1. Heavy Metal Free Online
2. Sources Of Heavy Metals Pdf
3. Heavy Metals In Water Pdf
4. Heavy Metals Affecting Humans
5. Heavy Metal Books Pdf

Are you always tired? Heavy metal build-up in the body could be to blame. Learn two simple strategies to detox heavy metals safely and naturally. Heavy metals are individual metals and metal com-pounds that can impact human health. Eight common heavy metals are discussed in this brief: arsenic, barium, cadmium, chromium, lead, mercury, selenium, and sil-ver. These are all naturally occurring substances which. Heavy metal-induced toxicity and carcinogenicity involves many mechanistic aspects, some of which are not clearly elucidated or understood. However, each metal is known to have unique features and physic-chemical properties that confer to its specific toxicological mechanisms of action.

Heavy metals are generally defined as metals with relatively high densities, atomic weights, or atomic numbers. The criteria used, and whether metalloids are included, vary depending on the author and context.^[2] 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. More specific definitions have been published, but none of these have been widely accepted. The definitions surveyed in this article encompass up to 96 out of the 118 known chemical elements; only mercury, lead and bismuth meet all of them. Despite this lack of agreement, the term (plural or singular) is widely used in science. A density of more than 5 g/cm³ is sometimes quoted as a commonly used criterion and is used in the body of this article.

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 onward, light metals, such as magnesium, aluminium, and titanium, were discovered, as well as less well-known heavy metals including gallium, thallium, and hafnium.

Some 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, tailings, industrial wastes, agricultural runoff, occupational exposure, paints and treated timber.

Physical and chemical characterisations 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 far fewer solublesulfides and hydroxides. 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.

Heavy metals are relatively scarce in the Earth's crust but are present in many aspects of modern life. They are used in, for example, golf clubs, cars, antiseptics, self-cleaning ovens, plastics, solar panels, mobile phones, and particle accelerators.

• 1Definitions
• 2Origins and use of the term
• 4Toxicity
• 7Uses
• 9Sources

Definitions[edit]

There is no widely agreed criterion-based definition of a heavy metal. Different meanings may be attached to the term, depending on the context. In metallurgy, for example, a heavy metal may be defined on the basis of density,^[17] whereas in physics the distinguishing criterion might be atomic number,^[18] and a chemist or biologist would likely be more concerned with chemical behaviour.^[10]

Density criteria range from above 3.5 g/cm³ to above 7 g/cm³.^[3] Atomic weight definitions can range from greater than sodium (atomic weight 22.98);^[3] greater than 40 (excluding s- and f-block metals, hence starting with scandium);^[4] or more than 200, i.e. from mercury onwards.^[5] Atomic numbers of heavy metals are generally given as greater than 20 (calcium);^[3] sometimes this is capped at 92 (uranium).^[6] Definitions based on atomic number have been criticised for including metals with low densities. For example, rubidium in group (column) 1 of the periodic table has an atomic number of 37 but a density of only 1.532 g/cm³, which is below the threshold figure used by other authors.^[19] The same problem may occur with atomic weight based definitions.^[20]

The United States Pharmacopeia includes a test for heavy metals that involves precipitating metallic impurities as their coloured sulfides.'^{[7][n 3]} In 1997, Stephen Hawkes, a chemistry professor writing in the context of fifty years' experience with the term, said it applied to 'metals with insoluble sulfides and hydroxides, whose salts produce colored solutions in water and whose complexes are usually colored'. On the basis of the metals he had seen referred to as heavy metals, he suggested it would useful to define them as (in general) all the metals in periodic table columns 3 to 16 that are in row 4 or greater, in other words, the transition metals and post-transition metals.^{[10][n 4]} The lanthanides satisfy Hawkes' three-part description; the status of the actinides is not completely settled.^{[n 5][n 6]}

In biochemistry, heavy metals are sometimes defined—on the basis of the Lewis acid (electronic pair acceptor) behaviour of their ions in aqueous solution—as class B and borderline metals.^[41] In this scheme, class A metal ions prefer oxygen donors; class B ions prefer nitrogen or sulfur donors; and borderline or ambivalent ions show either class A or B characteristics, depending on the circumstances.^{[n 7]} Class A metals, which tend to have low electronegativity and form bonds with large ionic character, are the alkali and alkaline earths, aluminium, the group 3 metals, and the lanthanides and actinides.^{[n 8]} Class B metals, which tend to have higher electronegativity and form bonds with considerable covalent character, are mainly the heavier transition and post-transition metals. Borderline metals largely comprise the lighter transition and post-transition metals (plus arsenic and antimony). The distinction between the class A metals and the other two categories is sharp.^[45] A frequently cited proposal^{[n 9]} to use these classification categories instead of the more evocative^[11] name heavy metal has not been widely adopted.^[47]

List of heavy metals based on density[edit]

A density of more than 5 g/cm³ is sometimes mentioned as a common heavy metal defining factor^[48] and, in the absence of a unanimous definition, is used to populate this list and (unless otherwise stated) guide the remainder of the article. Metalloids meeting the applicable criteria–arsenic and antimony for example—are sometimes counted as heavy metals, particularly in environmental chemistry,^[49] as is the case here. Selenium (density 4.8 g/cm³)^[50] is also included in the list. It falls marginally short of the density criterion and is less commonly recognised as a metalloid^[16] but has a waterborne chemistry similar in some respects to that of arsenic and antimony.^[51] Other metals sometimes classified or treated as 'heavy' metals, such as beryllium^[52] (density 1.8 g/cm³),^[53] aluminium^[52] (2.7 g/cm³),^[54] calcium^[55] (1.55 g/cm³),^[56] and barium^[55] (3.6 g/cm³)^[57] are here treated as light metals and, in general, are not further considered.

Origins and use of the term[edit]

The heaviness of naturally occurring metals such as gold, copper, and iron may have been noticed in prehistory and, in light of their malleability, led to the first attempts to craft metal ornaments, tools, and weapons.^[64] All metals discovered from then until 1809 had relatively high densities; their heaviness was regarded as a singularly distinguishing criterion.^[65]

From 1809 onwards, light metals such as sodium, potassium, and strontium were isolated. Their low densities challenged conventional wisdom and it was proposed to refer to them as metalloids (meaning 'resembling metals in form or appearance').^[66] This suggestion was ignored; the new elements came to be recognised as metals, and the term metalloid was then used to refer to nonmetallic elements and, later, elements that were hard to describe as either metals or nonmetals.^[67]

An early use of the term 'heavy metal' dates from 1817, when the German chemist Leopold Gmelin divided the elements into nonmetals, light metals, and heavy metals.^[68] Light metals had densities of 0.860–5.0 g/cm³; heavy metals 5.308–22.000.^{[69][n 10]} The term later became associated with elements of high atomic weight or high atomic number.^[19] It is sometimes used interchangeably with the term heavy element. For example, in discussing the history of nuclear chemistry, Magee^[70] notes that the actinides were once thought to represent a new heavy element transition group whereas Seaborg and co-workers 'favoured .. a heavy metal rare-earth like series ..'. In astronomy, however, a heavy element is any element heavier than hydrogen and helium.^[71]

Criticism[edit]

In 2002, Scottish toxicologist John Duffus reviewed the definitions used over the previous 60 years and concluded they were so diverse as to effectively render the term meaningless.^[72] Along with this finding, the heavy metal status of some metals is occasionally challenged on the grounds that they are too light, or are involved in biological processes, or rarely constitute environmental hazards. Examples include scandium (too light);^[19][73]vanadium to zinc (biological processes);^[74] and rhodium, indium, and osmium (too rare).^[75]

Popularity[edit]

Despite its questionable meaning, the term heavy metal appears regularly in scientific literature. A 2010 study found that it had been increasingly used and seemed to have become part of the language of science.^[76] It is said to be an acceptable term, given its convenience and familiarity, as long as it is accompanied by a strict definition.^[41] The counterparts to the heavy metals, the light metals, are alluded to by The Minerals, Metals and Materials Society as including 'aluminium, magnesium, beryllium, titanium, lithium, and other reactive metals.'^[77] The named metals have densities of 0.534 to 4.54 g/cm³.

Biological role[edit]

Trace amounts of some heavy metals, mostly in period 4, are required for certain biological processes. These are iron and copper (oxygen and electron transport); cobalt (complex syntheses and cell metabolism); zinc (hydroxylation);^[83]vanadium and manganese (enzyme regulation or functioning); chromium (glucose utilisation); nickel (cell growth); arsenic (metabolic growth in some animals and possibly in humans) and selenium (antioxidant functioning and hormone production).^[84] Periods 5 and 6 contain fewer essential heavy metals, consistent with the general pattern that heavier elements tend to be less abundant and that scarcer elements are less likely to be nutritionally essential.^[85] In period 5, molybdenum is required for the catalysis of redox reactions; cadmium is used by some marine diatoms for the same purpose; and tin may be required for growth in a few species.^[86] In period 6, tungsten is required by some archaea and bacteria for metabolic processes.^[87] A deficiency of any of these period 4–6 essential heavy metals may increase susceptibility to heavy metal poisoning^[88] (conversely, an excess may also have adverse biological effects). An average 70 kg human body is about 0.01% heavy metals (~7 g, equivalent to the weight of two dried peas, with iron at 4 g, zinc at 2.5 g, and lead at 0.12 g comprising the three main constituents), 2% light metals (~1.4 kg, the weight of a bottle of wine) and nearly 98% nonmetals (mostly water).^{[89][n 15]}

A few non-essential heavy metals have been observed to have biological effects. Gallium, germanium (a metalloid), indium, and most lanthanides can stimulate metabolism, and titanium promotes growth in plants^[90] (though it is not always considered a heavy metal).

Toxicity[edit]

The focus of this section is mainly on the more serious toxic effects of heavy metals, including cancer, brain damage or death, rather than the harm they may cause to one more of the skin, lungs, stomach, kidneys, liver, or heart. For more specific information see Metal toxicity, Toxic heavy metal, or the articles on individual elements or compounds.

Heavy metals are often assumed to be highly toxic or damaging to the environment.^[91] Some are, while certain others are toxic only if taken in excess or encountered in certain forms.

Environmental heavy metals[edit]

Chromium, arsenic, cadmium, mercury, and lead have the greatest potential to cause harm on account of their extensive use, the toxicity of some of their combined or elemental forms, and their widespread distribution in the environment.^[92]Hexavalent chromium, for example, is highly toxic as are mercury vapour and many mercury compounds.^[93] These five elements have a strong affinity for sulfur; in the human body they usually bind, via thiol groups (–SH), to enzymes responsible for controlling the speed of metabolic reactions. The resulting sulfur-metal bonds inhibit the proper functioning of the enzymes involved; human health deteriorates, sometimes fatally.^[94] Chromium (in its hexavalent form) and arsenic are carcinogens; cadmium causes a degenerative bone disease; and mercury and lead damage the central nervous system.

Lead is the most prevalent heavy metal contaminant.^[95] Levels in the aquatic environments of industrialised societies have been estimated to be two to three times those of pre-industrial levels.^[96] As a component of tetraethyl lead, (CH
₃CH
₂)
₄Pb, it was used extensively in gasoline during the 1930s–1970s.^[97] Although the use of leaded gasoline was largely phased out in North America by 1996, soils next to roads built before this time retain high lead concentrations.^[98] Later research demonstrated a statistically significant correlation between the usage rate of leaded gasoline and violent crime in the United States; taking into account a 22-year time lag (for the average age of violent criminals), the violent crime curve virtually tracked the lead exposure curve.^[99]

Other heavy metals noted for their potentially hazardous nature, usually as toxic environmental pollutants, include manganese (central nervous system damage);^[100] cobalt and nickel (carcinogens);^[101] copper,^[102] zinc,^[103] selenium^[104] and silver^[105] (endocrine disruption, congenital disorders, or general toxic effects in fish, plants, birds, or other aquatic organisms); tin, as organotin (central nervous system damage);^[106] antimony (a suspected carcinogen);^[107] and thallium (central nervous system damage).^{[102][n 16][n 17]}

Nutritionally essential heavy metals[edit]

Heavy metals essential for life can be toxic if taken in excess; some have notably toxic forms. Vanadium pentoxide (V₂O₅) is carcinogenic in animals and, when inhaled, causes DNA damage.^[102] The purple permanganate ion MnO^–
₄ is a liver and kidney poison.^[111] Ingesting more than 0.5 grams of iron can induce cardiac collapse; such overdoses most commonly occur in children and may result in death within 24 hours.^[102]Nickel carbonyl (Ni(CO)₄), at 30 parts per million, can cause respiratory failure, brain damage and death.^[102] Imbibing a gram or more of copper sulfate (CuSO₄) can be fatal; survivors may be left with major organ damage.^[112] More than five milligrams of selenium is highly toxic; this is roughly ten times the 0.45 milligram recommended maximum daily intake;^[113] long-term poisoning can have paralytic effects.^{[102][n 18]}

Other heavy metals[edit]

A few other non-essential heavy metals have one or more toxic forms. Kidney failure and fatalities have been recorded arising from the ingestion of germanium dietary supplements (~15 to 300 g in total consumed over a period of two months to three years).^[102] Exposure to osmium tetroxide (OsO₄) may cause permanent eye damage and can lead to respiratory failure^[115] and death.^[116] Indium salts are toxic if more than few milligrams are ingested and will affect the kidneys, liver, and heart.^[117]Cisplatin (PtCl₂(NH₃)₂), which is an important drug used to kill cancer cells, is also a kidney and nerve poison.^[102]Bismuth compounds can cause liver damage if taken in excess; insoluble uranium compounds, as well as the dangerous radiation they emit, can cause permanent kidney damage.^[118]

Exposure sources[edit]

Heavy metals can degrade air, water, and soil quality, and subsequently cause health issues in plants, animals, and people, when they become concentrated as a result of industrial activities.^[119] Common sources of heavy metals in this context include mining and industrial wastes; vehicle emissions; lead-acid batteries; fertilisers; paints; and treated timber;^[120]aging water supply infrastructure;^[121] and microplastics floating in the world's oceans.^[122] Recent examples of heavy metal contamination and health risks include the occurrence of Minamata disease, in Japan (1932–1968; lawsuits ongoing as of 2016);^[123] the Bento Rodrigues dam disaster in Brazil,^[124] and high levels of lead in drinking water supplied to the residents of Flint, Michigan, in the north-east of the United States.^[125]

Formation, abundance, occurrence, and extraction[edit]

Heavy metals up to the vicinity of iron (in the periodic table) are largely made via stellar nucleosynthesis. In this process, lighter elements from hydrogen to silicon undergo successive fusion reactions inside stars, releasing light and heat and forming heavier elements with higher atomic numbers.^[129]

Heavier heavy metals are not usually formed this way since fusion reactions involving such nuclei would consume rather than release energy.^[130] Rather, they are largely synthesised (from elements with a lower atomic number) by neutron capture, with the two main modes of this repetitive capture being the s-process and the r-process. In the s-process ('s' stands for 'slow'), singular captures are separated by years or decades, allowing the less stable nuclei to beta decay,^[131] while in the r-process ('rapid'), captures happen faster than nuclei can decay. Therefore, the s-process takes a more or less clear path: for example, stable cadmium-110 nuclei are successively bombarded by free neutrons inside a star until they form cadmium-115 nuclei which are unstable and decay to form indium-115 (which is nearly stable, with a half-life 30000 times the age of the universe). These nuclei capture neutrons and form indium-116, which is unstable, and decays to form tin-116, and so on.^{[129][132][n 20]} In contrast, there is no such path in the r-process. The s-process stops at bismuth due to the short half-lives of the next two elements, polonium and astatine, which decay to bismuth or lead. The r-process is so fast it can skip this zone of instability and go on to create heavier elements such as thorium and uranium.^[134]

Heavy metals condense in planets as a result of stellar evolution and destruction processes. Stars lose much of their mass when it is ejected late in their lifetimes, and sometimes thereafter as a result of a neutron star merger,^{[135][n 21]} thereby increasing the abundance of elements heavier than helium in the interstellar medium. When gravitational attraction causes this matter to coalesce and collapse, new stars and planets are formed.^[137]

The Earth's crust is made of approximately 5% of heavy metals by weight, with iron comprising 95% of this quantity. Light metals (~20%) and nonmetals (~75%) make up the other 95% of the crust.^[126] Despite their overall scarcity, heavy metals can become concentrated in economically extractable quantities as a result of mountain building, erosion, or other geological processes.^[138]

Heavy metals are primarily found as lithophiles (rock-loving) or chalcophiles (ore-loving). Lithophile heavy metals are mainly f-block elements and the more reactive of the d-block elements. They have a strong affinity for oxygen and mostly exist as relatively low density silicate minerals.^[139] Chalcophile heavy metals are mainly the less reactive d-block elements, and period 4–6 p-block metals and metalloids. They are usually found in (insoluble) sulfide minerals. Being denser than the lithophiles, hence sinking lower into the crust at the time of its solidification, the chalcophiles tend to be less abundant than the lithophiles.^[140]

On the other hand, gold is a siderophile, or iron-loving element. It does not readily form compounds with either oxygen or sulfur.^[141] At the time of the Earth's formation, and as the most noble (inert) of metals, gold sank into the core due to its tendency to form high-density metallic alloys. Consequently, it is a relatively rare metal.^[142] Some other (less) noble heavy metals—molybdenum, rhenium, the platinum group metals (ruthenium, rhodium, palladium, osmium, iridium, and platinum), germanium, and tin—can be counted as siderophiles but only in terms of their primary occurrence in the Earth (core, mantle and crust), rather the crust. These metals otherwise occur in the crust, in small quantities, chiefly as chalcophiles (less so in their native form).^{[143][n 22]}

Concentrations of heavy metals below the crust are generally higher, with most being found in the largely iron-silicon-nickel core. Platinum, for example, comprises approximately 1 part per billion of the crust whereas its concentration in the core is thought to be nearly 6,000 times higher.^[144][145] Recent speculation suggests that uranium (and thorium) in the core may generate a substantial amount of the heat that drives plate tectonics and (ultimately) sustains the Earth's magnetic field.^{[146][n 23]}

The winning of heavy metals from their ores is a complex function of ore type, the chemical properties of the metals involved, and the economics of various extraction methods. Different countries and refineries may use different processes, including those that differ from the brief outlines listed here.

