Nickel is a chemical element with symbol Ni
and atomic number 28. It is a silvery-white
lustrous metal with a slight golden tinge.
Nickel belongs to the transition metals and
is hard and ductile. Pure nickel, powdered
to maximize the reactive surface area, shows
a significant chemical activity, but larger
pieces are slow to react with air under standard
conditions because an oxide layer forms on
the surface and prevents further corrosion
(passivation). Even so, pure native nickel
is found in Earth's crust only in tiny amounts,
usually in ultramafic rocks, and in the interiors
of larger nickel–iron meteorites that were
not exposed to oxygen when outside Earth's
atmosphere.
Meteoric nickel is found in combination with
iron, a reflection of the origin of those
elements as major end products of supernova
nucleosynthesis. An iron–nickel mixture
is thought to compose Earth's inner core.Use
of nickel (as a natural meteoric nickel–iron
alloy) has been traced as far back as 3500
BCE. Nickel was first isolated and classified
as a chemical element in 1751 by Axel Fredrik
Cronstedt, who initially mistook the ore for
a copper mineral, in the cobalt mines of Los,
Hälsingland, Sweden. The element's name comes
from a mischievous sprite of German miner
mythology, Nickel (similar to Old Nick), who
personified the fact that copper-nickel ores
resisted refinement into copper. An economically
important source of nickel is the iron ore
limonite, which often contains 1–2% nickel.
Nickel's other important ore minerals include
pentlandite and a mixture of Ni-rich natural
silicates known as garnierite. Major production
sites include the Sudbury region in Canada
(which is thought to be of meteoric origin),
New Caledonia in the Pacific, and Norilsk
in Russia.
Nickel is slowly oxidized by air at room temperature
and is considered corrosion-resistant. Historically,
it has been used for plating iron and brass,
coating chemistry equipment, and manufacturing
certain alloys that retain a high silvery
polish, such as German silver. About 9% of
world nickel production is still used for
corrosion-resistant nickel plating. Nickel-plated
objects sometimes provoke nickel allergy.
Nickel has been widely used in coins, though
its rising price has led to some replacement
with cheaper metals in recent years.
Nickel is one of four elements (the others
are iron, cobalt, and gadolinium) that are
ferromagnetic at approximately room temperature.
Alnico permanent magnets based partly on nickel
are of intermediate strength between iron-based
permanent magnets and rare-earth magnets.
The metal is valuable in modern times chiefly
in alloys; about 68% of world production is
used in stainless steel. A further 10% is
used for nickel-based and copper-based alloys,
7% for alloy steels, 3% in foundries, 9% in
plating and 4% in other applications, including
the fast-growing battery sector. As a compound,
nickel has a number of niche chemical manufacturing
uses, such as a catalyst for hydrogenation,
cathodes for batteries, pigments and metal
surface treatments. Nickel is an essential
nutrient for some microorganisms and plants
that have enzymes with nickel as an active
site.
== Properties ==
=== 
Atomic and physical properties ===
Nickel is a silvery-white metal with a slight
golden tinge that takes a high polish. It
is one of only four elements that are magnetic
at or near room temperature, the others being
iron, cobalt and gadolinium. Its Curie temperature
is 355 °C (671 °F), meaning that bulk nickel
is non-magnetic above this temperature. The
unit cell of nickel is a face-centered cube
with the lattice parameter of 0.352 nm, giving
an atomic radius of 0.124 nm. This crystal
structure is stable to pressures of at least
70 GPa. Nickel belongs to the transition metals
and is hard and ductile.
==== Electron configuration dispute ====
The nickel atom has two electron configurations,
[Ar] 3d8 4s2 and [Ar] 3d9 4s1, which are very
close in energy – the symbol [Ar] refers
to the argon-like core structure. There is
some disagreement on which configuration has
the lowest energy. Chemistry textbooks quote
the electron configuration of nickel as [Ar]
4s2 3d8, which can also be written [Ar] 3d8
4s2. This configuration agrees with the Madelung
energy ordering rule, which predicts that
4s is filled before 3d. It is supported by
the experimental fact that the lowest energy
state of the nickel atom is a 3d8 4s2 energy
level, specifically the 3d8(3F) 4s2 3F, J
= 4 level.However, each of these two configurations
splits into several energy levels due to fine
structure, and the two sets of energy levels
overlap. The average energy of states with
configuration [Ar] 3d9 4s1 is actually lower
than the average energy of states with configuration
[Ar] 3d8 4s2. For this reason, the research
literature on atomic calculations quotes the
ground state configuration of nickel as [Ar]
3d9 4s1.
