Clinical Toxicology, 37(2), 201–216 (1999)

Cobalt
Donald G. Barceloux
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Topanga, California

ABSTRACT

Cobalt is a relatively rare magnetic element with properties similar to iron and
nickel. The two valance states are cobaltous (II) and cobaltic (III) and the for-
mer is the most common valance used in the chemical industry. Cobalt occurs
in nature primarily as arsenides, oxides, and sulfides. Most of the production
For personal use only.

of cobalt involves the metallic form used in the formation of cobalt superalloys.
The term ‘‘hard metal’’ refers to compounds containing tungsten carbide (80–
95%) combined with matrices formed from cobalt (5–20%) and nickel (0–5%).
For the general population, the diet is the main source of exposure to cobalt.
In the occupational setting, exposure to cobalt alone occurs primarily during
the production of cobalt powders. In other industrial exposures (e.g., hard
metal, diamond polishing), additional agents (tungsten) modulate the toxicity
of cobalt. Cobalt is an essential element necessary for the formation of vitamin
B12 (hydroxocobalamin); however, excessive administration of this trace ele-
ment produces goiter and reduced thyroid activity. In 1966, the syndrome
‘‘beer drinker’s cardiomyopathy’’ appeared in Quebec City, Canada, and was
characterized by pericardial effusion, elevated hemoglobin concentrations, and
congestive heart failure. An interstitial pulmonary fibrosis has been associated
with industrial exposure to hard metal dust (tungsten and cobalt), but not to
cobalt alone. Exposure to cobalt alone produces an allergic contact dermatitis
and occupational asthma. Treatment of cobalt toxicity is primarily supportive.

Correspondence: Dr. Donald Barceloux, PO Box 1750, Topanga, CA 90290. Tel/Fax: 310/455-2752; E-mail: dgbarcelou@aol.com

201
Copyright  1999 by Marcel Dekker, Inc. www.dekker.com
 202 Barceloux

HISTORY

The use of cobalt as a blue coloring agent for pottery,

jewelry, and glass began in Egypt and Persia around 2000
BC and currently, cobalt is an important constituent of
blue glaze in Danish porcelain.1,2 Leonardo Da Vinci was
one of the first artists to use the bright, blue pigment of
cobalt in oil paints. Although the blue pigments in Ming
Table of Contents dynasty pottery and in Venetian glass from the 15th cen-
tury contained cobalt, copper comprised most of the blue
History . . . . . . . . . . . . . . . . . . . . 202 pigment in earlier times. The Swedish chemist, George
Physical and Chemical Properties . . . 203 Brandt, first isolated cobalt in the 18th century and T.O.
Exposure . . . . . . . . . . . . . . . . . . 203 Bergman identified cobalt as an element in 1780.3 The
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Commercial Processes use of cobalt in industrial applications began in the 20th

Uses century. In the 1920s, the discovery that cobalt bound
Sources tungsten carbide into a hard substance initiated the use
Environmental Fate . . . . . . . . . . . . 206 of this ‘‘hard metal’’ in a variety of important industrial
Dose-Effect . . . . . . . . . . . . . . . . . 206 application, such as high-speed drills and cutting tools.
Acute Cobalt was a constituent of the first permanent magnetic
Chronic alloy, called alnico, which was developed in the 1930s.
Toxicokinetics . . . . . . . . . . . . . . . 207 The use of cobalt has increased rapidly since World War
Absorption II, reaching peak production in the middle 1980s. The
Distribution development of rare-earth cobalt magnets that possess
Elimination important power and size advantages contributed to the
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Pathophysiology . . . . . . . . . . . . . . 207 miniaturization of electrical and electronic equipment in

Mechanism of Toxicity the 1980s.
Pathological Changes Cobalt is an essential element in humans necessary for
Clinical Response . . . . . . . . . . . . . 209 the formation of vitamin B 12 (hydroxocobalamin), which
Lung catalyzes reactions, such as the synthesis of methionine,
Heart the metabolism of purines and folates, and the formation
Skin of methylmalonic acid in succinic acid. Excessive admin-
Carcinogenicity istration of this trace element may cause goiter and re-
Reproduction duced thyroid activity. The medicinal use of cobalt for
Laboratory . . . . . . . . . . . . . . . . . 211 the treatment of anemia in the 1940s was associated with
SI Units blockage of iodine uptake by the thyroid gland.4 Serious
Abnormalities pulmonary complications from exposure to the dust from
Cobalt Concentrations hard metals were first recognized in Germany during
Health Surveillance . . . . . . . . . . . . 212 World War II.5,6 In the industrial setting, cobalt is a com-
Medical Monitoring mon constituent of heat-resistant alloys and cobalt-con-
Biological Monitoring taining hard metals. Chronic exposure to cobalt dust from
Environmental Monitoring diamond polishing has been associated with a ‘‘hard-
Treatment . . . . . . . . . . . . . . . . . . 213 metal pneumoconiosis’’ in industrial workers.7 The acute
References . . . . . . . . . . . . . . . . . 213 form of the disease resembles a hypersensitivity reaction
with malaise, cough, and wheezing; the chronic form can
progress to pulmonary fibrosis and cor pulmonale.
In 1966, a syndrome characterized by pericardial effu-
sion, elevated hemoglobin levels, and congestive heart
failure occurred in heavy beer drinkers in Quebec City,
Canada.8 The following year, epidemics of ‘‘beer drink-
er’s cardiomyopathy’’ appeared in Omaha, Nebraska9
and in Minneapolis, Minnesota.10 These cardiomyopath-
 Cobalt 203