Broadly speaking, and with some exceptions, lithophile heavy metals can be extracted from their ores by electrical or chemical treatments, while chalcophile heavy metals are obtained by roasting their sulphide ores to yield the corresponding oxides, and then heating these to obtain the raw metals.^{[148][n 24]} Radium occurs in quantities too small to be economically mined and is instead obtained from spent nuclear fuels.^[151] The chalcophile platinum group metals (PGM) mainly occur in small (mixed) quantities with other chalcophile ores. The ores involved need to be smelted, roasted, and then leached with sulfuric acid to produce a residue of PGM. This is chemically refined to obtain the individual metals in their pure forms.^[152] Compared to other metals, PGM are expensive due to their scarcity^[153] and high production costs.^[154]

Gold, a siderophile, is most commonly recovered by dissolving the ores in which it is found in a cyanide solution.^[155] The gold forms a dicyanoaurate(I), for example: 2 Au + H₂O +½ O₂ + 4 KCN → 2 K[Au(CN)₂] + 2 KOH. Zinc is added to the mix and, being more reactive than gold, displaces the gold: 2[Au(CN)₂] + Zn → K₂[Zn(CN)₄] + 2 Au. The gold precipitates out of solution as a sludge, and is filtered off and melted.^[156]

Properties compared with light metals[edit]

Some general physical and chemical properties of light and heavy metals are summarised in the table. The comparison should be treated with caution since the terms light metal and heavy metal are not always consistently defined. Also the physical properties of hardness and tensile strength can vary widely depending on purity, grain size and pre-treatment.^[157]

These properties make it relatively easy to distinguish a light metal like sodium from a heavy metal like tungsten, but the differences become less clear at the boundaries. Light structural metals like beryllium, scandium, and titanium have some of the characteristics of heavy metals, such as higher melting points;^{[n 27]} post-transition heavy metals like zinc, cadmium, and lead have some of the characteristics of light metals, such as being relatively soft, having lower melting points,^{[n 28]} and forming mainly colourless complexes.^[21][23][24]

Uses[edit]

Heavy metals are present in nearly all aspects of modern life. Iron may be the most common as it accounts for 90% of all refined metals. Platinum may be the most ubiquitous given it is said to be found in, or used to produce, 20% of all consumer goods.^[181]

Some common uses of heavy metals depend on the general characteristics of metals such as electrical conductivity and reflectivity or the general characteristics of heavy metals such as density, strength, and durability. Other uses depend on the characteristics of the specific element, such as their biological role as nutrients or poisons or some other specific atomic properties. Examples of such atomic properties include: partly filled d- or f- orbitals (in many of the transition, lanthanide, and actinide heavy metals) that enable the formation of coloured compounds;^[182] the capacity of most heavy metal ions (such as platinum,^[183] cerium^[184] or bismuth^[185]) to exist in different oxidation states and therefore act as catalysts;^[186] poorly overlapping 3d or 4f orbitals (in iron, cobalt, and nickel, or the lanthanide heavy metals from europium through thulium) that give rise to magnetic effects;^[187] and high atomic numbers and electron densities that underpin their nuclear science applications.^[188] Typical uses of heavy metals can be broadly grouped into the following six categories.^{[189][n 29]}

Weight- or density-based[edit]

Some uses of heavy metals, including in sport, mechanical engineering, military ordnance, and nuclear science, take advantage of their relatively high densities. In underwater diving, lead is used as a ballast;^[191] in handicap horse racing each horse must carry a specified lead weight, based on factors including past performance, so as to equalize the chances of the various competitors.^[192] In golf, tungsten, brass, or copper inserts in fairwayclubs and irons lower the centre of gravity of the club making it easier to get the ball into the air;^[193] and golf balls with tungsten cores are claimed to have better flight characteristics.^[194] In fly fishing, sinking fly lines have a PVC coating embedded with tungsten powder, so that they sink at the required rate.^[195] In track and field sport, steel balls used in the hammer throw and shot put events are filled with lead in order to attain the minimum weight required under international rules.^[196] Tungsten was used in hammer throw balls at least up to 1980; the minimum size of the ball was increased in 1981 to eliminate the need for what was, at that time, an expensive metal (triple the cost of other hammers) not generally available in all countries.^[197] Tungsten hammers were so dense that they penetrated too deeply into the turf.^[198]

In mechanical engineering, heavy metals are used for ballast in boats,^[199] aeroplanes,^[200] and motor vehicles;^[201] or in balance weights on wheels and crankshafts,^[202]gyroscopes, and propellers,^[203] and centrifugal clutches,^[204] in situations requiring maximum weight in minimum space (for example in watch movements).^[200]

AM Russell and KL Lee
Structure–property relations
in nonferrous metals (2005, p. 16)

In military ordnance, tungsten or uranium is used in armour plating^[205] and armour piercing projectiles,^[206] as well as in nuclear weapons to increase efficiency (by reflecting neutrons and momentarily delaying the expansion of reacting materials).^[207] In the 1970s, tantalum was found to be more effective than copper in shaped charge and explosively formed anti-armour weapons on account of its higher density, allowing greater force concentration, and better deformability.^[208] Less-toxic heavy metals, such as copper, tin, tungsten, and bismuth, and probably manganese (as well as boron, a metalloid), have replaced lead and antimony in the green bullets used by some armies and in some recreational shooting munitions.^[209] Doubts have been raised about the safety (or green credentials) of tungsten.^[210]

Because denser materials absorb more radioactive emissions than lighter ones, heavy metals are useful for radiation shielding and to focus radiation beams in linear accelerators and radiotherapy applications.^[211]

Strength- or durability-based[edit]

The strength or durability of heavy metals such as chromium, iron, nickel, copper, zinc, molybdenum, tin, tungsten, and lead, as well as their alloys, makes them useful for the manufacture of artefacts such as tools, machinery,^[214]appliances,^[215] utensils,^[216] pipes,^[215]railroad tracks,^[217] buildings^[218] and bridges,^[219] automobiles,^[215] locks,^[220] furniture,^[221] ships,^[199] planes,^[222] coinage^[223] and jewellery.^[224] They are also used as alloying additives for enhancing the properties of other metals.^{[n 31]} Of the two dozen elements that have been used in the world's monetised coinage only two, carbon and aluminium, are not heavy metals.^{[226][n 32]} Gold, silver, and platinum are used in jewellery^{[n 33]} as are (for example) nickel, copper, indium, and cobalt in coloured gold.^[229]Low-cost jewellery and children's toys may be made, to a significant degree, of heavy metals such as chromium, nickel, cadmium, or lead.^[230]

Copper, zinc, tin, and lead are mechanically weaker metals but have useful corrosion prevention properties. While each of them will react with air, the resulting patinas of either various copper salts,^[231]zinc carbonate, tin oxide, or a mixture of lead oxide, carbonate, and sulfate, confer valuable protective properties.^[232] Copper and lead are therefore used, for example, as roofing materials;^{[233][n 34]} zinc acts as an anti-corrosion agent in galvanised steel;^[234] and tin serves a similar purpose on steel cans.^[235]

The workability and corrosion resistance of iron and chromium are increased by adding gadolinium; the creep resistance of nickel is improved with the addition of thorium. Tellurium is added to copper (Tellurium Copper) and steel alloys to improve their machinability; and to lead to make it harder and more acid-resistant.^[236]

Biological and chemical[edit]

The biocidal effects of some heavy metals have been known since antiquity.^[238] Platinum, osmium, copper, ruthenium, and other heavy metals, including arsenic, are used in anti-cancer treatments, or have shown potential.^[239] Antimony (anti-protozoal), bismuth (anti-ulcer), gold (anti-arthritic), and iron (anti-malarial) are also important in medicine.^[240] Copper, zinc, silver, gold, or mercury are used in antiseptic formulations;^[241] small amounts of some heavy metals are used to control algal growth in, for example, cooling towers.^[242] Depending on their intended use as fertilisers or biocides, agrochemicals may contain heavy metals such as chromium, cobalt, nickel, copper, zinc, arsenic, cadmium, mercury, or lead.^[243]

Selected heavy metals are used as catalysts in fuel processing (rhenium, for example), synthetic rubber and fibre production (bismuth), emission control devices (palladium), and in self-cleaning ovens (where cerium(IV) oxide in the walls of such ovens helps oxidisecarbon-based cooking residues).^[244] In soap chemistry, heavy metals form insoluble soaps that are used in lubricating greases, paint dryers, and fungicides (apart from lithium, the alkali metals and the ammonium ion form soluble soaps).^[245]

Colouring and optics[edit]

The colours of glass, ceramic glazes, paints, pigments, and plastics are commonly produced by the inclusion of heavy metals (or their compounds) such as chromium, manganese, cobalt, copper, zinc, selenium, zirconium, molybdenum, silver, tin, praseodymium, neodymium, erbium, tungsten, iridium, gold, lead, or uranium.^[247]Tattoo inks may contain heavy metals, such as chromium, cobalt, nickel, and copper.^[248] The high reflectivity of some heavy metals is important in the construction of mirrors, including precision astronomical instruments. Headlight reflectors rely on the excellent reflectivity of a thin film of rhodium.^[249]

Electronics, magnets, and lighting[edit]

Heavy metals or their compounds can be found in electronic components, electrodes, and wiring and solar panels where they may be used as either conductors, semiconductors, or insulators. Molybdenum powder is used in circuit board inks.^[250]Ruthenium(IV) oxide coated titanium anodes are used for the industrial production of chlorine.^[251] Home electrical systems, for the most part, are wired with copper wire for its good conducting properties.^[252] Silver and gold are used in electrical and electronic devices, particularly in contact switches, as a result of their high electrical conductivity and capacity to resist or minimise the formation of impurities on their surfaces.^[253] The semiconductors cadmium telluride and gallium arsenide are used to make solar panels. Hafnium oxide, an insulator, is used as a voltage controller in microchips; tantalum oxide, another insulator, is used in capacitors in mobile phones.^[254] Heavy metals have been used in batteries for over 200 years, at least since Volta invented his copper and silver voltaic pile in 1800.^[255]Promethium, lanthanum, and mercury are further examples found in, respectively, atomic, nickel-metal hydride, and button cell batteries.^[256]

Magnets are made of heavy metals such as manganese, iron, cobalt, nickel, niobium, bismuth, praseodymium, neodymium, gadolinium, and dysprosium. Neodymium magnets are the strongest type of permanent magnet commercially available. They are key components of, for example, car door locks, starter motors, fuel pumps, and power windows.^[257]

Heavy metals are used in lighting, lasers, and light-emitting diodes (LEDs). Flat panel displays incorporate a thin film of electrically conducting indium tin oxide. Fluorescent lighting relies on mercury vapour for its operation. Ruby lasers generate deep red beams by exciting chromium atoms; the lanthanides are also extensively employed in lasers. Gallium, indium, and arsenic;^[258] and copper, iridium, and platinum are used in LEDs (the latter three in organic LEDs).^[259]

Nuclear[edit]

Niche uses of heavy metals with high atomic numbers occur in diagnostic imaging, electron microscopy, and nuclear science. In diagnostic imaging, heavy metals such as cobalt or tungsten make up the anode materials found in x-ray tubes.^[263] In electron microscopy, heavy metals such as lead, gold, palladium, platinum, or uranium are used to make conductive coatings and to introduce electron density into biological specimens by staining, negative staining, or vacuum deposition.^[264] In nuclear science, nuclei of heavy metals such as chromium, iron, or zinc are sometimes fired at other heavy metal targets to produce superheavy elements;^[265] heavy metals are also employed as spallation targets for the production of neutrons^[266] or radioisotopes such as astatine (using lead, bismuth, thorium, or uranium in the latter case).^[267]

Notes[edit]

1. ^ Criteria used were density:^[3] (1) above 3.5 g/cm³; (2) above 7 g/cm³; atomic weight: (3) > 22.98;^[3] (4) > 40 (excluding s- and f-block metals);^[4] (5) > 200;^[5]atomic number: (6) > 20; (7) 21–92;^[6]chemical behaviour: (8) United States Pharmacopeia;^[7][8][9] (9) Hawkes' periodic table-based definition (excluding the lanthanides and actinides);^[10] and (10) Nieboer and Richardson's biochemical classifications.^[11] Densities of the elements are mainly from Emsley.^[12] Predicted densities have been used for At, Fr and Fm–Ts.^[13] Indicative densities were derived for Fm, Md, No and Lr based on their atomic weights, estimated metallic radii,^[14] and predicted close-packed crystalline structures.^[15] Atomic weights are from Emsley,^[12] inside back cover
2. ^Metalloids were, however, excluded from Hawkes' periodic table-based definition given he noted it was 'not necessary to decide whether semimetals [i.e. metalloids] should be included as heavy metals.'^[10]
3. ^The test is not specific for any particular metals but is said to be capable of at least detecting Mo, Cu, Ag, Cd, Hg, Sn, Pb, As, Sb, and Bi.^[8] In any event, when the test uses hydrogen sulfide as the reagent it cannot detect Th, Ti, Zr, Nb, Ta, or Cr.^[9]
4. ^Transition and post-transition metals that do not usually form coloured complexes are Sc and Y in group 3;^[21]Ag in group 11;^[22]Zn and Cd in group 12;^[21][23] and the metals of groups 13–16.^[24]
5. ^Lanthanide (Ln) sulfides and hydroxides are insoluble;^[25] the latter can be obtained from aqueous solutions of Ln salts as coloured gelatinous precipitates;^[26] and Ln complexes have much the same colour as their aqua ions (the majority of which are coloured).^[27] Actinide (An) sulfides may or may not be insoluble, depending on the author. Divalent uranium monosulfide is not attacked by boiling water.^[28] Trivalent actinide ions behave similarly to the trivalent lanthanide ions hence the sulfides in question may be insoluble but this is not explicitly stated.^[29] Tervalent An sulfides decompose^[30] but Edelstein et al. say they are soluble^[31] whereas Haynes says thorium(IV) sulfide is insoluble.^[32] Early in the history of nuclear fission it had been noted that precipitation with hydrogen sulfide was a 'remarkably' effective way of isolating and detecting transuranium elements in solution.^[33] In a similar vein, Deschlag writes that the elements after uranium were expected to have insoluble sulfides by analogy with third row transition metals. But he goes on to note that the elements after actinium were found to have properties different from those of the transition metals and claims they do not form insoluble sulfides.^[34] The An hydroxides are, however, insoluble^[31] and can be precipitated from aqueous solutions of their salts.^[35] Finally, many An complexes have 'deep and vivid' colours.^[36]
6. ^The heavier elements commonly to less commonly recognised as metalloids—Ge; As, Sb; Se, Te, Po; At—satisfy some of the three parts of Hawkes' definition. All of them have insoluble sulfides^[35][37] but only Ge, Te, and Po apparently have effectively insoluble hydroxides.^[38] All bar At can be obtained as coloured (sulfide) precipitates from aqueous solutions of their salts;^[35] astatine is likewise precipitated from solution by hydrogen sulfide but, since visible quantities of At have never been synthesised, the colour of the precipitate is not known.^[37][39] As p-block elements, their complexes are usually colourless.^[40]
7. ^The class A and class B terminology is analogous to the 'hard acid' and 'soft base' terminology sometimes used to refer to the behaviour of metal ions in inorganic systems.^[42]
8. ^Be and Al are exceptions to this general trend. They have somewhat higher electronegativity values.^[43] Being relatively small their +2 or +3 ions have high charge densities, thereby polarising nearby electron clouds. The net result is that Be and Al compounds have considerable covalent character.^[44]
9. ^Google Scholarhas recorded more than 1200 citations for the paper in question.^[46]
10. ^If Gmelin had been working with the imperial system of weights and measures he may have chosen 300 lb/ft³ as his light/heavy metal cutoff in which case selenium (density 300.27 lb/ft³ ) would have made the grade, whereas 5 g/cm³ = 312.14lb/ft³.
11. ^Lead, which is a cumulative poison, has a relatively high abundance due to its extensive historical use and human-caused discharge into the environment.^[79]
12. ^Haynes shows an amount of < 17 mg for tin^[80]
13. ^Iyengar records a figure of 5 mg for nickel;^[81] Haynes shows an amount of 10 mg^[80]
14. ^Encompassing 45 heavy metals occurring in quantities of less than 10 mg each, including As (7 mg), Mo (5), Co (1.5), and Cr (1.4)^[82]
15. ^Of the elements commonly recognised as metalloids, B and Si were counted as nonmetals; Ge, As, Sb, and Te as heavy metals.
16. ^Ni, Cu, Zn, Se, Ag and Sb appear in the United States Government's Toxic Pollutant List;^[108] Mn, Co, and Sn are listed in the Australian Government's National Pollutant Inventory.^[109]
17. ^Tungsten could be another such toxic heavy metal.^[110]
18. ^Selenium is the most toxic of the heavy metals that are essential for mammals.^[114]
19. ^Trace elements having an abundance equalling or much less than one part per trillion (namely Tc, Pm, Po, At, Ra, Ac, Pa, Np, and Pu) are not shown. Abundances are from Lide^[126] and Emsley;^[127] occurrence types are from McQueen.^[128]
20. ^In some cases, for example in the presence of high energy gamma rays or in a very high temperature hydrogen rich environment, the subject nuclei may experience neutron loss or proton gain resulting in the production of (comparatively rare) neutron deficient isotopes.^[133]
21. ^The ejection of matter when two neutron stars collide is attributed to the interaction of their tidal forces, possible crustal disruption, and shock heating (which is what happens if you floor the accelerator in car when the engine is cold).^[136]
22. ^Iron, cobalt, nickel, germanium and tin are also siderophiles from a whole of Earth perspective.^[128]
23. ^Heat escaping from the inner solid core is believed to generate motion in the outer core, which is made of liquid iron alloys. The motion of this liquid generates electrical currents which give rise to a magnetic field.^[147]
24. ^Heavy metals that occur naturally in quantities too small to be economically mined (Tc, Pm, Po, At, Ac, Np and Pu) are instead produced by artificial transmutation.^[149] The latter method is also used to produce heavy metals from americium onwards.^[150]
25. ^Sulfides of the Group 1 and 2 metals, and aluminium, are hydrolysed by water;^[165] scandium,^[166] yttrium^[167] and titanium sulfides^[168] are insoluble.
26. ^For example, the hydroxides of potassium, rubidium, and caesium have solubilities exceeding 100 grams per 100 grams of water^[170] whereas those of aluminium (0.0001)^[171] and scandium (<0.000 000 15 grams)^[172] are regarded as being insoluble.
27. ^Beryllium has what is described as a 'high' melting point of 1560 K; scandium and titanium melt at 1814 and 1941 K.^[177]
28. ^Zinc is a soft metal with a Moh's hardness of 2.5;^[178] cadmium and lead have lower hardness ratings of 2.0 and 1.5.^[179] Zinc has a 'low' melting point of 693 K; cadmium and lead melt at 595 and 601 K.^[180]
29. ^Some violence and abstraction of detail was applied to the sorting scheme in order to keep the number of categories to a manageable level.
30. ^The skin has largely turned green due to the formation of a protective patina composed of antlerite Cu₃(OH)₄SO₄, atacamite Cu₄(OH)₆Cl₂, brochantite Cu₄(OH)₆SO₄, cuprous oxide Cu₂O, and tenorite CuO.^[213]
31. ^For the lanthanides, this is their only structural use as they are otherwise too reactive, relatively expensive, and moderately strong at best.^[225]
32. ^Weller^[227] classifies coinage metals as precious metals (e.g., silver, gold, platinum); heavy metals of very high durability (nickel); heavy metals of low durability (copper, iron, zinc, tin, and lead); and light metals (aluminium).
33. ^Emsley^[228] estimates a global loss of six tonnes of gold a year due to 18-carat wedding rings slowly wearing away.
34. ^Sheet lead exposed to the rigours of industrial and coastal climates will last for centuries^[191]
35. ^Electrons impacting the tungsten anode generate X-rays;^[261] rhenium gives tungsten better resistance to thermal shock;^[262] molybdenum and graphite act as heat sinks. Molybdenum also has a density nearly half that of tungsten thereby reducing the weight of the anode.^[260]