=== Isotopes ===
The isotopes of nickel range in atomic weight
from 48 u (48Ni) to 78 u (78Ni).
Naturally occurring nickel is composed of
five stable isotopes; 58Ni, 60Ni, 61Ni, 62Ni
and 64Ni, with 58Ni being the most abundant
(68.077% natural abundance). Isotopes heavier
than 62Ni cannot be formed by nuclear fusion
without losing energy.
Nickel-62 has the highest mean nuclear binding
energy per nucleon of any nuclide, at 8.7946
MeV/nucleon. Its binding energy is greater
than both 56Fe and 58Fe, more abundant elements
often incorrectly cited as having the most
tightly-bound nuclides. Although this would
seem to predict nickel-62 as the most abundant
heavy element in the universe, the relatively
high rate of photodisintegration of nickel
in stellar interiors causes iron to be by
far the most abundant.Stable isotope nickel-60
is the daughter product of the extinct radionuclide
60Fe, which decays with a half-life of 2.6
million years. Because 60Fe has such a long
half-life, its persistence in materials in
the solar system may generate observable variations
in the isotopic composition of 60Ni. Therefore,
the abundance of 60Ni present in extraterrestrial
material may provide insight into the origin
of the solar system and its early history.
Some 18 nickel radioisotopes have been characterised,
the most stable being 59Ni with a half-life
of 76,000 years, 63Ni with 100 years, and
56Ni with 6 days. All of the remaining radioactive
isotopes have half-lives that are less than
60 hours and the majority of these have half-lives
that are less than 30 seconds. This element
also has one meta state.Radioactive nickel-56
is produced by the silicon burning process
and later set free in large quantities during
type Ia supernovae. The shape of the light
curve of these supernovae at intermediate
to late-times corresponds to the decay via
electron capture of nickel-56 to cobalt-56
and ultimately to iron-56. Nickel-59 is a
long-lived cosmogenic radionuclide with a
half-life of 76,000 years. 59Ni has found
many applications in isotope geology. 59Ni
has been used to date the terrestrial age
of meteorites and to determine abundances
of extraterrestrial dust in ice and sediment.
Nickel-78's half-life was recently measured
at 110 milliseconds, and is believed an important
isotope in supernova nucleosynthesis of elements
heavier than iron. The nuclide 48Ni, discovered
in 1999, is the most proton-rich heavy element
isotope known. With 28 protons and 20 neutrons
48Ni is "double magic", as is 78Ni with 28
protons and 50 neutrons. Both are therefore
unusually stable for nuclides with so large
a proton-neutron imbalance.
=== Occurrence ===
On Earth, nickel occurs most often in combination
with sulfur and iron in pentlandite, with
sulfur in millerite, with arsenic in the mineral
nickeline, and with arsenic and sulfur in
nickel galena. Nickel is commonly found in
iron meteorites as the alloys kamacite and
taenite.
The bulk of the nickel is mined from two types
of ore deposits. The first is laterite, where
the principal ore mineral mixtures are nickeliferous
limonite, (Fe,Ni)O(OH), and garnierite (a
mixture of various hydrous nickel and nickel-rich
silicates). The second is magmatic sulfide
deposits, where the principal ore mineral
is pentlandite: (Ni,Fe)9S8.
Australia and New Caledonia have the biggest
estimate reserves (45% all together).Identified
land-based resources throughout the world
averaging 1% nickel or greater comprise at
least 130 million tons of nickel (about the
double of known reserves). About 60% is in
laterites and 40% in sulfide deposits.On geophysical
evidence, most of the nickel on Earth is believed
to be in the Earth's outer and inner cores.
Kamacite and taenite are naturally occurring
alloys of iron and nickel. For kamacite, the
alloy is usually in the proportion of 90:10
to 95:5, although impurities (such as cobalt
or carbon) may be present, while for taenite
the nickel content is between 20% and 65%.
