Tellurium

C H A P T E R

54 Tellurium LARS GERHARDSSON

ABSTRACT

disturbances, changes in fur, and occasionally epilation and hind leg paralysis. Long-term studies of chronic effects are sparse. Dominant and critical effects have been reported from the nervous system, including peripheral neuropathy characterized by segmental demyelination and minor axonal degeneration. In the brain, black changes caused by dark tellurium particles localized to lipofuscin granules in neuronal cytoplasm have been observed. Other effects have been reported from the liver (fatty degeneration and necrosis), kidney (proximal tubular lesions, oliguria, or anuria), and heart (cell necrosis, edema, and congestion). Reproductive effects including, for example, hydrocephalus, edema, exophthalmia, and ocular hemorrhage have been described. Acute exposure to tellurium in occupational settings may cause acute respiratory irritation followed by the development of garlicky odor of the breath and sweat, drowsiness, headache, malaise, lassitude, weakness, and dizziness. Gastrointestinal symptoms such as anorexia, nausea, vomiting, metallic taste, dry mouth, and constipation may appear. Dermatitis and blue-black discoloration of the skin may follow exposure to tellurium hexafluoride. Severe intoxication may lead to depression of the respiratory system and circulatory collapse. No specific antidote for tellurium poisoning has been found. After inhalational exposure, treatment with fresh air, oxygen supply, assisted ventilation, β2-adrenergic agonists, and oral or parenteral corticosteroids can be tried. Reviews of tellurium toxicology have been published by ­Browning (1969), Izrael’son (1973), Fishbein (1977), Alexander et al., (1988) and Kobayashi (2004).

Food (e.g. meat, dairy products, and cereals) is the main source of tellurium exposure in the general population. In the working environment, inhalational exposure predominates. Small amounts of organic tellurium compounds can also be absorbed through the skin. No quantitative data have been published regarding the inhalational absorption of tellurium or tellurium compounds in humans. In experiments on healthy volunteers, a gastrointestinal absorption of 10-25% has been observed. In animal experiments, a similar absorption has been estimated. The highest tissue concentrations have been ob­­ served in the kidneys. Increased levels have also been noted in the blood, heart, lungs, liver, spleen, muscle, and bone. The main accumulation is in bone, which harbors > 90% of the total body burden. Tellurium can pass both the placenta and the blood-brain barrier. Parenterally administered tellurium is predominantly excreted in the urine, whereas orally ingested tellurium salts are transferred through biliary secretion and mainly excreted in the feces. Small amounts, probably approximately 0.1%, of absorbed tellurium are exhaled, presumably as dimethyl telluride. In rat experiments, biological half-times ranging from 9 days in blood to 23 days in the kidney have been reported. The whole-body retention model for humans estimates a biological half-time of approximately 3 weeks. Elimination from bone is slow, with an estimated half-time of approximately 600 days. Acute systemic effects of tellurium toxicity in rats include listlessness, decreased locomotor activity, somnolence, anorexia, weight loss, gastrointestinal Handbook on the Toxicology of Metals 4E http://dx.doi.org/10.1016/B978-0-444-59453-2.00054-8

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1  PHYSICAL AND CHEMICAL PROPERTIES Tellurium (Te): periodic system group VIb; atomic weight, 127.6; atomic number, 52; density, 6.2  g/cm3 (20°C); melting point, 449.5°C; boiling point, 989.8°C; specific gravity, 6.24 (20°C), Chemical Abstracts Service number, 13494-80-9. Tellurium exists in two allotropic forms: as a silvery white crystalline metal and as a black amorphous powder. Twenty-one isotopes of tellurium are known, with atomic masses ranging from 115 to 135. Natural tellurium consists of eight isotopes (mainly 130Te, 128Te, and 126Te), one of which (127Te) is unstable. It is present up to 0.87% and has a half-time of 1.2 × 1013 years. Chemically, tellurium resembles selenium and sulfur. Tellurium burns with a greenish-blue flame in air and forms tellurium dioxide, which is only sparingly soluble in water. It forms compounds in oxidation states −2, +2, +4, and +6. Of toxicological interest are elemental tellurium, hydrogen telluride, and tellurium hexafluoride (the last two being colorless gases), tellurium dioxide, tellurous and telluric acids, and sodium and potassium tellurites and tellurates, which are soluble in water. Organotellurium compounds are well documented in the literature. Several organometallic and complex compounds of tellurium have been described [e.g. aryl, diaryl, and triaryl tellurium(IV) chlorides]. Recently, a new series of organotellurium compounds has been prepared [i.e. bis(2-hydroxymethylphenyl) telluride, bis(2-hydroxymethylphenyl) ditelluride, and bis(4-hydroxymethylphenyl) telluride] (Al-Rubaie and Al-Jadaan, 2002). Elemental tellurium, which is insoluble in water (Cooper, 1971), does not easily form an oxide when heated in air. Tellurium dioxide is only sparingly soluble in water at temperatures up to 40°C, e.g. at 18°C and pH 6.5 its solubility is 3.75 × 10−5 mol/L.

2  METHODS AND PROBLEMS OF ANALYSIS Analyses of biological samples by photometry, conventional flame atomic absorption spectrometry (AAS), or inductively coupled argon plasma spectrometry (ICPMS) are often complicated by their low sensitivity. Other methods with higher sensitivity include neutron activation analysis (NAA) (Nason and Schroeder, 1967a), ICPMS, hydride generation AAS, and graphite furnace AAS (Welz and Sperling, 1999). To avoid disturbances from interfering elements, it is often necessary to separate tellurium from these elements before the determinations, for example by the use of ion exchange or solvent extraction methods. Lockwood and Limtiaco (1975) found a detection limit for tellurium of 0.50 μg/mL of the solubilized sample solution with electronically excited oxygen

and AAS. Later, Siddik and Newman (1988) used platinum as a modifier to increase the sensitivity when determining tellurium concentrations in biological samples by flameless AAS. Detection limits in urine, plasma, and tissues in mice were approximately 50, 5, and 170 ng/mL (or ng/g), respectively. Low detection limits, < 50 ng/L, have also been found when using ICP-MS for the determination of tellurium in urine of nonoccupationally exposed subjects (Schramel et al., 1997). Hydride generation AAS has been combined with preconcentration of the analyte by coprecipitation (Kaplan et al., 2005), giving a detection limit of 0.03 μg/L and a precision of 3.5% at the 10 μg/L level. Total tellurium and Te(IV) may be analyzed by solid-phase extraction (SPE) separation and ICP-MS detection with detection limits of 3 ng Te/L (Yu et al., 2003). A new method has been reported for the speciation of inorganic tellurium species in seawater by ICPMS following selective magnetic SPE (MSPE) separation (Huang and Hu, 2008). Under optimal conditions, the limits of detection obtained for Te(IV) was 0.079 ng/L.

3  PRODUCTION AND USES 3.1 Production Tellurium is rarely found in a free state, and there are no ore deposits that can be mined. It is sometimes found in its native copper tellurium lead form, but more often as the telluride of gold (calaverite) or bound to other metals such as silver and bismuth. The main part of commercial tellurium is recovered from electrolytic copper refinery slimes. The tellurium concentration of the slimes can range up to 10%. Through autoclaving slimes at elevated temperatures, the extraction of tellurium can range from 50 to 80%. Tellurium is recovered from the solution by cementation with copper. Copper telluride is leached with caustic soda and air to form a sodium tellurite solution. This solution, along with excess free caustic soda, is then electrolyzed in a cell using stainless steel anodes to produce tellurium metal (Kirk-Othmer, 1997). To form commercial tellurium metal (99.5%), tellurium dioxide is dissolved in hydrochloric acid. The tellurium solution is saturated with sulfur dioxide gas to yield commercial tellurium powder, which is washed, dried, and melted (Kirk-Othmer, 1997). The estimated global production of tellurium was approximately 135 tons in 2007 (USGS, 2008).

