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OCR for page 515
Tungsten
Tungsten (W) mete has the highest melting point (3,387°C) of any
element, and, because of this property, it is widely used as a filament
material in incandescent lamps and as a component of high-temperature
structural products. According to Standen (1970), tungsten is one of the
rarer elements in the earth's crust, occurring in concentrations that
average 5 ppm. Some fairly rich ores are available (e.g., scheelite and
wolframite), which contain ~3 percent of the metal and which permit
economical mining and production. In 1977, 3 million kilograms of
tungsten were mined domestically to produce alloys, tools, and wear-
resistant materials, plating and electrical materials, catalysts, pigments,
and corrosion inhibitors (U.S. Department of the Intenor, 19771. In-
terest in the biological effects of tungsten is derived both from its
antagonistic action on molybdenum metabolism (De Renzo, 1954) and
Tom potential exposure of industrial workers (Browning, 1969~.
ESSENTIALll Y
Although the interrelation between tungsten and molybdenum metab-
olism has been studied, no known essential role for tungsten has been
found In animals.
515
OCR for page 516
516 MINERAL TOLERANCE OF DOMESTIC ANIMALS
METABOLISM
Research on the metabolism of tungsten has dealt with determining its
tissue distribution, retention, and excretion after administration to
mice, rats, dogs, sheep, and swine.
Wase (1956) reported that mice rapidly eliminate tungsten given
as a single intraperitoneal dose (15 mg per kilogram of body weight as
K2~85WO4) so that, at 24 and 96 hours postdosing, 78 and 98 percent of
the administered amount, respectively, were found in the feces. At
8 hours postdosing, tungsten was widely distributed in tissues, with
bone and the gastrointestinal tract having the highest concentrations.
Kaye (1968) reported similar findings in rats given tungsten (tracer
quantity as either K2~85WO4 or K2~87WO4) by a single gavage. In this
case, 40 percent of the tungsten was found (approximately equally
divided between urine and feces) in the excrete by 24 hours postdosing,
while the like figure at 72 hours approximated 97 percent. Tungsten
elimination from the soft tissues was rapid and, again, bone was found
to be the principal storage tissue. In dogs, Aamodt (1973) found that
tungsten (tracer quantity as Na2 ~~WO4) given by intravenous injection
was also rapidly eliminated with 91 percent of the administered dose
appearing in the urine at 24 hours postdosing.
Bell and Sneed (1970) evaluated the metabolism of tungsten in sheep
and swine. In these tests, growing barrows and mature wethers were
dosed with tracer levels of (NH6~2 ~85WO4 . The swine were dosed either by
intravenous injection or by Savage, while the sheep were dosed either
orally by capsule or abomasally by injection. In swine, urinary excre-
tion appeared to be the principal method of elimination of tungsten
regardless of the route of administration. Most of the administered dose
was excreted at 24 hours postdosing. Contrariwise, sheep excreted only
15 percent of the administered dose during the same time period. With
regard to tissue distribution of tungsten at 48 hours pastoral dosing, the
concentrations in sheep tissues were in the following order: kid-
ney ~ liver ~ bone > muscle. In swine, these relationships were:
kidney ~ bone > liver > muscle.
Further studies on the metabolism of tungsten have concerned the
elucidation of its involvement in molybdenum metabolism. De Renzo
(1954) first observed that tungsten (as Na2WO4) fed to rats consuming
diets low in molybdenum inhibited the stimulation of intestinal xanthine
oxidase (a molybdenum-containing enzyme) caused by molybdenum
repletion. In like manner, Higgins et al. (1956a,b) found that in chickens
tungsten supplementation of molybdenum-low diets resulted in tissue
depletion of molybdenum with concomitant decreases in the xanthine
OCR for page 517
Tungsten
517
oxidase activities of small intestine, liver, kidney, and pancreas. Rats
behaved similarly, and the enzyme effects in both chickens and rats
could be reversed by molybdenum supplementation. Leach and Norris
(1957) confirmed the former observation in growing chickens with
regard to the effects on liver xanth~ne oxidase activity. In breeding
chickens, TeekeU and Watts (1959) demonstrated that 250 ppm of
tungsten (as Na2WO4) had no effect on the xanthine oxidase activity of
liver, kidney, and intestine, whereas 500 ppm caused a steady decline,
so that the values resulting after 30 days of feeding were about 10
percent of the optimal. Dietary tungsten has also been observed to
inhibit the activity of xanthine oxidase in the mink from lactating goats
and dairy cows and in the liver of growing kids (Owen and Proudfoot,
1968~.