Kamacite and taenite are also found in nickel
iron meteorites.
== Compounds ==
The most common oxidation state of nickel
is +2, but compounds of Ni0, Ni+, and Ni3+
are well known, and the exotic oxidation states
Ni2−, Ni1−, and Ni4+ have been produced
and studied.
=== Nickel(0) ===
Nickel tetracarbonyl (Ni(CO)4), discovered
by Ludwig Mond, is a volatile, highly toxic
liquid at room temperature. On heating, the
complex decomposes back to nickel and carbon
monoxide:
Ni(CO)4 ⇌ Ni + 4 COThis behavior is exploited
in the Mond process for purifying nickel,
as described above. The related nickel(0)
complex bis(cyclooctadiene)nickel(0) is a
useful catalyst in organonickel chemistry
because the cyclooctadiene (or cod) ligands
are easily displaced.
=== Nickel(I) ===
Nickel(I) complexes are uncommon, but one
example is the tetrahedral complex NiBr(PPh3)3.
Many nickel(I) complexes feature Ni-Ni bonding,
such as the dark red diamagnetic K4[Ni2(CN)6]
prepared by reduction of K2[Ni2(CN)6] with
sodium amalgam. This compound is oxidised
in water, liberating H2.It is thought that
the nickel(I) oxidation state is important
to nickel-containing enzymes, such as [NiFe]-hydrogenase,
which catalyzes the reversible reduction of
protons to H2.
=== Nickel(II) ===
Nickel(II) forms compounds with all common
anions, including sulfide, sulfate, carbonate,
hydroxide, carboxylates, and halides. Nickel(II)
sulfate is produced in large quantities by
dissolving nickel metal or oxides in sulfuric
acid, forming both a hexa- and heptahydrates
useful for electroplating nickel. Common salts
of nickel, such as the chloride, nitrate,
and sulfate, dissolve in water to give green
solutions of the metal aquo complex [Ni(H2O)6]2+.
The four halides form nickel compounds, which
are solids with molecules that feature octahedral
Ni centres. Nickel(II) chloride is most common,
and its behavior is illustrative of the other
halides. Nickel(II) chloride is produced by
dissolving nickel or its oxide in hydrochloric
acid. It is usually encountered as the green
hexahydrate, the formula of which is usually
written NiCl2•6H2O. When dissolved in water,
this salt forms the metal aquo complex [Ni(H2O)6]2+.
Dehydration of NiCl2•6H2O gives the yellow
anhydrous NiCl2.
Some tetracoordinate nickel(II) complexes,
e.g. bis(triphenylphosphine)nickel chloride,
exist both in tetrahedral and square planar
geometries. The tetrahedral complexes are
paramagnetic, whereas the square planar complexes
are diamagnetic. In having properties of magnetic
equilibrium and formation of octahedral complexes,
they contrast with the divalent complexes
of the heavier group 10 metals, palladium(II)
and platinum(II), which form only square-planar
geometry.Nickelocene is known; it has an electron
count of 20, making it relatively unstable.
=== Nickel(III) and (IV) ===
Numerous Ni(III) compounds are known, with
the first such examples being Nickel(III)
trihalophosphines (NiIII(PPh3)X3). Further,
Ni(III) forms simple salts with fluoride or
oxide ions. Ni(III) can be stabilized by σ-donor
ligands such as thiols and phosphines.Ni(IV)
is present in the mixed oxide BaNiO3, while
Ni(III) is present in nickel oxide hydroxide,
which is used as the cathode in many rechargeable
batteries, including nickel-cadmium, nickel-iron,
nickel hydrogen, and nickel-metal hydride,
and used by certain manufacturers in Li-ion
batteries. Ni(IV) remains a rare oxidation
state of nickel and very few compounds are
known to date.
== History ==
Because the ores of nickel are easily mistaken
for ores of silver, understanding of this
metal and its use dates to relatively recent
times. However, the unintentional use of nickel
is ancient, and can be traced back as far
as 3500 BCE. Bronzes from what is now Syria
have been found to contain as much as 2% nickel.
Some ancient Chinese manuscripts suggest that
"white copper" (cupronickel, known as baitong)
was used there between 1700 and 1400 BCE.