Sources[edit]

Citations[edit]

1. ^Emsley 2011, pp. 288; 374
2. ^Pourret, Olivier (August 2018). 'On the Necessity of Banning the Term 'Heavy Metal' from the Scientific Literature'(PDF). Sustainability. 10 (8): 2879. doi:10.3390/su10082879.
3. ^ ^abcdeDuffus 2002, p. 798
4. ^ ^abRand, Wells & McCarty 1995, p. 23
5. ^ ^abBaldwin & Marshall 1999, p. 267
6. ^ ^abLyman 2003, p. 452
7. ^ ^abThe United States Pharmacopeia 1985, p. 1189
8. ^ ^abRaghuram, Soma Raju & Sriramulu 2010, p. 15
9. ^ ^abThorne & Roberts 1943, p. 534
10. ^ ^abcdHawkes 1997
11. ^ ^abNieboer & Richardson 1980, p. 4
12. ^ ^abEmsley 2011
13. ^Hoffman, Lee & Pershina 2011, pp. 1691,1723; Bonchev & Kamenska 1981, p. 1182
14. ^Silva 2010, pp. 1628, 1635, 1639, 1644
15. ^Fournier 1976, p. 243
16. ^ ^abcVernon 2013, p. 1703
17. ^Morris 1992, p. 1001
18. ^Gorbachev, Zamyatnin & Lbov 1980, p. 5
19. ^ ^abcDuffus 2002, p. 797
20. ^Liens 2010, p. 1415
21. ^ ^abcLongo 1974, p. 683
22. ^Tomasik & Ratajewicz 1985, p. 433
23. ^ ^abHerron 2000, p. 511
24. ^ ^abNathans 1963, p. 265
25. ^Topp 1965, p. 106: Schweitzer & Pesterfield 2010, p. 284
26. ^King 1995, p. 297; Mellor 1924, p. 628
27. ^Cotton 2006, pp. 66
28. ^Albutt & Dell 1963, p. 1796
29. ^Wiberg 2001, pp. 1722–1723
30. ^Wiberg 2001, p. 1724
31. ^ ^abEdelstein et al. 2010, p. 1796
32. ^Haynes 2015, pp. 4–95
33. ^Weart 1983, p. 94
34. ^Deschlag 2011, p. 226
35. ^ ^abcWulfsberg 2000, pp. 209–211
36. ^Ahrland, Liljenzin & Rydberg 1973, p. 478
37. ^ ^abKorenman 1959, p. 1368
38. ^Yang, Jolly & O'Keefe 1977, p. 2980; Wiberg 2001, pp. 592; Kolthoff & Elving 1964, p. 529
39. ^Close 2015, p. 78
40. ^Parish 1977, p. 89
41. ^ ^abRainbow 1991, p. 416
42. ^Nieboer & Richardson 1980, pp. 6–7
43. ^Lee 1996, pp. 332; 364
44. ^Clugston & Flemming 2000, pp. 294; 334, 336
45. ^Nieboer & Richardson 1980, p. 7
46. ^Nieboer & Richardson 1980
47. ^Hübner, Astin & Herbert 2010, pp. 1511–1512
48. ^Järup & 2003, p. 168; Rasic-Milutinovic & Jovanovic 2013, p. 6; Wijayawardena, Megharaj & Naidu 2016, p. 176
49. ^Duffus 2002, pp. 794–795; 800
50. ^Emsley 2011, p. 480
51. ^USEPA 1988, p. 1; Uden 2005, pp. 347–348; DeZuane 1997, p. 93; Dev 2008, pp. 2–3
52. ^ ^abIkehata et al. 2015, p. 143
53. ^Emsley 2011, p. 71
54. ^Emsley 2011, p. 30
55. ^ ^abPodsiki 2008, p. 1
56. ^Emsley 2011, p. 106
57. ^Emsley 2011, p. 62
58. ^Chakhmouradian, Smith & Kynicky 2015, pp. 456–457
59. ^Cotton 1997, p. ix; Ryan 2012, p. 369
60. ^Hermann, Hoffmann & Ashcroft 2013, p. 11604-1
61. ^Emsley 2011, p. 75
62. ^Gribbon 2016, p. x
63. ^Emsley 2011, pp. 428–429; 414; Wiberg 2001, pp. 527; Emsley 2011, pp. 437; 21–22; 346–347; 408–409
64. ^Raymond 1984, pp. 8–9
65. ^Chambers 1743: 'That which distinguishes metals from all other bodies .. is their heaviness ..'
66. ^Oxford English Dictionary 1989; Gordh & Headrick 2003, p. 753
67. ^Goldsmith 1982, p. 526
68. ^Habashi 2009, p. 31
69. ^Gmelin 1849, p. 2
70. ^Magee 1969, p. 14
71. ^Ridpath 2012, p. 208
72. ^Duffus 2002, p. 794
73. ^Leeper 1978, p. ix
74. ^Housecroft 2008, p. 802
75. ^Shaw, Sahu & Mishra 1999, p. 89; Martin & Coughtrey 1982, pp. 2–3
76. ^Hübner, Astin & Herbert 2010, p. 1513
77. ^ ^abThe Minerals, Metals and Materials Society 2016
78. ^Emsley 2011, pp. 35; passim
79. ^Emsley 2011, pp. 280, 286; Baird & Cann 2012, pp. 549, 551
80. ^ ^abHaynes 2015, pp. 7–48
81. ^Iyengar 1998, p. 553
82. ^Emsley 2011, pp. 47; 331; 138; 133; passim
83. ^Nieboer & Richardson 1978, p. 2
84. ^Emsley 2011, pp. 604; 31; 133; 358; 47; 475
85. ^Valkovic 1990, pp. 214, 218
86. ^Emsley 2011, pp. 331; 89; 552
87. ^Emsley 2011, p. 571
88. ^Venugopal & Luckey 1978, p. 307
89. ^Emsley 2011, pp. 24; passim
90. ^Emsley 2011, pp. 192; 197; 240; 120, 166, 188, 224, 269, 299, 423, 464, 549, 614; 559
91. ^Duffus 2002, pp. 794; 799
92. ^Baird & Cann 2012, p. 519
93. ^Kozin & Hansen 2013, p. 80
94. ^Baird & Cann 2012, pp. 519–520; 567; Rusyniak et al. 2010, p. 387
95. ^Di Maio 2001, p. 208
96. ^Perry & Vanderklein 1996, p. 208
97. ^Love 1998, p. 208
98. ^Hendrickson 2016, p. 42
99. ^Reyes 2007, pp. 1, 20, 35–36
100. ^Emsley 2011, p. 311
101. ^Wiberg 2001, pp. 1474, 1501
102. ^ ^abcdefghTokar et al. 2013
103. ^Eisler 1993, pp. 3, passim
104. ^Lemly 1997, p. 259; Ohlendorf 2003, p. 490
105. ^State Water Control Resources Board 1987, p. 63
106. ^Scott 1989, pp. 107–108
107. ^International Antimony Association 2016
108. ^United States Government 2014
109. ^Australian Government 2016
110. ^United States Environmental Protection Agency 2014
111. ^Ong, Tan & Cheung 1997, p. 44
112. ^Emsley 2011, p. 146
113. ^Emsley 2011, p. 476
114. ^Selinger 1978, p. 369
115. ^Cole & Stuart 2000, p. 315
116. ^Clegg 2014
117. ^Emsley 2011, p. 240
118. ^Emsley 2011, p. 595
119. ^Stankovic & Stankovic 2013, pp. 154–159
120. ^Bradl 2005, pp. 15, 17–20
121. ^Harvey, Handley & Taylor 2015, p. 12276
122. ^Howell et al. 2012; Cole et al. 2011, pp. 2589–2590
123. ^Amasawa et al. 2016, pp. 95–101
124. ^Massarani 2015
125. ^Torrice 2016
126. ^ ^abcLide 2004, pp. 14–17
127. ^Emsley 2011, pp. 29; passim
128. ^ ^abcMcQueen 2009, p. 74
129. ^ ^abCox 1997, pp. 73–89
130. ^Cox 1997, pp. 32, 63, 85
131. ^Podosek 2011, p. 482
132. ^Padmanabhan 2001, p. 234
133. ^Rehder 2010, pp. 32, 33
134. ^Hofmann 2002, pp. 23–24
135. ^Hadhazy 2016
136. ^Choptuik, Lehner & Pretorias 2015, p. 383
137. ^Cox 1997, pp. 83, 91, 102–103
138. ^Berry & Mason 1959, pp. 210–211; Rankin 2011, p. 69
139. ^Hartmann 2005, p. 197
140. ^Yousif 2007, pp. 11–12
141. ^Berry & Mason 1959, pp. 214
142. ^Yousif 2007, pp. 11
143. ^Wiberg 2001, p. 1511
144. ^Emsley 2011, p. 403
145. ^Litasov & Shatskiy 2016, p. 27
146. ^Sanders 2003; Preuss 2011
147. ^Natural Resources Canada 2015
148. ^MacKay, MacKay & Henderson 2002, pp. 203–204
149. ^Emsley 2011, pp. 525–528; 428–429; 414; 57–58; 22; 346–347; 408–409; Keller, Wolf & Shani 2012, p. 98
150. ^Emsley 2011, pp. 32 et seq.
151. ^Emsley 2011, pp. 437
152. ^Chen & Huang 2006, p. 208; Crundwell et al. 2011, pp. 411–413; Renner et al. 2012, p. 332; Seymour & O'Farrelly 2012, pp. 10–12
153. ^Crundwell et al. 2011, p. 409
154. ^International Platinum Group Metals Association n.d., pp. 3–4
155. ^McLemore 2008, p. 44
156. ^Wiberg 2001, p. 1277
157. ^Russell & Lee 2005, p. 437
158. ^McCurdy 1992, p. 186
159. ^von Zeerleder 1949, p. 68
160. ^Chawla & Chawla 2013, p. 55
161. ^von Gleich 2006, p. 3
162. ^Biddle & Bush 1949, p. 180
163. ^Magill 1992, p. 1380
164. ^ ^abGidding 1973, pp. 335–336
165. ^Wiberg 2001, p. 520
166. ^ ^abSchweitzer & Pesterfield 2010, p. 230
167. ^Macintyre 1994, p. 334
168. ^Booth 1957, p. 85; Haynes 2015, pp. 4–96
169. ^Schweitzer & Pesterfield 2010, p. 230. The authors note, however, that, 'The sulfides of .. Ga(III) and Cr(III) tend to dissolve and/or decompose in water.'
170. ^Sidgwick 1950, p. 96
171. ^Ondreička, Kortus & Ginter 1971, p. 294
172. ^Gschneidner 1975, p. 195
173. ^Hasan 1996, p. 251
174. ^Brady & Holum 1995, p. 825
175. ^Cotton 2006, pp. 66; Ahrland, Liljenzin & Rydberg 1973, p. 478
176. ^Nieboer & Richardson 1980, p. 10
177. ^Russell & Lee 2005, pp. 158, 434, 180
178. ^Schweitzer 2003, p. 603
179. ^Samsonov 1968, p. 432
180. ^Russell & Lee 2005, pp. 338–339; 338; 411
181. ^Emsley 2011, pp. 260; 401
182. ^Jones 2001, p. 3
183. ^Berea, Rodriguez-lbelo & Navarro 2016, p. 203
184. ^Alves, Berutti & Sánchez 2012, p. 94
185. ^Yadav, Antony & Subba Reddy 2012, p. 231
186. ^Masters 1981, p. 5
187. ^Wulfsberg 1987, pp. 200–201
188. ^Bryson & Hammond 2005, p. 120 (high electron density); Frommer & Stabulas-Savage 2014, pp. 69–70 (high atomic number)
189. ^Landis, Sofield & Yu 2011, p. 269
190. ^Prieto 2011, p. 10; Pickering 1991, pp. 5–6, 17
191. ^ ^abEmsley 2011, p. 286
192. ^Berger & Bruning 1979, p. 173
193. ^Jackson & Summitt 2006, pp. 10, 13
194. ^Shedd 2002, p. 80.5; Kantra 2001, p. 10
195. ^Spolek 2007, p. 239
196. ^White 2010, p. 139
197. ^Dapena & Teves 1982, p. 78
198. ^Burkett 2010, p. 80
199. ^ ^abMoore & Ramamoorthy 1984, p. 102
200. ^ ^abNational Materials Advisory Board 1973, p. 58
201. ^Livesey 2012, p. 57
202. ^VanGelder 2014, pp. 354, 801
203. ^National Materials Advisory Board 1971, pp. 35–37
204. ^Frick 2000, p. 342
205. ^Rockhoff 2012, p. 314
206. ^Russell & Lee 2005, pp. 16, 96
207. ^Morstein 2005, p. 129
208. ^Russell & Lee 2005, pp. 218–219
209. ^Lach et al. 2015; Di Maio 2016, p. 154
210. ^Preschel 2005; Guandalini et al. 2011, p. 488
211. ^Scoullos et al. 2001, p. 315; Ariel, Barta & Brandon 1973, p. 126
212. ^Wingerson 1986, p. 35
213. ^Matyi & Baboian 1986, p. 299; Livingston 1991, pp. 1401, 1407
214. ^Casey 1993, p. 156
215. ^ ^abcBradl 2005, p. 25
216. ^Kumar, Srivastava & Srivastava 1994, p. 259
217. ^Nzierżanowski & Gawroński 2012, p. 42
218. ^Pacheco-Torgal, Jalali & Fucic 2012, pp. 283–294; 297–333
219. ^Venner et al. 2004, p. 124
220. ^Technical Publications 1958, p. 235: 'Here is a rugged hard metal cutter .. for cutting .. through .. padlocks, steel grilles and other heavy metals.'
221. ^Naja & Volesky 2009, p. 41
222. ^Department of the Navy 2009, pp. 3.3–13
223. ^Rebhandl et al. 2007, p. 1729
224. ^Greenberg & Patterson 2008, p. 239
225. ^Russell & Lee 2005, pp. 437, 441
226. ^Roe & Roe 1992
227. ^Weller 1976, p. 4
228. ^Emsley 2011, p. 208
229. ^Emsley 2011, p. 206
230. ^Guney & Zagury 2012, p. 1238; Cui et al. 2015, p. 77
231. ^Brephol & McCreight 2001, p. 15
232. ^Russell & Lee 2005, pp. 337, 404, 411
233. ^Emsley 2011, pp. 141; 286
234. ^Emsley 2011, pp. 625
235. ^Emsley 2011, pp. 555, 557
236. ^Emsley 2011, p. 531
237. ^Emsley 2011, p. 123
238. ^Weber & Rutula 2001, p. 415
239. ^Dunn 2009; Bonetti et al. 2009, pp. 1, 84, 201
240. ^Desoize 2004, p. 1529
241. ^Atlas 1986, p. 359; Lima et al. 2013, p. 1
242. ^Volesky 1990, p. 174
243. ^Nakbanpote, Meesungnoen & Prasad 2016, p. 180
244. ^Emsley 2011, pp. 447; 74; 384; 123
245. ^Elliot 1946, p. 11; Warth 1956, p. 571
246. ^McColm 1994, p. 215
247. ^Emsley 2011, pp. 135; 313; 141; 495; 626; 479; 630; 334; 495; 556; 424; 339; 169; 571; 252; 205; 286; 599
248. ^Everts 2016
249. ^Emsley 2011, p. 450
250. ^Emsley 2011, p. 334
251. ^Emsley 2011, p. 459
252. ^Moselle 2004, pp. 409–410
253. ^Russell & Lee 2005, p. 323
254. ^Emsley 2011, p. 212
255. ^Tretkoff 2006
256. ^Emsley 2011, pp. 428; 276; 326–327
257. ^Emsley 2011, pp. 73; 141; 141; 141; 355; 73; 424; 340; 189; 189
258. ^Emsley 2011, pp. 192; 242; 194
259. ^Baranoff 2015, p. 80; Wong et al. 2015, p. 6535
260. ^ ^abBall, Moore & Turner 2008, p. 177
261. ^Ball, Moore & Turner 2008, pp. 248–249, 255
262. ^Russell & Lee 2005, p. 238
263. ^Tisza 2001, p. 73
264. ^Chandler & Roberson 2009, pp. 47, 367–369, 373; Ismail, Khulbe & Matsuura 2015, p. 302
265. ^Ebbing & Gammon 2017, p. 695
266. ^Pan & Dai 2015, p. 69
267. ^Brown 1987, p. 48

