Tungsten - Toxicology of Metals - page 856

activity after a 20-30 minute interval, which increased
and resulted in sustained ictal activity. The effect pro-
duced was so consistent that tungsten has been used to
produce model systems of experimental epilepsy.
After the intraperitoneal injection of tungsten oxide
in rats, no cellular reaction has been observed (Fred-
erick and Bradley, 1946). Later studies by Lison et al .
(1990; 1991; 1992) clearly indicate that cell reactions
do occur in mouse peritoneal and rat alveolar macro-
phages related to the combined exposure to tungsten
carbide and cobalt.

exposed to human osteoblast cells (Miller et al ., 2001).
Transformed cells showed alterations in ras oncogene
expression and induced tumors when transplanted
to nude mice, which was interpreted as a neoplastic
transformation to a tumorigenic phenotype of the oste-
oblast cells.

7.3 Interaction with Molybdenum
Sodium tungstate antagonizes the normal meta-
bolic action of molybdate in its role as metal carrier for
the enzymes xanthine dehydrogenase (Higgins et al .,
1956), sulfi te oxidase and aldehyde oxidase (Johnson
and Rajagopalan, 1974), and nitrate reductase (Notton
and Hewitt, 1971). It is of interest in this respect that the
tungstate ion WO 4 2− is isomorphic with the molybdate
ion MoO 4 2− . Higgins et al . (1956) showed that sodium
tungstate added to the diet inhibited the intestinal dep-
osition of xanthine oxidase in the rat and reduced both
xanthine dehydrogenase and molybdenum concen-
trations in the liver of the chicken. Owen and Proud-
foot (1968) fed sodium tungstate to goats and cows
and showed a reduction in xanthine oxidase secreted
in milk, in some cases to an undetectable level. They
postulated that tungsten could preferentially occupy
enzyme sites normally occupied by molybdate.
Cohen et al . (1973) administered tungstate to rats
maintained on a low-molybdenum diet and dem-
onstrated a loss of both xanthine oxidase and sulfi te
oxidase activities. The tungsten-treated rats seemed
healthy but were more susceptible to bisulfi te toxicity.
On exposure to high levels of sulfur dioxide, the tung-
sten-treated, sulfi te oxidase-defi cient animals showed
evidence of systemic sulfi te toxicity and had much
shorter survival times than the controls. Sulfi te oxidase
seems to be involved in the oxidative metabolism and
thus in the detoxifi cation of sulfur dioxide as well as
bisulfi te.
Sulfi te oxidase activity in rat liver is negligible at
birth but increases rapidly between the fi fth and elev-
enth day after birth. Activity is considerably impaired
by administration of tungsten for 20 days before deliv-
ery (Cohen et al ., 1974).

7.2.2 Humans

There are no data available on occupational expo-
sures to compounds of tungsten that incriminate these
as toxic or as hazardous agents to other parts than
the direct local contact sites (i.e., in the lung). Kruger
(1912) observed no ill effects in patients given 25-80 g
powdered tungsten metal by mouth as a substitute
for barium in radiological examinations. However,
the occurrence of the interstitial lung disease termed
“hard-metal disease” led to fi ndings that the combined
exposure to cobalt and tungsten particles may be an
important explanatory factor (Lison et al ., 1996). Recent
fi ndings on human cell cultures in vitro and on rats
in vivo indicate that tungsten may have a synergistic
effect with cobalt or nickel leading to tumorigenicity
(Kalinich et al ., 2005; Miller et al ., 2001).
Recent studies by Gatti et al . (2004) have documented
nanometer-sized particles containing toxic metals (i.e.,
tungsten, aluminium, antimony, copper, gold, iron,
lead, mercury, nickel, silver, titanium, zinc) captured in
the bloodstream of humans. Because of the suspicion
of particles being a trigger of blood coagulation, this
fi nding addresses the emerging problem of the lack of
risk evaluation of nanoparticles in general.

7.2.2.1 Human Cell Culture
Studies on human peripheral lymphocytes showed
that genotoxic effects (DNA single strand breaks) were
evident after the exposure to a combination of tungsten
and cobalt (Anard et al ., 1997; De Boeck et al ., 1998).
The use of tungsten in some diagnostic equipment
such as radiopaque catheters has called for an increased
testing of biomaterials. Tungsten acid as a pure substance
added to cultivation medium resulted in a stimulated
metabolic activity in human urothelial cells (Pariente
et al ., 1999). Other studies using tungsten in water solu-
tion, support the view that tungsten itself will produce
toxicity at such high concentrations that may not be
exceeded in human serum (Peuster et al ., 2003).
However, a metal powder of tungsten in combination
with cobalt and nickel resulted in a synergistic increase
in DNA breakage and chromosomal aberrations when

References

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Anard, D., Kirsch-Volders, M., Elhajouji, A., et al . (1997). Carcino-
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ATSDR. (2005). “Toxicological Profi le of Tungsten.” Agency for Toxic
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