This Paktong white copper was exported to
Britain as early as the 17th century, but
the nickel content of this alloy was not discovered
until 1822. Coins of nickel-copper alloy were
minted by the Bactrian kings Agathocles, Euthydemus
II and Pantaleon in the 2nd Century BCE, possibly
out of the Chinese cupronickel.
In medieval Germany, a red mineral was found
in the Erzgebirge (Ore Mountains) that resembled
copper ore. However, when miners were unable
to extract any copper from it, they blamed
a mischievous sprite of German mythology,
Nickel (similar to Old Nick), for besetting
the copper. They called this ore Kupfernickel
from the German Kupfer for copper. This ore
is now known to be nickeline, a nickel arsenide.
In 1751, Baron Axel Fredrik Cronstedt tried
to extract copper from kupfernickel at a cobalt
mine in the Swedish village of Los, and instead
produced a white metal that he named after
the spirit that had given its name to the
mineral, nickel. In modern German, Kupfernickel
or Kupfer-Nickel designates the alloy cupronickel.
Originally, the only source for nickel was
the rare Kupfernickel. Beginning in 1824,
nickel was obtained as a byproduct of cobalt
blue production. The first large-scale smelting
of nickel began in Norway in 1848 from nickel-rich
pyrrhotite. The introduction of nickel in
steel production in 1889 increased the demand
for nickel, and the nickel deposits of New
Caledonia, discovered in 1865, provided most
of the world's supply between 1875 and 1915.
The discovery of the large deposits in the
Sudbury Basin, Canada in 1883, in Norilsk-Talnakh,
Russia in 1920, and in the Merensky Reef,
South Africa in 1924, made large-scale production
of nickel possible.
== Coinage ==
Aside from the aforementioned Bactrian coins,
nickel was not a component of coins until
the mid-19th century.
=== Canada ===
99.9% nickel five-cent coins were struck in
Canada (the world's largest nickel producer
at the time) during non-war years from 1922–1981;
the metal content made these coins magnetic.
During the wartime period 1942–45, most
or all nickel was removed from Canadian and
U.S. coins to save it for manufacturing armor.
Canada used 99.9% nickel from 1968 in its
higher-value coins until 2000.
=== Switzerland ===
Coins of nearly pure nickel were first used
in 1881 in Switzerland.
=== United Kingdom ===
Birmingham forged nickel coins in about 1833
for trading in Malaya.
=== United States ===
In the United States, the term "nickel" or
"nick" originally applied to the copper-nickel
Flying Eagle cent, which replaced copper with
12% nickel 1857–58, then the Indian Head
cent of the same alloy from 1859–1864. Still
later, in 1865, the term designated the three-cent
nickel, with nickel increased to 25%. In 1866,
the five-cent shield nickel (25% nickel, 75%
copper) appropriated the designation. Along
with the alloy proportion, this term has been
used to the present in the United States.
=== Current use ===
In the 21st century, the high price of nickel
has led to some replacement of the metal in
coins around the world. Coins still made with
nickel alloys include one- and two-euro coins,
5¢, 10¢, 25¢ and 50¢ U.S. coins, and 20p,
50p, £1 and £2 UK coins. Nickel-alloy in
5p and 10p UK coins was replaced with nickel-plated
steel began in 2012, causing allergy problems
for some people and public controversy.
== World production ==
Around 2 million tonnes of nickel are produced
annually worldwide. The Philippines, Indonesia,
Russia, Canada and Australia are the world's
largest producers of nickel, as reported by
the US Geological Survey. The largest deposits
of nickel in non-Russian Europe are located
in Finland and Greece. Identified land-based
resources averaging 1% nickel or greater contain
at least 130 million tons of nickel. About
60% is in laterites and 40% is in sulfide
deposits. In addition, extensive deep-sea
resources of nickel are in manganese crusts
and nodules covering large areas of the ocean
floor, particularly in the Pacific Ocean.The
one locality in the United States where nickel
has been profitably mined is Riddle, Oregon,
where several square miles of nickel-bearing
garnierite surface deposits are located. The
mine closed in 1987. The Eagle mine project
is a new nickel mine in Michigan's upper peninsula.
Construction was completed in 2013, and operations
began in the third quarter of 2014. In the
first full year of operation, Eagle Mine produced
18,000 tonnes.