3.2 Uses Tellurium compounds can be used in catalysts and catalytic processes (e.g. tellurium oxide, tellurium tetrachloride); as metal coatings (e.g. tellurium chloride); as

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pigments (e.g. cadmium-telluride); in thermoelectric materials and as semiconductors (e.g. tellurides of silver, bismuth, copper, germanium, manganese, lead, and antimony); as semiconductors and solar cells in pocket calculators and cameras (e.g. tellurides of Bi and Cd); for corrosion resistance of electroplated nickel (e.g. sodium telluride); in therapeutic applications (e.g. asatine-211-tellurium colloid); and in the vulcanization and curing of rubber, in primary (nonrechargeable) and secondary (chargeable batteries) and fuel cells (­Fishbein, 1991). It can be used to improve the crop strength of tin and the mechanical properties of lead. Tellurium can also be used as a coloring agent in chinaware, porcelains, enamels, and glass, and for producing a black finish on silverware (O’Neil, 2001). The largest use for tellurium (approximately 48% of the market) is as an alloy in steel as a free-machining additive, in copper to improve machinability, in lead to improve resistance, in cast iron to control the depth of chill, and in malleable iron as a carbide stabilizer. Chemicals and catalyst usage make up approximately 24% of the market. The remaining part is divided between electrical uses, e.g. photoreceptor and thermoelectric applications (22%), and other uses (6%) (USGS, 2004). Organic tellurium compounds (e.g. tellurides) have been used as initiators for tellurium radical polymerization. Electron-rich monotellurides and ditellurides possess antioxidant activity.

4  ENVIRONMENTAL LEVELS AND EXPOSURES 4.1  General Environment 4.1.1  Food and Daily Intake Schroeder et al. (1967) estimated the tellurium content in a number of food items. The concentrations reported were 4.2 mg/kg in meats, 4.8 mg/kg in dairy products, 2.8 mg/kg in cereals, 1.8 mg/kg in fats and oils, 1.1 mg/kg in fruits, and 0.44 mg/kg in hospital diets. After revising these analyses, Nason and ­Schroeder (1967b) estimated the daily intake in humans to be approximately 100 μg. Also this figure is probably an overestimation.

higher levels have been reported in the South (80 ng/L) and East (40-70 ng/L) China seas (An and Zhang, 1983). Values of about 10 ng/L have been reported from the Seto Inland Sea in Japan (Chung et al., 1984). Values of the same magnitude have also been observed in rainwater. Andreae (1984) found concentrations of 3.3 ng/L in Florida in February, 1984, and slightly lower levels, 0.51 ng/L, in repeated measures in March, 1984. Soil concentrations of 0.035 mg/kg have been report­ ­ed in Yokohama (Japan). Similar levels of 0.031 mg/ kg have been found in Seoul (Korea) (­Hashimoto et al., 1989). Reported levels in ambient air range from 0.12 ng/m3 in Yokohama, Japan (Hashimoto et al., 1989) to 0.46 ng/m3 in Missouri (Chou and Manuel, 1986) and up to 0.35-50 ng/m3 in the National Air Surveillance Network (Scott et al., 1976). Seljankina and Alekseeva (1971) found a concentration of approximately 2 μg Te/m3 at a distance of approximately 2 km from an electrolytic copper-refining plant. 4.1.3 Plants Data concerning the tellurium concentration in plants is very scanty. In one study of plants growing on natural tellurium-containing soil, tellurium concentrations in saltbush and cactus were 2 and 25 mg Te/kg, respectively (Beath et al., 1935). Flowers contain significantly more tellurium on average than other plant parts. In trees, the leaves absorb the most tellurium and branches the least. In a study from the Ely mining district of White Pine County, USA, no plants contained more than 1 mg Te/kg (Cowgill, 1988).

4.2  Working Environment In 1942, Steinberg et al., determined air concentrations in an iron foundry. The values ranged from 0.01-0.1 mg/m3. Approximately 70% of the observed values were in the range of 0.01-0.05 mg/m3. Values of the same magnitude, ranging from 0.01-0.7 mg/m3, were found in a more recent study of an iron foundry (­Blackadder and Manderson, 1975).

5 METABOLISM

4.1.2  Water, Soil, and Ambient Air Reported concentrations in natural water include 0.31 ng/L in China (Yu et al., 1983), 0.5 ng/L in the Florida Bay (Andreae, 1984), 0.9 ng/L in the Red Sea (Sugimura and Suzuki, 1981), 0.22 ng/L in the North Atlantic Ocean (Lee and Edmond, 1985), and 0.17 ng/L in the Panama Bay (Lee and Edmond, 1985). Somewhat

5.1 Absorption 5.1.1 Inhalation No quantitative information is available on the human respiratory absorption of inhaled tellurium or tellurium compounds.

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5.1.2 Ingestion Little is known about intestinal tellurium absorption in humans. In a study on healthy male volunteers, an intestinal absorption of 25% ± 10% was estimated for soluble tellurium salts (Kron et al., 1991). The introduction of tellurium to cress decreased intestinal absorption to about 15%. The lowest intestinal absorption, about 10%, was noted for metallic tellurium (Kron et al., 1991). In a 3-week study of rats fed large doses of elemental tellurium, 63-84% was recovered unabsorbed in the feces (De Meio, 1946), which suggests that approximately 25% was absorbed via the gastrointestinal tract. Similar results from later animal experiments indicated that up to 25% of orally administered tellurium (elemental tellurium and tellurium dioxide) is absorbed in the gut (Hollins, 1969; Taylor, 1996). The gastrointestinal absorption of tellurium is completed within 2 h after intake. In rats, the main absorption takes place in the duodenum and jejunum, and the total absorption was estimated to be in the range of 10-25% (Slouka and Hradil, 1970). In sheep and pigs, these compounds are mainly absorbed further down in the colon (Wright and Bell, 1966). 5.1.3  Skin Absorption The handling of tellurium compounds may cause skin burns or rashes, followed by a garlic odor in the breath indicating skin absorption. Blackadder and Manderson (1975) reported two cases of chemists who were accidentally exposed to tellurium hexafluoride gas when approximately 50 g leaked from a cylinder in the laboratory. They both showed the characteristic garlic odor of the breath, and one also developed an intradermal bluish-black pigmentation in the skin of the fingers, face, and neck that took several weeks to disappear. The authors suspected that volatile tellurium esters were absorbed through the skin.

5.2 Distribution In rat experiments, approximately 90% of tellurium in the blood enters erythrocytes, probably bound to hemoglobin (Agnew and Cheng, 1971; Slouka, 1970). Most of the remainder is bound to plasma proteins. Tellurium can pass both the placenta and the bloodbrain barrier (Agnew, 1972; Agnew et al., 1968). The highest tissue concentrations have been found in the kidney; levels observed in the heart, lung, and spleen are approximately 10-30% of the kidney concentrations; and levels in the liver are approximately 50% of those in the lungs, heart, and spleen. Measured concentrations in cardiac muscle are reported to be approximately 20 times higher than in skeletal muscle.

In the nervous system, intracerebrally injected tellurium accumulates in the gray matter. Tellurium also accumulates over time in bones (Browning, 1969), which harbor more than 90% of the total body burden (Schroeder et al., 1967).

