- Email: [email protected]
Pharmacology and toxicology of heavy metals: Tellurium
Pharmac. Ther. A, Vol. I, pp. 223-229, 1976. Pergamon Press.
Printed in Great Britain
Specialist Subject Editor: W. G. LEVINE
PHARMACOLOGY AND TOXICOLOGY HEAVY METALS: TELLURIUM*
OF
LESLIE M. KLEVAY**
University of Cincinnati College of Medicine, Kettering Laboratory, Eden Avenue, Cincinnati, Ohio 45219, U.S.A.
1. INTRODUCTION Tellurium, the seventy fifth most abundant element in the crust of the earth (Berry and Mason, 1959) is distributed widely in nature. Igneous rocks contain 0.001/~g/g (Bowen, 1966); some shales contain 0.1 to 2/~g/g (Elkin, 1969). Tellurium is a major component of forty mineral species (Elkin, 1969) and is a minor component of an undetermined number of other minerals. These minerals are widely disseminated and do not form an ore that can be mined for tellurium alone. Consequently tellurium is recovered as a by-product of mining for nickel, copper, silver, gold and lead. The oxide of tellurium was discovered by Reichstein (sometimes spelled Reichenstein) in 1782 (Ihde, 1964) and was named by Klaproth in 1798 who verified the discovery and isolated the elemental form. Four reviews of the medical aspects of tellurium are available (Shie and Deeds, 1920; Cerwenka and Cooper, 1961; Vignoli and Defretin, 1964; Sandratskaya, 1967). 2. CHEMISTRY Extensive reviews of the chemistry of tellurium are available (Mellor, 1931; Brasted, 1961; Cotton and Wilkinson, 1966; Elkin, 1969). Tellurium is the fifty second element in the periodic table and with the other members of group VIA is termed a chalcogen. Isotopes with masses 115-135 have been identified, but six, with masses 122, 124-126, 128, 130, constitute 99 per cent of natural tellurium (Weast, 1970). Half lives range from less than 2 rain-12 terayears; beta particles, positrons and gamma rays are emitted (Weast, 1970). Tellurium 127 m with a half life of 109 days and a beta and gamma emission has been the most frequently used isotope in biological experiments. It has an advantage over '~2Te in that no iodine daughter is produced (Lederer et al., 1967). The electronic structure of tellurium is that of krypton surrounded by 4d t°Ss 25p 4 electrons. Addition or removal of pairs of electrons result in valence states of - 2, + 4 and + 6. As atomic number increases in group VIA, the elements become increasingly metallic in character, so that tellurium has a few cationic properties. Selenium is completely nonmetallic and polonium, metallic. The compounds of medical interest are few. Those shown in Table 1 are angular telluHdes with a coordination number of two, pyramidal structures with a coordination number of three, ~-trigonal bipyramidal structures with a coordination number of four, or octahedral structures with a coordination number of 6. Tellurium tetrachloride hydrolyzes in water to give tellurium dioxide (Elkin, 1969). A similar fate is probable for tellurium tartrate. Tellurium dioxide is soluble in alkali giving a solution of mixed tellurites (Cotton and Wilkinson, 1966). Consequently, it seems likely that oral administration of any of these materials yields equivalent ionic species when they reach the duodenum. Tellurium hydride is a thermodynamically unstable (Cotton and Wilkinson, 1966) compound that decomposes in air under the influence of moisture and fight (Elkin, 1969). It is a weak acid in aqueous solution and is a strong reducing agent. A * References for this review were found by a search of Chem. Abs. (volumes 54-70) and Cure. Index Medicus (1960-1969). No effort was made to systematically search earlier literature; however, when certain important aspects of the topic were not under investigation during the recent decade, earlier data were sought. No reprints have been purchased for distribution. **Present address: 223 27th Avenue South, Grand Forks, North Dakota 58201, U.S.A. 223
224
LESLIE M. KLEVAY
review of its properties with a comparison with those of other volatile hydrides is available (Webster, 1946). TABLE 1. Tellurium Compounds of Interest. Compound Dimethyl telluride Hydrogen telluride Potassium metatellurate Sodium orthotellurate Sodium tellurite Tellurium dioxide Tellurium tetrachloride Tellurium tartrate Tellurous acid
Formula (CH3)2Teb H2Te~ K[TeO(OH)5].H20" Na~TeO2(OHL" Na~TeO3b unknown" TeCL b unknown unknown"
"Cotton and Wilkinson (1966). bWeast (1970).
3. ABSORPTION Mead and Gies (1901) have found tellurium dioxide to be absorbed from the gastrointestinal tract of dogs. The absorption of elementary tellurium from the gut of the rat has been shown by DeMeio (1946). Barnes et al. (1955) and Hollins (1969) demonstrated the intestinal absorption of tellurous acid in the rat. The amount or the site of absorption could not be established in these experiments. Wright and Bell (1966) administered sodium tellurite (labeled with ~27mTe) to sheep (wethers) and swine (barrows). Radioactivity measurements indicated 24 per cent of the tellurium was absorbed from the colon in these species. Following accidental injection of sodium tellurite instead of contrast medium for retrograde pyelograms, evidence of absorption of the compound from the lower urinary tract was obtained in three patients by Keall et al. (1946). Steinberg et al. (1942) have interpreted an increase in urinary tellurium following exposure of workers to fumes containing tellurium as evidence for absorption via the respiratory tract. 4. DISTRIBUTION DeMeio and Henriques (1947) found kidney, heart, spleen, lungs and liver (in descending order) to have the highest concentrations of radioactivity 24 hr after the intravenous administration of labeled sodium tellurite to rabbits. Kidney, liver, lung, stomach and heart contained the largest amounts of radioactivity. Similar data were obtained for sheep and swine in the work of Wright and Bell (1966). Hollins (1969) administered ~27mTe-tellurous acid to rats intraperitoneally and found the concentration of radioactivity highest in kidney, blood, liver and leg muscle throughout 200 days of observation. The concentration of label in the femur increased relative to the other organs during the course of the experiment until, at the end, femur exceeded all others. Mraz et al. (1964) found kidney, gall bladder, liver and tibia to have the highest concentrations of radioactivity 96hr after an intravenous dose of labeled sodium tellurite to chickens. 5. EXCRETION The most readily detectable excretory pathway for tellurium compounds is via the expired air. For over a century the ingestion of tellurium compounds has been known to be associated with a garlic-like odor of the breath. Reisert (1884) demonstrated that 0.5 ~g of tellurium dioxide was sufficient to impart the odor to human breath beginning in 75 min and lasting 30 hr. DeMeio (1947) found some individuals produced no odor until 50/~g of sodium tellurite had been ingested. More recently, Hollins (1969) calculated that only about 0.25 per cent of a dose of teUurous acid given to rats is
Tellurium
225
