MINOR TOXIC METALS

 Antimony  Germanium
 Barium  Indium
 Cesium  Palladium
 Fluorine
• Antimony (Sb) is a metalloid
• Fine casting qualities
• Greek words “anti” and “monos”
– which means “opposed to solitude”
Antimony
• Most antimony compounds are of tri-
and pentavalent states
• alloys, and in production of
fireproofing chemicals, ceramics,
glassware, and pigments
Antimony

• Antimony potassium tartrate

– Treatment for schistosomiasis
• Pentavalent antimony compounds
– Preferred drugs for leishmaniasis
• Similar to arsenic trioxide, trivalent
antimony compounds also show some
antitumor potential
Antimony Exposure

• Occupational antinomy exposure

comes from industrial emissions
• Food is the major route for
environmental exposure
– Average daily intake: estimated 5 μg
Disposition of Antimony

• Mostly absorbed in lungs and the

gastrointestinal tract
• The major sites of antimony
accumulation are:
– liver
– kidney
– lungs
– spleen
– blood
Disposition of Antimony

• In humans and rodents, pentavalent

antimony is only sparingly reduced to
the trivalent form
• evidence of antimony methylation in
mammals is low
• The pentavalent form is predominantly
excreted in urine,
• whereas trivalent antimony is
conjugated to GSH and is excreted via
the bile and found mainly in feces
• Occupational exposures are usually by
inhalation of dust containing antimony
compounds, such as:
– pentachloride
Toxicity of Antimony
– trichloride
– trioxide
– trisulfide
Toxicity of Antimony
• Acute toxicity from the pentachloride
and trichloride exposure includes
rhinitis while in severe exposure can
cause acute pulmonary edema
• Chronic exposure by inhalation of
other antimony compounds results in:
– rhinitis, pharyngitis, trachitis
– over the longer term, bronchitis and
eventually pneumoconiosis with
obstructive lung disease and emphysema.
Toxicity of Antimony
• Trivalent forms of antimony appear
more toxic and may produce
cardiotoxicity involving arrhythmias,
myocardial damage, and cardiac
arrest
Toxicity of Antimony
• Antimony compounds are generally
negative in nonmammalian
genotoxicity tests
• mammalian tests usually give positive
results for trivalent but negative results
for pentavalent antimony compounds
Toxicity of Antimony
• The metal hydride of antimony, stibine
(SbH3), is a highly toxic gas that can be
generated when antimony is exposed
to reducing acids or when certain
batteries are overcharged.
• High-purity stibine is also used in the
production of semiconductors and,
like arsine (AsH3), causes hemolysis.
• Greek word barys meaning “heavy”
• Barium and barium compounds are
used in electronics (barium alloys), as
Barium
rodenticides (barium carbonate), as
pigments (barium carbonate and
sulfate), and as X-ray contrast media
(barium sulfate).
 Barium
• Some foods, such as Brazil nuts,
pecans, and seafood, may contain high
amounts of barium.
• Occupational exposure to barium
primarily occurs in workers who inhale
barium sulfate from working with the
ore, barite, and barium carbonate dust
during the mining and manufacturing
 Barium
• Insoluble barium sulfate is not
absorbed from the gastrointestinal
tract, and is nontoxic to humans
• Aerosols of soluble barium compounds
are well absorbed in the lung
• Bone and teeth are the major sites of
barium deposition, containing up to
90% of the body burden
 Barium
• The remainder of barium in the body is
found in soft tissues, such as the
– Lungs
– Aorta
– Brain
– Heart
– Spleen
– Liver
– Pancreas
 Barium
• Once filtered by the glomeruli, barium
is reabsorbed by the renal tubules with
only small amounts appearing in the
urine
• The major route of barium excretion is
the feces.
• The elimination half-life is about 3 to 4
days
Toxicity of Barium

• Occupational poisoning by barium is

uncommon, but a benign
pneumoconiosis (baritosis) may result
from inhalation of barium sulfate
(barite) dust or barium carbonate
• Accidental poisoning from ingestion of
an acute toxic dose (over 200 mg) of
soluble barium salt results in
intractable vomiting, severe diarrhea,
and gastrointestinal hemorrhage
Toxicity of Barium

• Profound hypokalemia and muscle weakness

progressing to flaccid paralysis are the
hallmarks of barium poisoning
• The mechanism of toxicity probably involves
the blocking of calcium activated potassium
channels responsible for cellular efflux of
potassium
• As a result, intracellular potassium rises and
extracellular levels fall leading to
hypokalemia
Toxicity of Barium

