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Exposure to metals that have recently come into use
The Science of the Total Environment, 120 (1992) 85-91 Elsevier Science Publishers B.V., Amsterdam
85
Exposure to metals that have recently come into use G. Scansetti Department of Traumatology Orthopaedy and Occupational Health, Turin University, Via Zuretti 29, 10126 Turin, Italy
ABSTRACT The possibility of deriving normal biological values for some rare metals is investigated. The metals under study are gallium, germanium, indium, niobium and tellurium, i.e. a group of metals with increasing utilization in the electronics industry. So far some data are unavailable for some of the elements, e.g. daily intake, oral absorption and half-life time for gallium, and body burden for gallium and germanium. Reliable values of blood concentration are available only for gallium, niobium and tellurium. The problem related to a proposed urinary biological limit value for tellurium is also discussed.
Key words: gallium; germamium; niobium; tellurium; reference values; literature data
INTRODUCTION
The semantics of metals includes many expressions of different origin and age, some of which are, by now, historical or quite obsolete. Metals were named essential, heavy, hard, light, noble, toxic, in traces, rare, etc. There are 28 rare metals and 15 rare-earth metals, thus giving a total of 43, 5 of which are taken into account because they share the property of being used in the electronic industry. Gallium and germanium (Table 1) have been named after the country of their discoverer, tellurium after the Latin word tellus (earth). The name indium derives from indigo, because this element, when spectroscopically examined, shows a brilliant line in the dark blue region. In Europe, niobium derives from Niobe, the daughter of Tantalus, after whom the brother element tantalum was named [1]. Gallium is liquid at room temperature (its melting point, 29 7714°C, is a thermometric standard), and is more dense in the liquid than in the solid form. Germanium, indium and tellurium have some biological application, mainly in diagnostics and in cancer therapy. The concentration in the earth's crust ranges from 10 ppb (tellurium) to nearly 20-25 ppm (gallium; niobium) (Table 2). World production does not
86
G. SCANSETTI
TABLE 1 Nomenclature Name's origin
Relevant physical properties
Biological application
Gallium Ga
Country of discoverer
Liquid-more dense as a liquid than as a solid
Citrate: diagnostic nitrate, chloride: cancer therapy
Germanium Ge
Country of discoverer
Lustrous: brittle
Spirogermaniun: cancer therapy
Indium In
Indigo. The colour of the brilliant spectroscopic line of In
Ductile
Organ scanning cancer therapy
Niobium Nb
Niobe, the daughter of Tantalus who named the brother element tantalum
Lustrous
Tellurium Te
Tellus = earth
Lustrous
Tellurite: diptheria diagnostic immunomodulator
follow the same scale, being some 10 t/y in the case of gallium, germanium and indium, and 500 and 10.300 t/y for tellurium and niobium, respectively. Gallium and indium are used (Table 3) in the electronics industry in the form of similar compounds, i.e. arsenides and antimonides, whereas germanium, the transistor's father, is used as mono-crystal. The use of the metal
TABLE 2 Abundance
Ga Ge In Nb Te
Earth crust, ppm
World production, t/y
10-20 1.5-7 0.1 19-24 0.01
14-16 30-80 50 10.300 500
87
EXPOSURE TO METALS RECENTLY COME INTO USE
TABLE 3 Main use Ga
Ge
In
Nb
Te
Semiconductors Semiconductors Semiconductors (GaAs,GaSb) (InAs,InSb,InP)
Semiconductors (solar cells)
Glass sealing
Glass of high Glass sealing refractive index alloys
Colouring glass and ceramic
Fluorescent lamps
Phosphors
'Day light" lamps
Calibration of thermometers
High temperature alloys
Lead hardener
Hard metals
Vulcanization of rubber
Corrosion inhibitor in alloys
In/Ag brazing alloys
IR optics
IR detectors
Fiber optics
Corrosion inhibitor
Catalyst
Low melting safety devices
Catalyst
In/Ag/Cd alloys Permanent in nuclear magnet alloys reactor control rods
To produce radioactive iodine