ies occurred when local breweries used cobalt in doses gen or nitrogen. Cobalt is the only element capable of
of 1–1.5 mg cobalt chloride/L beer as a method to reduce increasing the saturation magnetization of iron and thus
the effect of soap residues from electric dishwashers on is an important constituent of permanent magnets.
the formation of foam. The fact that most of the cases
developed in heavy drinkers, who ingested doses of co-
balt much less than the dose previously used for refrac- EXPOSURE
tory anemia, suggests that other factors contributed to Commercial Processes
the development of the cardiomyopathy. Suspected co-
factors include inadequate protein and vitamin (thiamine) Cobalt exists in nature primarily as arsenides, oxides,
intake, zinc depletion, and alcohol-induced heart dam- and sulfides. The abundance of cobalt in the earth’s crust
age.11 Several case studies have associated exposure to is similar to the presence of silver, and important mineral
cobalt dust with the development of a cardiomyopathy, ores containing substantial amounts of cobalt include co-
but the frequent lack of an etiology in cases of cardiomy- baltite (CoAsS), erythrite [Co 3 (AsO 4 ) 2 ], and smaltite
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opathy limits conclusions about causation.12 (CoAs 2 ). Cobalt commonly is found with copper, iron,
lead, nickel, and silver ores in concentrations ⬍1%, and
most of the production of cobalt is a by-product of copper
PHYSICAL AND CHEMICAL or nickel production.14
PROPERTIES The first stage in the recovery of cobalt is the physical
separation of cobalt from other metals either by froth flo-
Cobalt is a relatively rare metal that is a gray, ductile, tation (sulfide ores) or by gravity (arsenide ores). Roast-
brittle, magnetic element. This relatively unreactive ing or acid leaching is necessary to concentrate the cobalt
metal does not oxidize in dry or moist air at normal envi- in the ores. Refined cobalt is available primarily as bro-
ronmental temperatures. The two valence states are co- ken or cut cathodes.
baltous (II) and cobaltic (III). Table 1 lists the physical
For personal use only.

and chemical properties of metallic cobalt and its stable

Hard Metals
salts. These properties are similar to iron and nickel,
which are neighbors in the periodic table. Cobalt is used as a matrix for the production of ce-
Cobalt is stable in atmospheric oxygen, but heating mented tungsten carbide, which is also called ‘‘hard
produces mixed oxides below 900°C and cobaltous (⫹2) metal.’’ These cemented carbides have important physi-
oxide above 900°C.13 When heated, cobalt also combines cal properties including heat resistance, hardness, and ex-
with carbon, phosphorus, and sulfur, but not with hydro- treme strength. A powdered metallurgic process forms

Table 1
Physical and Chemical Properties of Cobalt and Its Compounds
Molecular Molecular Melting Boiling
Substance Formula Weight Point Point Solubility in Water
Cobalt (II-III)* Co 58.94 1493°C 3100°C Limited
Cobaltous oxide (II)* CoO 74.94 1935°C 0.313 mg/100 g
Cobalt oxides (II-III)* Co 3O 4 240.80 900°C Limited
Cobaltic oxide (III) Co 2O 3H 2O 183.88 84 µg/100 g, 37°C
Cobaltous sulfate CoSO 4 155 39.3 g/100 g, 25°C
CoSO 47H 2O 96.8°C
Cobaltous chloride CoCl 2 129.84 724°C 1049°C 52.9 g/100 g, 20°C
Cobaltous carbonate CoCO 3 118.94 0.11 g/100 g, 15°C
under CO 2 pressure
Cobaltous acetate Co(C 2H 3O 2 ) 249.08 Soluble
Adapted from table 1 in Ferioli A, Roi R. Alessio L. Cobalt. In: Biological Indicators for the Assessment of Human Exposure to
Industrial Chemicals. Alessio L, Berlin A, Boni M, Roi R, eds., Commission of the European Communities, 1989:51.
 204 Barceloux

hard metal using cobalt as a binder. These cemented car- hard metals in grinders and cutting tools contain 6–9%
bides primarily contain tungsten carbide (80–95%) and cobalt with an upper limit of 30% cobalt. Electro-depos-
cobalt (5–20%). Occasionally, small amounts (⬍5%) of ited cobalt alloys (iron, nickel, platinum, phosphorus)
nickel and other metals are added to the cobalt. The tung- have magnetic properties that are important in computer
sten powder frequently consists of smaller amounts of applications and the recording industry. Cobalt is a con-
titanium, tantalum, and vanadium oxides. The heating of stituent of some implants. Although particulates from the
fine particles of tungsten with carbon produces tungsten corrosion of these implants may migrate from the implant
carbide. The resulting compound is mixed with powdered site, toxicity has not been a reported complication of
cobalt as well as small amounts of other metals (chro- these implants.17
mium, nickel, niobium, molybdenum, titanium, tanta- With the exception of mixed oxides (II, III), the most
lum) based on the desired properties of the final product. important cobalt-containing chemicals in industry are co-
The powder is poured into steel or rubber frames, pressed baltous (II) salts. Some diamond polishers work with pol-
into appropriate shapes, and attached to backing material. ishing disks composed of a half-hard steel frame (98%
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Pre-sintering of this material produces a chalk-like mate- iron) and a polishing surface consisting of 10–20% mi-
rial that is shaped into the final configuration. The final crodiamonds cemented into ultrafine cobalt metal pow-
mixture is heated to 1550°C and the hardness of the re- der. Less common uses of cobalt include catalysts (cobalt
sulting material is similar to the hardness of diamonds. molybdate oxide, cobalt sulfides, cobalt carbonyl) in the
The aerosol created from the cutting and polishing of chemical and oil refining industry, drying agent in paints
hard metal bathed in coolants and lubricants contains re- (cobalt naphthenate), electroplating, radiology (60 Co),
spirable particles of dissolved or ionized cobalt. Analysis and an additive in fertilizer and animal feed. The latter
of air in a hard metal tool production plant revealed that use involves the addition of small amounts of cobalt in
the highest exposure (range up to 0.032 mg Co/m 3 ) oc- order to prevent cobalt deficiency in sheep and cattle.
curred in the powder preparation, rubber press, and shap- Fluomine is a cobaltous chelate [bis(3-fluorosalicylalde-
ing areas.15 hyde) ethylenediimine cobalt] used as part of the oxygen
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recovery system on high-altitude aircraft.18 Table 2 lists