References[edit]

• Ahrland S., Liljenzin J. O. & Rydberg J. 1973, 'Solution chemistry,' in J. C. Bailar & A. F. Trotman-Dickenson (eds), Comprehensive Inorganic Chemistry, vol. 5, The Actinides, Pergamon Press, Oxford.
• Albutt M. & Dell R. 1963, The nitrites and sulphides of uranium, thorium and plutonium: A review of present knowledge, UK Atomic Energy Authority Research Group, Harwell, Berkshire.
• Alves A. K., Berutti, F. A. & Sánche, F. A. L. 2012, 'Nanomaterials and catalysis', in C. P. Bergmann & M. J. de Andrade (ads), Nanonstructured Materials for Engineering Applications, Springer-Verlag, Berlin, ISBN978-3-642-19130-5.
• Amasawa E., Yi Teah H., Yu Ting Khew, J., Ikeda I. & Onuki M. 2016, 'Drawing Lessons from the Minamata Incident for the General Public: Exercise on Resilience, Minamata Unit AY2014', in M. Esteban, T. Akiyama, C. Chen, I. Ikea, T. Mino (eds), Sustainability Science: Field Methods and Exercises, Springer International, Switzerland, pp. 93–116, doi:10.1007/978-3-319-32930-7_5ISBN978-3-319-32929-1.
• Ariel E., Barta J. & Brandon D. 1973, 'Preparation and properties of heavy metals', Powder Metallurgy International, vol. 5, no. 3, pp. 126–129.
• Atlas R. M. 1986, Basic and Practical Microbiology, Macmillan Publishing Company, New York, ISBN978-0-02-304350-5.
• Australian Government 2016, National Pollutant Inventory, Department of the Environment and Energy, accessed 16 August 2016.
• Baird C. & Cann M. 2012, Environmental Chemistry, 5th ed., W. H. Freeman and Company, New York, ISBN978-1-4292-7704-4.
• Baldwin D. R. & Marshall W. J. 1999, 'Heavy metal poisoning and its laboratory investigation', Annals of Clinical Biochemistry, vol. 36, no. 3, pp. 267–300, doi:10.1177/000456329903600301.
• Ball J. L., Moore A. D. & Turner S. 2008, Ball and Moore's Essential Physics for Radiographers, 4th ed., Blackwell Publishing, Chichester, ISBN978-1-4051-6101-5.
• Bánfalvi G. 2011, 'Heavy metals, trace elements and their cellular effects', in G. Bánfalvi (ed.), Cellular Effects of Heavy Metals, Springer, Dordrecht, pp. 3–28, ISBN978-94-007-0427-5.
• Baranoff E. 2015, 'First-row transition metal complexes for the conversion of light into electricity and electricity into light', in W-Y Wong (ed.), Organometallics and Related Molecules for Energy Conversion, Springer, Heidelberg, pp. 61–90, ISBN978-3-662-46053-5.
• Berea E., Rodriguez-lbelo M. & Navarro J. A. R. 2016, 'Platinum Group Metal—Organic frameworks' in S. Kaskel (ed.), The Chemistry of Metal-Organic Frameworks: Synthesis, Characterisation, and Applications, vol. 2, Wiley-VCH Weinheim, pp. 203–230, ISBN978-3-527-33874-0.
• Berger A. J. & Bruning N. 1979, Lady Luck's Companion: How to Play .. How to Enjoy .. How to Bet .. How to Win, Harper & Row, New York, ISBN978-0-06-014696-2.
• Berry L. G. & Mason B. 1959, Mineralogy: Concepts, Descriptions, Determinations, W. H. Freeman and Company, San Francisco.
• Biddle H. C. & Bush G. L 1949, Chemistry Today, Rand McNally, Chicago.
• Bonchev D. & Kamenska V. 1981, 'Predicting the properties of the 113–120 transactinide elements', The Journal of Physical Chemistry, vo. 85, no. 9, pp. 1177–1186, doi:10.1021/j150609a021.
• Bonetti A., Leone R., Muggia F. & Howell S. B. (eds) 2009, Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy: Molecular Mechanisms and Clinical Applications, Humana Press, New York, ISBN978-1-60327-458-6.
• Booth H. S. 1957, Inorganic Syntheses, vol. 5, McGraw-Hill, New York.
• Bradl H. E. 2005, 'Sources and origins of heavy metals', in Bradl H. E. (ed.), Heavy Metals in the Environment: Origin, Interaction and Remediation, Elsevier, Amsterdam, ISBN978-0-12-088381-3.
• Brady J. E. & Holum J. R. 1995, Chemistry: The Study of Matter and its Changes, 2nd ed., John Wiley & Sons, New York, ISBN978-0-471-10042-3.
• Brephohl E. & McCreight T. (ed) 2001, The Theory and Practice of Goldsmithing, C. Lewton-Brain trans., Brynmorgen Press, Portland, Maine, ISBN978-0-9615984-9-5.
• Brown I. 1987, 'Astatine: Its organonuclear chemistry and biomedical applications,' in H. J. Emeléus & A. G. Sharpe (eds), Advances in Inorganic Chemistry, vol. 31, Academic Press, Orlando, pp. 43–88, ISBN978-0-12-023631-2.
• Bryson R. M. & Hammond C. 2005, 'Generic methodologies for nanotechnology: Characterisation', in R. Kelsall, I. W. Hamley & M. Geoghegan, Nanoscale Science and Technology, John Wiley & Sons, Chichester, pp. 56–129, ISBN978-0-470-85086-2.
• Burkett B. 2010, Sport Mechanics for Coaches, 3rd ed., Human Kinetics, Champaign, Illinois, ISBN978-0-7360-8359-1.
• Casey C. 1993, 'Restructuring work: New work and new workers in post-industrial production', in R. P. Coulter & I. F. Goodson (eds), Rethinking Vocationalism: Whose Work/life is it?, Our Schools/Our Selves Education Foundation, Toronto, ISBN978-0-921908-15-9.
• Chakhmouradian A.R., Smith M. P. & Kynicky J. 2015, 'From 'strategic' tungsten to 'green' neodymium: A century of critical metals at a glance', Ore Geology Reviews, vol. 64, January, pp. 455–458, doi:10.1016/j.oregeorev.2014.06.008.
• Chambers E. 1743, 'Metal', in Cyclopedia: Or an Universal Dictionary of Arts and Sciences (etc.), vol. 2, D. Midwinter, London.
• Chandler D. E. & Roberson R. W. 2009, Bioimaging: Current Concepts in Light & Electron Microscopy, Jones & Bartlett Publishers, Boston, ISBN978-0-7637-3874-7.
• Chawla N. & Chawla K. K. 2013, Metal matrix composites, 2nd ed., Springer Science+Business Media, New York, ISBN978-1-4614-9547-5.
• Chen J. & Huang K. 2006, 'A new technique for extraction of platinum group metals by pressure cyanidation', Hydrometallurgy, vol. 82, nos. 3–4, pp. 164–171, doi:10.1016/j.hydromet.2006.03.041.
• Choptuik M. W., Lehner L. & Pretorias F. 2015, 'Probing strong-field gravity through numerical simulation', in A. Ashtekar, B. K. Berger, J. Isenberg & M. MacCallum (eds), General Relativity and Gravitation: A Centennial Perspective, Cambridge University Press, Cambridge, ISBN978-1-107-03731-1.
• Clegg B 2014, 'Osmium tetroxide', Chemistry World, accessed 2 September 2016.
• Close F. 2015, Nuclear Physics: A Very Short Introduction, Oxford University Press, Oxford, ISBN978-0-19-871863-5.
• Clugston M & Flemming R 2000, Advanced Chemistry, Oxford University, Oxford, ISBN978-0-19-914633-8.
• Cole M., Lindeque P., Halsband C. & Galloway T. S. 2011, 'Microplastics as contaminants in the marine environment: A review', Marine Pollution Bulletin, vol. 62, no. 12, pp. 2588–2597, doi:10.1016/j.marpolbul.2011.09.025.
• Cole S. E. & Stuart K. R. 2000, 'Nuclear and cortical histology for brightfield microscopy', in D. J. Asai & J. D. Forney (eds), Methods in Cell Biology, vol. 62, Academic Press, San Diego, pp. 313–322, ISBN978-0-12-544164-3.
• Cotton S. A. 1997, Chemistry of Precious Metals, Blackie Academic & Professional, London, ISBN978-94-010-7154-3.
• Cotton S. 2006, Lanthanide and Actinide Chemistry, reprinted with corrections 2007, John Wiley & Sons, Chichester, ISBN978-0-470-01005-1.
• Cox P. A. 1997, The elements: Their Origin, Abundance and Distribution, Oxford University Press, Oxford, ISBN978-0-19-855298-7.
• Crundwell F. K., Moats M. S., Ramachandran V., Robinson T. G. & Davenport W. G. 2011, Extractive Metallurgy of Nickel, Cobalt and Platinum Group Metals, Elsevier, Kidlington, Oxford, ISBN978-0-08-096809-4.
• Cui X-Y., Li S-W., Zhang S-J., Fan Y-Y., Ma L. Q. 2015, 'Toxic metals in children's toys and jewelry: Coupling bioaccessibility with risk assessment', Environmental Pollution, vol. 200, pp. 77–84, doi:10.1016/j.envpol.2015.01.035.
• Dapena J. & Teves M. A. 1982, 'Influence of the diameter of the hammer head on the distance of a hammer throw', Research Quarterly for Exercise and Sport, vol. 53, no. 1, pp. 78–81, doi:10.1080/02701367.1982.10605229.
• De Zuane J. 1997, Handbook of Drinking Water Quality, 2nd ed., John Wiley & Sons, New York, ISBN978-0-471-28789-6.
• Department of the Navy 2009, Gulf of Alaska Navy Training Activities: Draft Environmental Impact Statement/Overseas Environmental Impact Statement, U.S. Government, accessed 21 August 2016.
• Deschlag J. O. 2011, 'Nuclear fission', in A. Vértes, S. Nagy, Z. Klencsár, R. G. Lovas, F. Rösch (eds), Handbook of Nuclear Chemistry, 2nd ed., Springer Science+Business Media, Dordrecht, pp. 223–280, ISBN978-1-4419-0719-6.
• Desoize B. 2004, 'Metals and metal compounds in cancer treatment', Anticancer Research, vol. 24, no. 3a, pp. 1529–1544, PMID15274320.
• Dev N. 2008, 'Modelling Selenium Fate and Transport in Great Salt Lake Wetlands', PhD dissertation, University of Utah, ProQuest, Ann Arbor, Michigan, ISBN978-0-549-86542-1.
• Di Maio V. J. M. 2001, Forensic Pathology, 2nd ed., CRC Press, Boca Raton, ISBN0-8493-0072-X.
• Di Maio V. J. M. 2016, Gunshot Wounds: Practical Aspects of Firearms, Ballistics, and Forensic Techniques, 3rd ed., CRC Press, Boca Raton, Florida, ISBN978-1-4987-2570-5.
• Duffus J. H. 2002, ' 'Heavy metals'—A meaningless term?', Pure and Applied Chemistry, vol. 74, no. 5, pp. 793–807, doi:10.1351/pac200274050793.
• Dunn P. 2009, Unusual metals could forge new cancer drugs, University of Warwick, accessed 23 March 2016.
• Ebbing D. D. & Gammon S. D. 2017, General Chemistry, 11th ed., Cengage Learning, Boston, ISBN978-1-305-58034-3.
• Edelstein N. M., Fuger J., Katz J. L. & Morss L. R. 2010, 'Summary and comparison of properties of the actinde and transactinide elements,' in L. R. Morss, N. M. Edelstein & J. Fuger (eds), The Chemistry of the Actinide and Transactinide Elements, 4th ed., vol. 1–6, Springer, Dordrecht, pp. 1753–1835, ISBN978-94-007-0210-3.
• Eisler R. 1993, Zinc Hazards to Fish, Wildlife, and Invertebrates: A Synoptic Review, Biological Report 10, U. S. Department of the Interior, Laurel, Maryland, accessed 2 September 2016.
• Elliott S. B. 1946, The Alkaline-earth and Heavy-metal Soaps, Reinhold Publishing Corporation, New York.
• Emsley J. 2011, Nature's Building Blocks, new edition, Oxford University Press, Oxford, ISBN978-0-19-960563-7.
• Everts S. 2016, 'What chemicals are in your tattoo', Chemical & Engineering News, vol. 94, no. 33, pp. 24–26.
• Fournier J. 1976, 'Bonding and the electronic structure of the actinide metals,' Journal of Physics and Chemistry of Solids, vol 37, no. 2, pp. 235–244, doi:10.1016/0022-3697(76)90167-0.
• Frick J. P. (ed.) 2000, Woldman's Engineering Alloys, 9th ed., ASM International, Materials Park, Ohio, ISBN978-0-87170-691-1.
• Frommer H. H. & Stabulas-Savage J. J. 2014, Radiology for the Dental Professional, 9th ed., Mosby Inc., St. Louis, Missouri, ISBN978-0-323-06401-9.
• Gidding J. C. 1973, Chemistry, Man, and Environmental Change: An Integrated Approach, Canfield Press, New York, ISBN978-0-06-382790-5.
• Gmelin L. 1849, Hand-book of chemistry, vol. III, Metals, translated from the German by H. Watts, Cavendish Society, London.
• Goldsmith R. H. 1982, 'Metalloids', Journal of Chemical Education, vol. 59, no. 6, pp. 526–527, doi:10.1021/ed059p526.
• Gorbachev V. M., Zamyatnin Y. S. & Lbov A. A. 1980, Nuclear Reactions in Heavy Elements: A Data Handbook, Pergamon Press, Oxford, ISBN978-0-08-023595-0.
• Gordh G. & Headrick D. 2003, A Dictionary of Entomology, CABI Publishing, Wallingford, ISBN978-0-85199-655-4.
• Greenberg B. R. & Patterson D. 2008, Art in Chemistry; Chemistry in Art, 2nd ed., Teachers Ideas Press, Westport, Connecticut, ISBN978-1-59158-309-7.
• Gribbon J. 2016, 13.8: The Quest to Find the True Age of the Universe and the Theory of Everything, Yale University Press, New Haven, ISBN978-0-300-21827-5.
• Gschneidner Jr., K. A. 1975, Inorganic compounds, in C. T. Horowitz (ed.), Scandium: Its Occurrence, Chemistry, Physics, Metallurgy, Biology and Technology, Academic Press, London, pp. 152–251, ISBN978-0-12-355850-3.
• Guandalini G. S., Zhang L., Fornero E., Centeno J. A., Mokashi V. P., Ortiz P. A., Stockelman M. D., Osterburg A. R. & Chapman G. G. 2011, 'Tissue distribution of tungsten in mice following oral exposure to sodium tungstate,' Chemical Research in Toxicology, vol. 24, no. 4, pp 488–493, doi:10.1021/tx200011k.
• Guney M. & Zagury G. J. 2012, 'Heavy metals in toys and low-cost jewelry: Critical review of U.S. and Canadian legislations and recommendations for testing', Environmental Science & Technology, vol. 48, pp. 1238–1246, doi:10.1021/es4036122.
• Habashi F. 2009, 'Gmelin and his Handbuch', Bulletin for the History of Chemistry, vol. 34, no. 1, pp. 30–1.
• Hadhazy A. 2016, 'Galactic 'gold mine' explains the origin of nature's heaviest elements', Science Spotlights, 10 May 2016, accessed 11 July 2016.
• Hartmann W. K. 2005, Moons & Planets, 5th ed., Thomson Brooks/Cole, Belmont, California, ISBN978-0-534-49393-6.
• Harvey P. J., Handley H. K. & Taylor M. P. 2015, 'Identification of the sources of metal (lead) contamination in drinking waters in north-eastern Tasmania using lead isotopic compositions,' Environmental Science and Pollution Research, vol. 22, no. 16, pp. 12276–12288, doi:10.1007/s11356-015-4349-2PMID25895456.
• Hasan S. E. 1996, Geology and Hazardous Waste Management, Prentice Hall, Upper Saddle River, New Jersey, ISBN978-0-02-351682-5.
• Hawkes S. J. 1997, 'What is a 'heavy metal'?', Journal of Chemical Education, vol. 74, no. 11, p. 1374, doi:10.1021/ed074p1374.
• Haynes W. M. 2015, CRC Handbook of Chemistry and Physics, 96th ed., CRC Press, Boca Raton, Florida, ISBN978-1-4822-6097-7.
• Hendrickson D. J. 2916, 'Effects of early experience on brain and body', in D. Alicata, N. N. Jacobs, A. Guerrero and M. Piasecki (eds), Problem-based Behavioural Science and Psychiatry 2nd ed., Springer, Cham, pp. 33–54, ISBN978-3-319-23669-8.
• Hermann A., Hoffmann R. & Ashcroft N. W. 2013, 'Condensed astatine: Monatomic and metallic', Physical Review Letters, vol. 111, pp. 11604–1−11604-5, doi:10.1103/PhysRevLett.111.116404.
• Herron N. 2000, 'Cadmium compounds,' in Kirk-Othmer Encyclopedia of Chemical Technology, vol. 4, John Wiley & Sons, New York, pp. 507–523, ISBN978-0-471-23896-6.
• Hoffman D. C., Lee D. M. & Pershina V. 2011, 'Transactinide elements and future elements,' in L. R. Morss, N. Edelstein, J. Fuger & J. J. Katz (eds), The Chemistry of the Actinide and Transactinide Elements, 4th ed., vol. 3, Springer, Dordrecht, pp. 1652–1752, ISBN978-94-007-0210-3.
• Hofmann S. 2002, On Beyond Uranium: Journey to the End of the Periodic Table, Taylor & Francis, London, ISBN978-0-415-28495-0.
• Housecroft J. E. 2008, Inorganic Chemistry, Elsevier, Burlington, Massachusetts, ISBN978-0-12-356786-4.
• Howell N., Lavers J., Paterson D., Garrett R. & Banati R. 2012, Trace metal distribution in feathers from migratory, pelagic birds, Australian Nuclear Science and Technology Organisation, accessed 3 May 2014.
• Hübner R., Astin K. B. & Herbert R. J. H. 2010, ' 'Heavy metal'—time to move on from semantics to pragmatics?', Journal of Environmental Monitoring, vol. 12, pp. 1511–1514, doi:10.1039/C0EM00056F.
• Ikehata K., Jin Y., Maleky N. & Lin A. 2015, 'Heavy metal pollution in water resources in China—Occurrence and public health implications', in S. K. Sharma (ed.), Heavy Metals in Water: Presence, Removal and Safety,Royal Society of Chemistry, Cambridge, pp. 141–167, ISBN978-1-84973-885-9.
• International Antimony Association 2016, Antimony compounds, accessed 2 September 2016.
• International Platinum Group Metals Association n.d., The Primary Production of Platinum Group Metals (PGMs), accessed 4 September 2016.
• Ismail A. F., Khulbe K. & Matsuura T. 2015, Gas Separation Membranes: Polymeric and Inorganic, Springer, Cham, Switzerland, ISBN978-3-319-01095-3.
• IUPAC 2016, 'IUPAC is naming the four new elements nihonium, moscovium, tennessine, and oganesson' accessed 27 August 2016.
• Iyengar G. V. 1998, 'Reevaluation of the trace element content in Reference Man', Radiation Physics and Chemistry, vol. 51, nos 4–6, pp. 545–560, doi:10.1016/S0969-806X(97)00202-8
• Jackson J. & Summitt J. 2006, The Modern Guide to Golf Clubmaking: The Principles and Techniques of Component Golf Club Assembly and Alteration, 5th ed., Hireko Trading Company, City of Industry, California, ISBN978-0-9619413-0-7.
• Järup L 2003, 'Hazards of heavy metal contamination', British Medical Bulletin, vol. 68, no. 1, pp. 167–182, doi:10.1093/bmb/ldg032.
• Jones C. J. 2001, d- and f-Block Chemistry, Royal Society of Chemistry, Cambridge, ISBN978-0-85404-637-9.
• Kantra S. 2001, 'What's new', Popular Science, vol. 254, no. 4, April, p. 10.
• Keller C., Wolf W. & Shani J. 2012, 'Radionuclides, 2. Radioactive elements and artificial radionuclides', in F. Ullmann (ed.), Ullmann's Encyclopedia of Industrial Chemistry, vol. 31, Wiley-VCH, Weinheim, pp. 89–117, doi:10.1002/14356007.o22_o15.
• King R. B. 1995, Inorganic Chemistry of Main Group Elements, Wiley-VCH, New York, ISBN978-1-56081-679-9.
• Kolthoff I. M. & Elving P. J. FR 1964, Treatise on Analytical Chemistry, part II, vol. 6, Interscience Encyclopedia, New York, ISBN978-0-07-038685-3.
• Korenman I. M. 1959, 'Regularities in properties of thallium', Journal of General Chemistry of the USSR, English translation, Consultants Bureau, New York, vol. 29, no. 2, pp. 1366–90, ISSN0022-1279.
• Kozin L. F. & Hansen S. C. 2013, Mercury Handbook: Chemistry, Applications and Environmental Impact, RSC Publishing, Cambridge, ISBN978-1-84973-409-7.
• Kumar R., Srivastava P. K., Srivastava S. P. 1994, 'Leaching of heavy metals (Cr, Fe, and Ni) from stainless steel utensils in food simulates and food materials', Bulletin of Environmental Contamination and Toxicology, vol. 53, no. 2, doi:10.1007/BF00192942, pp. 259–266.
• Lach K., Steer B., Gorbunov B., Mička V. & Muir R. B. 2015, 'Evaluation of exposure to airborne heavy metals at gun shooting ranges', The Annals of Occupational Hygiene, vol. 59, no. 3, pp. 307–323, doi:10.1093/annhyg/meu097.
• Landis W., Sofield R. & Yu M-H. 2010, Introduction to Environmental Toxicology: Molecular Substructures to Ecological Landscapes, 4th ed., CRC Press, Boca Raton, Florida, ISBN978-1-4398-0411-7.
• Lane T. W., Saito M. A., George G. N., Pickering, I. J., Prince R. C. & Morel F. M. M. 2005, 'Biochemistry: A cadmium enzyme from a marine diatom', Nature, vol. 435, no. 7038, p. 42, doi:10.1038/435042a.
• Lee J. D. 1996, Concise Inorganic Chemistry, 5th ed., Blackwell Science, Oxford, ISBN978-0-632-05293-6.
• Leeper G. W. 1978, Managing the Heavy Metals on the LandMarcel Dekker, New York, ISBN0-8247-6661-X.
• Lemly A. D. 1997, 'A teratogenic deformity index for evaluating impacts of selenium on fish populations', Ecotoxicology and Environmental Safety, vol. 37, no. 3, pp. 259–266, doi:10.1006/eesa.1997.1554.
• Lide D. R. (ed.) 2004, CRC Handbook of Chemistry and Physics, 85th ed., CRC Press, Boca Raton, Florida, ISBN978-0-8493-0485-9.
• Liens J. 2010, 'Heavy metals as pollutants', in B. Warf (ed.), Encyclopaedia of Geography, Sage Publications, Thousand Oaks, California, pp. 1415–1418, ISBN978-1-4129-5697-0.
• Lima E., Guerra R., Lara V. & Guzmán A. 2013, 'Gold nanoparticles as efficient antimicrobial agents for Escherichia coli and Salmonella typhi ' Chemistry Central, vol. 7:11, doi:10.1186/1752-153X-7-11PMID23331621PMC3556127.