excreted via this pathway in the first 24 hr. Consequently, although the presence of the odor is dramatic, the pathway is quantitatively insignificant. Mead and Gies (1901) identified the biliary and urinary routes of excretion of tellurium compounds. More recently, DeMeio and Henriques (1947) demonstrated that radioactivity given intravenously to rabbits as ~2~Te-sodium tellurite appeared in urine and bile. Hollins (1969) noted the concentration of radioactivity in urine of rats exceeded that in the feces following intraperitoneal injection of labeled tellurous acid. Wright and Bell (1966) found urinary excretion to be about three times fecal excretion in both sheep and swine following intravenous administration of sodium tellurite. The ratio was reversed following oral administration. In similar oral experiments Barnes et al. (1955) found the ratio of fecal to urinary excretion to be 15 and 12 in guinea pigs and rats, respectively. Schroeder et al. (1967) found the concentration of tellurium in normal human urine to be 0.63 pg/ml, whereas Steinberg et al. (1942) were unable to find any using a method sensitive to less than 0.01 ~g/ml. 6. METABOLISM Alliaceous breath following the ingestion of tellurium compounds has been recorded many times. Elemental tellurium (DeMeio, 1947), sodium tellurate (Hofmeister, 1894; Mead and Gies, 1901), sodium tellurite (Reisert, 1884; Mead and Gies, 1901) and tellurium dioxide (Mead and Gies, 1901) have been implicated in several species including man. Hofmeister (1894) collected expired air from a dog, cat and goose following subcutaneous injection of sodium tellurate, characterized the excretion product by chemical means and concluded its identity to be, in contemporary terminology, dimethyl telluride. Considering the evidence for the mammalian synthesis of dimethyl selenide (Klevay, 1976b), it is unlikely that intestinal flora are necessary for the synthesis of dimethyl telluride. Indeed, according to Challenger (1945), bacteria are incapable of this synthesis. Mead and Gies (1901) described the reduction of tellurium dioxide to elemental tellurium in the intestine of the normal dog. A similar reduction of tellurium tetrachloride was noted in the intestine of the duckling by Carlton and Kelly (1967). As certain bacteria have the ability to perform this reduction (Buchanan and Fulmer, 1930; Tucker et al., 1962) it is not certain whether the reduction was a function of bacterial or host metabolism. However, liver and kidney slices of humans, rabbits and rats are capable of reducing tellurite to elemental tellurium (Wachstein, 1949). DeMeio (1946) was unable to demonstrate any effect upon respiration of kidney and liver slices by feeding rats elementary tellurium in amounts that inhibited growth. By subcutaneous injection of sodium tellurate, Svirbely (1938) was able to decrease the ascorbic acid content of several organs of the rat, a species which is able to synthesize ascorbic acid. The interrelationships between the essential nutrients selenium and vitamin E have been reviewed (Klevay, 1976b). Krishnamurthy and Bieri (1962) showed tellurium dioxide was not an effective substitute for either nutrient in experiments on lipid peroxidation in chicks. 7. PHYSIOLOGICAL EFFECTS ON ORGAN SYSTEMS 7.1. CIRCULATORY SYSTEM Carlton and Kelly (1967) found that feeding tellurium tetrachloride to ducklings produced myocardial necrosis and hemoporicardium. No lesions were found in the coronary arteries, endocardium or epicardium, but capillary congestion and hemorrhage were noted. 7.2. DIGESTIVE SYSTEM Mead and Gies (1901) noted that tellurium dioxide and tellurium tartrate fed with meat to dogs inhibited the gastric secretion of acid. DeMeio and Jetter (1948) were able to produce focal areas of fatty and granular degeneration in the livers of rats poisoned
226
LESI.IE M. KLEVAY
with tellurium dioxide added to feed. Carlton and Kelly (1967) found focal areas of necrosis around the central hepatic veins in ducklings poisoned with tellurium tetrachioride in a similar experiment. Steinberg et al. (1942) examined sixty two men who had long term exposures to the fumes produced when elemental tellurium was added to molten iron. The men complained of dryness of the mouth and a metallic taste. Abdominal examination was negative. Amdur (1947) examined three men poisoned by transient exposure to fumes produced by the addition of elemental tellurium to molten copper. The men complained of slight epigastric distress and a metallic taste. The man with the longest exposure had had several loose bowel movements. None of the victims experienced nausea or vomiting; each was found to have slight epigastric tenderness on examination. The cephalin flocculation test was negative in all cases. 7.3. SKIN Franke and Moxon (1937) noted hair loss in rats fed toxic amounts of sodium tellurate and sodium tellurite. The patients described by Steinberg et al. (1942) who were most severely exposed excreted sweat with a garlic odor. 7.4. NERVOUS SYSTEM
Garro and Pentschew (1%4) and Agnew et ai. (1%8) have produced hydrocephalus in rats whose dams were fed elemental tellurium during pregnancy. The amount of tellurium fed was about 3 mg/g of diet. No data were published regarding possible maternal toxic effects. In neither experiment was a gross or microscopic anatomical alteration found to explain the hydrocephalus. James et al. (1966) found normal lambs were born to ewes ingesting potassium tellurate (2 mg/kg body weight per day) throughout gestation. DeMeio and Jetter (1948) noted limb paralysis of rats poisoned with tellurium dioxide and Carlton and Kelly (1%7) found cerebral necrosis in ducklings poisoned with tellurium tetrachloride. Steinberg et al. (1942) reported somnolence as a symptom of intoxication by tellurium-containing fume; Amdur (1947) did not verify this complaint, but noted the victims complained of transient headaches. 7.5. RESPIRATORY SYSTEM The alliaceous breath caused by tellurium comoounds previously cited has also been reported in association with industrial exposure to tellurium-containing fumes (Steinberg et al., 1942; Amdur, 1947). 7.6. UROGENITAL SYSTEM
Poisoning of rats with tellurium dioxide (DeMeio and Jetter, 1948) has resulted in degenerative changes in the proximal kidney tubule. The production of hydrocephalus in offspring by the ingestion of elemental tellurium during pregnancy implies but does not prove placental transport of the teratogen (Garro and Pentshew, 1964; Agnew et al.,
1%8). 8. TREATMENT OF POISONING The amounts of tellurium salts that are acutely toxic amounts to animals have been defined and are shown in Table 2. In a subsequent experiment Franke and Moxon (1937) demonstrated that sodium tellurate or sodium tellurite added to the diets of rats (25/zg Te/g of diet) inhibited the growth of the animals. No references to the treatment of human poisoning by tellurium compounds are found in several recent, standard sources (Gellis and Kagan, 1970; Goodman and Gilman, 1970; Modell, 1970; Wintrobe et al., 1970; Beeson and McDermott, 1971; Conn, 1971). Factors that lessen selenium toxicity in animals have been recently reviewed (Klevay, 1976b) and may be presumed helpful in the absence of contrary data. The successful use of dimercapral (British antiLewisite or BAL) in the treatment of arsenic intoxication (Klevay, 1976a) has prompted
227
Tellurium TAB LE 2. Toxicity of Tellurium Compounds, mg of Element per kg Body Weight. Reference
Species
Route"
Tellurate
Tellurite
Muehlberger and Schrenk (1928)b
Rat Rabbit Rabbit Rat
i.v. i.v. p.o. i.p.