== Extraction and purification ==
Nickel is obtained through extractive metallurgy:
it is extracted from the ore by conventional
roasting and reduction processes that yield
a metal of greater than 75% purity. In many
stainless steel applications, 75% pure nickel
can be used without further purification,
depending on the impurities.
Traditionally, most sulfide ores have been
processed using pyrometallurgical techniques
to produce a matte for further refining. Recent
advances in hydrometallurgical techniques
resulted in significantly purer metallic nickel
product. Most sulfide deposits have traditionally
been processed by concentration through a
froth flotation process followed by pyrometallurgical
extraction. In hydrometallurgical processes,
nickel sulfide ores are concentrated with
flotation (differential flotation if Ni/Fe
ratio is too low) and then smelted. The nickel
matte is further processed with the Sherritt-Gordon
process. First, copper is removed by adding
hydrogen sulfide, leaving a concentrate of
cobalt and nickel. Then, solvent extraction
is used to separate the cobalt and nickel,
with the final nickel content greater than
99%.
=== Electrorefining ===
A second common refining process is leaching
the metal matte into a nickel salt solution,
followed by the electro-winning of the nickel
from solution by plating it onto a cathode
as electrolytic nickel.
=== Mond process ===
The purest metal is obtained from nickel oxide
by the Mond process, which achieves a purity
of greater than 99.99%. The process was patented
by Ludwig Mond and has been in industrial
use since before the beginning of the 20th
century. In this process, nickel is reacted
with carbon monoxide in the presence of a
sulfur catalyst at around 40–80 °C to form
nickel carbonyl. Iron gives iron pentacarbonyl,
too, but this reaction is slow. If necessary,
the nickel may be separated by distillation.
Dicobalt octacarbonyl is also formed in nickel
distillation as a by-product, but it decomposes
to tetracobalt dodecacarbonyl at the reaction
temperature to give a non-volatile solid.Nickel
is obtained from nickel carbonyl by one of
two processes. It may be passed through a
large chamber at high temperatures in which
tens of thousands of nickel spheres, called
pellets, are constantly stirred. The carbonyl
decomposes and deposits pure nickel onto the
nickel spheres. In the alternate process,
nickel carbonyl is decomposed in a smaller
chamber at 230 °C to create a fine nickel
powder. The byproduct carbon monoxide is recirculated
and reused. The highly pure nickel product
is known as "carbonyl nickel".
=== Metal value ===
The market price of nickel surged throughout
2006 and the early months of 2007; as of April
5, 2007, the metal was trading at US$52,300/tonne
or $1.47/oz. The price subsequently fell dramatically,
and as of September 2017, the metal was trading
at $11,000/tonne, or $0.31/oz.The US nickel
coin contains 0.04 ounces (1.1 g) of nickel,
which at the April 2007 price was worth 6.5
cents, along with 3.75 grams of copper worth
about 3 cents, with a total metal value of
more than 9 cents. Since the face value of
a nickel is 5 cents, this made it an attractive
target for melting by people wanting to sell
the metals at a profit. However, the United
States Mint, in anticipation of this practice,
implemented new interim rules on December
14, 2006, subject to public comment for 30
days, which criminalized the melting and export
of cents and nickels. Violators can be punished
with a fine of up to $10,000 and/or imprisoned
for a maximum of five years.
As of September 19, 2013, the melt value of
a U.S. nickel (copper and nickel included)
is $0.045, which is 90% of the face value.
== Applications ==
The global production of nickel is presently
used as follows: 68% in stainless steel; 10%
in nonferrous alloys; 9% in electroplating;
7% in alloy steel; 3% in foundries; and 4%
other uses (including batteries).Nickel is
used in many specific and recognizable industrial
and consumer products, including stainless
steel, alnico magnets, coinage, rechargeable
batteries, electric guitar strings, microphone
capsules, plating on plumbing fixtures, and
special alloys such as permalloy, elinvar,
and invar. It is used for plating and as a
green tint in glass. Nickel is preeminently
an alloy metal, and its chief use is in nickel
steels and nickel cast irons, in which it
typically increases the tensile strength,
toughness, and elastic limit. It is widely
used in many other alloys, including nickel
brasses and bronzes and alloys with copper,
chromium, aluminium, lead, cobalt, silver,
and gold (Inconel, Incoloy, Monel, Nimonic).