5.3 Excretion The excretion pattern depends on the chemical forms and the mode of administration of tellurium and tellurium compounds. Parenterally administered tellurium is predominantly excreted in the urine, whereas orally ingested tellurium salts are mainly excreted unabsorbed in the feces (Durbin, 1960). Tellurium is transferred to the intestine by biliary excretion (­Hollins, 1969; Slouka, 1970). Small amounts may also be excreted in milk and sweat. Inorganic tellurium in the form of tellurite is reduced and methylated in the body. By using high performance liquid chromatography-coupled ICP-MS and electrospray ionization tandem mass spectrometry, the metabolite trimethyltelluronium was identified in urine after inorganic tellurite intake in rats. Another characteristic of Te metabolism is the accumulation of dimethylated Te species in the red blood cells of rats (Ogra, 2009). Small amounts, probably approximately 0.1%, of absorbed elemental tellurium and tellurite are exhaled, presumably as dimethyl telluride, causing a characteristic garlic-like odor of the breath and sweat (Cooper, 1971; De Meio, 1946).

5.4  Biological Half-Time The whole-body excretion of tellurium and tellurium compounds followed a two-phase pattern in rats (Hollins, 1969; Slouka, 1970). The fast phase had a biological half-time of approximately 19 h (42-49% of the dose), and the figures for the slow phase were 13-15 days (51-58%). The whole-body retention model for humans (ICRP, 1968) estimates a biological half-time of approximately 3 weeks. In rat experiments, biological half-times of 9.2 days were found in blood, 10.2 days in the liver, 17.7 days in muscle, and 23 days in the kidney (Hollins, 1969). Elimination from bone seems to be very slow, with an estimated half-time of approximately 600 days (Hollins, 1969).

6  BIOLOGICAL MONITORING 6.1  Levels in Tissues and Biological Fluids Tellurium concentrations in whole blood in normal subjects may range from 0.15 to 0.3 μg/L (van Montfort et al., 1979). Tellurium levels in urine in normal subjects

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ranges from < 0.1 to 10 μg/L (Fodor and Barnes, 1983; Kobayashi and Imaizumi, 1991). Observed concentrations in the liver, lung, and kidney were 4-21, 0.04-1, and 0.6-16  μg/g wet weight, respectively (Iyengar et al., 1978). In a study of tellurium concentrations in the hair and nails of normal Japanese adults, the levels as measured by hydride generation AAS were lower than the detection limit of the instrument (< 1 ng/g) (Fukabori and Nakaaki, 1990; Nakaaki and Fukabori, 1990). The estimated whole-body content in normal subjects, as determined by NAA, is approximately 500 mg (Nason and Schroeder, 1967a), of which about 90% is contained in the skeleton.

6.2  Biomarkers of Exposure Blood and urinary analyses may be used for biological monitoring, but data are very scanty. Tellurium values for normal subjects have been reported for blood (0.15-0.3 μg/L) (van Montfort et al., 1979) and urine (< 0.1-10 μg/L) (Fodor and Barnes, 1983; Kobayashi and Imaizumi, 1991). Only a few incomplete datasets are, however, available from (1) the working environment and (2) regarding the relationship between tellurium in the air, blood, and urine. Accordingly, it is not clear whether these relationships are linear or nonlinear.

6.3  Biomarkers of Effects Quantitative data on the relationship between internal dose and adverse health effects are still lacking and, thus, risk assessment is more complicated. Accordingly, more studies are needed to produce data that can be used for determining dose-effect and dose-response parameters in humans. An early and classical sign of tellurium intoxication is the garlicky odor of the breath, caused by exhalation of dimethyl telluride (Muller et al., 1989). De Meio (1947) reported that small doses of sodium tellurite (1-50 μg) given perorally cause a garlic odor that appears within 30 min. In iron foundry workers exposed to air concentrations of 10-100 μg Te/m3 at the workplace over a 2-year period, a garlic odor of the breath was noted (Muller et al. 1989). Cerwenka and Cooper (1961) reported that the garlic odor lasted for 237 days in a subject given 15 mg sodium tellurite. Recently, Muller et al. (1989) observed a garlic breath odor that persisted for 10 months in a subject that had ingested a small piece of meat contaminated with 800-1000 μg Te/kg. Thus, patients exposed to tellurium must be informed that the garlic odor of their breath and urine may persist for weeks or months after the exposure (Yarema and Curry, 2005).

7  EFFECTS AND DOSE-RESPONSE RELATIONSHIPS Tellurium is not regarded as an essential trace element. Thus, tellurium deficiency is not a problem in humans or animals.

7.1  Local Effects and Dose-Response Relationships 7.1.1 Animals Inhalation of elemental tellurium and tellurium dioxide aerosols (10, 50, and 100 mg/m3, 2 h daily, 13-15 weeks) caused desquamatory bronchitis and lobar pneumonia in rats (Izrael’son, 1973; ­Sandrackaja, 1962a). Inhalation of high concentrations of tellurium hexafluoride (50 mg/m3; 1 h) produced pulmonary edema in rabbits, guinea pigs, rats, and mice (Kimmerle, 1960). Decreased body weight and black deposits in lung tissue were observed in male Harlan Wistar albino rats 6 months after a single endotracheal instillation of tellurium and tellurium dioxide (Geary et al., 1978). Demyelination and rapid reparative remyelination in the cerebral white matter, cortex, and optic nerve were observed after tellurium intoxication in adult rats. The findings indicate damage to the myelin sheath and glial cells, as well as ultrastructural changes to some axons (Smialek et al., 1994). 7.1.2 Humans Exposures to tellurium vapor and hydrogen telluride may cause irritation of the respiratory tract (Izrael’son, 1973; Popova et al., 1965), leading to bronchitis and pneumonia (Lewis, 1996). Dermatitis and blue-black skin discoloration may occur following exposure to tellurium hexafluoride. Ingestion of no more than 40 μg of soluble tellurium may lead to the unusual breath odor. It has been suggested that the formation of organic tellurium compounds (e.g. dimethyl telluride) may be responsible for the garlic-like odor to breath, possible by inhibiting the squalene epoxidase enzyme (Taylor, 1996).

7.2  Systemic Effects and Dose-Response Relationships 7.2.1 Animals Acute and subacute studies of systemic toxicity of tellurium and tellurium compounds in rats show a number of symptoms (e.g. listlessness, decreased locomotor activity, somnolence, anorexia, weight loss, gastrointestinal disturbances, changes in fur, and occasionally

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epilation and hind leg paralysis) (Amdur, 1958; De Meio, 1946; De Meio and Jetter, 1948; ­ Sandrackaja, 1962a).

areas of acute hemorrhagic necrosis in the ventricular myocardium, as well as signs of edema and congestion (Van Vleet and Ferrans, 1982).

7.2.1.1 Liver

7.2.1.5  Nervous System

Studies on rats, rabbits, and Peking ducks exposed to different tellurium compounds (tellurium dioxide, tellurium tetrachloride, and sodium tellurite) showed liver changes ranging from simple cellular swelling to hydropic and fatty degeneration and cell necrosis (Carlton and Kelly, 1967; De Meio and Jetter, 1948; Lencenko, 1967; Sandrackaja, 1962b). Other changes included impairment to glycogen function, detoxifying functions, and protein metabolism, as indicated by a dose-related reduction of galactose tolerance, hippuric acid excretion, decreased albumin:globulin ratio in serum, urinary bilirubin excretion, and inhibition of cholinesterase (Lencenko, 1967; Lencenko, and Plotko 1969; Sandrackaja, 1962b).