30.5 5.6 56.0 20.0-30.0
1.4 0.5 32.0 2.25-2.50
Franke and Moxon (1936)"
"i.v. = intravenous, p.o. = oral, i.p. = intraperitoneai. bDose survived by less than 50 per cent of the animals. Sodium tellurite and telluric acid were used. ORange of dose killing 75 per cent in 48 hr. Sodium salts were used.
use of this drug in the treatment of tellurium intoxication. Amdur (1947) treated three men with dimercapral who had alliaceous breath caused by industrial exposure to fumes containing tellurium. The disappearance of the garlic odor 1-4 days after termination of 8 days of therapy casts doubt on the efficacy of dimercapral in these cases. In a later work, Amdur (1958) increased the toxicity of tellurium oxide for guinea pigs by treatment with dimercapral; hematuria was more prominent in the treated groups. The use of dimercapral in the treatment of selenium toxicity is contraindicated (Klevay, 1976b) because the drug decreases survival and increases kidney damage, this fact together with the data quoted above suggests a similar conclusion regarding tellurium poisoning. DeMeio (1947) treated some workers exposed to tellurium dust with ascorbic acid (8-10 mg/kg body weight) one to three times a day. He concluded therapy was successful in reducing the alliaceous breath and justified its use by describing successful experiments with rabbits and guinea pigs. The route of administration was not revealed. Amdur (1958), however, found ascorbic acid did not benefit guinea pigs poisoned with tellurium oxide. The clinical course of three cases of poisoning with sodium tellurite has been described by Keall et al. (1946). The dose received by the surviving patient was probably less than that of the patients who died. The fact that only these two patients received morphine may be coincidental. 9. MEDICAL USES OF T E L L U R I U M COMPOUNDS No tellurium compounds have received official recognition by any of the national or international drug compendia quoted in the articles on arsenic (Klevay, 1976a) or selenium (Klevay, 1976b). Tellurium is, however, the source of much of the radioactive iodine used in the diagnosis and treatment of thyroid gland disorders (Elkin, 1969; Wellman et al., 1976). Various methods of transmutation are used. Bacterial culture media that include 0.04 per cent potassium tellurite are useful in the laboratory diagnosis of certain infections. Corynebacterium diphtheriae acquire a grey or black color due to the reduction of tellurite to tellurium and the accumulation of the latter inside the bacteria (Wilson and Miles, 1964; Smith et al., 1968). Growth of culture contaminants is suppressed. A similar suppressive action permits the growth of Staphylococcus aureus from cultures contaminated with other staphylococci, micrococci and gram-negative bacilli (Bodily et al., 1970). Resistance to tellurite is used in the classification of Group D, hemolytic streptococci (Wilson and Miles, 1964). Recently the ability to reduce tellurite to tellurium has been used in the differential diagnosis of urinary tract infections due to Staphylococcus albus (Alder et al., 1966). The method may have promise in the differentiation of atypical mycobacteria (Kilburn et al., 1969). REFERENCES 1. AONEW, W. F., FAUVRE, F. M. and PUDENZ, P. H. (1968) Tellurium hydrocephalus: Distribution of tellurium-127m between maternal, fetal and neonatal tissues of the rat. Exp. Neurol. 21: 120-131. 2. ALDER, V. (3., BROWN, A. M. and MITCHELL, R. (3. (1966) Tellurite reactions of coagulase negative staphylococci and micrococci. J. appl. Bacteriol. 29: 304-307. 3, AMDUR, M. L. (1947) Tellurium. Accidental exposure and treatment with BAL in oil. Occup. Med. 3: 386-391.
228
LESLIE M. KLEVAY
4. AMDUR, M. L. (1958) Tellurium oxide. Archs Ind. Hlth. 17: 665-667. 5. BARNES, D. W. H., COOK, G. B., HARRISON, G. E., LOUTIT, J. F. and RAYMOND, W. H. A. (1955) The metabolism of '32tellurium-iodine mixture in mammals. J. nucl. Energy 1: 218-230. 6. BEESON, P. B. and McDERMOTT, W. (Ed.) (1971) Cecil-Loeb Textbook o f Medicine, 13th ed. Saunders, Philadelphia. 7. BERRY, L. G. and MASON, B. (1959) Mineralogy, p. 212, Freeman, San Francisco. 8. BODILY, H. L., UPDYKE, E. L. and MASON, J. O. (1970) Diagnostic Procedures for Bacterial, Mycotic and Parasitic Infections, 5th ed., pp. 216-217. American Public Health Association, New York. 9. BOWEN, H. J. M. (1966) Trace Elements in Biochemistry, p. 205. Academic Press, London. 10. BRASTED, R. C. (1961) Sulfur, selenium and tellurium. In Comprehensive Inorganic Chemistry, Vol. 8, pp. 1-245. Van Nostrand, Princeton, N.J. 11. BUCHANAN, R. E. and FULMER, E. I. (1930) Physiology and Biochemistry of Bacteria, Vol. II, pp. 384--385. Williams & Wilkins, Baltimore. 12. CARLTON, W. W. and KELLY, W. A. (1967) Tellurium toxicosis in pekin ducks. Toxicol. appl. Pharmacol. 11: 203-214. 13. CERWENKA, E. A. and COOPER, W. C. (1961) Toxicology of selenium and tellurium and their compounds. Archs envir. Hlth. 3: 189-200. 14. CHALLENGER, F. (1945) Biological methylation. Chem. Rev. 36: 315-361. 15. CONN, H. F. (Ed.) (1971) Current Therapy 1971. Saunders, Philadelphia. 16. COTTON, F. A. and WILKINSON, G. (1966) Advanced Inorganic Chemistry pp. 528, 547, 549, 2nd ed., Interscience, New York. 17. DEMEIO, R. H. (1946) Tellurium I. The toxicity of ingested elementary tellurium for rats and rat tissues. J. ind. Hyg. Toxicol. 28: 229-232. 18. DEMEIO, R. H. (1947) Tellurium II. Effect of ascorbic acid on the tellurium breath. J. ind. Hyg. Toxicol. 29: 393-395. 19. DEMEIO, R. H. and HENRIQUES, F. C., JR. (1947) Tellurium IV. Excretion and distribution in tissues studied with radioactive isotope. J. biol. Chem. 169: 609-623. 