• Litasov K. D. & Shatskiy A. F. 2016, 'Composition of the Earth's core: A review', Russian Geology and Geophysics, vol. 57, no. 1, pp. 22–46, doi:10.1016/j.rgg.2016.01.003.
• Livesey A. 2012, Advanced Motorsport Engineering, Routledge, London, ISBN978-0-7506-8908-3.
• Livingston R. A. 1991, 'Influence of the Environment on the Patina of the Statue of Liberty', Environmental Science & Technology, vol. 25, no. 8, pp. 1400–1408, doi:10.1021/es00020a006.
• Longo F. R. 1974, General Chemistry: Interaction of Matter, Energy, and Man, McGraw-Hill, New York, ISBN978-0-07-038685-3.
• Love M. 1998, Phasing Out Lead from Gasoline: Worldwide Experience and Policy Implications, World Bank Technical Paper volume 397, The World Bank, Washington DC, ISBN0-8213-4157-X.
• Lyman W. J. 1995, 'Transport and transformation processes', in Fundamentals of Aquatic Toxicology, G. M. Rand (ed.), Taylor & Francis, London, pp. 449–492, ISBN978-1-56032-090-6.
• Macintyre J. E. 1994, Dictionary of inorganic compounds, supplement 2, Dictionary of Inorganic Compounds, vol. 7, Chapman & Hall, London, ISBN978-0-412-49100-9.
• MacKay K. M., MacKay R. A. & Henderson W. 2002, Introduction to Modern Inorganic Chemistry, 6th ed., Nelson Thornes, Cheltenham, ISBN978-0-7487-6420-4.
• Magee R. J. 1969, Steps to Atomic Power, Cheshire for La Trobe University, Melbourne.
• Magill F. N. I (ed.) 1992, Magill's Survey of Science, Physical Science series, vol. 3, Salem Press, Pasadena, ISBN978-0-89356-621-0.
• Martin M. H. & Coughtrey P. J. 1982, Biological Monitoring of Heavy Metal Pollution, Applied Science Publishers, London, ISBN978-0-85334-136-9.
• Massarani M. 2015, 'Brazilian mine disaster releases dangerous metals,' Chemistry World, November 2015, accessed 16 April 2016.
• Masters C. 1981, Homogenous Transition-metal Catalysis: A Gentle Art, Chapman and Hall, London, ISBN978-0-412-22110-1.
• Matyi R. J. & Baboian R. 1986, 'An X-ray Diffraction Analysis of the Patina of the Statue of Liberty', Powder Diffraction, vol. 1, no. 4, pp. 299–304, doi:10.1017/S0885715600011970.
• McColm I. J. 1994, Dictionary of Ceramic Science and Engineering, 2nd ed., Springer Science+Business Media, New York, ISBN978-1-4419-3235-8.
• McCurdy R. M. 1975, Qualities and quantities: Preparation for College Chemistry, Harcourt Brace Jovanovich, New York, ISBN978-0-15-574100-3.
• McLemore V. T. (ed.) 2008, Basics of Metal Mining Influenced Water, vol. 1, Society for Mining, Metallurgy, and Exploration, Littleton, Colorado, ISBN978-0-87335-259-8.
• McQueen K. G. 2009, Regolith geochemistry, in K. M. Scott & C. F. Pain (eds), Regolith Science, CSIRO Publishing, Collingwood, Victoria, ISBN978-0-643-09396-6.
• Mellor J. W. 1924, A comprehensive Treatise on Inorganic and Theoretical Chemistry, vol. 5, Longmans, Green and Company, London.
• Moore J. W. & Ramamoorthy S. 1984, Heavy Metals in Natural Waters: Applied Monitoring and Impact Assessment, Springer Verlag, New York, ISBN978-1-4612-9739-0.
• Morris C. G. 1992, Academic Press Dictionary of Science and Technology, Harcourt Brace Jovanovich, San Diego, ISBN978-0-12-200400-1.
• Morstein J. H. 2005, 'Fat Man', in E. A. Croddy & Y. Y. Wirtz (eds), Weapons of Mass Destruction: An Encyclopedia of Worldwide Policy, Technology, and History, ABC-CLIO, Santa Barbara, California, ISBN978-1-85109-495-0.
• Moselle B. (ed.) 2005, 2004 National Home Improvement Estimator, Craftsman Book Company, Carlsbad, California, ISBN978-1-57218-150-2.
• Naja G. M. & Volesky B. 2009, 'Toxicity and sources of Pb, Cd, Hg, Cr, As, and radionuclides', in L. K. Wang, J. P. Chen, Y. Hung & N. K. Shammas, Heavy Metals in the Environment, CRC Press, Boca Raton, Florida, ISBN978-1-4200-7316-4.
• Nakbanpote W., Meesungneon O. & Prasad M. N. V. 2016, 'Potential of ornamental plants for phytoremediation of heavy metals and income generation', in M. N. V. Prasad (ed.), Bioremediation and Bioeconomy, Elsevier, Amsterdam, pp. 179–218, ISBN978-0-12-802830-8.
• Nathans M. W. 1963, Elementary Chemistry, Prentice Hall, Englewood Cliffs, New Jersey.
• National Materials Advisory Board 1971, Trends in the Use of Depleted Uranium, National Academy of Sciences – National Academy of Engineering, Washington DC.
• National Materials Advisory Board 1973, Trends in Usage of Tungsten, National Academy of Sciences – National Academy of Engineering, Washington DC.
• National Organization for Rare Disorders 2015, Heavy metal poisoning, accessed 3 March 2016.
• Natural Resources Canada 2015, 'Generation of the Earth's magnetic field', accessed 30 August 2016.
• Nieboer E. & Richardson D. 1978, 'Lichens and 'heavy metals' ', International Lichenology Newsletter, vol. 11, no. 1, pp. 1–3.
• Nieboer E. & Richardson D. H. S. 1980, 'The replacement of the nondescript term 'heavy metals' by a biologically and chemically significant classification of metal ions', Environmental Pollution Series B, Chemical and Physical, vol. 1, no. 1, pp. 3–26, doi:10.1016/0143-148X(80)90017-8.
• Nzierżanowski K. & Gawroński S. W. 2012, 'Heavy metal concentration in plants growing on the vicinity of railroad tracks: a pilot study', Challenges of Modern Technology, vol. 3, no. 1, pp. 42–45, ISSN2353-4419, accessed 21 August 2016.
• Ohlendorf H. M. 2003, 'Ecotoxicology of selenium', in D. J. Hoffman, B. A. Rattner, G. A. Burton & J. Cairns, Handbook of Ecotoxicology, 2nd ed., Lewis Publishers, Boca Raton, pp. 466–491, ISBN978-1-56670-546-2.
• Ondreička R., Kortus J. & Ginter E. 1971, 'Aluminium, its absorption, distribution, and effects on phosphorus metabolism', in S. C. Skoryna & D. Waldron-Edward (eds), Intestinal Absorption of Metal Ions, Trace Elements and Radionuclides, Pergamon press, Oxford.
• Ong K. L., Tan T. H. & Cheung W. L. 1997, 'Potassium permanganate poisoning—a rare cause of fatal poisoning', Journal of Accident & Emergency Medicine, vol. 14, no. 1, pp. 43–45, PMC1342846.
• Oxford English Dictionary 1989, 2nd ed., Oxford University Press, Oxford, ISBN978-0-19-861213-1.
• Pacheco-Torgal F., Jalali S. & Fucic A. (eds) 2012, Toxicity of building materials, Woodhead Publishing, Oxford, ISBN978-0-85709-122-2.
• Padmanabhan T. 2001, Theoretical Astrophysics, vol. 2, Stars and Stellar Systems, Cambridge University Press, Cambridge, ISBN978-0-521-56241-6.
• Pan W. & Dai J. 2015, 'ADS based on linear accelerators', in W. Chao & W. Chou (eds), Reviews of accelerator science and technology, vol. 8, Accelerator Applications in Energy and Security, World Scientific, Singapore, pp. 55–76, ISBN981-3108-89-4.
• Parish R. V. 1977, The Metallic Elements, Longman, New York, ISBN978-0-582-44278-8.
• Perry J. & Vanderklein E. L. Water Quality: Management of a Natural Resource, Blackwell Science, Cambridge, Massachusetts ISBN0-86542-469-1.
• Pickering N. C. 1991, The Bowed String: Observations on the Design, Manufacture, Testing and Performance of Strings for Violins, Violas and Cellos, Amereon, Mattituck, New York.
• Podosek F. A. 2011, 'Noble gases', in H. D. Holland & K. K. Turekian (eds), Isotope Geochemistry: From the Treatise on Geochemistry, Elsevier, Amsterdam, pp. 467–492, ISBN978-0-08-096710-3.
• Podsiki C. 2008, 'Heavy metals, their salts, and other compounds', AIC News, November, special insert, pp. 1–4.
• Preschel J. July 29, 2005, 'Green bullets not so eco-friendly', CBS News, accessed 18 March 2016.
• Preuss P. 17 July 2011, 'What keeps the Earth cooking?,' Berkeley Lab, accessed 17 July 2016.
• Prieto C. 2011, The Adventures of a Cello: Revised Edition, with a New Epilogue,University of Texas Press, Austin, ISBN978-0-292-72393-1
• Raghuram P., Soma Raju I. V. & Sriramulu J. 2010, 'Heavy metals testing in active pharmaceutical ingredients: an alternate approach', Pharmazie, vol. 65, no. 1, pp. 15–18, doi:10.1691/ph.2010.9222.
• Rainbow P. S. 1991, 'The biology of heavy metals in the sea', in J. Rose (ed.), Water and the Environment, Gordon and Breach Science Publishers, Philadelphia, pp. 415–432, ISBN978-2-88124-747-7.
• Rand G. M., Wells P. G. & McCarty L. S. 1995, 'Introduction to aquatic toxicology', in G. M. Rand (ed.), Fundamentals of Aquatic Toxicology: Effects, Environmental Fate and Risk Assessment, 2nd ed., Taylor & Francis, London, pp. 3–70, ISBN978-1-56032-090-6.
• Rankin W. J. 2011, Minerals, Metals and Sustainability: Meeting Future Material Needs, CSIRO Publishing, Collingwood, Victoria, ISBN978-0-643-09726-1.
• Rasic-Milutinovic Z. & Jovanovic D. 2013, 'Toxic metals', in M. Ferrante, G. Oliveri Conti, Z. Rasic-Milutinovic & D. Jovanovic (eds), Health Effects of Metals and Related Substances in Drinking Water, IWA Publishing, London, ISBN978-1-68015-557-0.
• Raymond R. 1984, Out of the Fiery Furnace: The Impact of Metals on the History of Mankind, Macmillan, South Melbourne, ISBN978-0-333-38024-6.
• Rebhandl W., Milassin A., Brunner L., Steffan I., Benkö T., Hörmann M., Burschen J. 2007, 'In vitro study of ingested coins: Leave them or retrieve them?', Journal of Paediatric Surgery, vol. 42, no. 10, pp. 1729–1734, doi:10.1016/j.jpedsurg.2007.05.031.
• Rehder D. 2010, Chemistry in Space: From Interstellar Matter to the Origin of Life, Wiley-VCH, Weinheim, ISBN978-3-527-32689-1.
• Renner H., Schlamp G., Kleinwächter I., Drost E., Lüchow H. M., Tews P., Panster P., Diehl M., Lang J., Kreuzer T., Knödler A., Starz K. A., Dermann K., Rothaut J., Drieselmann R., Peter C. & Schiele R. 2012, 'Platinum Group Metals and compounds', in F. Ullmann (ed.), Ullmann's Encyclopedia of Industrial Chemistry, vol. 28, Wiley-VCH, Weinheim, pp. 317–388, doi:10.1002/14356007.a21_075.
• Reyes J. W. 2007, Environmental Policy as Social Policy? The Impact of Childhood Lead Exposure on Crime, National Bureau of Economic Research Working Paper 13097, accessed 16 October 2016.
• Ridpath I. (ed.) 2012, Oxford Dictionary of Astronomy, 2nd ed. rev., Oxford University Press, New York, ISBN978-0-19-960905-5.
• Rockhoff H. 2012, America's Economic Way of War: War and the US Economy from the Spanish–American War to the Persian Gulf War, Cambridge University Press, Cambridge, ISBN978-0-521-85940-0.
• Roe J. & Roe M. 1992, 'World's coinage uses 24 chemical elements', World Coinage News, vol. 19, no. 4, pp. 24–25; no. 5, pp. 18–19.
• Russell A. M. & Lee K. L. 2005, Structure–Property Relations in Nonferrous Metals, John Wiley & Sons, Hoboken, New Jersey, ISBN978-0-471-64952-6.
• Rusyniak D. E., Arroyo A., Acciani J., Froberg B., Kao L. & Furbee B. 2010, 'Heavy metal poisoning: Management of intoxication and antidotes', in A. Luch (ed.), Molecular, Clinical and Environmental Toxicology, vol. 2, Birkhäuser Verlag, Basel, pp. 365–396, ISBN978-3-7643-8337-4.
• Ryan J. 2012, Personal Financial Literacy, 2nd ed., South-Western, Mason, Ohio, ISBN978-0-8400-5829-4.
• Samsonov G. V. (ed.) 1968, Handbook of the Physicochemical Properties of the Elements, IFI-Plenum, New York, ISBN978-1-4684-6066-7.
• Sanders R. 2003, 'Radioactive potassium may be major heat source in Earth's core,' UCBerkelyNews, 10 December, accessed 17 July 20016.
• Schweitzer P. A. 2003, Metallic materials: Physical, Mechanical, and Corrosion properties, Marcel Dekker, New York, ISBN978-0-8247-0878-8.
• Schweitzer G. K. & Pesterfield L. L. 2010, The Aqueous Chemistry of the Elements, Oxford University Press, Oxford, ISBN978-0-19-539335-4.
• Scott R. M. 1989, Chemical Hazards in the Workplace, CRC Press, Boca Raton, Orlando, ISBN978-0-87371-134-0.
• Scoullos M. (ed.), Vonkeman G. H., Thornton I. & Makuch Z. 2001, Mercury — Cadmium — Lead Handbook for Sustainable Heavy Metals Policy and Regulation, Kluwer Academic Publishers, Dordrecht, ISBN978-1-4020-0224-3.
• Selinger B. 1978, Chemistry in the Market Place, 2nd ed., Australian National University Press, Canberra, ISBN978-0-7081-0728-7.
• Seymour R. J. & O'Farrelly J. 2012, 'Platinum Group Metals', Kirk-Other Encyclopaedia of Chemical Technology, John Wiley & Sons, New York, doi:10.1002/0471238961.1612012019052513.a01.pub3.
• Shaw B. P., Sahu S. K. & Mishra R. K. 1999, 'Heavy metal induced oxidative damage in terrestrial plants', in M. N. V. Prased (ed.), Heavy Metal Stress in Plants: From Biomolecules to Ecosystems Springer-Verlag, Berlin, ISBN978-3-540-40131-5.
• Shedd K. B. 2002, 'Tungsten', Minerals Yearbook, United States Geological Survey.
• Sidgwick N. V. 1950, The Chemical Elements and their Compounds, vol. 1, Oxford University Press, London.
• Silva R. J. 2010, 'Fermium, mendelevium, nobelium, and lawrencium', in L. R. Morss, N. Edelstein & J. Fuger (eds), The Chemistry of the Actinide and Transactinide Elements, vol. 3, 4th ed., Springer, Dordrecht, pp. 1621–1651, ISBN978-94-007-0210-3.
• Spolek G. 2007, 'Design and materials in fly fishing', in A. Subic (ed.), Materials in Sports Equipment, Volume 2, Woodhead Publishing, Abington, Cambridge, pp. 225–247, ISBN978-1-84569-131-8.
• Stankovic S. & Stankocic A. R. 2013, 'Bioindicators of toxic metals', in E. Lichtfouse, J. Schwarzbauer, D. Robert 2013, Green materials for energy, products and depollution, Springer, Dordrecht, ISBN978-94-007-6835-2, pp. 151–228.
• State Water Control Resources Board 1987, Toxic substances monitoring program, issue 79, part 20 of the Water Quality Monitoring Report, Sacramento, California.
• Technical Publications 1953, Fire Engineering, vol. 111, p. 235, ISSN0015-2587.
• The Minerals, Metals and Materials Society, Light Metals Division 2016, accessed 22 June 2016.
• The United States Pharmacopeia 1985, 21st revision, The United States Pharmacopeial Convention, Rockville, Maryland, ISBN978-0-913595-04-6.
• Thorne P. C. L. & Roberts E. R. 1943, Fritz Ephraim Inorganic Chemistry, 4th ed., Gurney and Jackson, London.
• Tisza M. 2001, Physical Metallurgy for Engineers, ASM International, Materials Park, Ohio, ISBN978-0-87170-725-3.
• Tokar E. J., Boyd W. A., Freedman J. H. & Wales M. P. 2013, 'Toxic effects of metals', in C. D. Klaassen (ed.), Casarett and Doull's Toxicology: the Basic Science of Poisons, 8th ed., McGraw-Hill Medical, New York, ISBN978-0-07-176923-5, accessed 9 September 2016 (subscription required).
• Tomasik P. & Ratajewicz Z. 1985, Pyridine metal complexes, vol. 14, no. 6A, The Chemistry of Heterocyclic Compounds, John Wiley & Sons, New York, ISBN978-0-471-05073-5.
• Topp N. E. 1965, The Chemistry of the Rare-earth Elements, Elsevier Publishing Company, Amsterdam.
• Torrice M. 2016, 'How lead ended up in Flint's tap water,' Chemical & Engineering News, vol. 94, no. 7, pp. 26–27.
• Tretkoff E. 2006, 'March 20, 1800: Volta describes the Electric Battery', APS News, This Month in Physics History, American Physical Society, accessed 26 August 2016.
• Uden P. C. 2005, 'Speciation of Selenium,' in R. Cornelis, J. Caruso, H. Crews & K. Heumann (eds), Handbook of Elemental Speciation II: Species in the Environment, Food, Medicine and Occupational Health, John Wiley & Sons, Chichester, pp. 346–65, ISBN978-0-470-85598-0.
• United States Environmental Protection Agency 1988, Ambient Aquatic Life Water Quality Criteria for Antimony (III), draft, Office of Research and Development, Environmental Research Laboratories, Washington.
• United States Environmental Protection Agency 2014, Technical Fact Sheet–Tungsten, accessed 27 March 2016.
• United States Government 2014, Toxic Pollutant List, Code of Federal Regulations, 40 CFR 401.15., accessed 27 March 2016.
• Valkovic V. 1990, 'Origin of trace element requirements by living matter', in B. Gruber & J. H. Yopp (eds), Symmetries in Science IV: Biological and biophysical systems, Plenum Press, New York, pp. 213–242, ISBN978-1-4612-7884-9.
• VanGelder K. T. 2014, Fundamentals of Automotive Technology: Principles and Practice, Jones & Bartlett Learning, Burlington MA, ISBN978-1-4496-7108-2.
• Venner M., Lessening M., Pankani D. & Strecker E. 2004, Identification of Research Needs Related to Highway Runoff Management, Transportation Research Board, Washington DC, ISBN978-0-309-08815-2, accessed 21 August 2016.
• Venugopal B. & Luckey T. D. 1978, Metal Toxicity in Mammals, vol. 2, Plenum Press, New York, ISBN978-0-306-37177-6.
• Vernon R. E. 2013, 'Which elements are metalloids', Journal of Chemical Education, vol. 90, no. 12, pp. 1703–1707, doi:10.1021/ed3008457.
• Volesky B. 1990, Biosorption of Heavy Metals, CRC Press, Boca Raton, ISBN978-0-8493-4917-1.
• von Gleich A. 2013, 'Outlines of a sustainable metals industry', in A. von Gleich, R. U. Ayres & S. Gößling-Reisemann (eds), Sustainable Metals Management, Springer, Dordrecht, pp. 3–40, ISBN978-1-4020-4007-8.
• von Zeerleder A. 1949, Technology of Light Metals, Elsevier Publishing Company, New York.
• Warth A. H. 1956, The Chemistry and Technology of Waxes, Reinhold Publishing Corporation, New York.
• Weart S. R. 1983, 'The discovery of nuclear fission and a nuclear physics paradigm', in W. Shea (ed.), Otto Hahn and the Rise of Nuclear Physics, D. Reidel Publishing Company, Dordrecht, pp. 91–133, ISBN978-90-277-1584-5.
• Weber D. J. & Rutula W. A. 2001, 'Use of metals as microbicides in preventing infections in healthcare', in Disinfection, Sterilization, and Preservation, 5th ed., S. S. Block (ed.), Lippincott, Williams & Wilkins, Philadelphia, ISBN978-0-683-30740-5.
• Weller G. 1976, Cleaning and Preservation of Coins and Medals, S. J. Durst, New York, ISBN978-0-915262-03-8.
• White C. 2010, Projectile Dynamics in Sport: Principles and Applications, Routledge, London, ISBN978-0-415-47331-6.
• Wiberg N. 2001, Inorganic Chemistry, Academic Press, San Diego, ISBN978-0-12-352651-9.
• Wijayawardena M. A. A., Megharaj M. & Naidu R. 2016, 'Exposure, toxicity, health impacts and bioavailability of heavy metal mixtures', in D. L. Sparks, Advances in Agronomy, vol. 138, pp. 175–234, Academic Press, London, ISBN978-0-12-804774-3.
• Wingerson L. 1986, 'America cleans up Liberty', New Scientist, 25 December/1 January 1987, pp. 31–35, accessed 1 October 2016.
• Wong M. Y., Hedley G. J., Xie G., Kölln L. S, Samuel I. D. W., Pertegaś A., Bolink H. J., Mosman-Colman, E., 'Light-emitting electrochemical cells and solution-processed organic light-emitting diodes using small molecule organic thermally activated delayed fluorescence emitters', Chemistry of Materials, vol. 27, no. 19, pp. 6535–6542, doi:10.1021/acs.chemmater.5b03245.
• Wulfsberg G. 1987, Principles of Descriptive Inorganic Chemistry, Brooks/Cole Publishing Company, Monterey, California, ISBN978-0-534-07494-4.
• Wulfsberg G. 2000, Inorganic Chemistry, University Science Books, Sausalito, California, ISBN978-1-891389-01-6.
• Yadav J. S., Antony A., Subba Reddy, B. V. 2012, 'Bismuth(III) salts as synthetic tools in organic transformations', in T. Ollevier (ed.), Bismuth-mediated Organic Reactions, Topics in Current Chemistry 311, Springer, Heidelberg, ISBN978-3-642-27238-7.
• Yang D. J., Jolly W. L. & O'Keefe A. 1977, 'Conversion of hydrous germanium(II) oxide to germynyl sesquioxide, (HGe)₂O₃', 'Inorganic Chemistry, vol. 16, no. 11, pp. 2980–2982, doi:10.1021/ic50177a070.
• Yousif N. 2007, Geochemistry of stream sediment from the state of Colorado using NURE data, ETD Collection for the University of Texas, El Paso, paper AAI3273991.