Uses the industrial applications of a variety of cobalt com-
pounds.
Categories of cobalt alloys include the following:
high-temperature, corrosion-resistant superalloys (alumi- Sources
num, chromium, nickel, tantalum, titanium, tungsten, zir-
conium), magnetic alloys (aluminum, copper nickel, tita- For the general population, the diet is the main source
nium), high-strength steels, electro-deposited alloys, and of exposure to cobalt. The concentration in drinking wa-
alloys with special properties. Technically, hard metals ter is low (⬍5 µg Co/L). In the occupational setting, ex-
are not cobalt alloys, because the cobalt acts as a binding posure to cobalt alone occurs primarily during the pro-
agent for the metal carbides. Superalloys combine high- duction of cobalt powders. In other industries, such as
temperature mechanical properties with resistance to the hard metal industry, exposure to cobalt involves other
creep and to oxidation at these high temperatures. The compounds, which modulate the effect of cobalt. For ex-
base of these superalloys may be cobalt, nickel, or iron ample, exposure to tungsten carbide increases the reten-
and applications of these alloys include the production tion of cobalt in the lungs.19
of jet engines and magnetic material. In 1987, the approx-
imate end use of cobalt in the US was as follows: super-
Air
alloys, 41%; drier in paint, 13%; magnetic alloy, 11%;
cutting and wear-resistant alloys, 8%; catalyst, 7%; Sources of cobalt in the air are both natural (erosion,
ground coat or frit for porcelain enameling of steel fix- volcanic eruptions, forest fires, seawater spray) and an-
tures and kitchen appliances, 5%; and pigment manufac- thropogenic (fossil fuel burning, engine emissions, sew-
ture, 4%.16 Most of the production of cobalt involves the age sludge, phosphate fertilizers, processing of cobalt-
metallic form. For example, heat-resisting steels contain containing alloys).16 The concentration of cobalt in
25–65% cobalt and vitallium alloys in prostheses com- ambient air depends on the dispersion of particles to soil
prise about 65% cobalt along with chromium, nickel, and by the wind.13 Typically, the mean concentration in air
molybdenum. The powder metallurgy sector uses cobalt is small (about 1–2 ng Co/m 3 ) in urban areas and some-
as a binding agent for tungsten carbide. Typically, these what less in remote areas.16,20 Concentrations exceeding
 Cobalt 205

Table 2
Industrial Uses of Cobalt Compounds
Compound Formula Uses
Acetate (III) Co(C 2H 2O 2) 9 Catalyst
Acetate (II) Co(C 2H 2O 2) 2 ⋅ 4H 2O Driers for lacquers and varnishes, sympathetic inks, cat-
alysts, pigment for oil-cloth, mineral supplement, an-
odizer, stabilizer for malt beverages
Acetylacetonate Co(C 5H 7O 2) 3 Vapour plating of cobalt
Aluminate CoAl 2O 4 Pigment, catalysts, grain refining
Ammonium sulfate CoSO 4(NH 4) 2SO 4 ⋅ 6H 2O Catalysts, plating solutions
Arsenate Co 3(AsO 4) 2 ⋅ 8H 2O Pigment for paint, glass and porcelain
Bromide CoBr 2 Catalyst, hydrometers
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Carbonate CoCO 3 Pigment, ceramics, feed supplements, catalyst

Carbonate (basic) 2CoCO 3 ⋅ Co(OH) 2 ⋅ H 2O Chemicals
Carbonyl Co 2(CO) 2 Catalyst
Chloride CoCl 2 ⋅ 6H 2O Chemicals sympathetic inks, hydrometers, plating baths,
metal refining, pigment, catalyst
Chromate CoCrO 4 Pigment
Citrate Co 3(C 6H 5O 7) 2 ⋅ 2H 2O Therapeutic agents, vitamin preparations
Dicobalt manganese tetroxide MnCo 2O 4 Catalyst
Dicobalt nickel tetroxide NiCo 2O 4 Catalyst, anode
Dilanthanum tetroxide La 2CoO 4 Catalyst, anode
2-Ethylhexanoate Co(C 4H 15O 2) 2 Paint and varnish drier
Ferrate CoFe 2O 4 Catalyst, pigment
For personal use only.

Fluoride (II) CoF 2 Fluorinating agent

Fluoride (III) CoF 3 Fluorinating agent
Fluoride CoF 2 ⋅ 4H 2O Catalyst
Fluorosilicate CoSiF 6 ⋅ 6H 2O Ceramics
Formate Co(CHO 2) 2 ⋅ 2H 2O Catalyst
Hydroxide Co(OH) 2 Paints, chemicals, catalysts, printing inks
Iodide CoI 2 Moisture indicator
Lanthanum trioxide LaCoO 3 Electrode
Linoleate Co(C 19H 31O 2) 2 Paint and varnish drier
Lithium oxide LiCoO 2 Battery electrode
Manganate CoMn 2O 4 Catalyst, electrocatalyst
Naphthenate Co(C 15H 10O 2) 2 Catalyst, paint and varnish drier
Nitrate Co(NO 3) 2 ⋅ 6H 2O Pigments, chemicals ceramics, feed supplements,
catalyst
Oleate Co(C 10H 33O 2) 2 Paint and varnish drier
Oxalate CoC 2O 4 Catalysts, cobalt powders
Oxide (II) CoO Chemicals, catalysts, pigments
Oxide (II,III) Co 3O 4 Enamels, semiconductors
Oxides Mixed metal Pigments
Phosphate Co 3(PO 4) 2 ⋅ 8H 2O Glazes, enamels, pigments, steel pretreatment
Potassium nitrite K 3Co(NO 2) 4 ⋅ 1.5H 2O Pigment
Resinate Co(C 44H 32O 4) 2 Paint and varnish drier, catalyst
Sodium oxide NaCoO 2 Battery electrode
Stearate Co(C 18H 36O 2) 2 Paint and varnish drier, tyre cord adhesives
Succinate Co(C 4H 4O 4) ⋅ 4H 2O Therapeutic agents, vitamin preparations
Sulfamate Co(NH 2SO 3) ⋅ 3H 2O Plating baths
Sulfate CoSO 4 ⋅ xH 2O Chemicals, ceramics, pigments
Sulfide CoS Catalysts
Tricobalt tetralanthanum La 4Co 3O 10 Catalyst
decaoxide
Tungstate CoWO 4 Drier for paints and varnishes
Reprinted with permission from reference 13, table 11.
 206 Barceloux