20. DEMEIO, R. H. and JETTER, W. W. (1948) Tellurium III. The toxicity of ingested tellurium dioxide for rats. J. ind. Hyg. Toxicol. 30: 53-58. 21. ELKIN, E. M. (1969) Tellurium and tellurium compounds. In Kirk-Othmer Encyclopedia o f Chemical Technology, Vol. 19, 2nd ed., pp. 756-774. MARK, H. F., MCKETTA, J. J., JR. and OTHMER, O. F. Interscience, New York. 22. FRANKE, K. W. and MOXON, A. L. (1936) A comparison of the minimum fatal doses of selenium, tellurium, arsenic and vanadium. J. Pharmac. exp. Ther. 58: 454-459. 23. FRANKE, K. W. and MOXON, A. L. (1937) The toxicity of orally ingested arsenic, selenium, tellurium, vanadium and molybdenum. J. Pharmac. exp. Ther. 61: 89-102. 24. GARRO, F. and PENTSCHEW, A. (1964) Neonatal hydrocephalus in the offspring of rats fed during pregnancy non-toxic amounts of tellurium. Archiv f. psychiatrie u. Z. f.d. ges. Neurologie 206: 272-280. 25. GELLIS, S. S. and KAt3AN, B. M. (1970) Current Pediatric Therapy 4. Saunders, Philadelphia. 26. GOODMAN, L. S. and GILMAN, A. (1970) The Pharmacological Basis of Therapeutics, 4th ed. MacMillan, New York. 27. HOFMEISTER, F. (1894) Ueber Methylirung im Thierk6rper. Archiv. f. exp. Path u. Pharm. 33: 198-215. 28. HOLLINS, J. G. (1969) The metabolism of tellurium in rats. Hlth. Phys. 17: 497-505. 29. [HDE, A. J. (1964) The Development o f Modern Chemistry, pp. 90-91. Harper & Row, New York. 30. JAMES, L. F., LAZAR, V. A. and BINNS, W. (1966) Effects of sublethal doses of certain minerals on pregnant ewes and fetal development. Am. J. vet. Res. 27: 132-135. 31. KEALL, J. H. H., MARTIN, N. H. and TUNBRIDGE, R. E. (1946) A report of three cases of accidental poisoning by sodium tellurite. Br. J. ind. Med. 3" 175-176. 32. KILBURN, J. O., SILCOX, V. A. and KUBICA, G. P. (1969) Differential identification of mycobacteria. V. The tellurite reduction test. Am. Rev. resp. Dis. 99: 94-100. 33. KLEVAY, L. M. (1976a) Arsenic. Pharmac. Ther. A, 1: 189-209. 34. KLEVAY, L. M. (1976b) Selenium. Pharmac. Ther. A, 1: 211-222. 35. KRISHNAMURTHY, S. and BIERI, J. G. (1962) Dietary antioxidants as related to vitamin E function. J. Nutr. 77: 245-252. 36. LARDY, H. A. and MOXON, A. L. (1942) The ascorbic acid content of the livers of selenized rats and chicks. Proc. S. Dakota Acad. Sci. 22: 39-42. 37. LEDERER, C. M., HOLLANDER, J. M. and PERLMAN, I. (1967) Table o f Isotopes 6th ed., pp. 67, 279. Wiley, New York. 38. MEAD, L. D. and GIES, W. J. (1901) Physiological and toxicological effects of tellurium compounds with a special study of their influence on nutrition. Am. J. Physiol. 5: 104-149. 39. MELLOR, J. W. (1931) A Comprehensive Treatise on Inorganic and Theoretical Chemistry, Vol. I1, pp. 1-121. Longman Green, London. 40. MODELL, W. (ed.). (1970) Drugs o f Choice 1970--1971. C. V. Mosby, St. Louis. 41. MRAZ, F. R., WRIGHT, P. L., FEROUSON, T. M. and ANDERSON, D. L. (1964) Fission product metabolism in hens and transference to eggs. Hlth. Phys. 10: 777-782. 42. MUEHLBERGER, C. W. and SCHRENK, H. H. (1928) The effect of the state of oxidation on the toxicity of certain elements. J. Pharmac. exp. Ther. 33; 270-271. 43. REISERT, W. (1884) The so-called bismuth breath. Am. J. Pharmacol. 56: 177-180. 44. ROSENBERG, H. R. (1945) Chemistry and Physiology o f the Vitamins, p. 317. Interscience, New York. 45. SANDRATSKAYA, S. E. (1967) Tellurium. In Toxicology o f t h e R a r e Metals, pp. 76-88, IZRAEL'SON, Z. I. (ed.), HALPERIN, Y. and LIEnER, E. (trans.). Clearinghouse for Federal Scientific and Technical Information, Springfield, Va. 46. SCHROEDER, H. A., BUCKMAN, J. and BALASSA, J. J. (1967) Abnormal trace elements in man: tellurium. J. chron. Dis. 20: 147-161.
Tellurium
229
47. SHIE, M. D. and DEEDS, F. E. (1920) The importance of tellurium as a health hazard in industry--A preliminary report. Publ Hlth. Rep. 35: 939-954. 48. SMITH, D.T., CONANT, N. F. and WILLETT, H. P. (1968) Zinsser Microbiology 14th ed., p. 508. Appleton-Century-Crofts, New York. 49. STEINBERG, H. H., MASSARI, S. C., MINER, A. C. and RINK, R. (1942) Industrial exposure to tellurium: atmospheric studies and clinical evaluation. J. ind. Hyg. Toxicol. 24: 183-192. 50. SVIRBELY, J. L. (1938) Vitamin C studies in the rat. The effect of selenium dioxide, sodium selenate and tellurate. Biochem. J. 32: 467-473. 51. TUCKER, F. L., WALPER, J. F., APPLEMAN, M. D. and DONOHUE, J. (1962) Complete reduction of tellurite to pure tellurium metal by microorganisms. J. Bacteriol. 83: 1313-1314. 52. VIONOLI, L. and DEFRETIN, J. P. (1964) The toxicology of tellurium. Ann. Biol. Clin. 22: 399-417. Cited in Chem. Abs. 61: 6252a. 53. WACHSTEIN, M. (1949) Reduction of potassium tellurite by living tissues. Proc. Soc. exp. Biol. Med. 72: 175-178. 54. WEAST, R. C. (ed.) (1970) Handbook of Chemistry and Physics, pp. B-141,144, C-706. Chemical Rubber, Cleveland. 55. WEBSTER, S. H. (1946) Volatile hydrides of toxicological importance. J. Ind. Hyg. Toxicol. 28: 167-182. 56. WELLMAN, H. N., ANGER, R. T. and ROHRER, R. H. (1976) Radiation dose to humans from ~23I, l~'I, ~sI, ~sI, ~°I, J~I and mI administered as iodide ion. J. nucl. Medicine Medical Internal Radiation Dose Committee, Pamphlet ¢/9, In preparation. 57. WILSON, G. S. and MILES, A. A. (1964) Topley and Wilson's Principles of Bacteriology and Immunity, 5th ed., pp. 717, 1677-1679. Williams & Wilkins, Baltimore. 58. WINTROBE, M. M., THORN, G. W., ADAMS, R. D., BENNETT, I. L., JR., BRAUNWALD, E., ISSELBACHER, K. J. and PETERSDORF, R. G. (ed.) (1970) Harrison "s Principles o/lnternal Medicine, 6th ed. McGraw-Hill, New York. 59. WRIGHT, P. L. and BELL, M. C. (1966) Comparative metabolism of selenium and tellurium in sheep and swine. Am..I. Physiol. 211: 6-10.