• The progressive muscle weakness seen in

barium intoxication in humans could be due
to barium-induced hypokalemia rather than
a direct effect on muscles, which is not
observed in experimental animals
• Latin word caesius meaning “sky blue.”
• 137Cesium is a by-product of nuclear
reactions and is used in radiation
therapy Cesium
• Most cesium compounds are water
soluble and are well absorbed through
inhalation, ingestion, or skin contact
 Cesium
• Once in the blood, cesium is rapidly
distributed throughout the body, with
higher concentrations in muscles
• Cesium can cross the placenta and
appears in milk
• Cesium mimics potassium for cellular
transport. Urinary excretion is the
primary route of elimination of cesium
from the body
 Cesium
• The biological half-life of cesium is
variable, ranging from 50 to 150 days
Toxicity of Cesium

• Radioactive Cesium
– The initial symptoms following radioactive
cesium exposure include nausea, vomiting, and
diarrhea
– Local skin blistering is common when there is
significant dermal contact
– Local skin blistering is common when there is
significant dermal contact
– Symptoms can eventually progress to bone
morrow suppression, infection, hemorrhage, and
even death
Toxicity of Cesium
• Non-radioactive Cesium Compounds
– Stable (nonradioactive) cesium compounds
are relatively less toxic
– High-dose exposure can cause irritation to
the gastrointestinal tract and to the eye
– Cardiac arrhythmia and QT wave
prolongation have been observed in several
case reports following ingestion of cesium
salts as homeopathic remedies for cancer
treatment
– Adverse developmental effects of cesium
chloride have been observed in rodents
• Fluorides are organic and inorganic
compounds containing the nonmetallic
element fluorine
• Fluoride is an essential component for
Fluorine
normal mineralization of bones and
dental enamel, and it has been widely
used to reduce the prevalence and
severity of dental caries in children
and adults
Fluorine
• Fluoride is an essential component for
normal mineralization of bones and
dental enamel, and it has been widely
used to reduce the prevalence and
severity of dental caries in children
and adults
• Flurosilicic acid and sodium
fluorosilicate have been used in water
fluoridation since 1940s
Fluorine
• Adequate intake level is about 0.05
mg/kg/day in adults but is much lower for
infants
• Toxicologically important fluoride
compounds include hydrogen fluoride
and sodium fluoride.
• The major sources of fluorides intake in
the general population are water, food,
and fluoride-containing dental products
Fluorine
• Fluorides are readily absorbed (75–90%)
from the gastrointestinal tract
• Approximately 99% of the fluoride in the
body is found in bones and teeth
• Fluoride is incorporated into bone by
replacing the hydroxyl ion in
hydroxyapatite to form hydroxyfluoapatite
• Fluoride in bone can be remobilized
slowly as a result of the ongoing process
of bone remodeling, especially in the
young children
Fluorine
• Fluoride is readily transferred across
the placenta but poorly transferred to
breast milk
• Fluorides are mainly excreted in urine
• Plasma and urine fluoride levels are
related to fluoride intake and are a
biomarker for excess exposure, while
hair, fingernails, and tooth enamel are
indicators of long-term response
Toxicity of Fluorine

• Dental Fluorosis Excessive fluoride

intake from water during the period of
enamel formation in children can
cause dental fluorosis
• In its mild form, dental fluorosis is
characterized by white, opaque areas
on the tooth surface
• In its severe form, it is manifested as
yellowish brown to black stains and
severe pitting of the teeth
Toxicity of Fluorine

• Dental fluorosis incidence and severity

in some instances can be decreased
by the cessation of water fluoridation
• Skeletal Fluorosis Long-term exposure
to very high oral doses of fluoride or
occupational exposure to cryolite
dusts can result in skeletal fluorosis
Toxicity of Fluorine

• Cases of skeletal fluorosis are

predominantly found in developing
countries, particularly in India and
China, and are associated with high
fluoride intake coupled with
malnutrition
• Skeletal fluorosis does not usually
manifest symptomatically until the
disease attains an advanced stage
Toxicity of Fluorine