tellurium in rubber compounding is unusual but relevant: it acts as an accelerator in vulcanizing and as an anti-aging agent in the final product. Tellurium is also used in nuclear reactors to produce I ~31 whereas indium is contained in special alloys used for control rods in the same industry. As can be seen from Table 4, the data on biological availability still shows some gaps of knowledge. Gallium, in spite of its extensive biological application as a nitrate and chloride in cancer therapy, was chiefly studied as GaAs, the c o m p o u n d more commonly used in the electronics industry. Interest was focused on the possibility of As release in biological media and to the related consequences. The daily intake of indium in the diet may be regarded as minimal, traces being sometimes undiscovered even by analytical means. The available
88
G. SCANSETTI
TABLE 4 Biological availability Daily intake mg
Ga
Oral absorption %
Half-life time
Body burden ppm
(slow)
(short)
(bone)
1.5 days 2 weeks/ 2 months 4 months 3 weeks
Ge In
0.4-1.5 0.008-0.01
96 0.1-2
Nb Te
0.62 0.6
0.01-2 25
less than 0.05 (kidney) 1.6 (bone) 0.12 (bone)
values for the other metals range between 0.4 and 1.5 mg/day. Oral uptake is probably the sole route of entry for germanium, and for 25% of tellurium. Minimal amounts of indium and niobium are absorbed when administered by the oral route. Half-life times rank in the same order, being short for germanium (1.5 days) and medium (weeks or months) for indium, niobium and tellurium. The body burden of indium, < 50 ppm, is related to its minimal uptake through the oral route. Gallium, niobium and tellurium accumulate mainly in bone, indium in the kidney. Balance studies published by the International Commission for Radiological Protection [2] (Table 5) indicate urine as the main route for germanium and tellurium excretion. The latter shows also some elimination through the expired air as volatile telluride (approximately 1.5%), which accounts for the garlic odour of the breath of exposed people. Some toxicological information is listed in Table 6. Gallium and niobium toxicity is low. Germanium chloride and fluoride are highly irritant to the
TABLE 5 Losses for reference man, % (rag/day) (see Ref. 2)
Ge Nb Te
Urine
Feces
Expired air
93.33 (1.4) 58 (0.36) 82.8 (0.53)
6.66 (0.1) 42 (0.26) 15.6 (0.1)
1.56 (0.01)
89
EXPOSURE TO METALS RECENTLY COME INTO USE
TABLE 6 Toxicity Ga
Ge
In
Low
GeC14, GeF4: highly irritant for eyes, skin, airways
InCl3:Nephro- Low toxicity inhibition of Carciovascular ALA-D, ALA-S effects
G-cH4 Hemolytic
Colloidal In: hepatotoxicity
Salts: may irritate skin or mucous membranes
Nb
Te Te < tellurates < tellurites < tellurides Airways irritant
Liver changes Sweating suppressor
Nephrotoxicity In(NO3)3: embryotoxicity
GaF 3 A case of radial nerve paresis (skin absorption)
Digestion disturbances, garlic odour (breath), sonnolence H2Te: Hemolysis pneumonia Embryotoxicity TeC14: reduced growth
eyes, skin a n d airways. T h e r e is some c o n c e r n o v e r the e m b r y o t o x i c i t y o f ind i u m a n d tellurium in animal experiments, the f o r m e r (as nitrate) giving rise to m a l f o r m a t i o n s o f the limbs in h a m s t e r s [3], the latter (as metal) inducing h y d r o c e p h a l u s in rats [4]. I n d i u m chloride is n e p h r o t o x i c , whereas colloidal i n d i u m is h e p a t o t o x i c . This metal also inhibits A L A - D and A L A - S , with
TABLE 7 Blood concentration
Ga Nb Te
g/1 (10 -6)
n
Method
Reference
3 4 4.7 0.2-0.3
48 31 85 7
MS MS MS AES
5 5 5 6
90
G. SCANSETTI
possible consequences in heme metabolism resembling the similar and well known effect of lead. Tellurium toxicity increases when proceeding from the element to tellurates, tellurites and tellurides, hydrogen telluride being the most toxic compound. Tellurium in also a sweating suppressor. LITERATURE DATA ON REFERENCE VALUES