10 ng Co/m 3 may occur in ambient air near point sources corn cereal (74 ng/g), and potato chips (70 ng/g). The
in heavily industrialized cities with concentrations near uptake of cobalt by plants is species-dependent and vege-
industrial sources ranging up to 600 ng Co/m 3.16,21 Typi- tables account for the majority of cobalt ingested from
cal ambient air levels in occupational setting range from the US diet. Green leafy vegetables and fresh cereals are
0.01–1.7 mg Co/m 3.14 the richest sources of cobalt (0.2–0.6 µg Co/g dry
weight), while dairy products, refined cereals, and sugar
Soil contain the least cobalt (0.1–0.3 µg Co/g dry weight).13
Animal livers also contain high concentrations of cobalt.
Cobalt is a relatively rare trace element. The average Tobacco contains about ⬍0.3–2.3 mg Co/kg dry weight26
concentration in the earth’s crust is 25 mg Co/kg. Basic and approximately 0.5% of the cobalt appears in the
and ultrabasic rocks contain about 100 ppm cobalt, while mainstream smoke.27 The exact bioavailability of cobalt
mantle-type rocks (basalt) contain 40–50 ppm Co and in tobacco is unknown.
acidic rocks (granite) contain 1–10 ppm Co.3 Soils that
contain ⬍0.5–3 mg Co/kg have insufficient cobalt to
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ENVIRONMENTAL FATE
meet the nutritional needs of grazing animals and there-
fore are considered cobalt-deficient. Examples of soils, Cobalt exists in ambient air in particulate form with
which are frequently deficient in cobalt, include soils de- a mass median diameter of 2.6 µm.28 The fate of cobalt
rived from sand, sandstone, limestone, some types of in the atmosphere depends on the size and the density of
acidic rocks (e.g., granite), and shale. Cobalt is a frequent the particles as well as the type of speciation. From
addition to fertilizers (commercial, compost, manure, sources of combustion, cobalt exists primarily as an oxide
sewage sludge) used on agricultural soils. Soil is not a while cobalt arsenide and cobalt sulfide complexes occur
significant route of exposure. Concentrations in the soil near extraction processes. Wet and dry deposition deposit
range from 1–40 mg Co/kg with an average in the US of cobalt on surface waters and on soil. Sediment is the pri-
7.2 mg Co/kg.16,22 Generally, cobalt-containing minerals mary repository for cobalt in contaminated water. Precip-
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appear in relatively small quantities in ores, such as arse- itation and adsorption to suspended particles account for
nides, oxides, and sulfides. Smaltite (CoAs 2 ), which con- ⬎98% of the cobalt present in freshwaters, while the re-
tains 25% cobalt, is an important source of cobalt in the mainder exists in the dissolved state. The mobility of co-
US. balt from sediment is enhanced by acidic pH, excess
chloride anions, and chelating agents. Most of the cobalt
Water released into water reaches the coastal zones of the
oceans through transport as suspended matter in rivers.
Cobalt is detected rarely in drinking water. When
In the deep sea, the formation of manganese nodules re-
present, the concentration in drinking water is low and
moves cobalt by interaction with MnO. In most soils, the
ranges from 0.1–5 µg Co/L.23 Trace amounts of cobalt mobility of cobalt is less than the mobility of cadmium,
occur in rivers, lakes, and groundwater.3 Coastal seawater
but the mobility of cobalt is greater compared with the
generally contains more cobalt compared with open
following metals: chromium (⫹2), lead, nickel, and
ocean waters as a result of the transport of cobalt dis- zinc.29 At higher soil pH, the formation of hydroxide and
solved with natural organic substances in river waters.
carbonate complexes with cobalt limits the mobility of
Average concentrations in open ocean waters are about cobalt in soil. The translocation of cobalt from roots to
0.3 µg/L. Mining activities and industrial use do not sig- the parts of the plant above ground is limited in most
nificantly affect the natural transport of cobalt in water
soils as a result of factors that limit the mobility of cobalt
because most of the cobalt resides in the sediment. in soil and water. Little biomagnification of cobalt occurs
in animals while the bioaccumulation factor for freshwa-
Diet ter fish and for marine fish ranges from 40–1000 and
The average daily intake of cobalt from the diet ranges 100–4000, respectively.16
from 5–45 µg Co/d with relatively high concentrations of
DOSE-EFFECT
cobalt occurring in fish and in vegetables.24 The estimated
average daily intake in a sample from the Canadian popu- Acute
lation was 11 µg Co (range 4–15 µg).25 In a sample of
Canadian foods, the concentration of Co was low in most A 19-month-old male died several hours after the in-
foods with the highest concentration in waffles (76 ng/g), gestion of approximately 30 mL of a cobalt chloride solu-
 Cobalt 207

tion despite lavage and supportive care within 1/2 hour of mulates about 20% of the administered dose of radioac-
the ingestion.30 tive cobalt chloride.35 There is no accumulation of cobalt
in the body with age.14
Chronic
Elimination
Roncovite was a cobalt-iron medication previously
used to treat refractory anemia. The daily administration Elimination of cobalt occurs rapidly with most of the
of this preparation at doses of 50–100 mg cobalt chloride absorbed dose of cobalt appearing in the urine. Most of
(18.5–37 mg Co/d) was tolerated for long periods of time the absorbed dose (80–90%) has a biological half-life of
without significant toxicity. The ingestion of 75–100 mg several days based on the excretion of radioactive cobalt
cobalt chloride daily by a group of pregnant women was following accidental inhalation, but a small portion of
associated with a slight decrease in the hemoglobin level, this dose has a half-life of several years.39,40
but no other toxic effects were noted. The oral adminis-
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tration of 3–4 mg cobalt chloride/kg body weight to chil-

PATHOPHYSIOLOGY
dren with sickle cell resulted in goitrogenic effects that
resolved after cessation of therapy.31 The estimated daily Mechanism of Toxicity
intake of beer drinkers, who developed cardiomyopath-
Beer Drinkers’ Cardiomyopathy
ies, was 6–8 mg Co as the chloride or sulfate salts.32 A
5-year follow-up cohort study of 16 Belgian patients with A suggested mechanism of action is the depression of
beer drinker’s cardiomyopathy indicated that the progres- oxygen uptake in the myocardial mitochondria by co-
sion of this disease required reduced protein intake and balt.41 This action may result from cobalt-induced inhibi-
a poor diet.33 The risk of pulmonary fibrosis in hard metal tion of the sulfhydryl groups of α-lipoic acid in the citric
workers increases when the cobalt concentration in air is acid cycle. This action inhibits the oxidation of α-keto-
⬎100 µg Co/m3.34
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glutarate and pyruvate to succinyl CoA and acetyl CoA,