Other adverse effects of dietary tungsten on tissue enzyme activity
have been observed by Cohen et al. (1973), who noted a decrease In
liver sulfite oxidase, and Chattered et al. (1973), who noted an ac-
celerated breakdown of -ascorbic acid by rat liver enzymes upon
supplementation with Na2WO4.
SOURCES
No literature is available with regard to the occurrence of tungsten
In commonly used feedstuffs. Potential entry may occur through in-
dustrial contamination and environmental cycling. As with other ele-
ments, the toxicity of tungsten is dependent to a certain extent on the
chemical form that is administered. For example, in the studies of
K'nard and Van de Erve (1941), ammonium paratungstate was much
less toxic (about one-fifth) than either tungstic oxide or sodium tung-
state, which were of equivalent toxicity.
.
TOXICOSIS
LOW LEVELS
Several studies are available that involve the effects of tungsten
administration to animals at relatively low levels (Table 37~. In the
experiment performed by Owen and Proudfoot (1968), growing kids
were fed 22.5 ppm of dietary tungsten, as Na2WO4 2H2O, for a
5-month period. This treatment caused a marked depression in liver
xanthine oxidase activity. In growing chickens, Higgins et al. (1956a,b)
OCR for page 518
/
518 MINERAL TOLERANCE OF DOMESTIC ANIMALS
fed diets low in molybdenum and supplemented with tungsten, as
sodium tungstate, at either 45 or 94 ppm. At the end of the 5-week
experimental period, these treatments depressed growth rates by 8 and
19 percent, respectively, and increased death rates to 24 and 28
percent, respectively.
Two studies are of pertinence in laboratory animals. Higgins et al.
(1956a,b) also noted that dietary concentrations of tungsten (45 or 94
ppm) that produced adverse effects in chickens did not adversely affect
the livability or rate of gain In growing rats. This species difference in
tolerance was hypothesized to be due to the Increased need for
xanthine oxidation in the chick. In the second pertinent study,
Schroeder and Mitchener (1975) did not observe any adverse effects in
rats reared for a lifetime on drinking water containing 5 ppm tungsten
as sodium tungstate.
HIGH LEVELS
Owen and Proudfoot (1968) included in their studies observations on
the effects of tungsten administered to lactating dairy cows and lactat-
~ng goats. Thus, a cow was treated with discrete oral doses of tungsten
as sodium tungstate in accord with the following regimen: 12.5 mg/kg
of body weight on the first day followed 20 days later by two consecu-
tive daily doses of 12.5 mg/kg of body weight. In a second cow, the first
treatment was 25.0 mg/kg of body weight, whereas the second treat-
ment was 12.5 mg/kg of body weight. Although the milk production of
both cows was unaffected, the milk xanthine oxidase activity was
markedly decreased. The experiment in lactating goats yielded similar
results. In breeding chickens, Teekell and Watts (1959) did not observe
adverse effects on the rate of egg production or hatchability from tung-
sten, as sodium tungstate, supplementation at levels of 2S0 and 500 ppm
for a Today period.
Considerably more data have been collected on the toxicosis of tung-
sten in laboratory animals. Thus, using rats of both sexes, Selle (1942)
observed that tungsten injected subcutaneously in daily doses of 92
mg/kg of body weight caused a weight loss of 11 and 26 percent for
females and males, respectively. No corresponding weight loss, how-
ever, was observed in rats receiving the same dose of tungsten by
gavage.