• Fluoride is mainly deposited in the

neck, knee, pelvic, and shoulder joints
and/or bones, which makes it difficult
to move or walk
• The symptoms of skeletal fluorosis are
similar to arthritis, and early on include
sporadic pain, back stiffness, burning-
like sensation, pricking and tingling in
the limbs, muscle weakness, and
chronic fatigue
Toxicity of Fluorine
• Other health effects include respiratory
tract, skin, and eye irritation following
inhalation exposure to hydrogen fluoride
or fluorine gas.
• Gastrointestinal symptoms occur with
excess ingestion of fluoride
• Chronic endemic fluorosis may also lead
to muscle fiber degeneration, low
hemoglobin levels, skin ruches,
neurological manifestations,
compromised immunity, and endocrine
effects
• Germanium (Ge) is a metalloid-like
antimony and arsenic.
• The discovery of germanium as a
predicted analog of silicon in the
Germanium
1880s was a key confirmation of the
developing theory of elemental
periodicity
• Stable oxidation states include divalent
and tetravalent germanium
Germanium
• Currently it is used in infrared night vision
systems, fiber optics, as a polymerization
catalyst, and in alloys with other metals
• Germanium is commercially derived from
zinc ore processing or as a combustion
by-product of certain coals.
• Ultra pure germanium can be obtained
from other metals by fractional distillation
of the volatile germanium tetrachloride
Germanium
• Germanium concentrations in most
foods are similar to the natural
abundance level of about 0.6 to 1.0
ppm in soils, although higher levels
have been reported in some canned
foods
• Daily germanium intake from food in
humans is reported to be about 1.5 mg
of which 96% is absorbed
Germanium
• Inorganic germanium compounds are
rapidly and effectively absorbed after
oral exposure.
• Absorbed germanium is widely
distributed throughout the body with
the highest concentrations occurring
in many tissues including the liver,
kidney, and spleen
Germanium
• Absorption and distribution appears to be
largely independent of the germanium
compound, as both sodium germanate
and tetraethylgermanium are widely
distributed without evidence of selective
retention or storage after oral exposure in
mice
• Absorbed germanium is widely
distributed throughout the body with the
highest concentrations occurring in many
tissues including the liver, kidney, and
spleen
Germanium
• There appear to be no reports on
systemic toxicity of germanium after
occupational exposure.
• There are, however, at least 31 case
reports of renal failure in humans after
ingestion of inorganic or organometallic
germanium compounds mainly through
consumption of germanium-containing
dietary supplements or elixirs for various
diseases
Germanium
• Levels of germanium consumed were
∼15 to 300 g and were ingested over a
period of 2 to 36 months
• Excessive germanium consumption
from such sources induces various
symptoms including renal dysfunction
involving tubular degeneration,
anemia, muscle weakness, and
peripheral neuropathy
Germanium
• Excessive germanium consumption
from such sources induces various
symptoms including
– renal dysfunction involving tubular
degeneration,
– anemia,
– muscle weakness, and peripheral
neuropathy
Germanium
• Spirogermanium (2-aza-8-
germanspiro[4,5] decane-2-
propamine-8,8-diethyl-N,N-dimethyl
dichloride) was neurotoxic to humans
after intravenous injection for the
treatment of cancer
• Indium (In) is a posttransitional metal,
named after the indigo line in its
atomic spectrum, which was
discovered and isolated in the 1860s
Indium
• Indium is a rare metal with a principal
valence state of 3+ and is recovered as
a by-product of zinc smelting.
 Indium
• The human daily intake of indium has
been estimated in the range of 8 to 10
μg.
• The most common routes of exposure
for the general population are
inhalation and ingestion while in
occupational exposure inhalation
predominates
 Indium
• Indium compounds are poorly
absorbed when ingested or after
intratracheal instillation but may show
moderate absorption after inhalation
• Indium derived from oral or
intratracheal instillation of indium
phosphide is uniformly distributed
between major organs and is excreted
in the urine and feces
Toxicity of Palladium

• Acute toxicity in animals is generally

greatest after inhalation or intravenous
injection, and limited after oral
exposure
• Intravenous injection of indium
chloride in mice or rats produces
extensive renal and liver necrosis
Toxicity of Indium

• Lung instillation of indium phosphide

can produce alveolar or bronchiolar
cell hyperplasia in hamsters
• The intratracheal instillation of indium
phosphide produces little systemic
toxicity
Toxicity of Indium

• Inhalation of indium phosphide or oral

exposure to indium chloride by
pregnant rats results in fetal indium
concentrations that are similar to
maternal blood levels indicating the
placenta does not perturb indium
• Palladium (Pd) belongs to the platinum
group metals
• Palladium was discovered in 1803, and
named afterPalladium
the asteroid Pallas.
• Palladium compounds commonly
exhibit oxidation state of 2+, although
compounds with the oxidation state 4+
are observed
Palladium
• Palladium is used in automobile
catalysts, in dentistry in electrical
appliances, and in jewelry
• Environmental palladium levels are
increasing, but exposure in the general
population is low
• Dental alloys and work in metal
refining or catalyst manufacture can
be major sources of palladium
exposure
Palladium
• Palladium chloride is poorly absorbed
from the gastrointestinal tract or from
subcutaneous injection sites
• After intravenous administration of
palladium compounds, palladium is
distributed to kidney, liver, spleen,
lung, and bone
• In cells, palladium compounds likely
complex with amino acids, proteins,
DNA, and other macromolecules
Palladium
• Orally administered palladium is poorly
absorbed and eliminated in feces,
whereas intravenous palladium is
mainly eliminated in the urine
• Half-lives range from 5 to 12 days
Toxicity of Indium

• Palladium sensitization is a major

health concern, as very low doses are
sufficient to cause allergic reactions in
susceptible individuals
• Contact dermatitis is a main
manifestation of palladium sensitivity,
unlike that with platinum
Toxicity of Indium

• Immediate hypersensitivity (type I)

reactions to palladium have been
reported in refinery workers sensitized
to platinum