Because it is resistant to corrosion, nickel
was occasionally used as a substitute for
decorative silver. Nickel was also occasionally
used in some countries after 1859 as a cheap
coinage metal (see above), but in the later
years of the 20th century was replaced by
cheaper stainless steel (i.e., iron) alloys,
except in the United States and Canada.
Nickel is an excellent alloying agent for
certain precious metals and is used in the
fire assay as a collector of platinum group
elements (PGE). As such, nickel is capable
of fully collecting all six PGE elements from
ores, and of partially collecting gold. High-throughput
nickel mines may also engage in PGE recovery
(primarily platinum and palladium); examples
are Norilsk in Russia and the Sudbury Basin
in Canada.
Nickel foam or nickel mesh is used in gas
diffusion electrodes for alkaline fuel cells.Nickel
and its alloys are frequently used as catalysts
for hydrogenation reactions. Raney nickel,
a finely divided nickel-aluminium alloy, is
one common form, though related catalysts
are also used, including Raney-type catalysts.
Nickel is a naturally magnetostrictive material,
meaning that, in the presence of a magnetic
field, the material undergoes a small change
in length. The magnetostriction of nickel
is on the order of 50 ppm and is negative,
indicating that it contracts.
Nickel is used as a binder in the cemented
tungsten carbide or hardmetal industry and
used in proportions of 6% to 12% by weight.
Nickel makes the tungsten carbide magnetic
and adds corrosion-resistance to the cemented
parts, although the hardness is less than
those with a cobalt binder.63Ni, with its
half-life of 100.1 years, is useful in krytron
devices as a beta particle (high-speed electron)
emitter to make ionization by the keep-alive
electrode more reliable.Around 27% of all
nickel production is destined for engineering,
10% for building and construction, 14% for
tubular products, 20% for metal goods, 14%
for transport, 11% for electronic goods, and
5% for other uses.
== Biological role ==
Although not recognized until the 1970s, nickel
is known to play an important role in the
biology of some plants, eubacteria, archaebacteria,
and fungi. Nickel enzymes such as urease are
considered virulence factors in some organisms.
Urease catalyzes the hydrolysis of urea to
form ammonia and carbamate. The NiFe hydrogenases
can catalyze the oxidation of H2 to form protons
and electrons, and can also catalyze the reverse
reaction, the reduction of protons to form
hydrogen gas. A nickel-tetrapyrrole coenzyme,
cofactor F430, is present in methyl coenzyme
M reductase, which can catalyze the formation
of methane, or the reverse reaction, in methanogenic
archaea. One of the carbon monoxide dehydrogenase
enzymes consists of an Fe-Ni-S cluster. Other
nickel-bearing enzymes include a rare bacterial
class of superoxide dismutase and glyoxalase
I enzymes in bacteria and several parasitic
eukaryotic trypanosomal parasites (in higher
organisms, including yeast and mammals, this
enzyme contains divalent Zn2+).Dietary nickel
may affect human health through infections
by nickel-dependent bacteria, but it is also
possible that nickel is an essential nutrient
for bacteria residing in the large intestine,
in effect functioning as a prebiotic. The
U.S. Institute of Medicine has not confirmed
that nickel is an essential nutrient for humans,
so neither a Recommended Dietary Allowance
(RDA) nor an Adequate Intake have been established.
The Tolerable Upper Intake Level of dietary
nickel is 1000 µg/day as soluble nickel salts.
Dietary intake is estimated at 70 to 100 µg/day,
with less than 10% absorbed. What is absorbed
is excreted in urine. Relatively large amounts
of nickel – comparable to the estimated
average ingestion above – leach into food
cooked in stainless steel. For example, the
amount of nickel leached after 10 cooking
cycles into one serving of tomato sauce averages
88 µg.Nickel released from Siberian Traps
volcanic eruptions is suspected of assisting
the growth of Methanosarcina, a genus of euryarchaeote
archaea that produced methane during the Permian–Triassic
extinction event, the biggest extinction event
on record.
== Toxicity ==
The major source of nickel exposure is oral
consumption, as nickel is essential to plants.