Further reading[edit]

Definition and usage

• Ali H. & Khan E. 2017, 'What are heavy metals? long-standing controversy over the scientific use of the term 'heavy metals'—proposal of a comprehensive definition', Toxicological & Environmental Chemistry, pp. 1–25, doi:10.1080/02772248.2017.1413652. Suggests defining heavy metals as 'naturally occurring metals having atomic number (Z) greater than 20 and an elemental density greater than 5 g cm⁻³'.
• Duffus J. H. 2002, 'Heavy metals'—A meaningless term?', Pure and Applied Chemistry, vol. 74, no. 5, pp. 793–807, doi:10.1351/pac200274050793. Includes a survey of the term's various meanings.
• Hawkes S. J. 1997, 'What is a 'heavy metal'?', Journal of Chemical Education, vol. 74, no. 11, p. 1374, doi:10.1021/ed074p1374. A chemist's perspective.
• Hübner R., Astin K. B. & Herbert R. J. H. 2010, ' 'Heavy metal'—time to move on from semantics to pragmatics?', Journal of Environmental Monitoring, vol. 12, pp. 1511–1514, doi:10.1039/C0EM00056F. Finds that, despite its lack of specificity, the term appears to have become part of the language of science.

Toxicity and biological role

• Baird C. & Cann M. 2012, Environmental Chemistry, 5th ed., chapter 12, 'Toxic heavy metals', W. H. Freeman and Company, New York, ISBN1-4292-7704-1. Discusses the use, toxicity, and distribution of Hg, Pb, Cd, As, and Cr.
• Nieboer E. & Richardson D. H. S. 1980, 'The replacement of the nondescript term 'heavy metals' by a biologically and chemically significant classification of metal ions', Environmental Pollution Series B, Chemical and Physical, vol. 1, no. 1, pp. 3–26, doi:10.1016/0143-148X(80)90017-8. A widely cited paper, focusing on the biological role of heavy metals.

Formation

• Hadhazy A. 2016, 'Galactic 'gold mine' explains the origin of nature's heaviest elements', Science Spotlights, 10 May, accessed 11 July 2016

Uses

• Koehler C. S. W. 2001, 'Heavy metal medicine', Chemistry Chronicles, American Chemical Society, accessed 11 July 2016
• Morowitz N. 2006, 'The heavy metals,' Modern Marvels, season 12, episode 14, HistoryChannel.com
• Öhrström L. 2014, 'Tantalum oxide', Chemistry World, 24 September, accessed 4 October 2016. The author explains how tantalum(V) oxide banished brick-sized mobile phones. Also available as a podcast.

External links[edit]

• Media related to Heavy metals at Wikimedia Commons

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, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity.

Introduction

Heavy metals are defined as metallic elements that have a relatively high density compared to water [1]. With the assumption that heaviness and toxicity are inter-related, heavy metals also include metalloids, such as arsenic, that are able to induce toxicity at low level of exposure [2]. In recent years, there has been an increasing ecological and global public health concern associated with environmental contamination by these metals. Also, human exposure has risen dramatically as a result of an exponential increase of their use in several industrial, agricultural, domestic and technological applications [3]. Reported sources of heavy metals in the environment include geogenic, industrial, agricultural, pharmaceutical, domestic effluents, and atmospheric sources []. Environmental pollution is very prominent in point source areas such as mining, foundries and smelters, and other metal-based industrial operations [1, 3, ].

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 [–]. 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]. Natural phenomena such as weathering and volcanic eruptions have also been reported to significantly contribute to heavy metal pollution [1, 3, , , 8]. Industrial sources include metal processing in refineries, coal burning in power plants, petroleum combustion, nuclear power stations and high tension lines, plastics, textiles, microelectronics, wood preservation and paper processing plants [–11].

It has been reported that metals such as cobalt (Co), copper (Cu), chromium (Cr), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), selenium (Se) and zinc (Zn) are essential nutrients that are required for various biochemical and physiological functions [12]. Inadequate supply of these micro-nutrients results in a variety of deficiency diseases or syndromes [12].

Heavy metals are also considered as trace elements because of their presence in trace concentrations (ppb range to less than 10ppm) in various environmental matrices [13]. Their bioavailability is influenced by physical factors such as temperature, phase association, adsorption and sequestration. It is also affected by chemical factors that influence speciation at thermodynamic equilibrium, complexation kinetics, lipid solubility and octanol/water partition coefficients [14]. Biological factors such as species characteristics, trophic interactions, and biochemical/physiological adaptation, also play an important role [15].