Printed in Great Britain
Specialist Subject Editor: W. G. LEVINE
PHARMACOLOGY AND TOXICOLOGY HEAVY METALS: TELLURIUM*
OF
LESLIE M. KLEVAY**
University of Cincinnati College of Medicine, Kettering Laboratory, Eden Avenue, Cincinnati, Ohio 45219, U.S.A.
1. INTRODUCTION Tellurium, the seventy fifth most abundant element in the crust of the earth (Berry and Mason, 1959) is distributed widely in nature. Igneous rocks contain 0.001/~g/g (Bowen, 1966); some shales contain 0.1 to 2/~g/g (Elkin, 1969). Tellurium is a major component of forty mineral species (Elkin, 1969) and is a minor component of an undetermined number of other minerals. These minerals are widely disseminated and do not form an ore that can be mined for tellurium alone. Consequently tellurium is recovered as a by-product of mining for nickel, copper, silver, gold and lead. The oxide of tellurium was discovered by Reichstein (sometimes spelled Reichenstein) in 1782 (Ihde, 1964) and was named by Klaproth in 1798 who verified the discovery and isolated the elemental form. Four reviews of the medical aspects of tellurium are available (Shie and Deeds, 1920; Cerwenka and Cooper, 1961; Vignoli and Defretin, 1964; Sandratskaya, 1967). 2. CHEMISTRY Extensive reviews of the chemistry of tellurium are available (Mellor, 1931; Brasted, 1961; Cotton and Wilkinson, 1966; Elkin, 1969). Tellurium is the fifty second element in the periodic table and with the other members of group VIA is termed a chalcogen. Isotopes with masses 115-135 have been identified, but six, with masses 122, 124-126, 128, 130, constitute 99 per cent of natural tellurium (Weast, 1970). Half lives range from less than 2 rain-12 terayears; beta particles, positrons and gamma rays are emitted (Weast, 1970). Tellurium 127 m with a half life of 109 days and a beta and gamma emission has been the most frequently used isotope in biological experiments. It has an advantage over '~2Te in that no iodine daughter is produced (Lederer et al., 1967). The electronic structure of tellurium is that of krypton surrounded by 4d t°Ss 25p 4 electrons. Addition or removal of pairs of electrons result in valence states of - 2, + 4 and + 6. As atomic number increases in group VIA, the elements become increasingly metallic in character, so that tellurium has a few cationic properties. Selenium is completely nonmetallic and polonium, metallic. The compounds of medical interest are few. Those shown in Table 1 are angular telluHdes with a coordination number of two, pyramidal structures with a coordination number of three, ~-trigonal bipyramidal structures with a coordination number of four, or octahedral structures with a coordination number of 6. Tellurium tetrachloride hydrolyzes in water to give tellurium dioxide (Elkin, 1969). A similar fate is probable for tellurium tartrate. Tellurium dioxide is soluble in alkali giving a solution of mixed tellurites (Cotton and Wilkinson, 1966). Consequently, it seems likely that oral administration of any of these materials yields equivalent ionic species when they reach the duodenum. Tellurium hydride is a thermodynamically unstable (Cotton and Wilkinson, 1966) compound that decomposes in air under the influence of moisture and fight (Elkin, 1969). It is a weak acid in aqueous solution and is a strong reducing agent. A * References for this review were found by a search of Chem. Abs. (volumes 54-70) and Cure. Index Medicus (1960-1969). No effort was made to systematically search earlier literature; however, when certain important aspects of the topic were not under investigation during the recent decade, earlier data were sought. No reprints have been purchased for distribution. **Present address: 223 27th Avenue South, Grand Forks, North Dakota 58201, U.S.A. 223
224
LESLIE M. KLEVAY
review of its properties with a comparison with those of other volatile hydrides is available (Webster, 1946). TABLE 1. Tellurium Compounds of Interest. Compound Dimethyl telluride Hydrogen telluride Potassium metatellurate Sodium orthotellurate Sodium tellurite Tellurium dioxide Tellurium tetrachloride Tellurium tartrate Tellurous acid
Formula (CH3)2Teb H2Te~ K[TeO(OH)5].H20" Na~TeO2(OHL" Na~TeO3b unknown" TeCL b unknown unknown"
"Cotton and Wilkinson (1966). bWeast (1970).
3. ABSORPTION Mead and Gies (1901) have found tellurium dioxide to be absorbed from the gastrointestinal tract of dogs. The absorption of elementary tellurium from the gut of the rat has been shown by DeMeio (1946). Barnes et al. (1955) and Hollins (1969) demonstrated the intestinal absorption of tellurous acid in the rat. The amount or the site of absorption could not be established in these experiments. Wright and Bell (1966) administered sodium tellurite (labeled with ~27mTe) to sheep (wethers) and swine (barrows). Radioactivity measurements indicated 24 per cent of the tellurium was absorbed from the colon in these species. Following accidental injection of sodium tellurite instead of contrast medium for retrograde pyelograms, evidence of absorption of the compound from the lower urinary tract was obtained in three patients by Keall et al. (1946). Steinberg et al. (1942) have interpreted an increase in urinary tellurium following exposure of workers to fumes containing tellurium as evidence for absorption via the respiratory tract. 4. DISTRIBUTION DeMeio and Henriques (1947) found kidney, heart, spleen, lungs and liver (in descending order) to have the highest concentrations of radioactivity 24 hr after the intravenous administration of labeled sodium tellurite to rabbits. Kidney, liver, lung, stomach and heart contained the largest amounts of radioactivity. Similar data were obtained for sheep and swine in the work of Wright and Bell (1966). Hollins (1969) administered ~27mTe-tellurous acid to rats intraperitoneally and found the concentration of radioactivity highest in kidney, blood, liver and leg muscle throughout 200 days of observation. The concentration of label in the femur increased relative to the other organs during the course of the experiment until, at the end, femur exceeded all others. Mraz et al. (1964) found kidney, gall bladder, liver and tibia to have the highest concentrations of radioactivity 96hr after an intravenous dose of labeled sodium tellurite to chickens. 5. EXCRETION The most readily detectable excretory pathway for tellurium compounds is via the expired air. For over a century the ingestion of tellurium compounds has been known to be associated with a garlic-like odor of the breath. Reisert (1884) demonstrated that 0.5 ~g of tellurium dioxide was sufficient to impart the odor to human breath beginning in 75 min and lasting 30 hr. DeMeio (1947) found some individuals produced no odor until 50/~g of sodium tellurite had been ingested. More recently, Hollins (1969) calculated that only about 0.25 per cent of a dose of teUurous acid given to rats is
Tellurium
225