Rats fed 0.2 g/day tellurium showed black brain changes caused by dark tellurium particles localized in lipofuscin granules within neuronal cytoplasm throughout the brain. These changes are probably due to the effects of tellurium on brain mitochondria (Duckett and White, 1974). Peroxidation-related effects on the brain were studied in 15 male Wistar rats fed drinking water containing tellurium tetrachloride at a level of 100 mg/L. Control rats were given tap water. Rats were killed in groups of five at time points of 7, 21, and 35 days after exposure. Succinic dehydrogenase activity was above the control range after 21 days, whereas creatinine kinase activity decreased or remained stable. The brain glutathione content was above the control range after 35 days (Valkonen and Savolainen, 1985). Rats fed a diet containing 1.25% elemental tellurium starting on postnatal day 20 developed garlic odor within 48 h and usually developed hindlimb paresis within 72 h. Treated rats showed progressive increases in blood-nerve barrier permeability 24-72 h after exposure. The blood-brain barrier, however, was not affected. Other effects included increased numbers of intracytoplasmic lipid droplets, intracytoplasmic membrane-delimited clear vacuoles, and cytoplasmic excrescences within myelinating Schwann cells after 24 h; axon demyelination after 48 h; and endoneurial edema after 72 h. The synthesis of cholesterol was sharply inhibited after tellurium exposure for 12 h (Bouldin et al., 1989). Weanling rats fed a diet containing elemental tellurium may develop peripheral neuropathy characterized by segmental demyelination and minimal axonal degeneration. An early neuropathic sign is an increasing number of cytoplasmic lipid droplets in myelinating Schwann cells. These are probably derived from newly synthesized lipid rather than from the early breakdown and internalization of myelin lipids. The earliest observed biochemical abnormality in tellurium neuropathy is inhibition of cholesterol synthesis at the squalene epoxidase step, causing an accumulation of squalene within the nerve (Goodrum et al., 1990). Metabolic changes observed in the sciatic nerve, for example, probably initially involve inhibition of squalene conversion to 2,3-epoxysqualene. This blockage in the cholesterol biosynthesis pathway may, directly or indirectly, lead to inhibition of the synthesis of myelin components and to the breakdown of myelin (Harry et al., 1989; Morell et al., 1994). Accordingly, Laden and Porter (2001) found transient, peripheral

7.2.1.2 Kidney Rats exposed to tellurium dioxide through inhalational exposure (condensation aerosol; 10 and 50 mg/ m3, 2 h daily, 13-15 weeks) showed signs of focal vacuolization of cells and hemorrhage in the glomeruli, followed by albuminuria and hematuria (Sandrackaja, 1962a,b). In another study (De Meio and Jetter, 1948), rats were fed tellurium dioxide (375-1500 mg Te/kg diet, 24-128 days). The treatment resulted in changes ranging from cellular swelling to necrosis, accompanied in some rats by oliguria and anuria. The findings indicated severe lesions in the proximal tubular epithelium (De Meio and Jetter, 1948). 7.2.1.3 Blood Rats exposed to tellurium dioxide and elemental tellurium aerosol (50-100 mg/m3, 2 h daily, 13-15 weeks) developed normochromic, possibly hemolytic, anemia with signs of dose-related reductions in hemoglobin concentration and erythrocyte numbers, as well as hematuria (Sandrackaja, 1962a,b). It has been shown that tellurite can induce a thiol-dependent alteration of the erythrocyte membrane (Deuticke et al., 1992). 7.2.1.4 Heart Peking ducks fed tellurium tetrachloride in the diet (50-1000 mg Te/kg, 2-4 weeks) developed myocardial hemorrhage, hydropericardium, and cardiac muscle necrosis (Carlton and Kelly, 1967). Similar changes, including cardiac damage with hydropericardium and myocardial hemorrhage, were observed in newly hatched ducklings fed a commercial diet containing 500 mg tellurium tetrachloride per kilogram of feed for 2-4 weeks. A histopathological investigation showed

54 Tellurium

demyelination caused by the disruption of cholesterol synthesis in Schwann cells secondary to inhibition of squalene monooxygenase in weanling rats fed a diet containing 1% elemental tellurium. Similar effects have also been observed in other experiments on weanling rats (Chugh et al., 2003). Starting at postnatal day 21, weaned rats were fed a diet containing 1.1% elemental tellurium. After 7 days of tellurium treatment and at several time points after tellurium treatment had finished, the animals were processed for ultrastructural analysis, Schwann cell nuclei quantification, and teased fiber preparations. The quantitative determination of Schwann cell nuclei per transverse section of sciatic nerve showed a dramatic increase in Schwann cells after 2 days of tellurium treatment compared with control nerves. The number of Schwann cell nuclei then decreased progressively during long-term recovery (330 days after the end of tellurium treatment). Dying cells exhibited morphological features of apoptosis. Both healthy immature Schwann cells and endoneurial macrophages were involved in the phagocytosis of apoptotic Schwann cells. Other distinct biological mechanisms such as the persistence of supernumerary Schwann cells in the endoneurium and shortening of the internodal length are involved in the regulation of Schwann cell numbers during the remyelination stage (Berciano et al., 1998). Developing rats fed a diet containing 1.1% tellurium develop primary demyelination of the peripheral nerves, which is followed by a period of rapid remyelination. This demyelination, which is caused by limiting the supply of cholesterol, leads to repression of the expression of mRNA for myelin-specific proteins. Tellurium exposure was followed by an increase in total RNA [largely ribosomal RNA (rRNA)] in the sciatic nerve, which could not be accounted for by cellular proliferation. The increased concentrations of rRNA may represent a Schwann cell response to toxic insult and may relate to the increased levels of protein synthesis required during remyelination. On the other hand, steady-state levels of mRNA, determined by Northern blot analysis, for P0 and myelin basic protein were markedly decreased. Transcript levels increased during the subsequent period of remyelination and reached almost normal levels 30 days after the start of tellurium exposure. The coordinated alterations in transcript levels for myelin proteins indicate that Schwann cells can downregulate and then upregulate the synthesis of myelin in response to alterations in the supply of membrane components (Toews et al., 1990). Ingestion of tellurium can produce paralysis of the hindlimbs in weanling rats due to segmental demyelination of the sciatic nerves bilaterally. Widened endoneurial spaces, disrupted myelin sheaths, swollen