In a series of studies on the acute toxicity of group VI elements,
Pham-Huu-Chanh (1965) evaluated the ~D50 of tungsten administered as
sodium tungstate by intraperitoneal injection in mice and rats. The
resulting values were 112 mg/kg of body weight and 79 mg/kg of body
OCR for page 519
Tungsten
519
weight for adult male rats and adult male mice, respectively. The
signs of the acute intoxication include asthenia, a~lynamia, prostration,
coma, and, finally, death. Similar signs were summarized by Browning
(1969), who characterized the toxicosis as resulting in nervous prostra-
tion, diarrhea, coma, and death with the immediate cause being
respiratory paralysis.
In a study designed to assess the toxicity of various tungsten salts,
Kinard and Van de Erve (1941) measured the effects of dietary tungsten
as tungstic oxide, sodium tungstate, and ammonium paratungstate In
growing rats. They found that 1,000 ppm of tungsten as sodium tung-
state and tungstic oxide and 5,000 ppm of tungsten as ammonium para-
tungstate produced a similar and slight growth depression during the
70~1ay expenmental period. The higher doses of these salts tested (see
Table 37) ah produced extensive mortality.
FACTORS INFLUENCING TOXICITY
The primary factor influencing chronic tungsten toxicity is the molyb-
denum content of the animal diet. Accordingly, in the studies of Higgins
et al. (1956a,b), the growth rate depression, increased mortality, and
decreased xanthine oxidase activity caused by tungsten administration
to chicks were completely reversed by dietary supplementation with
molybdenum (see also Leach and Norris, 19571.
Therapy of acute tungsten intoxication has been the subject of two
papers, Lusky et al. (1949) and Sivjakov and Braun (1959~. Lusky e! al.
(1949) demonstrated that 2,3-dimercaptopropanol could be used to treat
rabbits poisoned with sodium tungstate. Similarly, Sivjakov and Braun
(1959) demonstrated that calcium disodium ethylenediaminetetraace-
tate could be used to treat tungsten poisoning in rats.
TISSUE LEVELS
There is a lack of information on the levels of tungsten in the tissues of
food-producing animals. In rodents, however, Kinard and Aull (1944)
did evaluate the distribution of tungsten in tissues of rats fed tungsten
from various sources. After 100 days of dietary treatment with 1,000
ppm tungsten as tungstic oxide, sodium tungstate, or ammonium para-
tungstate, the rats were observed to have appreciable quantities of
tungsten in bone, skin, and spleen tissues (values ranged from 2~120
ppm fresh weight basis). All other tissues contained trace quantities,
i.e., less than 10 ppm. Tungsten, fed in this experiment as the free metal
OCR for page 520
520 MINERAL TOLERANCE OF DOMESTIC ANIMALS
at levels of 2 and 10 percent of the diet, was also found in the tissues
at levels comparable to those observed with the various salts.
MAXIMUM TOLERABLE LEVEL
The available data permit the establishment of 20 ppm as the maximum
tolerable level of tungsten in animals. This dose is about twice that
observed to have no adverse effects in lifetime studies in rats and well
below those causing adverse effects in shorter-term studies. It is less
than half of the dose that caused adverse effects in chickens, but it is
to be recalled that the chickens were being reared on diets low in
molybdenum. Likewise it is below the level fed to growing kids that did
not adversely affect production parameters.
SUMMARY
Acute tungsten intoxication results in death from respiratory paralysis,
preceded by nervous prostration, diarrhea, and coma. The most fre-
quently observed sign of chronic intoxication is poor growth, however
the most sensitive sign is decreased levels of tissue and/or milk xanthine
oxidase activity. In this regard, tungsten is antagonistic to molybdenum
in that dietary tungsten will precipitate signs of molybdenum deficiency
that can be reversed (within limits) by supplemental molybdenum. Both
2,3-dimercaptopropanol and calcium disodium ethylenediaminetetra-
acetate have been effective in mitigating acute tungsten toxicosis. Tis-
sue residue data for tungsten in food-producing animals are presently
unavailable.