respectively. Because cobalt has a high affinity for sulf-
hydryl (SH) groups, the protective effect of proteins and
TOXICOKINETICS amino acids probably results from the sequestration of
Absorption free cobalt in the cell. Other proposed mechanisms of
toxicity include the following: (1) cobalt-induced dam-
The bioavailability of cobalt via the gastrointestinal age to the transmembrane transport system resulting in
tract depends on the solubility of the compound, the increased intracellular calcium concentrations,42 and (2)
amount of coingested material, and inter-individual vari- chronic inhibition of sympathetic tone.43
ation. Studies of the absorption of CoCl 2 in volunteers
indicate that the absorption rate from the gastrointestinal Hard Metal Asthma
tract ranges from 5 to ⬎20% between doses of ⬍1 µg Cobalt is a known allergen that produces contact der-
Co and 1.2 mg Co.35 Depletion of iron stores increases matitis44 as well as asthma in workers exposed to cobalt
absorption of CoCl 2 in volunteers to concentrations alone (e.g., cobalt powder, cobalt salts)45 or to cobalt in
above 42%.36 Substantial uptake of cobalt occurs through association with other metals (e.g., hard metal dust). The
the lungs, although limited data are available in humans. etiology of this disease is probably a type I allergic reac-
Animal studies in hamsters suggest that the lungs absorb tion based on the demonstration of specific IgE antibod-
approximately 30% of an inhaled dose of cobalt oxide.37 ies against a complex of cobalt and albumin in workers
Generally the quantity of cobalt in the lungs is low in with hard metal asthma.46 Cobalt is considered the pri-
patients with hard metal pneumoconiosis.38 mary causal agent, although specific IgE antibodies to
nickel may be present and may contribute to the etiology
Distribution of hard metal asthma in some individuals.47 Both environ-
mental factors and individual susceptibility contribute to
The highest concentrations of cobalt in normal sub- the development of hard metal asthma. An epidemiologi-
jects appear in the liver (median 30 µg Co/kg with range cal study of hard metal workers demonstrated that age
6–151 µg Co/kg), followed by the kidney.13 Following and atopy were risk factors for hard metal asthma.48
the intravenous administration of cobalt, the liver accu- Multilogistic analysis of the data indicated that the devel-
 208 Barceloux

opment of hard metal asthma was not dose-related be- radicals. The exact cause of these effects remains to be
cause exposure to cobalt concentrations ⬍50 µg/m3 was determined.
a significant risk factor, but exposure to higher cobalt
concentrations was not. Pathological Changes
Hard Metal Lung Disease
Hard Metal Disease A diffuse interstitial lung disease develops after pro-
Hard metal disease is a pathological process of the longed exposure to high concentrations of dust from
pulmonary parenchyma that ranges from an intense alve- tungsten carbide–based hard metals that contain cobalt
olitis to end-stage pulmonary fibrosis. This disease is or from cobalt in association with other metals (diamond
called hard metal disease because it rarely, if ever, occurs polishers). Cobalt lung (diamond polisher’s lung) is the
following exposure to cobalt alone. Hard metal contains name given to the interstitial disease that occurs in dia-
tungsten and cobalt with small amounts of titanium, tan- mond polishers, who use a high speed-polishing disk
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talum, and vanadium oxides. Because tungsten is rela- consisting of a diamond-cobalt surface without tungsten
tively inert and the inhalation of cobalt in animal studies carbide.55,56 These polishing discs contain 10–20% mi-
produces pulmonary lesions, some authors believe the re- crodiamonds cemented with cobalt metal powder (80–
spiratory effects of exposure to dust from hard metal re- 90%). Depending on the disc type, other components
sult from cobalt.49,53 However, the lesions in animals are (carbon, iron, manganese, nickel, silicon, sulfur) may be
not identical to the pathological changes in humans with present. The two histological patterns of hard metal dis-
hard metal lung disease and the dose of cobalt required ease are (1) an acute or subacute desquamative pneumo-
to produce the lesions in animal studies are much higher nitis and (2) a more latent fibrotic form characterized by
compared with the exposure to cobalt in industry. Epide- progressive interstitial fibrosis.
miological data indicates that interstitial lung disease oc- Histological features of the acute or subacute desqua-
curs only among hard metal and diamond workers where mative pneumonitis primarily involve intra-alveolar des-
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exposure involves both cobalt dust and other compo- quamation of large vacuolated mononuclear cells and
nents.50 A cross-sectional study of workers exposed only limited interstitial fibrosis. The pulmonary changes are
to cobalt suggests that exposure to other dusts (e.g., tung- relatively uniform. The filling of alveoli with macro-
sten, titanium, iron, silica, diamond) in the hard metal phages is significant enough to resemble desquamative
process is necessary to produce the clinical picture of pul- interstitial pneumonitis. The presence of unusual, multi-
monary fibrosis.51 nucleated giant cells on lung biopsy or on bronchoal-
The low incidence fibrosing alveolitis in cobalt-ex- veolar lavage is a distinctive,57 but not invariable feature
posed workers and similarities to extrinsic allergic alveo- of hard metal lung disease. Electron microscopy indicates
litis (positive lymphocyte transformation test, reduced that these giant cells are both pneumocytes and macro-
helper/suppressor T cell ratios52 ) suggest that hypersensi- phages.58
tivity is the etiology of these effects rather than direct The more chronic form is characterized by diffuse mu-
toxicity.53 A study of Italian workers with hard metal dis- ral pulmonary fibrosis with few intra-alveolar cells. Peri-
ease suggested a genetic predisposition (residue Glu-69 bronchial and perivascular fibrosis may be present. The
of the HLA-DP β-chain) to the development of hard extent of fibrosis depends on the duration of the inflam-
metal disease.54 However, specific precipitins have not matory process, but substantial variation in the amount
been demonstrated in exposed workers or in patients with of inflammation and fibrosis occurs in different areas of
hard metal diseases. the lung of an individual. Often, hard metal particles in
Several histological features of fibrosing alveolitis ar- the lung contain high concentrations of tungsten and tan-
gue against delayed-hypersensitivity as an etiology. For talum but cobalt usually, but not always,59 clears rapidly
example, epithelioid cell granulomas and lymphocytic in- from the lung. Transmission electron microscopy detects
filtration are typically absent in cobalt-induced fibrosing cobalt in pulmonary particles more effectively than scan-
alveolitis while unusual multinucleated giant cells are ning electron microscopy.55
commonly present. An alternative hypothesis is the non-
Beer Drinkers’ Cardiomyopathy
immunologic activation of macrophages and macro-
phage-derived mediators (interleukin-1, leukotrienes, Postmortem histological changes involve myocardial
prostaglandins) by cobalt that generates toxic oxygen fiber degeneration, increased vacuolation, and interstitial
 Cobalt 209