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Schwann cells, and a few instances of axonal degeneration were reported (Pun et al., 2005). The demyelination observed in young animals after tellurium intoxication is coincident with toxin-induced interference of cholesterol synthesis by Schwann cells (Jortner, 2000). 7.2.1.6  Reproductive and Developmental Effects Pregnant rats fed 500-3000 ppm tellurium in the diet developed a high incidence of hydrocephalic offspring (Mackison et al., 1981). The teratogenicity and lethality of tellurium diethyldithiocarbamate (TeDE) have been investigated in 3-day chicken embryos. TeDE had a greater toxicity with respect to the effect parameters, i.e. early deaths, late deaths of malformed embryos, late deaths of nonmalformed embryos, and malformed survivors, compared with, for example, copper and zinc acetate (Korhonen et al., 1983). The developmental toxicity of tellurium was studied in Crl Sprague-Dawley rats and New Zealand white rabbits. Groups of pregnant rats were fed a diet containing 0, 30, 300, 3000, or 15,000 ppm elemental tellurium on days 6 through 15 of gestation. Artificially inseminated rabbits were fed a diet containing 0, 17.5, 175, 1750, or 5250 ppm elemental tellurium during days 6-18 of gestation. Signs of maternal toxicity were detected in a statistically significant and dose-related manner at dietary concentrations of 300 ppm and greater in rats and of 1750 ppm and greater in rabbits. Skeletal (mainly skeletal maturational delays) and soft tissue (primarily hydrocephalus) malformations were observed in the offspring of pregnant rats exposed to the highest levels (3000 and 15,000 ppm) of tellurium. Rabbit fetuses in the highest exposure group (5250 ppm) showed slightly elevated signs of skeletal delays and nonspecific abnormalities (Johnson et al., 1988). The effects of multiple maternal subcutaneous injections of tellurium dioxide (TeO2) suspended in olive oil (0-1000 μmol/kg) from day 15 to 19 of gestation have been studied in Wistar rats. Multiple maternal injections at doses exceeding 10 μmol/kg caused a dose-related appearance of hydrocephalus, edema, exophthalmia, ocular hemorrhage, umbilical hernia, undescended testis, and small kidneys in fetuses on day 20 of gestation. At 500 μmol/kg, a reduction in maternal weight was also noted. At this level, the incidence of the anomalies mentioned previously was 100%. The 100 μmol/kg dose of Te resulted in a 100% incidence of hydrocephalus and edema without causing any apparent maternal toxic responses. Therefore, tellurium can be teratogenic to the rat fetus without causing concomitant maternal toxicity (­Perez-D’Gregorio and Miller, 1988). Tellurium, however, may induce both maternal toxicity (e.g. reduction

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in maternal weight gain) and teratogenic effects in the rat when the teratogenicity is not mediated by alterations in the diet (­Perez-D’Gregorio et al., 1988). Teratogenic effects have also been observed in Wistar rats after single maternal subcutaneous injections of 0.12 mg/kg diphenyl ditelluride diluted in canola oil at days 6, 10, or 17 of gestation. A single maternal injection at day 10 caused malformation of the forelimbs and hindlimbs, an absent or short tail, subcutaneous blood clots, exophthalmia, hydrocephalus, and an absence of the cranial bone and cutaneous tissue in fetuses on day 20 of gestation (Stangherlin et al., 2005). Effects of diphenyl ditelluride on the in vitro incorporation of 32P into intermediate filament proteins from slices of cerebral cortex of 17-day-old rats have been studied by Moretto et al. (2005). Concentrations of 1, 15, and 50 μmol/L ditelluride induced hyperphosphorylation of the high-salt/Triton-insoluble subunits, glial fibrillary acidotic protein (GFAP) and vimentin, without altering the immunocontent of these proteins. Neonatal rats were fed tellurium through the mother’s milk from the day of birth until sacrifice at 7, 14, 21, and 28 days. Investigations with light and electron microscopy revealed degeneration of Schwann cells and myelin in the sciatic nerves at each time point studied. In the central nervous system (CNS), hypomyelination of the optic nerves was convincingly demonstrated at days 14, 21, and 28 days, accompanied by some evidence of myelin degeneration. These changes were also observed in the ventral columns of the cervical spinal cords, although less markedly. There was little evidence of oligodendrocyte pathology in the CNS, and it seems that degeneration of these cells is not the primary cause of CNS hypomyelination, in contrast to the peripheral nervous system, where Schwann cell degeneration has been shown to precede the myelin pathology (Jackson et al., 1989). Tellurium damages the endothelium; crosses the vascular wall of endoneurial and perineurial vessels in weanling rats; causes perivascular edema, cytoplasmic anomalies in Schwann cells, and destruction of myelin; and apparently invades axons (Duckett, 1982). Tellurium has been found to penetrate more quickly and in larger amounts the walls of blood vessels in the sciatic nerve of weanling rats intoxicated with tellurium compared to adult rats. 7.2.1.7  Miscellaneous Biochemical Effects Rats fed sodium tellurite orally (daily doses of ≥  0.005  mg Te/kg) for 7 months showed reduced activities of catalase and free thiol groups in the blood ­(Lencenko, 1967). Similar findings have been reported by Sandrackaja (1962a,b). Other studies in rats exposed to maximum tolerable doses of 0.5 mg and 0.1 mg Te/kg

body weight showed a significant reduction in acetylcholine esterase and monoamine oxidase activities in serum and brain, as well as a significant decrease in hepatic glutathione, glutathione-S-transferase, and alkaline phosphatase in the liver and kidney (­Srivastava et al., 1983). Most tellurium(IV) derivatives can inactivate cysteine proteases, but cannot inactivate members of other protease families. This is probably an effect of the ability of Te(IV) compounds to bind to the thiol catalytic site of cysteine proteases. These findings suggest that tellurium compounds can interact with biological systems through specific chemical interactions with endogenous thiols (Cunha et al., 2009). Khayat and Dencker (1984) compared the effects of tellurium and selenium in the lung and other organs. They showed that tellurium(IV) was as effective as selenium(IV and VI; all given at a dose of 10 μmol/kg body weight) in retaining inhaled 203Hg0 (1.5 μmol/kg body weight) in the lung (probably transformed to 203Hg2+ after oxidation). Tellurium(IV) had to be given at a dose of 100 μmol/kg body weight to give the same effect. At a dose of 10 μmol Te(IV) per kg body weight, the mercury retention ratios (treated:control) were 140 for the lung and 8.6 for the whole body. The corresponding figures for Te(VI) for the doses 10, 30, and 100 μmol/kg body weight were 10, 73, and 120 (for the lung) and 3.7, 3.9, and 4.3 (for the whole body). The retention of intravenously injected 203HgCl2 was increased in a dosedependent manner by preadministration of tellurium; Te(IV) was 3-10 times more effective than Te(VI). The kidney and spleen were the dominant organs, as was the case after Se pretreatment (Khayat and Dencker, 1984). 7.2.2 Humans 7.2.2.1  Occupational Exposures Thirteen workers had suspected exposure to tellurium, possibly in the form of hydrogen telluride and tellurium dioxide dust, when working at blast furnaces where the slime of an electrolytic lead refinery was treated (Shie and Deeds, 1920). Seven of the exposed workers showed classical signs of tellurium intoxication, with symptoms such as garlic odor of the breath, sweat, and urine; and a metallic taste and dryness in the mouth. Five of the workers showed decreased sweat production, and three had dry, itchy skin, anorexia, nausea, vomiting, depression, and somnolence. Similar symptoms were reported by Steinberg et al. (1942) in iron foundry workers exposed to 0.01-0.1 mg Te/m3 for almost 2 years. Of the 98 exposed workers, garlic breath odor was found in 84 workers and garlic body (sweat) odor in 30 workers. All exposed workers (but none of the referents) showed excretion of tellurium