OCR for page 521
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OCR for page 524
524 MINERAL TOLERANCE OF DOMESTIC ANIMALS
REFERENCES
Aamodt, R. L. 1973. Retention and excretion of injected ~8'W labeled sodium tungstate
by beagles. Health Phys. 24:519.
Bell, M. C., and N. N. Sneed. 1970. Metabolism of tungsten by sheep and swine. In
C. F. Mills, ed. Trace Element Metabolism in Animals. E ~ S Livingstone, Edinburgh
and London.
Browning, E. 1969. Toxicity of Industrial Metals. Butterworths, London.
Chatte~ee, G. C., R. K. Roy, N. Sasmal, S. K. Bane~ce, and P. K. Majumder. 1973.
Effect of chromium and tungsten on r-ascorbic acid metabolism in rats. J. Nutr.
103:509.
Cohen, H. J., R. T. Drew, J. L. Johnson, and K. V. Rajagopalan. 1973. Molecular basis
of the biological function of molybdenum. The relationship between sulfite oxidase and
the acute toxicity of bisulfite and SO2. Proc. Natl. Acad. Sci. 70:3655.
De Renzo, E. C. 1954. Studies on the nature of the xanthine oxidase factor. Ann. N.Y.
Acad. Sci. 57:905.
Higgins, E. S., D. A. Richert, and W. W. Westerfeld. 1956a. Competitive role of tungsten
in molybdenum nutrition. Fed. Proc. 15:274. (Abstr.)
Higgins, E. S., D. A. Richert, and W. W. Westerfeld. 1956b. Molybdenum deficiency and
tungstate inhibition studies. J. Nutr. 59.539.
Kaye, S. V. 1968. Distribution and retention of orally administered radiotungsten in the
rat. Health Phys. 15:399.
Kinard, F. W., and J. C. Aull. 1944. Distribution of tungsten in the rat following ingestion
of tungsten compounds. J. Pharmacol. Exp. Ther. 83:53.
Kinard, F. W., and J. Van de Erve. 1941. The toxicity of orally-ingested tungsten
compounds in the rat. J. Pharmacol. Exp. Ther. 72:196.
Leach, R. M., and L. C. Norris. 1957. Studies on factors affecting the response of chicks
to molybdenum. Poult. Sci. 36:1136. (Abstr.)
Lusky, L. B., H. A. Braun, and E. P. Lang. 1949. Effect of BAL on experimental lead,
tungsten, vanadium, etc., poisoning. J. Ind. Hyg. 31:301.
Owen, E. C., and R. Proudfoot. 1968. The effect of tungstate ingestion on xanthine
oxidase in milk and liver. Br. J. Nutr. 22:331.
Pham-Huu-Chanh. 1965. The comparative toxicity of sodium chromate, molybdate, tung-
state and metavanadate. Arch. Int. Pharmacodyn. 154:243.
Schroeder, H. A., and M. Mitchener. 1975. Life-term studies in rats. Effects of alumi-
num, barium, beryllium, and tungsten. J. Nutr. 105:421.
Selle, R. M. 1942. Effects of subcutaneous injections of sodium tungstate on the rat. Fed.
Proc. 1:165. (Abstr.)
Sivjakov, K. I., and H. A. Braun. 1959. The treatment of acute selenium, cadmium,
and tungsten intoxication in rats with calcium disodium ethylene-diaminetetraacetate.
Toxicol. Appl. Pharmacol. 1:602.
Standen, A., ed. 1970. Kirk-Othmer Encyclopedia of Chemical Technology, vol. 22. John
Wiley & Sons, New York.
Teekell, R. A., and A. B. Watts. 1959. Tungsten supplementation of breeder hens. Poult.
Sci. 38:791.
U.S. Department of the Interior. 1977. Bureau of Mines Minerals Yearbook, Tungsten
chapter.
Wase, A. W. 1956. Absorption and distribution of radio-tungstate in bone and soft
tissues. Arch. Biochem. Biophys. 61:272.
Representative terms from entire chapter:
xanthine oxidase