Information on the concentration of these five metals in biological media more easily available for monitoring of internal exposure, i.e. blood and urine, has been scarcely studied and poorly documented. Available data often concern few or single subjects. Moreover, the data were obtained some 20-30 years ago and thus are based on analytical procedures which are no longer acceptable today, such as colorimetric methods. Such values should be disregarded since they exceed the predictable values by some orders of magnitude. Table 7 lists blood concentration values for gallium, niobium and tellurium, as obtained in reliable samples utilizing MS and AES methods [5,6]. Tellurium blood concentration is lower than gallium and niobium concentrations by one order of magnitude or more. There are no reliable urine concentration values available for the five metals, although a biological limit value of 0.05 mg/1 was proposed for urinary tellurium [7]. However, as already mentioned, this problem is far from being resolved, because of the garlic odour of breath, sweat, urine and body of exposed people. At present ambient air TLV-TWA (0.1 mg/m 3 Te) gives rise to the unavoidable garlic odour, due to di-methyl telluride excretion. As already noted by Gmelin [8], and more recently by Einbrodt and Michels [10], it is a social problem. This was also reported by Hamilton and Hardy I11], the latter having been asked for counselling by a group of male exposed workers who complained of no longer being kissed by their wives because of the garlic smell of their breath. Garlic odour from di-methyl telluride is one of the examples of the nuisance factors which should be taken into account when establishing ambient air limit values. Only the lowering of the TLV-TWA for tellurium from the present value of 0.1 mg/m 3, to 0.01 mg/m 3 will avoid this annoyance. REFERENCES G.P. McCord and S.J. Baylis, The origin of the names of elemental metals. JOM, 15 (1973) 531-534. International Commission for Radiological Protection, in W.S. Snyder, M.J. Cook, E.S. Nasset, L.R. Karkausen, G, Parvy Howells and I.H. Tipton (Eds.), Report of the Task Group on Reference Man, ICRP Rep. No. 23, Pergamon Press, Oxford, 1975, pp. 365-418.
EXPOSURE TO METALS RECENTLY COME INTO USE
91
3 U.H. Ferm and S.J. Carpenter, Teratogenic and embryopathic effects of indium, gallium and germanium. Toxicol. Appl. Pharmacol., 16 (1970) 166-170. 4 L. Fishbein, Toxicology of selenium and tellurium, in R.A. Goyer and M.A. Mehlman (Eds.), Toxicology of Trace Elements, Hemisphere, Washington, 1977, pp. 191-240. 5 E.J. Hamilton, N.J. Minski and J.J. Cleary, The concentration and distribution of some stable elements in healthy human tissues from United Kingdom. Sci. Tot. Environ., 1 (1972/73) 341-374. 6 P.F.E. Van Montfort, J. Agterdenbos and B.A.H.G., Jute, Determination of antimony and tellurium in human blood by microwave induced emission spectrometry, Anal. Chem., 51 (1979) 1552-1557. 7 J.R. Glover, Tellurium and compounds, in L. Parmeggiani (Ed.), Encyclopaedia of Occupational Health and Safety, 3rd edn, ILO, Geneva, 1983, pp. 2156-2157. 8 C. Gmelin, (1824): cited in Hunter D. (1955). 9 D. Hunter, The Diseases of Occupations. English University Press, London, 1955, pp. 436-438. 10 H.J. Einbrodt and S. Michels, Tellur, in E. Merian (Ed.), MetaUe in der Umwelt, Verlag Chemie, Weinheim, 1984, pp. 561-569. 11 A. Hamilton and H.L. Hardy, Industrial Toxicology. Science Group, Acton, 1974, pp. 173-174.
85
Exposure to metals that have recently come into use G. Scansetti Department of Traumatology Orthopaedy and Occupational Health, Turin University, Via Zuretti 29, 10126 Turin, Italy
ABSTRACT The possibility of deriving normal biological values for some rare metals is investigated. The metals under study are gallium, germanium, indium, niobium and tellurium, i.e. a group of metals with increasing utilization in the electronics industry. So far some data are unavailable for some of the elements, e.g. daily intake, oral absorption and half-life time for gallium, and body burden for gallium and germanium. Reliable values of blood concentration are available only for gallium, niobium and tellurium. The problem related to a proposed urinary biological limit value for tellurium is also discussed.