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in the urine. The same disease pattern developed in three laboratory workers after approximately 30 min of accidental exposure to tellurium-containing fumes (Amdur, 1947). The tellurium concentrations in urine ranged between 8 and 16 μg/L. Two cases of nonfatal intoxication after occupational exposure to tellurium vapor were reported by Popova et al. (1965). Signs and symptoms included garlic breath odor, general weakness, coughing, shivering, amnesia, pallor of the skin, and black-green discoloration of the mucosa of the tongue and nasopharynx. Both temperature and pulse rate were increased, and moderate leukopenia, neutrophilia, and leukocytosis were present. Two postgraduate chemists were hospitalized for 2 and 3 days, respectively, after accidentally inhaling tellurium hexafluoride gas when 50 g leaked from a cylinder in the laboratory (Blackadder and Manderson, 1975). Both showed typical signs and symptoms of intoxication: in particular, the stench of sour garlic was noted on the breath and from excreta. One of the subjects showed an unusual bluish-black discoloration of the webs of the fingers and streaks on the face and neck. Neither of the patients developed any signs of permanent damage, and both made a full spontaneous recovery without treatment. In a recent study from Canada (Berriault and Lightfoot, 2011) of workers at an Ontario silver refinery, logistic regression models using age at sampling, urine concentrations of tellurium, and duration of employment as predictor variables showed an association between the reporting of garlic odor and urinary tellurium concentrations. The likelihood of garlic reporting increased as workers reached urinary tellurium concentrations exceeding 1 μmol/mol creatinine. 7.2.2.2  Accidental Nonoccupational Exposure Tellurium intoxications are rare and are almost exclusively confined to occupationally exposed workers. Only a few cases of nonoccupational poisoning have been reported so far. Three cases of accidental tellurium poisoning were presented by Keall et al. (1946): patients were mistakenly given a solution of sodium tellurite instead of sodium iodide during retrograde pyelography. For two of the patients, the estimated dose was approximately 2 g (30 mg/kg). Two of the patients developed symptoms such as vomiting, renal pain, stupor, loss of consciousness, irregular breathing, and cyanosis, and died after approximately 6 h. At autopsy, all tissues emitted a strong garlic odor. A deposition of black tellurium was found in the mucosa of the bladder and of the ureter. Congestion was found in the lungs, liver, spleen, and kidney. The predominant symptoms during intoxication include loss of appetite, dryness of the mouth, suppression of sweating, a metallic taste in the mouth,

and, most notably, a sharp garlic odor of the breath, sweat, and urine. These symptoms were observed in a 37-year-old woman nonoccupationally exposed with tellurium intoxication (Muller et al., 1989). 7.2.3  Summary of Systemic Effects There are insufficient data to present a dose-response pattern for the different systemic effects reported. In humans, data are particularly sparse and are mainly confined to case reports of accidental occupational or nonoccupational exposure. In animals, long-term studies are lacking. Critical and dominant effects seem to appear in the nervous system, as described previously. An early, critical sign in peripheral neuropathy is a block in the cholesterol biosynthesis pathway, causing accumulation of squalene within the nerve, followed by the breakdown of myelin.

8  CARCINOGENICITY AND MUTAGENICITY Tellurium has not been reported to be a human or animal carcinogen. Mutagenicity studies are sparse, and more information is needed before firm conclusions can be made. Kanematsu et al. (1980) carried out recombination assays in Bacillus subtilis to check the DNA-­damaging capacity and mutagenicity of 127 metal compounds. Reverse mutation assays in Escherichia coli and Salmonella strains showed that tellurium compounds (Na2H4TeO6, Na2TeO3) were potent mutagens. More recently Tiano et al. (2000) studied the ability of three diaryl tellurides to protect trout (Salmo irideus) erythrocytes against oxidative stress, induced thermally and by varying the pH. At low concentrations (< 10 μmol/L), all three tellurides had a protective effect against DNA damage without altering the hemolysis rate. At higher concentrations, they accelerated the hemolysis rate and two of the diaryl tellurides were strongly genotoxic. There are also several reports of an anticarcinogenic effect for tellurium. Bloomer et al. (1981) found in experiments on mice that astatine-211-tellurium colloid (an alpha-emitting radiocolloid) had a curative effect versus experimental malignant ascites without causing undue toxicity to normal tissue. Similarly, in vivo experiments showed that Te significantly prolonged the survival of mice implanted with tumors (Sun et al., 1996). Experiments on cancer cell lines have indicated a protective effect by some organotellurium compounds (e.g. diaryl telluride, alkyl aryl telluride, and dialkyl telluride) (Engman et al., 1997, 2000; Powis et al., 1997; Sun et al., 1996). Two tellurium compounds, ammonium trichloro (dioxoethylene-O,Oʹ-)tellurate (or AS101) as well

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as octa-O-bis-(R,R)-tartarate ditellurane (or SAS) have shown several mechanisms of antitumor activity, e.g. inactivation of cysteine proteases such as cathepsin B, inhibition of specific tumor survival proteins, and inhibition of tumor interleukin-10 production. These findings suggest a possible anticancer therapeutic potential for this type of tellurium compound (Sredni, 2012).

9  DIAGNOSIS, PREVENTION, AND TREATMENT OF TELLURIUM POISONING Tellurium intoxications are rare and almost exclusively confined to occupationally exposed workers. There have been no reports of workers dying from exposure to tellurium or tellurium compounds. Accidental deaths have occurred, however. Two out of three patients given sodium tellurite instead of sodium iodide during retrograde pyelography died (Keall et al., 1946). Acute exposure to tellurium may cause acute respiratory irritation followed by the development of a garlicky odor of the breath and sweat. Systemic effects may include fatigue, headache, malaise, lassitude, weakness, dizziness, somnolence, alopecia, and gastritis. Chronic exposure may lead to garlic breath, a metallic taste in the mouth, decreased sweating, dryness in the mouth, fatigue, anorexia, and nausea. The skin may develop a blue-black discoloration after exposure to tellurium hexafluoride (Rumack, 2003; Yarema and Curry, 2005). The garlicky odor of the breath and sweat is an early classical sign and may also be found in urine and feces. Ingestion of small doses of sodium tellurite (1-50 μg) may cause the development of garlic odor of the breath within half an hour (De Meio, 1947). It is important to inform patients that garlic odor of breath and urine may persist for weeks or months after an exposure (Yarema and Curry, 2005). Tellurium hexafluoride is especially toxic by inhalation and may produce respiratory depression, pulmonary edema, cardiovascular collapse, and death in experimental animals (Rumack, 2003). Medical surveillance of tellurium-exposed workers should include careful skin and CNS examination, which can be followed by chest radiography, pulmonary function tests, and urine analysis. After a significant exposure to tellurium hexafluoride, arterial blood gases, or pulse oximetry can be checked and hematological parameters should also be monitored. For treatment of tellurium poisoning after oral exposure, administration of activated charcoal as a slurry (240 mL water/30 g charcoal) may be tried. The usual dose is 25-100 g in adults, 25-50 g in children (1-12 years), and 1 g/kg in infants (< 1 year).

Most cases require no treatment after inhalational exposure. As a first step, the patient should be moved to fresh air. If signs of coughing or difficulty in breathing appear, check whether the patient has developed respiratory tract irritation, bronchitis, or pneumonitis: oxygen supply and assisted ventilation may be required. Bronchospasms can be treated with β2 agonists and oral or parenteral corticosteroids (Rumack, 2003). If the eyes have been exposed, they should be irrigated with copious amounts of water for at room temperature for at least 15 min. If irritation, pain, swelling, lacrimation, or photophobia persists, the patient should be sent to a health-care facility. After dermal exposure, contaminated clothing should be removed, and the exposed area should be thoroughly washed with soap and water. If irritation or pain persists, the patient should be sent to a healthcare facility (Rumack, 2003).

10  STANDARDS: THRESHOLD LIMIT VALUES Elemental tellurium and tellurium compounds, e.g. Te dioxide and Te chloride, have a time-weighted average (TWA) of 0.1 mg/m3 from the National Institute for Occupational Safety and Health (NIOSH, 2012), a recommended exposure limit and current Occupational Safety and Health Administration (OSHA, 2012) permissible exposure limit (PEL) values. The ­American Conference of Governmental Industrial Hygienists (ACGIH, 2012) threshold limit value (TLV) and the German MAK (DFG, 2010) values are of the same level. The corresponding TWA of Te hexafluoride is 0.2 mg/m3 for ACGIH (TLV), NIOSH REL, OSHA PEL and German MAK values. The TWA for Te in dust or fume is 0.1 mg/m3 for OSHA PEL and German MAK values.