excreted via this pathway in the first 24 hr. Consequently, although the presence of the odor is dramatic, the pathway is quantitatively insignificant. Mead and Gies (1901) identified the biliary and urinary routes of excretion of tellurium compounds. More recently, DeMeio and Henriques (1947) demonstrated that radioactivity given intravenously to rabbits as ~2~Te-sodium tellurite appeared in urine and bile. Hollins (1969) noted the concentration of radioactivity in urine of rats exceeded that in the feces following intraperitoneal injection of labeled tellurous acid. Wright and Bell (1966) found urinary excretion to be about three times fecal excretion in both sheep and swine following intravenous administration of sodium tellurite. The ratio was reversed following oral administration. In similar oral experiments Barnes et al. (1955) found the ratio of fecal to urinary excretion to be 15 and 12 in guinea pigs and rats, respectively. Schroeder et al. (1967) found the concentration of tellurium in normal human urine to be 0.63 pg/ml, whereas Steinberg et al. (1942) were unable to find any using a method sensitive to less than 0.01 ~g/ml. 6. METABOLISM Alliaceous breath following the ingestion of tellurium compounds has been recorded many times. Elemental tellurium (DeMeio, 1947), sodium tellurate (Hofmeister, 1894; Mead and Gies, 1901), sodium tellurite (Reisert, 1884; Mead and Gies, 1901) and tellurium dioxide (Mead and Gies, 1901) have been implicated in several species including man. Hofmeister (1894) collected expired air from a dog, cat and goose following subcutaneous injection of sodium tellurate, characterized the excretion product by chemical means and concluded its identity to be, in contemporary terminology, dimethyl telluride. Considering the evidence for the mammalian synthesis of dimethyl selenide (Klevay, 1976b), it is unlikely that intestinal flora are necessary for the synthesis of dimethyl telluride. Indeed, according to Challenger (1945), bacteria are incapable of this synthesis. Mead and Gies (1901) described the reduction of tellurium dioxide to elemental tellurium in the intestine of the normal dog. A similar reduction of tellurium tetrachloride was noted in the intestine of the duckling by Carlton and Kelly (1967). As certain bacteria have the ability to perform this reduction (Buchanan and Fulmer, 1930; Tucker et al., 1962) it is not certain whether the reduction was a function of bacterial or host metabolism. However, liver and kidney slices of humans, rabbits and rats are capable of reducing tellurite to elemental tellurium (Wachstein, 1949). DeMeio (1946) was unable to demonstrate any effect upon respiration of kidney and liver slices by feeding rats elementary tellurium in amounts that inhibited growth. By subcutaneous injection of sodium tellurate, Svirbely (1938) was able to decrease the ascorbic acid content of several organs of the rat, a species which is able to synthesize ascorbic acid. The interrelationships between the essential nutrients selenium and vitamin E have been reviewed (Klevay, 1976b). Krishnamurthy and Bieri (1962) showed tellurium dioxide was not an effective substitute for either nutrient in experiments on lipid peroxidation in chicks. 7. PHYSIOLOGICAL EFFECTS ON ORGAN SYSTEMS 7.1. CIRCULATORY SYSTEM Carlton and Kelly (1967) found that feeding tellurium tetrachloride to ducklings produced myocardial necrosis and hemoporicardium. No lesions were found in the coronary arteries, endocardium or epicardium, but capillary congestion and hemorrhage were noted. 7.2. DIGESTIVE SYSTEM Mead and Gies (1901) noted that tellurium dioxide and tellurium tartrate fed with meat to dogs inhibited the gastric secretion of acid. DeMeio and Jetter (1948) were able to produce focal areas of fatty and granular degeneration in the livers of rats poisoned
226
LESI.IE M. KLEVAY
with tellurium dioxide added to feed. Carlton and Kelly (1967) found focal areas of necrosis around the central hepatic veins in ducklings poisoned with tellurium tetrachioride in a similar experiment. Steinberg et al. (1942) examined sixty two men who had long term exposures to the fumes produced when elemental tellurium was added to molten iron. The men complained of dryness of the mouth and a metallic taste. Abdominal examination was negative. Amdur (1947) examined three men poisoned by transient exposure to fumes produced by the addition of elemental tellurium to molten copper. The men complained of slight epigastric distress and a metallic taste. The man with the longest exposure had had several loose bowel movements. None of the victims experienced nausea or vomiting; each was found to have slight epigastric tenderness on examination. The cephalin flocculation test was negative in all cases. 7.3. SKIN Franke and Moxon (1937) noted hair loss in rats fed toxic amounts of sodium tellurate and sodium tellurite. The patients described by Steinberg et al. (1942) who were most severely exposed excreted sweat with a garlic odor. 7.4. NERVOUS SYSTEM
Garro and Pentschew (1%4) and Agnew et ai. (1%8) have produced hydrocephalus in rats whose dams were fed elemental tellurium during pregnancy. The amount of tellurium fed was about 3 mg/g of diet. No data were published regarding possible maternal toxic effects. In neither experiment was a gross or microscopic anatomical alteration found to explain the hydrocephalus. James et al. (1966) found normal lambs were born to ewes ingesting potassium tellurate (2 mg/kg body weight per day) throughout gestation. DeMeio and Jetter (1948) noted limb paralysis of rats poisoned with tellurium dioxide and Carlton and Kelly (1%7) found cerebral necrosis in ducklings poisoned with tellurium tetrachloride. Steinberg et al. (1942) reported somnolence as a symptom of intoxication by tellurium-containing fume; Amdur (1947) did not verify this complaint, but noted the victims complained of transient headaches. 7.5. RESPIRATORY SYSTEM The alliaceous breath caused by tellurium comoounds previously cited has also been reported in association with industrial exposure to tellurium-containing fumes (Steinberg et al., 1942; Amdur, 1947). 7.6. UROGENITAL SYSTEM
Poisoning of rats with tellurium dioxide (DeMeio and Jetter, 1948) has resulted in degenerative changes in the proximal kidney tubule. The production of hydrocephalus in offspring by the ingestion of elemental tellurium during pregnancy implies but does not prove placental transport of the teratogen (Garro and Pentshew, 1964; Agnew et al.,
1%8). 8. TREATMENT OF POISONING The amounts of tellurium salts that are acutely toxic amounts to animals have been defined and are shown in Table 2. In a subsequent experiment Franke and Moxon (1937) demonstrated that sodium tellurate or sodium tellurite added to the diets of rats (25/zg Te/g of diet) inhibited the growth of the animals. No references to the treatment of human poisoning by tellurium compounds are found in several recent, standard sources (Gellis and Kagan, 1970; Goodman and Gilman, 1970; Modell, 1970; Wintrobe et al., 1970; Beeson and McDermott, 1971; Conn, 1971). Factors that lessen selenium toxicity in animals have been recently reviewed (Klevay, 1976b) and may be presumed helpful in the absence of contrary data. The successful use of dimercapral (British antiLewisite or BAL) in the treatment of arsenic intoxication (Klevay, 1976a) has prompted
227
Tellurium TAB LE 2. Toxicity of Tellurium Compounds, mg of Element per kg Body Weight. Reference
Species
Route"
Tellurate
Tellurite
Muehlberger and Schrenk (1928)b
Rat Rabbit Rabbit Rat
i.v. i.v. p.o. i.p.