edema, but there is no histological evidence of acute in- cles may produce inflammation of the upper respiratory
flammation.60 Typically, the pericardium contains fluid, tract as a result of either direct inflammation or an immu-
but it is not inflamed. The heart is enlarged, dilated, and nological reaction.
flabby, and the chambers may contain mural thrombi.10
Electron microscopy demonstrates extensive intracellular
Interstitial Lung Disease
changes involving glycogen, lipid, mitochondria, and
myofibrils. The mitochondria are swollen with alterations The manifestations of cobalt-induced interstitial lung
in the cristae. Myofibrils, Z lines, and A bands demon- disease probably results from a continuous process,
strate little detail after staining. which varies from an acute alveolitis to chronic pulmo-
The histological changes associated with beer drink- nary fibrosis depending on the individual susceptibility
ers’ cardiomyopathy are not unique and occur also in pa- as well as the duration and severity of exposure. Episodes
tients with ischemia. The myofibrillar loss and atrophy of alveolitis are characterized by the acute occurrence of
are more prominent in cobalt-induced cardiomyopathy fever, anorexia, cough, and dyspnea with exertion, typi-
Clinical Toxicology Downloaded from informahealthcare.com by University of Calgary on 10/05/12

compared with idiopathic forms of cardiomyopathy.61 In cally after months to several years of exposure. Symp-
animal experiments, cobalt-induced cardiomyopathy is toms may improve following removal from the work-
similar to alcoholic cardiomyopathy with vacuolation and place, but may recur following re-exposure. Repeat
loss of myofibrils as well as randomly scattered areas of episodes of alveolitis may produce interstitial fibrosis.
coagulation necrosis.62,63 The most common early symptoms of interstitial fibrosis
involve dry cough with the occasional production of
Cobalt Chloride scant, mucoid sputum and dyspnea on exertion.
The fibrotic form of this disease is more progressive
The autopsy of a 19-month-old child who died within and insidious than the alveolar form. Tachypnea at rest,
several hours of an ingestion of cobalt chloride revealed weight loss, and clubbing are late manifestations of pul-
few specific findings.30 The stomach mucosa was con- monary fibrosis. Inspiratory rales may occur either as a
For personal use only.

gested with a thin layer of coagulative necrosis involving result of active alveolitis or diffuse pulmonary fibrosis.
the inner one-third of the stomach mucosa. The esopha- As the extent of pulmonary fibrosis progresses, pulmo-
geal mucosa demonstrated a few small bullae. Micro- nary hypertension and cor pulmonale supervenes. Typi-
scopic examination of the brain revealed only edema. cally, evidence of interstitial lung disease appears after
10–12 years of exposure to hard metal dust,65 but the ap-
pearance of symptoms or signs may be shorter (2–7
CLINICAL RESPONSE
years) depending on the duration and intensity of expo-
Lung sure.58 Individuals with increased susceptibility may de-
velop interstitial lung disease at lower concentrations and
The main pulmonary effects of a chronic exposure to shorter durations of exposure compared with the general
hard metal dust include: (1) reversible airway obstruc- population of workers.66 Pulmonary abnormalities usu-
tion, (2) subacute fibrosing alveolitis with intra-alveolar ally improve considerable upon removal of the worker
desquamation that includes giant cells, and (3) chronic, from exposure to cobalt dust,67,68 and continued exposure
diffuse interstitial pulmonary fibrosis.64 Hard metal dis- to high concentrations of cobalt may produce rapid pro-
ease typically refers to the parenchymal manifestations gression of the pulmonary fibrosis55 and even death.69
(i.e., the later two pulmonary effects) that result from ex- The presence of interstitial fibrosis in populations of
posure to hard metal dust. active diamond polishers and in tungsten carbide produc-
Similar pulmonary changes occur in workers using tion workers is relatively rare (⬍1%). A cross-sectional
high-speed diamond-cobalt grinding tools. These pol- study of tungsten carbide production workers with pro-
ishing disks possess a cutting surface consisting of micro- longed exposure to high concentrations of cobalt above
diamonds cemented into a fine cobalt mesh and placed current occupational standards revealed a 3.8% preva-
over a frame of half-hard steel that contains mostly iron. lence of interstitial infiltrates and a 5% prevalence of ob-
The pulmonary changes in these workers are given the structive defects in non-smoking workers.70 A prelimi-
acronym of cobalt lung because of the absence of sus- nary cross-sectional study of active workers, who
pected effects from other metals present in the hard volunteered for the study in a plant producing diamond-
metal. In addition, exposure to cobalt-containing parti- cobalt tools, demonstrated a moderate restrictive defect
 210 Barceloux

in the workers exposed more than 5 years to cobalt con- progressive dyspnea.78 Co-factors (mineral and protein
centrations exceeding 50 µg Co/m.71 This concentration deficiencies, alcoholic cardiomyopathy) were probably
is the current Occupational Safety and Health Adminis- involved in the development of beer drinkers’ cardiomy-
tration (OSHA) PEL-TWA for cobalt metal dust and opathy because of the low dose of cobalt consumed by
fume, although the currently recommended TLV-TWA these patients. Several case reports associated the abrupt
from the American Conference of Governmental and In- development of cardiomyopathy in workers with expo-
dustrial Hygienists (ACGIH) is 20 µg Co/m3 . The data sure to cobalt.12,79,80 However, the lack of exposure data,
associating exposure to cobalt with obstructive lung dis- the absence of a unique marker of cobalt cardiomyopa-
ease are less convincing. A statistically significant reduc- thy, and the dearth of epidemiological data73 supporting
tion in FEV1 occurred in hard metal workers exposed to a causal connection limits conclusions about the inci-
an average concentration of 0.126 mg Co/m3 , suggesting dence of cobalt-induced heart disease at the present time.
that this concentration of exposure to cobalt can produce
chronic obstructive disease.72 A study of Danish porce- Skin
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lain workers associated long-term exposure to cobalt blue

dyes with small airway obstruction.73 Cobalt is one of the three most common metallic
sources of contact dermatitis along with nickel and chro-
Occupational Asthma mium. In the occupational setting, cobalt-induced contact
dermatitis characterized by erythematous papules occurs
Occupational asthma characterized by wheezing, commonly on the hand of workers in the hard metal in-
cough, and dyspnea occurs in hard metal workers who dustries. The prevalence of hand eczema and irritant reac-
demonstrate the presence of cobalt-specific IgE com- tions in a group of 776 workers in a hard metal factory
plexes with albumin46 and a positive bronchoprovocation was approximately 10% and 15%, respectively.81 The
test with cobalt chloride.74 These tests demonstrate early, majority of these rashes begin within the first year of em-
late, and dual reactions to the inhalation of cobalt. In con- ployment. Risk factors for the development of severe ec-
For personal use only.