References ACGIH (American Conference of Governmental Industrial Hygienists), 2012. http://www.acgih.org/ (accessed 25.11.13). Agnew, W.F., 1972. Teratology 6, 331–337. Agnew, W.F., Cheng, J.T., 1971. Toxicol. Appl. Pharmacol. 20, 346–356. Agnew, W.F., Fauvre, F.M., Pudenz, R.H., 1968. Exp. Neurol. 21, 120–132. Alexander, J., Thomassen, Y., Aaseth, J., 1988. In: Seiler, H.G., Sigel, H., Sigel, A. (Eds.), Handbook on Toxicity of Inorganic Compounds. Marcel Dekker Inc., New York, pp. 669–674. Al-Rubaie, A.Z., Al-Jadaan, S.A.S., 2002. Appl. Organometallic Chem. 16, 649–654. Amdur, M.L., 1947. Occup. Med. 3, 386–391. Amdur, M.L., 1958. Arch. Ind. Health 17, 665–667. An, J., Zhang, Q., 1983. Int. J. Environ. Anal. Chem. 14, 73–80.

54 Tellurium Andreae, M.O., 1984. Anal. Chem. 56, 2064–2066. Beath, O.A., Eppson, H.F., Gilbert, C.S., 1935. Wyo. Agric. Exp. Stn. Bull. 206, 1–55. Berciano, M.T., Calle, E., Fernandez, R., et al., 1998. Acta Neuropathol. 95, 269–279. Berriault, C.J., Lightfoot, N.E., 2011. Occup. Med. (Lond) 61 (2), 132–135. Blackadder, E.S., Manderson, W.G., 1975. Br. J. Ind. Med. 32, 59–61. Bloomer, W.D., McLaughlin, W.H., Neirinckx, R.D., et al., 1981. Science 212 (4492), 340–341. Bouldin, T.W., Earnhardt, T.S., Goines, N.D., et al., 1989. Neurotoxicology 10, 79–89. Browning, E., 1969. In: Toxicity Ind. Metals, second ed. Butterworths, London, pp. 310–316. Carlton, W.W., Kelly, W.A., 1967. Toxicol. Appl. Pharmacol. 11, 203–214. Cerwenka Jr, E.A., Cooper, W.C., 1961. Arch. Environ. Health 3, 189–200. Chou, K.Y., Manuel, O.K., 1986. Environ. Sci. Technol. 20, 987–991. Chugh, A., Ray, A., Gupta, J.B., 2003. Prog. Lipid. Res. 42 (1), 37–50. Chung, C.H., Iwamoto, E., Yamamoto, M., et al., 1984. Spectrochim. Acta Part B 39, 459–466. Cooper, W.C. (Ed.), 1971. Tellurium. Van Nostrand Reinhold, New York. Cowgill, U.M., 1988. Biol. Trace Elem. Res. 17, 43–67. Cunha, R.L., Gouvea, I.E., Juliano, L., 2009. An. Acad. Bras. Ciênc. 81 (3), 393–407. De Meio, R.H., 1946. J. Ind. Hyg. Toxicol. 28, 229–232. De Meio, R.H., 1947. J. Ind. Hyg. Toxicol. 29 (6), 393–395. De Meio, R.H., Jetter, W.W., 1948. J. Ind. Hyg. Toxicol. 30 (1), 53–58. Deuticke, B., Lütkemeier, P., Poser, B., 1992. Biochim. Biophys. Acta 1109 (1), 97–107. DFG (Deutsche Forschungsgemeinschaft), 2010. MAK- und BATWerte-Liste 2010. Maximale Arbeitsplatzkonzentrationen und Biologische Arbeitsstofftoleranzwerte Wiley-VCH Verlag GmbH & Co.. KGaA, Weinheim, Germany. ISBN 978-3-527-32814-7. Duckett, S., 1982. Neurotoxicol 3, 63–73. Duckett, S., White, R., 1974. Brain Res. 73, 205–214. Durbin, P.W., 1960. Health Phys. 2, 225. Engman, L., Cotgreave, I., Angulo, M., et al., 1997. Anticancer Res. 17 (6D), 4599–4605. Engman, L., Kandra, T., Gallegos, A., et al., 2000. Anticancer Drug Des. 15, 323–330. Fishbein, L., 1977. Adv. Mod. Toxicol. 2, 191–240. Fishbein, L., 1991. In: Merian E., E. (Ed.), Metals and Their Compounds in the Environment. Weinheim, Germany, pp. 1211–1226. Fodor, P., Barnes, R.M., 1983. Spectrochim. Acta 38B, 229–236. Fukabori, S., Nakaaki, K., 1990. Sci. J. Labour. 65, 218–226. Geary Jr., D.L., Myers, R.C., Nachreiner, D.J., et al., 1978. Am. Ind. Hyg. Assoc. J. 39, 100–109. Goodrum, J.F., Earnhardt, T.S., Goines, N.D., et al., 1990. J. Neurochem. 55, 1928–1932. Harry, G.J., Goodrum, J.F., Bouldin, T.W., et al., 1989. J. Neurochem. 52, 938–945. Hashimoto, Y., Watanabe, K., Yumoto, K., et al., 1989. Taikiosengattkaishi 24, 45–51. Hollins, J.G., 1969. Health Phys. 17, 495–505. Huang, C., Hu, B., 2008. J. Sep. Sci. 31 (4), 760–767. ICRP (International Commission on Radiological Protection), 1968. ICRP Publ. 10, 58–64. Iyengar, G.V., Kollmer, W.E., Bowen, H.J.M., 1978. The Elemental Composition of Human Tissues and Body Fluids: a Compilation of Values for Adults. Verlag Chemie, Weinheim, New York. Izrael’son, Z.I., 1973. In: Izrael’son, Z.I., Mogilevskaja, O.J., Suvorov, S.V. (Eds.), Problems of Industrial Hygiene and Occupational Diseases in Work with Rare Metals. Medicina, Moscow, pp. 258–266 (in Russian).