The essential heavy metals exert biochemical and physiological functions in plants and animals. They are important constituents of several key enzymes and play important roles in various oxidation-reduction reactions [12]. Copper for example serves as an essential co-factor for several oxidative stress-related enzymes including catalase, superoxide dismutase, peroxidase, cytochrome c oxidases, ferroxidases, monoamine oxidase, and dopamine β-monooxygenase [–18]. Hence, it is an essential nutrient that is incorporated into a number of metalloenzymes involved in hemoglobin formation, carbohydrate metabolism, catecholamine biosynthesis, and cross-linking of collagen, elastin, and hair keratin. The ability of copper to cycle between an oxidized state, Cu(II), and reduced state, Cu(I), is used by cuproenzymes involved in redox reactions [–18]. However, it is this property of copper that also makes it potentially toxic because the transitions between Cu(II) and Cu(I) can result in the generation of superoxide and hydroxyl radicals [–]. Also, excessive exposure to copper has been linked to cellular damage leading to Wilson disease in humans [18, ]. Similar to copper, several other essential elements are required for biologic functioning, however, an excess amount of such metals produces cellular and tissue damage leading to a variety of adverse effects and human diseases. For some including chromium and copper, there is a very narrow range of concentrations between beneficial and toxic effects [, 20]. Other metals such as aluminium (Al), antinomy (Sb), arsenic (As), barium (Ba), beryllium (Be), bismuth (Bi), cadmium (Cd), gallium (Ga), germanium (Ge), gold (Au), indium (In), lead (Pb), lithium (Li), mercury (Hg), nickel (Ni), platinum (Pt), silver (Ag), strontium (Sr), tellurium (Te), thallium (Tl), tin (Sn), titanium (Ti), vanadium (V) and uranium (U) have no established biological functions and are considered as non-essential metals [20].

In biological systems, heavy metals have been reported to affect cellular organelles and components such as cell membrane, mitochondrial, lysosome, endoplasmic reticulum, nuclei, and some enzymes involved in metabolism, detoxification, and damage repair []. Metal ions have been found to interact with cell components such as DNA and nuclear proteins, causing DNA damage and conformational changes that may lead to cell cycle modulation, carcinogenesis or apoptosis [20–]. Several studies from our laboratory have demonstrated that reactive oxygen species (ROS) production and oxidative stress play a key role in the toxicity and carcinogenicity of metals such as arsenic [, , ], cadmium [], chromium [, ], lead [, ], and mercury [, 32]. Because of their high degree of toxicity, these five elements rank among the priority metals that are of great public health significance. They are all systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. According to the United States Environmental Protection Agency (U.S. EPA), and the International Agency for Research on Cancer (IARC), these metals are also classified as either “known” or “probable” human carcinogens based on epidemiological and experimental studies showing an association between exposure and cancer incidence in humans and animals.

Heavy metal-induced toxicity and carcinogenicity involves many mechanistic aspects, some of which are not clearly elucidated or understood. However, each metal is known to have unique features and physic-chemical properties that confer to its specific toxicological mechanisms of action. This review provides an analysis of the environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity of arsenic, cadmium, chromium, lead, and mercury.

Arsenic

Environmental Occurrence, Industrial Production and Use

Arsenic is a ubiquitous 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, algicides, sheep dips, wood preservatives, and dye-stuffs. They have also been used in veterinary medicine for the eradication of tapeworms in sheep and cattle []. 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 [,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 []. Its therapeutic action has been attributed to the induction of programmed cell death (apoptosis) in leukemia cells [].

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. Exposure to arsenic occurs via the oral route (ingestion), inhalation, dermal contact, and the parenteral route to some extent [33,37]. 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. Its water concentration is usually less than 10µg/L, although higher levels can occur near natural mineral deposits or mining sites. Its 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 [].

Diet, for most individuals, is the largest source of exposure, with an average intake of about 50 µg per day. Intake from air, water and soil are usually much smaller, but exposure from these media may become significant in areas of arsenic contamination. Workers who produce or use arsenic compounds in such occupations as vineyards, ceramics, glass-making, smelting, refining of metallic ores, pesticide manufacturing and application, wood preservation, semiconductor manufacturing can be exposed to substantially higher levels of arsenic [39]. Arsenic has also been identified at 781 sites of the 1,300 hazardous waste sites that have been proposed by the U.S. EPA for inclusion on the national priority list [33,39]. Human exposure at these sites may occur by a variety of pathways, including inhalation of dusts in air, ingestion of contaminated water or soil, or through the food chain [40].

Contamination with high levels of arsenic is of concern because arsenic can cause a number of human health effects. Several epidemiological studies have reported a strong association between arsenic exposure and increased risks of both carcinogenic and systemic health effects []. Interest in the toxicity of arsenic has been heightened by recent reports of large populations in West Bengal, Bangladesh, Thailand, Inner Mongolia, Taiwan, China, Mexico, Argentina, Chile, Finland and Hungary that have been exposed to high concentrations of arsenic in their drinking water and are displaying various clinico-pathological conditions including cardiovascular and peripheral vascular disease, developmental anomalies, neurologic and neurobehavioural disorders, diabetes, hearing loss, portal fibrosis, hematologic disorders (anemia, leukopenia and eosinophilia) and carcinoma [, 33, 35, 39]. Arsenic exposure affects virtually all organ systems including the cardiovascular, dermatologic, nervous, hepatobilliary, renal, gastro-intestinal, and respiratory systems []. Research has also pointed to significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, and liver in many areas of arsenic pollution. The severity of adverse health effects is related to the chemical form of arsenic, and is also time- and dose-dependent [42,]. Although the evidence of carcinogenicity of arsenic in humans seems strong, the mechanism by which it produces tumors in humans is not completely understood [].

Mechanisms of 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 []. Most cases of human toxicity from arsenic have been associated with exposure to inorganic arsenic. Inorganic trivalent arsenite (As^III) is 2–10 times more toxic than pentavalent arsenate (As^V) [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. As (V) can replace phosphate, which is involved in many biochemical pathways [5, ].

One of the mechanisms by which arsenic exerts its toxic effect is through impairment of cellular respiration by the inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorous in a variety of biochemical reactions [48]. Arsenic in vitro reacts with protein sulfhydryl groups to inactivate enzymes, such as dihydrolipoyl dehydrogenase and thiolase, thereby producing inhibited oxidation of pyruvate and betaoxidation of fatty acids [49]. The major metabolic pathway for inorganic arsenic in humans is methylation. Arsenic trioxide is methylated to two major metabolites via a non-enzymatic process to monomethylarsonic acid (MMA), which is further methylated enzymatically to dimethyl arsenic acid (DMA) before excretion in the urine [40, ]. It was previously thought that this methylation process is a pathway of arsenic detoxification, however, recent studies have pointed out that some methylated metabolites may be more toxic than arsenite if they contain trivalent forms of arsenic [].

Tests for genotoxicity have indicated that arsenic compounds inhibit DNA repair, and induce chromosomal aberrations, sister-chromatid exchanges, and micronuclei formation in both human and rodent cells in culture [–] and in cells of exposed humans []. Reversion assays with Salmonella typhimurium fail to detect mutations that are induced by arsenic compounds. Although arsenic compounds are generally perceived as weak mutagens in bacterial and animal cells, they exhibit clastogenic properties in many cell types in vivo and in vitro []. In the absence of animal models, in vitro cell transformation studies become a useful means of obtaining information on the carcinogenic mechanisms of arsenic toxicity. Arsenic and arsenical compounds are cytotoxic and induce morphological transformations of Syrian hamster embryo (SHE) cells as well as mouse C3H10T1/2 cells and BALB/3T3 cells [, ].

Based on the comet assay, it has been reported that arsenic trioxide induces DNA damage in human lymphophytes [] and also in mice leukocytes []. Arsenic compounds have also been shown to induce gene amplification, arrest cells in mitosis, inhibit DNA repair, and induce expression of the c-fos gene and the oxidative stress protein heme oxygenase in mammalian cells [, ]. They have been implicated as promoters and comutagens for a variety of toxic agents []. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic and able to transcriptionally induce a significant number of stress genes and related proteins in human liver carcinoma cells [].

Epidemiological investigations have indicated that long-term arsenic exposure results in promotion of carcinogenesis. Several hypotheses have been proposed to describe the mechanism of arsenic-induced carcinogenesis. Zhao et al. [] reported that arsenic may act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression. Additionally, it was found that arsenic is a potent stimulator of extracellular signal-regulated protein kinase Erk1 and AP-1 transactivational activity, and an efficient inducer of c-fos and c-jun gene expression []. Induction of c-jun and c-fos by arsenic is associated with activation of JNK []. However, the role of JNK activation by arsenite in cell transformation or tumor promotion is unclear.

In another study, Trouba et al. [] concluded that long-term exposure to high levels of arsenic might make cells more susceptible to mitogenic stimulation and that alterations in mitogenic signaling proteins might contribute to the carcinogenic action of arsenic. Collectively, several recent studies have demonstrated that arsenic can interfere with cell signaling pathways (e.g., the p53 signaling pathway) that are frequently implicated in the promotion and progression of a variety of tumor types in experimental animal models, and of some human tumors [, ]. However, the specific alterations in signal transduction pathways or the actual targets that contribute to the development of arsenic-induced tumors in humans following chronic consumption of arsenic remains uncertain.

Recent clinical trials have found that arsenic trioxide has therapeutic value in the treatment of acute promyelocytic leukemia, and there is interest in exploring its effectiveness in the treatment of a variety of other cancers [,]. In acute promyelocytic leukemia, the specific molecular event critical to the formation of malignant cells is known. A study by Puccetti et al. [] found that forced overexpression of BCR-ABL susceptibility in human lymphoblasts cells resulted in greatly enhanced sensitivity to arsenic-induced apoptosis. They also concluded that arsenic trioxide is a tumor specific agent capable of inducing apoptosis selectively in acute promyelocytic leukemia cells. Several recent studies have shown that arsenic can induce apoptosis through alterations in other cell signaling pathways [,]. In addition to acute peomyelocytic leukemia, arsenic is thought to have therapeutic potential for myeloma []. In summary, numerous cancer chemotherapy studies in cell cultures and in patients with acute promyelocytic leukemia demonstrate that arsenic trioxide administration can lead to cell-cycle arrest and apoptosis in malignant cells.

Previous studies have also examined p53 gene expression and mutation in tumors obtained from subjects with a history of arsenic ingestion. p53 participates in many cellular functions, cell-cycle control, DNA repair, differentiation, genomic plasticity and programmed cell death. Additional support for the hypothesis that arsenic can modulate gene expression has been provided by several different studies [,]. Collectively, these studies provide further evidence that various forms of arsenic can alter gene expression and that such changes could contribute substantially to the toxic and carcinogenic actions of arsenic treatment in human populations [].

Several in vitro studies in our laboratory have demonstrated that arsenic modulates DNA synthesis, gene and protein expression, genotoxicity, mitosis and/or apoptotic mechanisms in various cell lines including keratinocytes, melanocytes, dendritic cells, dermal fibroblasts, microvascular endothelial cells, monocytes, and T-cells [], colon cancer cells [], lung cancer cells [], human leukemia cells [], Jurkat-T lymphocytes [], and human liver carcinoma cells []. We have also shown that oxidative stress plays a key role in arsenic induced cytotoxicity, a process that is modulated by pro- and/or anti-oxidants such as ascorbic acid and n-acetyl cysteine [–]. We have further demonstrated that the toxicity of arsenic depends on its chemical form, the inorganic form being more toxic than the organic one [42].

Various hypotheses have been proposed to explain the carcinogenicity of inorganic arsenic. Nevertheless, the molecular mechanisms by which this arsenical induces cancer are still poorly understood. Results of previous studies have indicated that inorganic arsenic does not act through classic genotoxic and mutagenic mechanisms, but rather may be a tumor promoter that modifies signal transduction pathways involved in cell growth and proliferation []. Although much progress has been recently made in the area of arsenic’s possible mode(s) of carcinogenic action, a scientific consensus has not yet reached. A recent review discusses nine different possible modes of action of arsenic carcinogenesis: induced chromosomal abnormalities, oxidative stress, altered DNA repair, altered DNA methylation patterns, altered growth factors, enhanced cell proliferation, promotion/progression, suppression of p53, and gene amplification []. Presently, three modes (chromosomal abnormality, oxidative stress, and altered growth factors) of arsenic carcinogenesis have shown a degree of positive evidence, both in experimental systems (animal and human cells) and in human tissues. The remaining possible modes of carcinogenic action (progression of carcinogenesis, altered DNA repair, p53 suppression, altered DNA methylation patterns and gene amplification) do not have as much evidence, particularly from in vivo studies with laboratory animals, in vitro studies with cultured human cells, or human data from case or population studies. Thus, the mode-of-action studies suggest that arsenic might be acting as a cocarcinogen, a promoter, or a progressor of carcinogenesis.

Cadmium

Environmental Occurrence, Industrial Production and Use

Cadmium 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 contain 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 plating works and, more recently, to the introduction of general restrictions on cadmium consumption in certain countries.

Potential for Human Exposure

The main routes of exposure to cadmium are via 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, ]. 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 []. 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 []. Workplace exposure to airborne cadmium particulates has been associated with decreases in olfactory function []. Several epidemiologic studies have documented an association of chronic low-level cadmium exposure with decreases in bone mineral density and osteoporosis [–].

Exposure to cadmium is commonly determined by measuring cadmium levels in blood or urine. Blood cadmium reflects recent cadmium exposure (from smoking, for example). Cadmium in urine (usually adjusted for dilution by calculating the cadmium/creatinine ratio) indicates accumulation, or kidney burden of cadmium [, ]. It is estimated that about 2.3% of the U.S. population has elevated levels of urine cadmium (>2µg/g creatinine), a marker of chronic exposure and body burden []. Blood and urine cadmium levels are typically higher in cigarette smokers, intermediate in former smokers and lower in nonsmokers [, ]. Because of continuing use of cadmium in industrial applications, the environmental contamination and human exposure to cadmium have dramatically increased during the past century [104].

Molecular Mechanisms of 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 []. 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 [].

Although the mechanisms of cadmium toxicity are poorly understood, it has been speculated that cadmium causes damage to cells primarily through the generation of ROS [], which causes single-strand DNA damage and disrupts the synthesis of nucleic acids and proteins []. Studies using two-dimensional gel electrophoresis have shown that several stress response systems are expressed in response to cadmium exposure, including those for heat shock, oxidative stress, stringent response, cold shock, and SOS [– ]. In vitro studies indicate that cadmium induces cytotoxic effects at the concentrations 0.1 to 10 mM and free radical-dependent DNA damage [, 117]. In vivo studies have shown that cadmium modulates male reproduction in mice model at a concentration of 1 mg/kg body weight []. However, cadmium is a weak mutagen when compared with other carcinogenic metals []. Previous reports have indicated that cadmium affects signal transduction pathways; inducing inositol polyphosphate formation, increasing cytosolic free calcium levels in various cell types [], and blocking calcium channels [, ]. At lower concentrations (1–100 µM), cadmium binds to proteins, decreases DNA repair [], activates protein degradation, up-regulates cytokines and proto-oncogenes such as c-fos, c-jun, and c-myc [], and induces expression of several genes including metallothioneins [], heme oxygenases, glutathione transferases, heat-shock proteins, acute-phase reactants, and DNA polymerase β [].

Cadmium compounds are classified as human carcinogens by several regulatory agencies. The International Agency for Research on Cancer [91] and the U.S. National Toxicology Program have concluded that there is adequate evidence that cadmium is a human carcinogen. This designation as a human carcinogen is based primarily on repeated findings of an association between occupational cadmium exposure and lung cancer, as well as on very strong rodent data showing the pulmonary system as a target site [91]. Thus, the lung is the most definitively established site of human carcinogenesis from cadmium exposure. Other target tissues of cadmium carcinogenesis in animals include injection sites, adrenals, testes, and the hemopoietic system [91, 108, 109]. In some studies, occupational or environmental cadmium exposure has also been associated with development of cancers of the prostate, kidney, liver, hematopoietic system and stomach [108, 109]. Carcinogenic metals including arsenic, cadmium, chromium, and nickel have all been associated with DNA damage through base pair mutation, deletion, or oxygen radical attack on DNA []. Animal studies have demonstrated reproductive and teratogenic effects. Small epidemiologic studies have noted an inverse relationship between cadmium in cord blood, maternal blood or maternal urine and birth weight and length at birth [, ].

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 []. 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. Industries with the largest contribution to chromium release include metal processing, tannery facilities, chromate production, stainless steel welding, and ferrochrome and chrome pigment production. 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, however, 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 []. Chromium is widely used in numerous industrial processes and as a result, is a contaminant of many environmental systems []. 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 [, ].

Potential 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-hr time-weighted average, even though this revised level may still pose a carcinogenic risk []. 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.

Non-occupational exposure occurs via ingestion of chromium containing food and water whereas occupational exposure occurs via inhalation []. Chromium concentrations range between 1 and 3000 mg/kg in soil, 5 to 800 µg/L in sea water, and 26 µg/L to 5.2 mg/L in rivers and lakes [129]. Chromium content in foods varies greatly and depends on the processing and preparation. In general, most fresh foods typically contain chromium levels ranging from <10 to 1,300 µg/kg. Present day workers in chromium-related industries can be exposed to chromium concentrations two orders of magnitude higher than the general population [141]. Even though the principal route of human exposure to chromium is through inhalation, and the lung is the primary target organ, significant human exposure to chromium has also been reported to take place through the skin [, ]. For example, the widespread incidence of dermatitis noticed among construction workers is attributed to their exposure to chromium present in cement []. Occupational and environmental exposure to Cr(VI)-containing compounds is known to cause multiorgan toxicity such as renal damage, allergy and asthma, and cancer of the respiratory tract in humans [5, 144].