30.5 5.6 56.0 20.0-30.0
1.4 0.5 32.0 2.25-2.50
Franke and Moxon (1936)"
"i.v. = intravenous, p.o. = oral, i.p. = intraperitoneai. bDose survived by less than 50 per cent of the animals. Sodium tellurite and telluric acid were used. ORange of dose killing 75 per cent in 48 hr. Sodium salts were used.
use of this drug in the treatment of tellurium intoxication. Amdur (1947) treated three men with dimercapral who had alliaceous breath caused by industrial exposure to fumes containing tellurium. The disappearance of the garlic odor 1-4 days after termination of 8 days of therapy casts doubt on the efficacy of dimercapral in these cases. In a later work, Amdur (1958) increased the toxicity of tellurium oxide for guinea pigs by treatment with dimercapral; hematuria was more prominent in the treated groups. The use of dimercapral in the treatment of selenium toxicity is contraindicated (Klevay, 1976b) because the drug decreases survival and increases kidney damage, this fact together with the data quoted above suggests a similar conclusion regarding tellurium poisoning. DeMeio (1947) treated some workers exposed to tellurium dust with ascorbic acid (8-10 mg/kg body weight) one to three times a day. He concluded therapy was successful in reducing the alliaceous breath and justified its use by describing successful experiments with rabbits and guinea pigs. The route of administration was not revealed. Amdur (1958), however, found ascorbic acid did not benefit guinea pigs poisoned with tellurium oxide. The clinical course of three cases of poisoning with sodium tellurite has been described by Keall et al. (1946). The dose received by the surviving patient was probably less than that of the patients who died. The fact that only these two patients received morphine may be coincidental. 9. MEDICAL USES OF T E L L U R I U M COMPOUNDS No tellurium compounds have received official recognition by any of the national or international drug compendia quoted in the articles on arsenic (Klevay, 1976a) or selenium (Klevay, 1976b). Tellurium is, however, the source of much of the radioactive iodine used in the diagnosis and treatment of thyroid gland disorders (Elkin, 1969; Wellman et al., 1976). Various methods of transmutation are used. Bacterial culture media that include 0.04 per cent potassium tellurite are useful in the laboratory diagnosis of certain infections. Corynebacterium diphtheriae acquire a grey or black color due to the reduction of tellurite to tellurium and the accumulation of the latter inside the bacteria (Wilson and Miles, 1964; Smith et al., 1968). Growth of culture contaminants is suppressed. A similar suppressive action permits the growth of Staphylococcus aureus from cultures contaminated with other staphylococci, micrococci and gram-negative bacilli (Bodily et al., 1970). Resistance to tellurite is used in the classification of Group D, hemolytic streptococci (Wilson and Miles, 1964). Recently the ability to reduce tellurite to tellurium has been used in the differential diagnosis of urinary tract infections due to Staphylococcus albus (Alder et al., 1966). The method may have promise in the differentiation of atypical mycobacteria (Kilburn et al., 1969). REFERENCES 1. AONEW, W. F., FAUVRE, F. M. and PUDENZ, P. H. (1968) Tellurium hydrocephalus: Distribution of tellurium-127m between maternal, fetal and neonatal tissues of the rat. Exp. Neurol. 21: 120-131. 2. ALDER, V. (3., BROWN, A. M. and MITCHELL, R. (3. (1966) Tellurite reactions of coagulase negative staphylococci and micrococci. J. appl. Bacteriol. 29: 304-307. 3, AMDUR, M. L. (1947) Tellurium. Accidental exposure and treatment with BAL in oil. Occup. Med. 3: 386-391.
228
LESLIE M. KLEVAY
4. AMDUR, M. L. (1958) Tellurium oxide. Archs Ind. Hlth. 17: 665-667. 5. BARNES, D. W. H., COOK, G. B., HARRISON, G. E., LOUTIT, J. F. and RAYMOND, W. H. A. (1955) The metabolism of '32tellurium-iodine mixture in mammals. J. nucl. Energy 1: 218-230. 6. BEESON, P. B. and McDERMOTT, W. (Ed.) (1971) Cecil-Loeb Textbook o f Medicine, 13th ed. Saunders, Philadelphia. 7. BERRY, L. G. and MASON, B. (1959) Mineralogy, p. 212, Freeman, San Francisco. 8. BODILY, H. L., UPDYKE, E. L. and MASON, J. O. (1970) Diagnostic Procedures for Bacterial, Mycotic and Parasitic Infections, 5th ed., pp. 216-217. American Public Health Association, New York. 9. BOWEN, H. J. M. (1966) Trace Elements in Biochemistry, p. 205. Academic Press, London. 10. BRASTED, R. C. (1961) Sulfur, selenium and tellurium. In Comprehensive Inorganic Chemistry, Vol. 8, pp. 1-245. Van Nostrand, Princeton, N.J. 11. BUCHANAN, R. E. and FULMER, E. I. (1930) Physiology and Biochemistry of Bacteria, Vol. II, pp. 384--385. Williams & Wilkins, Baltimore. 12. CARLTON, W. W. and KELLY, W. A. (1967) Tellurium toxicosis in pekin ducks. Toxicol. appl. Pharmacol. 11: 203-214. 13. CERWENKA, E. A. and COOPER, W. C. (1961) Toxicology of selenium and tellurium and their compounds. Archs envir. Hlth. 3: 189-200. 14. CHALLENGER, F. (1945) Biological methylation. Chem. Rev. 36: 315-361. 15. CONN, H. F. (Ed.) (1971) Current Therapy 1971. Saunders, Philadelphia. 16. COTTON, F. A. and WILKINSON, G. (1966) Advanced Inorganic Chemistry pp. 528, 547, 549, 2nd ed., Interscience, New York. 17. DEMEIO, R. H. (1946) Tellurium I. The toxicity of ingested elementary tellurium for rats and rat tissues. J. ind. Hyg. Toxicol. 28: 229-232. 18. DEMEIO, R. H. (1947) Tellurium II. Effect of ascorbic acid on the tellurium breath. J. ind. Hyg. Toxicol. 29: 393-395. 19. DEMEIO, R. H. and HENRIQUES, F. C., JR. (1947) Tellurium IV. Excretion and distribution in tissues studied with radioactive isotope. J. biol. Chem. 169: 609-623. 