), cobalt (Co), and chromium (Cr), are common trace constituents in the earth crust. Their concentrations in the ambient environment have increased dramatically since the Industrial Revolution, as have lead and copper since Roman times. Many of these metals play an essential role in human physiology. For example, the enzymes that synthesize DNA and RNA contain zinc ions, and cobalt is an integral part of coenzyme B 12 . However, nonessential elements such as chromium, lead, and mercury have little or no beneficial role in the human body, and the daily intake of these metals is often toxic or lethal. Many heavy metals cause nervous-system damage, with resulting learning disorders in children. Ingestion of mercury can cause the severe breakdown of the nervous system, and metals such as lead and nickel can cause autoimmune reactions. Chromium occurs in a relatively harmless form and a much more dangerous, oxidized hexavalent form. Most heavy-metal contamination stems from high-temperature combustion sources, such as coal-fired power plants and solid-waste incinerators. Local metal sources may include metal-plating industries and other metal industries. The use of leaded gasoline has led to global lead pollution even in the most pristine environments, from arctic ice fields to alpine glaciers. The metal fluxes from point sources have been strictly regulated, and the introduction of unleaded gasoline has taken a major lead source away. Formation and location The base metals copper, lead and zinc are often considered as a group because of two or more are commonly associated in sulphide orebodies. However, they have few common properties. Copper, lead and zinc are relatively abundant in the Earth’s crust with average concentrations of about 55, 12 and 70 grams per tonne respectively (compared to goldat 0.001 g/t). To form a viable deposit, copper needs to be concentrated about 350 times, lead about 4,000 times and zinc 1,300 times. Copper is often found in alloy form with silver, lead, zinc and gold in sulphide, oxide and carbonate minerals. Copper, lead and zinc deposits often form in a similar way. Hot (hydrothermal) fluids laden with dissolved metals move up through the crust along fractures and faults. Volcanic activity or hot granite bodies (batholiths) forcing their way to the surface often activates the fluid circulation. These fluids can be trapped below the surface in cracks where sphalerite, galena, copper sulphides, silver and trace amounts of gold may precipitate to make vein deposits. Lead is number 2 on the ATSDR's "Top 20 List." Lead accounts for most of the cases of pediatric heavy metal poisoning. It is a very soft metal and was used in pipes, drains, and soldering materials for many years. Millions of homes built contain lead (e.g., in painted surfaces), leading to chronic exposure from weathering, flaking, chalking, and dust. Every year, industry produces about 2.5 million tons of lead throughout the world. Most of this lead is used for batteries. The remainder is used for cable coverings, plumbing, ammunition, and fuel additives. Other uses are as paint pigments and in PVC plastics, x-ray shielding, crystal glass production, and pesticides. Target organs are the bones, brain, blood, kidneys, and thyroid gland. Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high _thermal_ and _electrical_conductivity_. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish. It is used as a conductor of heat and electricity, a building material, and a constituent of various metal _alloys_. Copper(II) ions are water-soluble, where they function at low concentration as _bacteriostatic_substances_, _fungicides_, and wood preservatives. In sufficient amounts, they are poisonous to higher organisms; at lower concentrations it is an essential trace _nutrient_ to all _higher_plant_ and animal life. The main areas where copper is found in animals are tissues, liver, muscle and bone. Zinc also known as spelter, is a _metallic_ _chemical_element_; it has the symbol Zn and _atomic_number_ 30. It is the first element in _group_12_ of the _periodic_table_. Zinc is, in some respects, chemically similar to _magnesium_, because its _ion_ is of similar size and its only common _oxidation_state_ is +2. Zinc is the 24th most abundant element in the Earth's crust and has five stable _isotopes_. The most exploited zinc _ore_ is _sphalerite_, a _zinc_sulfide_. Zinc is an _essential_mineral_ of "exceptional biologic and public health importance". _Zinc_deficiency_ affects about two billion people in the developing world and is associated with many diseases. In children it causes growth retardation, delayed sexual maturation, infection susceptibility, and diarrhea, contributing to the death of about 800,000 children worldwide per year. _Enzymes_ with a zinc atom in the _reactive_center_ are widespread in biochemistry, such as _alcohol_dehydrogenase_ in humans. Consumption of excess zinc can cause _ataxia_, _lethargy_ and _copper_deficiency_. Chelation Chelating is the use of a chemical substance to bind molecules, such as metals or minerals, and hold them tightly so they can be removed from the body. Chelating has been scientifically proven to remove excess or toxic metals before they can cause damage to the body. The most common form of chelation therapy uses a man-made amino acid called EDTA (ethylene diamine tetra-acetic acid). EDTA removes heavy metals and minerals from the blood, such as lead, iron, copper, and calcium, and is approved by the U.S. Food and Drug Administration (FDA) for treating lead poisoning and poisoning from other heavy metals. EDTA chelation is used by some physicians and alternative medicine practitioners to improve circulation and treat this disorder by removing calcium deposits and plaques from the arteries. Popularity of this treatment is growing, however this use is still considered controversial among the medical community. The National Institutes of Health is conducting a $30 million study to test whether EDTA chelation therapy and/or high-dose vitamin therapy is effective for the treatment of arterial disease. Conditions Treated Circulatory disorders, such as coronary artery disease, angina, gangrene Lead or other heavy metal poisoning Typical Treatment is like First, tests are conducted on blood pressure, cholesterol, blood sugar, kidney function, and circulation to ensure safety. During the chelating treatment, a needle is inserted into the patient's vein, which is connected to an intravenous (IV) drip containing EDTA. A typical session is about 3 hours long, and they are scheduled 1 to 3 times a week. Twenty to 30 sessions are usually necessary. The chelate effect Ethylenediamine ligand, binding to a central metal ion with two bonds. Cu2+ complexes with methylamine (left) and ethylenediamine (right). The chelate effect describes the enhanced affinity of chelating ligands for a metal ion compared to the affinity of a collection of similar nonchelating (monodentate) ligands for the same metal. Consider the two equilibria, in aqueous solution, between the copper(II) ion, Cu2+ and ethylenediamine (en) on the one hand and methylamine, MeNH2 on the other. Cu2+ + en [Cu(en)]2+ (1) Cu2+ + 2 MeNH2 [Cu(MeNH2)2]2+ (2) In (1) the bidentate ligand ethylene diamine forms a chelate complex with the copper ion. Chelation results in the formation of a five–membered ring. In (2) the bidentate ligand is replaced by two monodentate methylamine ligands of approximately the same donor power, meaning that the enthalpy of formation of Cu—N bonds is approximately the same in the two reactions. Under conditions of equal copper concentrations and when the concentration of methylamine is twice the concentration of ethylenediamine, the concentration of the complex (1) will be greater than the concentration of the complex (2). The effect increases with the number of chelate rings so the concentration of the EDTA complex, which has six chelate rings, is much much higher than a corresponding complex with two monodentate nitrogen donor ligands and four monodentate carboxylate ligands. Thus, the phenomenon of the chelate effect is a firmly established empirical fact. The thermodynamic approach to explaining the chelate effect considers the equilibrium constant for the reaction: the larger the equilibrium constant, the higher the concentration of the complex. [Cu(en)] =?11[Cu][en] [Cu(MeNH2)2]= ?12[Cu][MeNH2]2 Electrical charges have been omitted for simplicity of notation. The square brackets indicate concentration, and the subscripts to the stability constants, ?, indicate the stoichiometry of the complex. When the analytical concentration of methylamine is twice that of ethylenediamine and the concentration of copper is the same in both reactions, the concentration [Cu(en)] is much higher than the concentration [Cu(MeNH2)2] because ?11 >> ?12. An equilibrium constant, K, is related to the standard Gibbs free energy, ?G by ?G = ?RT ln K = ?H ? T?S where R is the gas constant and T is the temperature in kelvins. ?H is the standard enthalpy change of the reaction and ?S is the standard entropy change. It has already been posited that the enthalpy term should be approximately the same for the two reactions. Therefore the difference between the two stability constants is due to the entropy term. In equation (1) there are two particles on the left and one on the right, whereas in equation (2) there are three particles on the left and one on the right. This means that less entropy of disorder is lost when the chelate complex is formed than when the complex with monodentate ligands is formed. This is one of the factors contributing to the entropy difference. Other factors include solvation changes and ring formation. Some experimental data to illustrate the effect are shown in the following table._[3]_ Equilibrium log ? ?G ?H /kJ mol?1 ?T?S /kJ mol?1 Cd2+ + 4 MeNH2 Cd(MeNH2)42+ 6.55 -37.4 -57.3 19.9 Cd2+ + 2 en Cd(en)22+ 