Breathing high levels of chromium (VI) can cause irritation to the lining of the nose, and nose ulcers. The main health problems seen in animals following ingestion of chromium (VI) compounds are irritation and ulcers in the stomach and small intestine, anemia, sperm damage and male reproductive system damage. Chromium (III) compounds are much less toxic and do not appear to cause these problems. Some individuals are extremely sensitive to chromium(VI) or chromium(III), allergic reactions consisting of severe redness and swelling of the skin have been noted. An increase in stomach tumors was observed in humans and animals exposed to chromium(VI) in drinking water. Accidental or intentional ingestion of extremely high doses of chromium (VI) compounds by humans has resulted in severe respiratory, cardiovascular, gastrointestinal, hematological, hepatic, renal, and neurological effects as part of the sequelae leading to death or in patients who survived because of medical treatment [141]. Although the evidence of carcinogenicity of chromium in humans and terrestrial mammals seems strong, the mechanism by which it causes cancer is not completely understood [].

Mechanisms of 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, ]. 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. Since Cr(III) is poorly absorbed by any route, the toxicity of chromium is mainly attributable to the Cr(VI) form. 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 []. 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 [].

For example you can set ammo packs to explode when shot, allowing you to play devious tricks on bots or unsuspecting human players who are just about to pick up ammunition boxes. Unreal tournament 2004 goty download. The resulting fireworks and charred polygonal remains are hilarious.

Cr(VI) enters many types of cells and under physiological conditions can be reduced by hydrogen peroxide (H₂O₂), glutathione (GSH) reductase, ascorbic acid, and GSH to produce reactive intermediates, including Cr(V), Cr(IV), thiylradicals, hydroxyl radicals, and ultimately, Cr(III). Any of these species could attack DNA, proteins, and membrane lipids, thereby disrupting cellular integrity and functions [, ].

Studies with animal models have also reported many harmful effects of Cr (VI) on mammals. Subcutaneous administration of Cr (VI) to rats caused severe progressive proteinuria, urea nitrogen and creatinine, as well as elevation in serum alanine aminotransferase activity and hepatic lipid peroxide formation []. Similar studies reported by Gumbleton and Nicholls [] found that Cr (VI) induced renal damage in rats when administered by single sub-cutaneous injections. Bagchi et al. demonstrated that rats received Cr (VI) orally in water induced hepatic mitochondrial and microsomal lipid peroxidation, as well as enhanced excretion of urinary lipid metabolites including malondialdehyde [, ].

Adverse health effects induced by Cr (VI) have also been reported in humans. Epidemiological investigations have reported respiratory cancers in workers occupationally exposed to Cr (VI)-containing compounds [, ]. Torrent pro download for pc. DNA strand breaks in peripheral lymphocytes and lipid peroxidation products in urine observed in chromium-exposed workers also support the evidence of Cr (VI)-induced toxicity to humans [, ]. Oxidative damage is considered to be the underlying cause of these genotoxic effects including chromosomal abnormalities [, ], and DNA strand breaks []. Nevertheless, recent studies indicate a biological relevance of non-oxidative mechanisms in Cr(VI) carcinogenesis [].

Carcinogenicity appears to be associated with the inhalation of the less soluble/insoluble Cr(VI) compounds. The toxicology of Cr(VI) does not reside with the elemental form. It varies greatly among a wide variety of very different Cr(VI) compounds []. Epidemiological evidence strongly points to Cr(VI) as the agent in carcinogenesis. Solubility and other characteristics of chromium, such as size, crystal modification, surface charge, and the ability to be phagocytized might be important in determining cancer risk [].

Studies in our laboratory have indicated that chromium (VI) is cytotoxic and able to induce DNA damaging effects such as chromosomal abnormalities [162], DNA strand breaks, DNA fragmentation and oxidative stress in Sprague-Dawley rats and human liver carcinoma cells [, ]. Recently, our laboratory has also demonstrated that chromium (VI) induces biochemical, genotoxic and histopathologic effects in liver and kidney of goldfish, carassius auratus [].

Various hypotheses have been proposed to explain the carcinogenicity of chromium and its salts, however some inherent difficulties exist when discussing metal carcinogenesis. A metal cannot be classified as carcinogenic per se since its different compounds may have different potencies. Because of the multiple chemical exposure in industrial establishments, it is difficult from an epidemiological standpoint to relate the carcinogenic effect to a single compound. Thus, the carcinogenic risk must often be related to a process or to a group of metal compounds rather than to a single substance. Differences in carcinogenic potential are related not only to different chemical forms of the same metal but also to the particle size of the inhaled aerosol and to physical characteristics of the particle such as surface charge and crystal modification [].

Lead

Environmental Occurrence, Industrial Production and Use

Lead 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 fuels 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, 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].

In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder [167]. Despite this progress, it has been reported that among 16.4 million United States homes with more than one child younger than 6 years per household, 25% of homes still had significant amounts of lead-contaminated deteriorated paint, dust, or adjacent bare soil []. Lead in dust and soil often re-contaminates cleaned houses [] and contributes to elevating blood lead concentrations in children who play on bare, contaminated soil [170]. Today, the largest source of lead poisoning in children comes from dust and chips from deteriorating lead paint on interior surfaces []. Children who live in homes with deteriorating lead paint can achieve blood lead concentrations of 20µg/dL or greater [].

Potential for Human Exposure

Exposure to lead occurs mainly via 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].

Since the late 1970’s, lead exposure has decreased significantly as a result of multiple efforts including the elimination of lead in gasoline, and the reduction of lead levels in residential paints, food and drink cans, and plumbing systems [173, 174]. Several federal programs implemented by state and local health governments have not only focused on banning lead in gasoline, paint and soldered cans, but have also supported screening programs for lead poisoning in children and lead abatement in housing [167]. Despite the progress in these programs, human exposure to lead remains a serious health problem [, ]. Lead is the most systemic toxicant that affects several organs in the body including the kidneys, liver, central nervous system, hematopoetic system, endocrine system, and reproductive system [173].

Lead exposure usually results from lead in deteriorating household paints, lead in the work place, lead in crystals and ceramic containers that leaches into water and food, lead use in hobbies, and lead use in some traditional medicines and cosmetics [167, 174]. Several studies conducted by the National Health and Nutrition Examination surveys (NHANES) have measured blood lead levels in the U.S. populations and have assessed the magnitude of lead exposure by age, gender, race, income and degree of urbanization []. Although the results of these surveys have demonstrated a general decline in blood lead levels since the 1970s, they have also shown that large populations of children continue to have elevated blood lead levels (> 10µg/dL). Hence, lead poisoning remains one of the most common pediatric health problems in the United States today [167, 173, 174, –]. Exposure to lead is of special concern among women particularly during pregnancy. Lead absorbed by the pregnant mother is readily transferred to the developing fetus []. Human evidence corroborates animal findings [], linking prenatal exposure to lead with reduced birth weight and preterm delivery [], and with neuro-developmental abnormalities in offspring [].

Molecular Mechanisms of Toxicity and Carcinogenicity

There are many published studies that have documented the adverse effects of lead in children and the adult population. 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, , , ]. 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 [, ]. 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, , –].

One of the major mechanisms by which lead exerts its toxic effect is through biochemical processes that include lead's ability to inhibit or mimic the actions of calcium and to interact with proteins [173]. Within the skeleton, lead is incorporated into the mineral in place of calcium. Lead binds to biological molecules and thereby interfering with their function by a number of mechanisms. Lead binds to sulfhydryl and amide groups of enzymes, altering their configuration and diminishing their activities. Lead may also compete with essential metallic cations for binding sites, inhibiting enzyme activity, or altering the transport of essential cations such as calcium []. Many investigators have demonstrated that lead intoxication induces a cellular damage mediated by the formation of reactive oxygen species (ROS) []. In addition, Jiun and Hseien [] demonstrated that the levels of malondialdehyde (MDA) in blood strongly correlate with lead concentration in the blood of exposed workers. Other studies showed that the activities of antioxidant enzymes, including superoxide dismutase (SOD), and glutathione peroxidase in erythrocytes of workers exposed to lead are remarkably higher than that in non-exposed workers [191]. A series of recent studies in our laboratory demonstrated that lead-induced toxicity and apoptosis in human cancer cells involved several cellular and molecular processes including induction of cell death and oxidative stress [, 192], transcriptional activation of stress genes [], DNA damage [], externalization of phosphatidylserine and activation of caspase-3 []. Microsoft expression studio 4 ultimate free download.

A large body of research has indicated that lead acts by interfering with calcium-dependent processes related to neuronal signaling and intracellular signal transduction. Lead perturbs intracellular calcium cycling, altering releasability of organelle stores, such as endoplasmic reticulum and mitochondria [, ]. In some cases lead inhibits calcium-dependent events, including calcium-dependent release of several neurotransmitters and receptor-coupled ionophores in glutamatergic neurons []. In other cases lead appears to augment calcium-dependent events, such as protein kinase C and calmodulin [, ].

Experimental studies have indicated that lead is potentially carcinogenic, inducing renal tumors in rats and mice [, ], and is therefore considered by the IARC as a probable human carcinogen [200]. Lead exposure is also known to induce gene mutations and sister chromatid exchanges [, ], morphological transformations in cultured rodent cells [], and to enhance anchorage independence in diploid human fibroblasts []. In vitro and in vivo studies indicated that lead compounds cause genetic damage through various indirect mechanisms that include inhibition of DNA synthesis and repair, oxidative damage, and interaction with DNA-binding proteins and tumor suppressor proteins. Studies by Roy and his group showed that lead acetate induced mutagenicity at a toxic dose at the E. coli gpt locus transfected to V79 cells []. They also reported that toxic doses of lead acetate and lead nitrate induced DNA breaks at the E. coli gpt locus transfected to V79 cells []. Another study by Wise and his collaborators found no evidence for direct genotoxic or DNA-damaging effects of lead except for lead chromate. They pointed out that the genotoxicity may be due to hexavalent chromate rather than lead [].

Mercury

Environmental Occurrence, Industrial Production and Use

Mercury 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 []. At room temperature elemental mercury exists as a liquid which has a high vapor pressure and is released into the environment as mercury vapor. Mercury also exists as a cation with oxidation states of +1 (mercurous) or +2 (mercuric) []. 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 [].

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 []. Both humans and animals are exposed to various chemical forms of mercury in the environment. These include elemental mercury vapor (Hg⁰), inorganic mercurous (Hg⁺¹), mercuric (Hg⁺²), and the organic mercury compounds []. Because mercury is ubiquitous in the environment, humans, plants and animals are all unable to avoid exposure to some form of mercury [].

Mercury is utilized in the electrical industry (switches, thermostats, batteries), dentistry (dental amalgams), and numerous industrial processes including the production of caustic soda, in nuclear reactors, as antifungal agents for wood processing, as a solvent for reactive and precious metal, and as a preservative of pharmaceutical products []. The industrial demand for mercury peaked in 1964 and began to sharply decline between 1980 and 1994 as a result of federal bans on mercury additives in paints, pesticides, and the reduction of its use in batteries [214].

Potential 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 []. 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 []. 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 [].

The two most highly absorbed species are elemental mercury (Hg⁰) and methyl mercury (MeHg). Dental amalgams contain over 50% elemental mercury []. The elemental vapor is highly lipophilic and is effectively absorbed through the lungs and tissues lining the mouth. After Hg⁰ enters the blood, it rapidly passes through cell membranes, which include both the blood-brain barrier and the placental barrier []. Once it gains entry into the cell, Hg⁰ is oxidized and becomes highly reactive Hg²⁺. Methyl mercury derived from eating fish is readily absorbed in the gastrointestinal tract and because of its lipid solubility, can easily cross both the placental and blood-brain barriers. Once mercury is absorbed it has a very low excretion rate. A major proportion of what is absorbed accumulates in the kidneys, neurological tissue and the liver. All forms of mercury are toxic and their effects include gastrointestinal toxicity, neurotoxicity, and nephrotoxicity [].

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 []. 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 defense against mercury compounds []. 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.

In eukaryotic organisms the primary site for the production of reactive oxygen species (ROS) occurs in the mitochondria through normal metabolism []. Inorganic mercury has been reported to increase the production of these ROS by causing defects in oxidative phosphorylation and electron transport at the ubiquinone-cytochrome b5 step []. Through the acceleration of the rate of electron transfer in the electron transport chain in the mitochondria, mercury induces the premature shedding of electrons to molecular oxygen which causes an increase in the generation of reactive oxygen species [].

Oxidative stress appears to also have an effect on calcium homeostasis. The role of calcium in the activation of proteases, endonucleases and phospholipases is well established. The activation of phospholipase A₂ has been shown to result in an increase in reactive oxygen species through the increase generation of arachidonic acid. Arachidonic acid has also been shown to be an important target of reactive oxygen species []. Both organic and inorganic mercury have been shown to alter calcium homeostasis but through different mechanisms. Organic mercury compounds (MeHg) are believed to increase intracellular calcium by accelerating the influx of calcium from the extracellular medium and mobilizing intracellular stores, while inorganic mercury (Hg²⁺⁾ compounds increase intracellular calcium stores only through the influx of calcium from the extracellular medium []. Mercury compounds have also been shown to induce increased levels of MDA in both the livers, kidneys, lungs and testes of rats treated with HgCl₂ []. This increase in concentration was shown to correlate with the severity of hepatotoxicity and nephrotoxicity []. HgCl_2-induced lipid peroxidation was shown to be significantly reduced by antioxidant pretreatment with selenium. Selenium has been shown to achieve this protective effect through direct binding to mercury or serving as a cofactor for glutathione peroxidase and facilitating its ability to scavenge ROS []. Vitamin E has also been reported to protect against HgCl₂-induced lipid peroxidation in the liver [].

Metal-induced carcinogenicity has been a research subject of great public health interest. Generally, carcinogenesis is considered to have three stages including initiation, promotion, and progression and metastasis. Although mutations of DNA, which can activate oncogenesis or inhibit tumor suppression, were traditionally thought to be crucial factors for the initiation of carcinogenesis, recent studies have demonstrated that other molecular events such as transcription activation, signal transduction, oncogene amplification, and recombination, also constitute significant contributing factors [231, ]. Studies have shown that mercury and other toxic metals effect cellular organelles and adversely affect their biologic functions [231, 233]. Accumulating evidence also suggests that ROS play a major role in the mediation of metal-induced cellular responses and carcinogenesis [–].

The connection between mercury exposure and carcinogenesis is very controversial. While some studies have confirmed its genotoxic potential, others have not shown an association between mercury exposure and genotoxic damage []. In studies implicating mercury as a genotoxic agent, oxidative stress has been described has the molecular mechanism of toxicity. Hence, mercury has been shown to induce the formation of ROS known to cause DNA damage in cells, a process which can lead to the initiation of carcinogenic processes [, ]. The direct action of these free radicals on nucleic acids may generate genetic mutations. Although mercury-containing compounds are not mutagenic in bacterial assays, inorganic mercury has been shown to induce mutational events in eukaryotic cell lines with doses as low as 0.5 µM []. These free radicals may also induce conformational changes in proteins that are responsible for DNA repair, mitotic spindle, and chromosomal segregation []. To combat these effects, cells have antioxidant mechanisms that work to correct and avoid the formation of ROS (free radicals) in excess. These antioxidant mechanisms involve low molecular weight compounds such as vitamins C and E, melatonin, glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase that protect the cells by chelating mercury and reducing its oxidative stress potential [].

Glutathione levels in human populations exposed to methylmercury intoxication by eating contaminated fish have been shown to be higher than normal []. These studies were also able to confirm a direct and positive correlation between mercury and glutathione levels in blood. They also confirmed an increased mitotic index and polyploidal aberrations associated with mercury exposure []. Epidemiological studies have demonstrated that enzymatic activity was altered in populations exposed to mercury; producing genotoxic alterations, and suggesting that both chronic and relatively low level mercury exposures may inhibit enzyme activity and induce oxidative stress in the cells []. There is no doubt that the connection between mercury exposure and carcinogenesis is very controversial. However, in-vitro studies suggest that the susceptibility to DNA damage exists as a result of cellular exposure to mercury. These studies also indicate that mercury-induced toxicity and carcinogenicity may be cell-, organ- and/or species- specific.

Prospects

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 [, ]. However, the literature is scarce regarding the combined toxicity of heavy metals. Simultaneous exposure to multiple heavy metals may produce a toxic effect that is either additive, antagonistic or synergistic.

A recent review of a number of individual studies that addressed metals interactions reported that co-exposure to metal/metalloid mixtures of arsenic, lead and cadmium produced more severe effects at both relatively high dose and low dose levels in a biomarker-specific manner []. These effects were found to be mediated by dose, duration of exposure and genetic factors. Also, human co-exposure to cadmium and inorganic arsenic resulted in a more pronounced renal damage than exposure to each of the elements alone []. 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. Hence, research is needed to further elucidate the molecular mechanisms and public health impact associated with human exposure to mixtures of toxic metals.

Acknowledgement

This research was supported in by the National Institutes of Health RCMI Grant No. 2G12RR013459, and in part by the National Oceanic and Atmospheric Administration ECSC Grant No. NA06OAR4810164 & Subcontract No. 000953.

References

Heavy Metal Free Online

Sources Of Heavy Metals Pdf

Heavy Metals In Water Pdf

Heavy Metals Affecting Humans

Heavy Metal Books Pdf