trast to hard metal disease, exposure only to cobalt is suf- zema include prior nickel sensitization and irritative der-
ficient to produce asthma. Clinically, asthmatic symp- matitis.82 In a study of 853 hard metal workers, 25% of
toms usually appear about 4–6 hours after exposure and the nickel sensitive individuals developed cobalt allergy
the symptoms often worsen in the early evening.75 Char- compared with 5% in the total population tested.83 Almost
acteristic improvement occurs on the weekend and on all (88%) of the nickel sensitive individuals were women
holidays; however, the presence of late reactions to in- who developed nickel sensitivity as a result of the prior
haled cobalt indicates that symptoms of asthma may ap- use of pierced earrings.
pear up to 48 hours after exposure. Sensitization to these metals results from co-exposure
The prevalence of occupational asthma in hard metal to these metals rather than cross-reactivity among these
workers depends on the population studied (i.e., healthy metals.84 The incidence of contact dermatitis from chro-
worker effect) as well as the intensity of exposure. A mium, cobalt, and nickel in a group of 1782 workers ex-
cross-sectional study of hard metal workers revealed a posed to cement, waste fly ash, and asbestos cement was
prevalence of 5.6% for asthma in active workers.76 The 8.6%, 3.1%, and 1.1%, respectively.85 The diagnosis was
presence of concurrent sensitivity to nickel indicates that based on definitively positive patch tests to these metals.
nickel may contribute to the development of hard metal This diagnosis of cobalt sensitivity is complicated by the
asthma.77 Although there is no evidence that workers with fact that nickel contamination of cobalt patch tests may
cobalt-induced occupational asthma develop interstitial produce false positive skin tests for cobalt in patients who
fibrosis, workers with asthma may rarely develop hyper- are highly sensitive to nickel.86
sensitivity pneumonitis.
Carcinogenicity
Heart
Cancer in humans as a result of exposure to cobalt by
Cases of beer drinkers’ cardiomyopathy associated any route has not been demonstrated. The US National
with the consumption of beer containing about 1 ppm Toxicology Program does not list cobalt as a recognized
cobalt as a foam-stabilizing agent were characterized by animal or human carcinogen. The International Agency
the following: acute onset of left- and then right-sided for Research on Cancer (IARC) recently classified cobalt
heart failure with hypotension, pericardial effusion, and and cobalt compounds as possibly carcinogenic to hu-
 Cobalt 211

mans (Class 2B) based on sufficient evidence that cobalt Abnormalities

metal powder and cobaltous oxide are carcinogenic in
Hard Metal Disease
animals.13 These studies involved the development of sar-
comas at the site of the injection only. The IARC deter- Hard metal disease demonstrates the same radio-
mined that the evidence for the carcinogenicity of cobalt graphic and physiologic features as other forms of inter-
and cobalt compounds in humans was inadequate. Cobalt stitial lung disease with the exception that small multiple
salts are only weakly genotoxic in bacterial systems. Di- nodules may appear initially on the chest X-ray.64 Mag-
rect implantation of cobalt-chromium alloy and cobalt netic resonance imaging may reveal residual parenchy-
salts has produced tumors, mainly rhabdomyosarcomas, mal activity before the presence of an abnormal chest
in rats, but not in mice.2 In an experiment in rats, the X-ray.95 Abnormalities on bronchoalveolar lavage and
intratracheal instillation of cobalt oxide produced a slight transbronchial biopsy include multinucleated giant cells,
excess of benign and malignant lung tumors.87 fibrosis, excessive mast cells and eosinophils, and in-
Epidemiological evidence of cancer in humans fol- creased T-lymphocytes with abnormal helper/suppressor
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lowing exposure to cobalt is weak. A cohort mortality ratios.96 Additionally, evidence of a restrictive impair-
study of 1143 French workers exposed to cobalt in an ment on pulmonary function tests may precede changes
electrochemical plant revealed an excess of lung cancer. on the chest X-ray. A reduction in the Pa o 2 also may oc-
The small number (4) of cases of lung cancer and the lack cur during exercise.
of control of confounding variables (smoking, arsenic,
nickel) prevent the establishment of a causal relationship Hard Metal Asthma
between exposure to cobalt and the development of lung
Bronchoprovocation tests with cobaltous chloride are
cancer.88 A follow-up study of this cohort of cobalt pro-
the gold standard for determining the presence of hard
duction workers for an additional 7 years revealed no ex-
metal asthma.47 Positive reactions to bronchoprovocation
cess (SMR ⫽ 0.85, 95% CI 0.18–2.50) mortality from
challenges include early, late, and dual reactions. Patch
lung cancer.89 A retrospective cohort study of 874 women
For personal use only.