Key words: gallium; germamium; niobium; tellurium; reference values; literature data
INTRODUCTION
The semantics of metals includes many expressions of different origin and age, some of which are, by now, historical or quite obsolete. Metals were named essential, heavy, hard, light, noble, toxic, in traces, rare, etc. There are 28 rare metals and 15 rare-earth metals, thus giving a total of 43, 5 of which are taken into account because they share the property of being used in the electronic industry. Gallium and germanium (Table 1) have been named after the country of their discoverer, tellurium after the Latin word tellus (earth). The name indium derives from indigo, because this element, when spectroscopically examined, shows a brilliant line in the dark blue region. In Europe, niobium derives from Niobe, the daughter of Tantalus, after whom the brother element tantalum was named [1]. Gallium is liquid at room temperature (its melting point, 29 7714°C, is a thermometric standard), and is more dense in the liquid than in the solid form. Germanium, indium and tellurium have some biological application, mainly in diagnostics and in cancer therapy. The concentration in the earth's crust ranges from 10 ppb (tellurium) to nearly 20-25 ppm (gallium; niobium) (Table 2). World production does not
86
G. SCANSETTI
TABLE 1 Nomenclature Name's origin
Relevant physical properties
Biological application
Gallium Ga
Country of discoverer
Liquid-more dense as a liquid than as a solid
Citrate: diagnostic nitrate, chloride: cancer therapy
Germanium Ge
Country of discoverer
Lustrous: brittle
Spirogermaniun: cancer therapy
Indium In
Indigo. The colour of the brilliant spectroscopic line of In
Ductile
Organ scanning cancer therapy
Niobium Nb
Niobe, the daughter of Tantalus who named the brother element tantalum
Lustrous
Tellurium Te
Tellus = earth
Lustrous
Tellurite: diptheria diagnostic immunomodulator
follow the same scale, being some 10 t/y in the case of gallium, germanium and indium, and 500 and 10.300 t/y for tellurium and niobium, respectively. Gallium and indium are used (Table 3) in the electronics industry in the form of similar compounds, i.e. arsenides and antimonides, whereas germanium, the transistor's father, is used as mono-crystal. The use of the metal
TABLE 2 Abundance
Ga Ge In Nb Te
Earth crust, ppm
World production, t/y
10-20 1.5-7 0.1 19-24 0.01
14-16 30-80 50 10.300 500
87
EXPOSURE TO METALS RECENTLY COME INTO USE
TABLE 3 Main use Ga
Ge
In
Nb
Te
Semiconductors Semiconductors Semiconductors (GaAs,GaSb) (InAs,InSb,InP)
Semiconductors (solar cells)
Glass sealing
Glass of high Glass sealing refractive index alloys
Colouring glass and ceramic
Fluorescent lamps
Phosphors
'Day light" lamps
Calibration of thermometers
High temperature alloys
Lead hardener
Hard metals
Vulcanization of rubber
Corrosion inhibitor in alloys
In/Ag brazing alloys
IR optics
IR detectors
Fiber optics
Corrosion inhibitor
Catalyst
Low melting safety devices
Catalyst
In/Ag/Cd alloys Permanent in nuclear magnet alloys reactor control rods
To produce radioactive iodine
tellurium in rubber compounding is unusual but relevant: it acts as an accelerator in vulcanizing and as an anti-aging agent in the final product. Tellurium is also used in nuclear reactors to produce I ~31 whereas indium is contained in special alloys used for control rods in the same industry. As can be seen from Table 4, the data on biological availability still shows some gaps of knowledge. Gallium, in spite of its extensive biological application as a nitrate and chloride in cancer therapy, was chiefly studied as GaAs, the c o m p o u n d more commonly used in the electronics industry. Interest was focused on the possibility of As release in biological media and to the related consequences. The daily intake of indium in the diet may be regarded as minimal, traces being sometimes undiscovered even by analytical means. The available
88
G. SCANSETTI
TABLE 4 Biological availability Daily intake mg
Ga
Oral absorption %
Half-life time
Body burden ppm
(slow)
(short)
(bone)
1.5 days 2 weeks/ 2 months 4 months 3 weeks
Ge In
0.4-1.5 0.008-0.01
96 0.1-2
Nb Te
0.62 0.6
0.01-2 25
less than 0.05 (kidney) 1.6 (bone) 0.12 (bone)