20. DEMEIO, R. H. and JETTER, W. W. (1948) Tellurium III. The toxicity of ingested tellurium dioxide for rats. J. ind. Hyg. Toxicol. 30: 53-58. 21. ELKIN, E. M. (1969) Tellurium and tellurium compounds. In Kirk-Othmer Encyclopedia o f Chemical Technology, Vol. 19, 2nd ed., pp. 756-774. MARK, H. F., MCKETTA, J. J., JR. and OTHMER, O. F. Interscience, New York. 22. FRANKE, K. W. and MOXON, A. L. (1936) A comparison of the minimum fatal doses of selenium, tellurium, arsenic and vanadium. J. Pharmac. exp. Ther. 58: 454-459. 23. FRANKE, K. W. and MOXON, A. L. (1937) The toxicity of orally ingested arsenic, selenium, tellurium, vanadium and molybdenum. J. Pharmac. exp. Ther. 61: 89-102. 24. GARRO, F. and PENTSCHEW, A. (1964) Neonatal hydrocephalus in the offspring of rats fed during pregnancy non-toxic amounts of tellurium. Archiv f. psychiatrie u. Z. f.d. ges. Neurologie 206: 272-280. 25. GELLIS, S. S. and KAt3AN, B. M. (1970) Current Pediatric Therapy 4. Saunders, Philadelphia. 26. GOODMAN, L. S. and GILMAN, A. (1970) The Pharmacological Basis of Therapeutics, 4th ed. MacMillan, New York. 27. HOFMEISTER, F. (1894) Ueber Methylirung im Thierk6rper. Archiv. f. exp. Path u. Pharm. 33: 198-215. 28. HOLLINS, J. G. (1969) The metabolism of tellurium in rats. Hlth. Phys. 17: 497-505. 29. [HDE, A. J. (1964) The Development o f Modern Chemistry, pp. 90-91. Harper & Row, New York. 30. JAMES, L. F., LAZAR, V. A. and BINNS, W. (1966) Effects of sublethal doses of certain minerals on pregnant ewes and fetal development. Am. J. vet. Res. 27: 132-135. 31. KEALL, J. H. H., MARTIN, N. H. and TUNBRIDGE, R. E. (1946) A report of three cases of accidental poisoning by sodium tellurite. Br. J. ind. Med. 3" 175-176. 32. KILBURN, J. O., SILCOX, V. A. and KUBICA, G. P. (1969) Differential identification of mycobacteria. V. The tellurite reduction test. Am. Rev. resp. Dis. 99: 94-100. 33. KLEVAY, L. M. (1976a) Arsenic. Pharmac. Ther. A, 1: 189-209. 34. KLEVAY, L. M. (1976b) Selenium. Pharmac. Ther. A, 1: 211-222. 35. KRISHNAMURTHY, S. and BIERI, J. G. (1962) Dietary antioxidants as related to vitamin E function. J. Nutr. 77: 245-252. 36. LARDY, H. A. and MOXON, A. L. (1942) The ascorbic acid content of the livers of selenized rats and chicks. Proc. S. Dakota Acad. Sci. 22: 39-42. 37. LEDERER, C. M., HOLLANDER, J. M. and PERLMAN, I. (1967) Table o f Isotopes 6th ed., pp. 67, 279. Wiley, New York. 38. MEAD, L. D. and GIES, W. J. (1901) Physiological and toxicological effects of tellurium compounds with a special study of their influence on nutrition. Am. J. Physiol. 5: 104-149. 39. MELLOR, J. W. (1931) A Comprehensive Treatise on Inorganic and Theoretical Chemistry, Vol. I1, pp. 1-121. Longman Green, London. 40. MODELL, W. (ed.). (1970) Drugs o f Choice 1970--1971. C. V. Mosby, St. Louis. 41. MRAZ, F. R., WRIGHT, P. L., FEROUSON, T. M. and ANDERSON, D. L. (1964) Fission product metabolism in hens and transference to eggs. Hlth. Phys. 10: 777-782. 42. MUEHLBERGER, C. W. and SCHRENK, H. H. (1928) The effect of the state of oxidation on the toxicity of certain elements. J. Pharmac. exp. Ther. 33; 270-271. 43. REISERT, W. (1884) The so-called bismuth breath. Am. J. Pharmacol. 56: 177-180. 44. ROSENBERG, H. R. (1945) Chemistry and Physiology o f the Vitamins, p. 317. Interscience, New York. 45. SANDRATSKAYA, S. E. (1967) Tellurium. In Toxicology o f t h e R a r e Metals, pp. 76-88, IZRAEL'SON, Z. I. (ed.), HALPERIN, Y. and LIEnER, E. (trans.). Clearinghouse for Federal Scientific and Technical Information, Springfield, Va. 46. SCHROEDER, H. A., BUCKMAN, J. and BALASSA, J. J. (1967) Abnormal trace elements in man: tellurium. J. chron. Dis. 20: 147-161.
Tellurium
229
47. SHIE, M. D. and DEEDS, F. E. (1920) The importance of tellurium as a health hazard in industry--A preliminary report. Publ Hlth. Rep. 35: 939-954. 48. SMITH, D.T., CONANT, N. F. and WILLETT, H. P. (1968) Zinsser Microbiology 14th ed., p. 508. Appleton-Century-Crofts, New York. 49. STEINBERG, H. H., MASSARI, S. C., MINER, A. C. and RINK, R. (1942) Industrial exposure to tellurium: atmospheric studies and clinical evaluation. J. ind. Hyg. Toxicol. 24: 183-192. 50. SVIRBELY, J. L. (1938) Vitamin C studies in the rat. The effect of selenium dioxide, sodium selenate and tellurate. Biochem. J. 32: 467-473. 51. TUCKER, F. L., WALPER, J. F., APPLEMAN, M. D. and DONOHUE, J. (1962) Complete reduction of tellurite to pure tellurium metal by microorganisms. J. Bacteriol. 83: 1313-1314. 52. VIONOLI, L. and DEFRETIN, J. P. (1964) The toxicology of tellurium. Ann. Biol. Clin. 22: 399-417. Cited in Chem. Abs. 61: 6252a. 53. WACHSTEIN, M. (1949) Reduction of potassium tellurite by living tissues. Proc. Soc. exp. Biol. Med. 72: 175-178. 54. WEAST, R. C. (ed.) (1970) Handbook of Chemistry and Physics, pp. B-141,144, C-706. Chemical Rubber, Cleveland. 55. WEBSTER, S. H. (1946) Volatile hydrides of toxicological importance. J. Ind. Hyg. Toxicol. 28: 167-182. 56. WELLMAN, H. N., ANGER, R. T. and ROHRER, R. H. (1976) Radiation dose to humans from ~23I, l~'I, ~sI, ~sI, ~°I, J~I and mI administered as iodide ion. J. nucl. Medicine Medical Internal Radiation Dose Committee, Pamphlet ¢/9, In preparation. 57. WILSON, G. S. and MILES, A. A. (1964) Topley and Wilson's Principles of Bacteriology and Immunity, 5th ed., pp. 717, 1677-1679. Williams & Wilkins, Baltimore. 58. WINTROBE, M. M., THORN, G. W., ADAMS, R. D., BENNETT, I. L., JR., BRAUNWALD, E., ISSELBACHER, K. J. and PETERSDORF, R. G. (ed.) (1970) Harrison "s Principles o/lnternal Medicine, 6th ed. McGraw-Hill, New York. 59. WRIGHT, P. L. and BELL, M. C. (1966) Comparative metabolism of selenium and tellurium in sheep and swine. Am..I. Physiol. 211: 6-10.