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Jackson, K.F., Hammang, J.P., Worth, S.F., et al., 1989. Acta Neuropathol. (Berl) 78, 301–309. Johnson, E.M., Christian, M.S., Hoberman, A.M., et al., 1988. Fundam. Appl. Toxicol. 11, 691–702. Jortner, B.S., 2000. Toxicol. Pathol. 28 (1), 54–69. Kanematsu, N., Hara, M., Kada, T., 1980. Mutat. Res. 77, 109–116. Kaplan, M.M., Cerutti, S., Salonia, J.A., et al., 2005. J. AOAC Int. 88, 1242–1246. Keall, J.H.H., Martin, N.H., Tunbridge, R.E., 1946. Br. J. Ind. Med. 3, 175–176. Khayat, A., Dencker, L., 1984. Chem. Biol. Interact. 50, 123–133. Kimmerle, G., 1960. Arch. Toxicol. 18, 140–144. fourth ed.Kirk-Othmer Encyclopedia of Chemical Technology, vol. 1, 1997. John Wiley and Sons, New York. 1991-Present. Kobayashi, R., 2004. In: Merian, E., Anke, M., Ihnat, M., et al. (Eds.), Elements and their Compounds in the Environment, Part IV, second ed. WILEYVCH Verlag, Weinheim, Germany, pp. 1407–1414. Kobayashi, K., Imaizumi, K., 1991. Anal. Sci. 7, 447–452. Korhonen, A., Hemminki, K., Vainio, H., 1983. Teratog. Carcinog. Mutagen. 3, 163–175. Kron, T., Hansen, C., Werner, E., 1991. J. Trace Elem. Electrol. Health Dis. 5 (4), 239–244. Laden, B.P., Porter, T.D., 2001. J. Lipid Res. 42 (2), 235–240. Lee, D., Edmond, S., 1985. Nature 313, 782–785. Lencenko, V.G., 1967. Gig. Sanit. 32, 15–18 (in Russian). Lencenko, V.G., Plotko, E.G., 1969. Clinical Aspects, Pathogenesis and Prophylaxis of Occupational Diseases of Chemical Etiology in Ferrous and Non-Ferrous Metallurgy.” Part II. In: Mihailov, V.A. (Ed.), Sverdlovsk Research Institute for Industrial Hygiene and Occupational Diseases. Sverdlovsk, pp. 137–147 (in Russian). Lewis, R.J., 1996. nineth ed. Sax’s Dangerous Properties of Industrial Materials, vols. 1-3, Van Nostrand Reinhold, New York. Lockwood, T.H., Limtiaco, L.P., 1975. Am. Ind. Hyg. Assoc. J. 36, 57–62. Mackison, F.W., Stricoff, R.S., Partridge Jr, L.J. (Eds.), 1981. NIOSH/ OSHA—Occupational Health Guidelines for Chemical Hazards. “DHHS (NIOSH) Publication No. 81-123 (3 Vols.). U.S. Government Printing Office, Washington, DC. Morell, P., Toews, A.D., Wagner, M., et al., 1994. Neurotoxicology 15, 171–180. Moretto, M.B., Funchal, C., Zeni, G., et al., 2005. Toxicology 210, 213–222. Muller, R., Zschiesche, W., Steffen, H.M., et al., 1989. Klin. ­Wochenschr. 67, 1152–1155. Nakaaki, K., Fukabori, S., 1990. J. Lab. Sci. 65, 353–360. Nason, A.P., Schroeder, H.A., 1967a. J. Chron. Dis. 20, 199–210. Nason, A.P., Schroeder, H.A., 1967b. J. Chronic. Dis. 20, 671. NIOSH (National Institute for Occupational Safety and Health), 2012. http://www.cdc.gov/niosh/ (accessed 25.11.13). Ogra, Y., 2009. Anal. Sci. 25 (10), 1189–1195. O’Neil, M.J. (Ed.), 2001. The Merck Index—An Encyclopedia of Chemicals, Drugs and Biologicals. , thirteenth ed.Merck and Co., Inc., Whitehouse Station, NJ. OSHA (Occupational Safety and Health Administration, U.S. Department of Labor), 2012. http://www.osha.gov/ (accessed 25.11.13). Perez-D’Gregorio, R.E., Miller, R.K., 1988. Teratology 37, 307–316. Perez-D’Gregorio, R.E., Miller, R.K., Baggs, R.B., 1988. Reprod. Toxicol. 2, 55–61. Popova, T.B., Ryzkova, M.N., Glotova, K.V., 1965. In: Letavet, A.A. (Ed.), Occupational Diseases in Chemical Industry. Medicina, Moscow, pp. 246–250 (in Russian). Powis, G., Gasdaska, J.R., Gasdaska, P.Y., et al., 1997. Oncol. Res. 9 (6-7), 303–312. Pun, T.W., Odrobina, E., Xu, Q.G., et al., 2005. J. Peripher. Nerv. System 10 (1), 38–46.

1228

Lars Gerhardsson

Rumack, B.H., 2003. “POISINDEX(R) Information System.” CCIS Volume 116, edition exp May, 2003. In: Hall, A.H., Rumack, B.H. (Eds.). Micromedex, Inc., Englewood, CO. Sandrackaja, S.E., 1962a. Experimental Studies of the Characteristics of Tellurium as an Industrial Poison. First Moscow Medical Institute, Moscow. Russia (in Russian). Sandrackaja, S.E., 1962b. Gig. Tr. Prof. Zabol. 2, 44–50 (in Russian). Schramel, P., Wendler, I., Angerer, J., 1997. Int. Arch. Occup. Environ. Health 69, 219–223. Schroeder, H.A., Buckman, J., Balassa, J.J., 1967. J. Chronic Dis. 20, 147–161. Scott, D.R., Loseke, W.A., Holboke, L.E., et al., 1976. Appl. Spectrosc. 30, 392–405. Seljankina, K.P., Alekseeva, L.S., 1971. Gig. Sanit. 35, 95–96 (in Russian). Shie, M.D., Deeds, F.E., 1920. Public Health Rep. 35, 939–954. Siddik, Z.H., Newman, R.A., 1988. Anal. Biochem. 172, 190–196. Slouka, V., 1970. Sb. Ved. Pr. Lek. Fak. Karlovy Univ. Hradci Kralove 47. 3–19 (in Czech). Slouka, V., Hradil, J., 1970. Sb. Ved. Pr. Lek. Fak. Karlovy Univ. ­Hradci Kralove 47. 21–43 (in Czech). Smialek, M., Gajkowska, B., Otrebska, D., 1994. J. Hirnforsch. 35 (2), 223–232. Sredni, B., 2012. Semin. Cancer Biol. 22 (1), 60–69. Srivastava, R.C., Srivastava, R., Srivastava, T.N., et al., 1983. Toxicol. Lett. 16, 311–316. Stangherlin, E.C., Favero, A.M., Zeni, G., et al., 2005. Toxicology 207, 231–239. Steinberg, H.H., Massari, S.C., Miner, A.C., et al., 1942. J. Ind. Hyg. 29, 183–191.

Sugimura, Y., Suzuki, Y., 1981. Pap. Meteorol. Geophys. 32, 163–165. Sun, X., Wong, J.R., Song, K., et al., 1996. Clin. Cancer Res. 2, 1335–1340. Taylor, A., 1996. Biol. Trace Elem. Res. 55 (3), 231–239. Tiano, L., Fedeli, D., Santroni, A.M., et al., 2000. Mutat. Res. 464, 269–277. Toews, A.D., Lee, S.Y., Popko, B., et al., 1990. J. Neurosci. Res. 26, 501–507. USGS (U.S. Geological Survey), 2004. Minerals Yearbook, Selenium and Tellurium. http://minerals.usgs.gov/minerals/pubs/ commodity/selenium/selenmyb04.pdf (accessed 25.11.13). USGS, 2008. Mineral Commodity Summaries. Available at http:/ /minerals.usgs.gov/minerals/pubs/commodity/selenium/ mcs-2008-tellu.pdf (accessed 25.11.13). Valkonen, S., Savolainen, H., 1985. Bull. Environ. Contam. Toxicol. 34, 170–174. van Montfort, P.F.E., Agterdenbos, J., Jütte, B.A.H.G., 1979. Anal. Chem. 51, 1553–1557. Van Vleet, J.F., Ferrans, V.J., 1982. Am. J. Vet. Res. 43, 2000–2009. Welz, B., Sperling, M., 1999. Atomic Absorption Spectrometry, third completely revised edition. Wiley-VCH, Weinheim, New York. 558–559. Wright, P.L., Bell, M.C., 1966. Am. J. Physiol. 211, 6–10. Yarema, M.C., Curry, S.C., 2005. Pediatrics 116, e319–321. Yu, M.Q., Liu, G.Q., Jin, Q., 1983. Talanta 30, 57–62. Yu, C., Cai, Q., Guo, Z.X., et al., 2003. Anal., Bioanal. Chem. 376 (2), 236–242.