10.62 -60.67 -56.48 -4.19 These data show that the standard enthalpy changes are indeed approximately equal for the two reactions and that the main reason why the chelate complex is so much more stable is that the standard entropy term is much less unfavourable, indeed, it is favourable in this instance. In general it is difficult to account precisely for thermodynamic values in terms of changes in solution at the molecular level, but it is clear that the chelate effect is predominantly an effect of entropy. In nature Virtually all biochemicals exhibit the ability to dissolve certain metal cations. Thus, proteins, polysaccharides, and polynucleic acids are excellent polydentate ligands for many metal ions. In addition to these adventitious chelators, several biomolecules are produced to specifically bind certain metals . Histidine, malate and phytochelatin are typical chelators used by plants. In biochemistry and microbiology Virtually all metalloenzymes feature metals that are chelated, usually to peptides or cofactors and prosthetic groups.Such chelating agents include the porphyrin rings in hemoglobin and chlorophyll. Many microbial species produce water-soluble pigments that serve as chelating agents, termed siderophores. For example, species of Pseudomonas are known to secrete pyocyanin and pyoverdin that bind iron. Enterobactin, produced by E. coli, is the strongest chelating agent known. In geology In earth science, chemical weathering is attributed to organic chelating agents, e.g. peptides and sugars, that extract metal ions from minerals and rocks. Most metal complexes in the environment and in nature are bound in some form of chelate ring, e.g. with a humic acid or a protein. Thus, metal chelates are relevant to the mobilization of metals in the soil, the uptake and the accumulation of metals into plants and micro-organisms. Selective chelation of heavy metals is relevant to bioremediation, e.g. removal of 137Cs from radioactive waste. Applications Chelators are used in chemical analysis, as water softeners, and are ingredients in many commercial products such as shampoos and food preservatives. Citric acid is used to soften water in soaps and laundry detergents. A common synthetic chelator is EDTA. Phosphonates are also well known chelating agents. Chelators are used in water treatment programs and specifically in steam engineering, e.g., boiler water treatment system: Chelant Water Treatment system. Heavy metal detoxification Chelation therapy is the use of chelating agents to detoxify poisonous metal agents such as copper , zinc and lead by converting them to a chemically inert form that can be excreted without further interaction with the body, and was approved by the U.S. Food and Drug Administration in 1991. In alternative medicine, chelation is used as a treatment for autism, though this practice is controversial due to the absence of scientific plausibility, lack of FDA approval, and its potentially deadly side-effects. Though they can be beneficial in cases of heavy metal poisoning, chelating agents can also be dangerous. Chelation Therapy Benefits and Risks Chelation therapy is being promoted as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been recommended as a safe, relatively inexpensive and non-surgical method of restoring blood flow in atherosclerotic vessels. The benefit of chelation therapy remains controversial at best. Chelation therapy is the controvesial process of using the amino acid EDTA to go through the bloodstream and attach to unwanted minerals, metals and other toxic substances in your body. These substances are thought to be the culprit in many health concerns. Chelation can also be used to remove plaque that lines the walls of arteries. Chelation therapy uses Ethylene-diamine-tetra-acetic acid, or EDTA, to grab onto minerals, metals and other toxic substances in your body such as lead, iron, magnesium, and zinc. An excess of certain minerals and metals in the blood may cause conditions such as hardening of the arteries or atherosclerosis, mercury poisoning, cancer, learning disabilities and possibly autism. EDTA and DMSA benefits and risks Since heavy metals are now present in higher amounts in certain fish such as tuna steaks, manypeople are concerned about heavy metal exposure. Over-the-counter chelation agents are promoted as a way to bind heavy metals and flush them out of the body. Chelation products are available several ways, including DMSA (dimercaptosuccinic acid) and EDTA (ethylene diamine tetra-acetic acid). DMSA and EDTA are traditional medications. A prescription version of DMSA -- brand name Chemet -- is used (rarely) to treat severe overdoses of lead. Some poisoning centers treat metal poisoning by giving EDTA through an IV. EDTA is not absorbed well when ingested as a supplement. DMSA is also sold over the counter as oral pills. So is EDTA. But there may be a risk to using these chelation products. DMSA and EDTA may bind to many types