and intradermal skin tests do not discriminate patients

exposed to cobalt in two Danish porcelain factories did
with hard metal asthma from controls in the general pop-
not demonstrate a significantly increased relative risk
ulation.
(RR ⫽ 1.2, 95% CI 0.4–3.8) of developing lung cancer.90
Direct measurements of cobalt concentrations were not
Beer Drinkers’ Cardiomyopathy
available.
The mean concentration of cobalt in the cardiac tissue
Reproduction from postmortem examination of 8 patients, who died
from this disease, was 0.69 ⫾ 0.32 µg/g wet cardiac tis-
There is little data on the reproductive effects of expo- sue as measured by atomic absorption spectrophotome-
sure to cobalt. In bacterial systems, cobaltous salts are try.97 Concentrations of cobalt in normal cardiac tissue
not mutagenic, but studies in mammalian cultures indi- ranges from 0.05–0.4 µg Co/g dry weight tissue.12
cate that cobaltous salts inhibit DNA repair and thus may
enhance the genotoxicity of other mutagenic agents.91 Cobalt Concentrations
Cobaltous chloride induced a low frequency of cleft
palate in mice.92 No fetotoxic or teratogenic effects oc- A progressive reduction in the reported range of cobalt
curred in rats gavaged with daily doses of 100 mg cobal- concentrations of the general population resulted from
tous chloride/kg body weight.93 A woman, who devel- the improvement in analytical methods.13 Significant ex-
oped severe pulmonary fibrosis secondary to hard metal posure to cobalt occurs primarily in occupational settings
disease before her pregnancy, delivered a healthy full- because the concentrations of cobalt in the environment
term infant.94 are generally low. The average daily intake of cobalt in
the general population is about 20 µg Co, which results
in a mean serum concentration of approximately 0.1–0.3
LABORATORY
µg Co/L98 and a mean urine concentration of about 0.1 µg
SI Units Co/L.13 The level of cobalt in urine is somewhat higher in
smokers (mean 0.6 µg Co/L) compared with nonsmokers
1 µg ⫽ 16.9 nmol (mean 0.3 µg Co/L), but there was no difference in serum
1 nmol ⫽ 0.06 µg concentrations of cobalt.99 In a study of the US population
 212 Barceloux

(National Health and Nutrition Examination Survey for the surveillance of hard metal workers. The specific
[NHANES] III), the 95th percentile Co concentration guidelines necessary to monitor workers depend on the
was 8.3 µg/L urine as measured by inductively coupled amount of exposure to dusts from hard metals. Workers
argon plasma mass spectrometry.100 Toxic concentrations should be observed for the development of skin sensitiza-
of cobalt in urine and blood are not well defined. tion, hypersensitivity pneumonitis, and occupational
asthma. Such workers should be referred to appropriate
specialists for allergy testing. The development of inter-
HEALTH SURVEILLANCE
stitial lung disease (e.g., progressive reduction in pulmo-
Medical Monitoring nary diffusion) in a worker exposed to cobalt indicates
the need to terminate the exposure.
Preplacement examination should focus on the respi-
ratory tract (interstitial disease, asthma), skin, blood Biological Monitoring
(polycythemia), and the thyroid (thyromegaly). Labora-
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tory examination should include chest X-ray and com- The exact concentration of cobalt in the urine and the
plete pulmonary function tests. Table 3 lists guidelines serum at which the risk of adverse effects is negligible

Table 3
Guidelines for Health Surveillance of Hard Metal Workers
Pre-exposure clinical assessment
■ History and physical examination;
■ Laboratory examination: peripheral blood examination with differential cell count, renal and hepatic function
■ Lung function tests: spirometry, single-breath diffusing capacity for carbon monoxide; metacholine challenge
For personal use only.

■ Electrocardiogram;
■ Chest X-ray: postero-anterior and lateral view;
■ Urinary cobalt determination (spot sample);
■ Questionnaire for hard metal-related symptoms
Periodical assessment
■ History and physical examination (yearly);
■ Lung function tests: spirometry, single-breath diffusing capacity for carbon monoxide (yearly);
■ Chest X-ray (yearly);
■ Urinary cobalt determination (six-monthly on end-week collected sample);
■ Quesionnaire for hard metal-related symptoms (yearly)
Questionnaire for hard metal-related symptoms
■ Have you suffered in the last year from persistent
Non-productive cough? Y 䊐 N 䊐
if yes, during workshift? Y 䊐 N 䊐
even after workshift? Y 䊐 N 䊐
Sudden shortness of breath? Y 䊐 N 䊐
if yes, during workshift? Y 䊐 N 䊐
some hour past workshift? Y 䊐 N 䊐
during the night? Y 䊐 N 䊐
Shortness of breath during exertion? Y 䊐 N 䊐
Repeated episodes of mild fever? Y 䊐 N 䊐
Weight loss? Y 䊐 N 䊐
Asthenia? Y 䊐 N 䊐
Eczematous dermatitis of the exposed surfaces? Y 䊐 N 䊐
■ Did any symptom disappear after removal from the workplace? Y 䊐 N 䊐
If yes, which symptoms?
Reprinted with permission from Suggested Guidelines for the Health Surveillance of Hard Metal Workers (reference 89, table 2,
page 267).
 Cobalt 213

has not been defined. Biological monitoring of cobalt mg Co/m3 . The US NIOSH established an IDLH value
does provide objective data for the evaluation of changes of 20 mg Co/m3.
in workplace practices and personal hygiene based on the
amount of cobalt absorbed by the workers. Determination
of cobalt in urine is a better measure of exposure to solu- TREATMENT
ble cobalt compounds (metal, salts, hard metals) com-
pared with exposure to insoluble cobalt compounds, such Little human data are available on the treatment of
as cobalt oxides.101 The ACGIH recommends a BEI of acute cobalt intoxication. Animal experiments suggest
15 µg Co/L urine at the end of shift/workweek. Workers that N-acetylcysteine is a more effective chelating agent
sensitized to cobalt may react to concentrations of cobalt than CaNa 2 EDTA or DMSA,111 but there are no human
much lower than nonsensitized workers react. data to confirm the efficacy of these chelation agents.
The 95% upper limit of a reference group of Danish Otherwise, treatment is supportive.
men and women from the general population was 23 Management of hard metal disease is also supportive.
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nmol (1.38 µg) Co/L urine and 31 nmol (1.86 µg) Co/ There is no specific pharmacological treatment for hard
L urine, respectively.102 A study of workers exposed to metal disease. Improvement in patients with hard metal
the maximum PEL-TWA (50 µg Co/m3) suggests that disease occurred following the administration of cortico-
the mean serum concentration in workers exposed to this steroids (40–60 mg prednisone daily)64 and cyclophos-
air concentration is about 2.5 µg Co/L103 or about 32 µg phamide (25 mg twice daily), but there are no clinical
Co/g creatinine postshift Monday urine.101 The kidneys studies confirming the effectiveness of these agents.
initially eliminate cobalt rapidly, but the level of cobalt
in the urine gradually rises during the workweek as a
result of a slower secondary elimination phase. In work- REFERENCES
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 Cobalt 215

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