Nickel is found naturally in both food and
water, and may be increased by human pollution.
For example, nickel-plated faucets may contaminate
water and soil; mining and smelting may dump
nickel into waste-water; nickel–steel alloy
cookware and nickel-pigmented dishes may release
nickel into food. The atmosphere may be polluted
by nickel ore refining and fossil fuel combustion.
Humans may absorb nickel directly from tobacco
smoke and skin contact with jewelry, shampoos,
detergents, and coins. A less-common form
of chronic exposure is through hemodialysis
as traces of nickel ions may be absorbed into
the plasma from the chelating action of albumin.
The average daily exposure does not pose a
threat to human health. Most of the nickel
absorbed every day by humans is removed by
the kidneys and passed out of the body through
urine or is eliminated through the gastrointestinal
tract without being absorbed. Nickel is not
a cumulative poison, but larger doses or chronic
inhalation exposure may be toxic, even carcinogenic,
and constitute an occupational hazard.Nickel
compounds are classified as human carcinogens
based on increased respiratory cancer risks
observed in epidemiological studies of sulfidic
ore refinery workers. This is supported by
the positive results of the NTP bioassays
with Ni sub-sulfide and Ni oxide in rats and
mice. The human and animal data consistently
indicate a lack of carcinogenicity via the
oral route of exposure and limit the carcinogenicity
of nickel compounds to respiratory tumours
after inhalation. Nickel metal is classified
as a suspect carcinogen; there is consistency
between the absence of increased respiratory
cancer risks in workers predominantly exposed
to metallic nickel and the lack of respiratory
tumours in a rat lifetime inhalation carcinogenicity
study with nickel metal powder. In the rodent
inhalation studies with various nickel compounds
and nickel metal, increased lung inflammations
with and without bronchial lymph node hyperplasia
or fibrosis were observed. In rat studies,
oral ingestion of water-soluble nickel salts
can trigger perinatal mortality effects in
pregnant animals. Whether these effects are
relevant to humans is unclear as epidemiological
studies of highly exposed female workers have
not shown adverse developmental toxicity effects.People
can be exposed to nickel in the workplace
by inhalation, ingestion, and contact with
skin or eye. The Occupational Safety and Health
Administration (OSHA) has set the legal limit
(permissible exposure limit) for the workplace
at 1 mg/m3 per 8-hour workday, excluding nickel
carbonyl. The National Institute for Occupational
Safety and Health (NIOSH) specifies the recommended
exposure limit (REL) of 0.015 mg/m3 per 8-hour
workday. At 10 mg/m3, nickel is immediately
dangerous to life and health. Nickel carbonyl
[Ni(CO)4] is an extremely toxic gas. The toxicity
of metal carbonyls is a function of both the
toxicity of the metal and the off-gassing
of carbon monoxide from the carbonyl functional
groups; nickel carbonyl is also explosive
in air.Sensitized individuals may show a skin
contact allergy to nickel known as a contact
dermatitis. Highly sensitized individuals
may also react to foods with high nickel content.
Sensitivity to nickel may also be present
in patients with pompholyx. Nickel is the
top confirmed contact allergen worldwide,
partly due to its use in jewelry for pierced
ears. Nickel allergies affecting pierced ears
are often marked by itchy, red skin. Many
earrings are now made without nickel or low-release
nickel to address this problem. The amount
allowed in products that contact human skin
is now regulated by the European Union. In
2002, researchers found that the nickel released
by 1 and 2 Euro coins was far in excess of
those standards. This is believed to be the
result of a galvanic reaction. Nickel was
voted Allergen of the Year in 2008 by the
American Contact Dermatitis Society. In August
2015, the American Academy of Dermatology
adopted a position statement on the safety
of nickel: "Estimates suggest that contact
dermatitis, which includes nickel sensitization,
accounts for approximately $1.918 billion
and affects nearly 72.29 million people."Reports
show that both the nickel-induced activation
of hypoxia-inducible factor (HIF-1) and the
up-regulation of hypoxia-inducible genes are
caused by depletion of intracellular ascorbate.
The addition of ascorbate to the culture medium
increased the intracellular ascorbate level
and reversed both the metal-induced stabilization
of HIF-1- and HIF-1α-dependent gene expression