of metals including iron, calcium and manganese along with mercury and lead. Chelation agents may also harm the liver. The risks involved with chelation therapy are kidney failure if done improperly, excess removal of calcium leading to cramps or future bone loss, swollen and inflamed veins, low blood sugar or insulin shock and congestive heart failure. Proponents of chelation therapy say that all these risks are very minimal to non-existent if the treatment is done correctly. Patient with lead nephropathy and gout was treated with three months of edetic acid chelation. The therapy resulted in normalization of a previously abnormal result of edetic acid lead mobilization test. Nevertheless, progressive renal insufficiency occurred. At autopsy, an increased bone lead content was documented, suggesting that the edetic acid lead mobilization test may underestimate total body lead stores and that chelation therapy may not be effective in reversing advanced lead nephropathy. Alternatively, a longer period of therapy may be necessary to remove lead stores. More studies are needed to determine the relationship between the results of the edetic acid test and bone lead stores. Also, Patients diagnosed with incurable or fatal diseases may seek alternatives to standard medical therapy and spend significant amounts of money for these therapies. One alternative medical therapy, chelation therapy with edetic acid (EDTA), has gained considerable popularity for the alleged treatment of atherosclerotic vascular disease; however, its efficacy for this indication remains unproven and its use is controversial. In patients with thalassemia major (TM) who are non-compliant with long-term desferrioxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional hemosiderosis. Combined chelation therapy with DFO and deferiprone has maximized the efficacy of the therapy and reduced cardiological complications. Research has shown that EDTA suppositories can remove toxic metals from the body just as effectively as IV chelation. Also, it shows that 10 consecutive days of treatment with EDTA suppositories significantly reduced blood lead levels in children with proven lead toxicity. After treatment with just one suppository, the children's urinary lead excretion skyrocketed from 4.23 mcd/gL to more than 325 mcd/gL.9 Detoxamin suppositories do not contain salt, yeast, sugar, artificial coloring or preservatives. They are Kosher and contain no meat products. Oral chelation Prevention of cardiac mortality is the most important beneficial effect of iron chelation therapy. Unfortunately, compliance with the rigorous requirements of daily subcutaneous deferoxamine (DFO) infusions is still a serious limiting factor in treatment success. The development of orally effective _iron_ chelators such as deferiprone and ICL670 is intended to improve compliance. Although total iron excretion with deferiprone is somewhat less than with DFO, deferiprone may have a better cardioprotective effect than DFO due to deferiprone's ability to penetrate cell membranes. Recent clinical studies indicate that oral ICL670 treatment is well tolerated and is as effective as parenteral DFO used at the standard dose of 40 mg/kg of body weight/day. Chelation treatment - Heavy metal chelation Human exposure to a number of metals such as lead, manganese, copper, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-Acetyl-L-Cysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Other medical applications Antibiotic drugs of the tetracycline family are chelators of Ca2+ and Mg2+ ions. EDTA is also used in root canal treatment as a way to irrigate the canal. EDTA softens the dentin facilitating access to the entire canal length and to remove the smear layer formed during instrumentation. Chelate complexes of gadolinium are often used as contrast agents in MRI scans. Chemical applications : Homogeneous catalysts are often chelated complexes. A typical example is the ruthenium(II) chloride chelated with BINAP (a bidentate phosphine) used in e.g. Noyori asymmetric hydrogenation and asymmetric isomerization. The latter has the practical use of manufacture of synthetic (–)-menthol. Products such as Evapo-Rust are chelating agents sold for the removal of rust from iron and steel. In conculsion, Toxic metals, including "heavy metals," are individual metals and metal compounds that negatively affect people's health. Some toxic, semi-metallic elements, including arsenic and selenium, are discussed in this page. In very small amounts, many of these metals are necessary to support life. However, in larger amounts, they become toxic. They may build up in biological systems and become a significant health hazard. However, Chelation therapy is being promoted as a form of alternative medicine in the treatment of atherosclerotic cardiovascular disease. It has been recommended as a safe, relatively inexpensive and non-surgical method of restoring blood flow in atherosclerotic vessels.