values for the other metals range between 0.4 and 1.5 mg/day. Oral uptake is probably the sole route of entry for germanium, and for 25% of tellurium. Minimal amounts of indium and niobium are absorbed when administered by the oral route. Half-life times rank in the same order, being short for germanium (1.5 days) and medium (weeks or months) for indium, niobium and tellurium. The body burden of indium, < 50 ppm, is related to its minimal uptake through the oral route. Gallium, niobium and tellurium accumulate mainly in bone, indium in the kidney. Balance studies published by the International Commission for Radiological Protection [2] (Table 5) indicate urine as the main route for germanium and tellurium excretion. The latter shows also some elimination through the expired air as volatile telluride (approximately 1.5%), which accounts for the garlic odour of the breath of exposed people. Some toxicological information is listed in Table 6. Gallium and niobium toxicity is low. Germanium chloride and fluoride are highly irritant to the
TABLE 5 Losses for reference man, % (rag/day) (see Ref. 2)
Ge Nb Te
Urine
Feces
Expired air
93.33 (1.4) 58 (0.36) 82.8 (0.53)
6.66 (0.1) 42 (0.26) 15.6 (0.1)
1.56 (0.01)
89
EXPOSURE TO METALS RECENTLY COME INTO USE
TABLE 6 Toxicity Ga
Ge
In
Low
GeC14, GeF4: highly irritant for eyes, skin, airways
InCl3:Nephro- Low toxicity inhibition of Carciovascular ALA-D, ALA-S effects
G-cH4 Hemolytic
Colloidal In: hepatotoxicity
Salts: may irritate skin or mucous membranes
Nb
Te Te < tellurates < tellurites < tellurides Airways irritant
Liver changes Sweating suppressor
Nephrotoxicity In(NO3)3: embryotoxicity
GaF 3 A case of radial nerve paresis (skin absorption)
Digestion disturbances, garlic odour (breath), sonnolence H2Te: Hemolysis pneumonia Embryotoxicity TeC14: reduced growth
eyes, skin a n d airways. T h e r e is some c o n c e r n o v e r the e m b r y o t o x i c i t y o f ind i u m a n d tellurium in animal experiments, the f o r m e r (as nitrate) giving rise to m a l f o r m a t i o n s o f the limbs in h a m s t e r s [3], the latter (as metal) inducing h y d r o c e p h a l u s in rats [4]. I n d i u m chloride is n e p h r o t o x i c , whereas colloidal i n d i u m is h e p a t o t o x i c . This metal also inhibits A L A - D and A L A - S , with
TABLE 7 Blood concentration
Ga Nb Te
g/1 (10 -6)
n
Method
Reference
3 4 4.7 0.2-0.3
48 31 85 7
MS MS MS AES
5 5 5 6
90
G. SCANSETTI
possible consequences in heme metabolism resembling the similar and well known effect of lead. Tellurium toxicity increases when proceeding from the element to tellurates, tellurites and tellurides, hydrogen telluride being the most toxic compound. Tellurium in also a sweating suppressor. LITERATURE DATA ON REFERENCE VALUES
Information on the concentration of these five metals in biological media more easily available for monitoring of internal exposure, i.e. blood and urine, has been scarcely studied and poorly documented. Available data often concern few or single subjects. Moreover, the data were obtained some 20-30 years ago and thus are based on analytical procedures which are no longer acceptable today, such as colorimetric methods. Such values should be disregarded since they exceed the predictable values by some orders of magnitude. Table 7 lists blood concentration values for gallium, niobium and tellurium, as obtained in reliable samples utilizing MS and AES methods [5,6]. Tellurium blood concentration is lower than gallium and niobium concentrations by one order of magnitude or more. There are no reliable urine concentration values available for the five metals, although a biological limit value of 0.05 mg/1 was proposed for urinary tellurium [7]. However, as already mentioned, this problem is far from being resolved, because of the garlic odour of breath, sweat, urine and body of exposed people. At present ambient air TLV-TWA (0.1 mg/m 3 Te) gives rise to the unavoidable garlic odour, due to di-methyl telluride excretion. As already noted by Gmelin [8], and more recently by Einbrodt and Michels [10], it is a social problem. This was also reported by Hamilton and Hardy I11], the latter having been asked for counselling by a group of male exposed workers who complained of no longer being kissed by their wives because of the garlic smell of their breath. Garlic odour from di-methyl telluride is one of the examples of the nuisance factors which should be taken into account when establishing ambient air limit values. Only the lowering of the TLV-TWA for tellurium from the present value of 0.1 mg/m 3, to 0.01 mg/m 3 will avoid this annoyance. REFERENCES G.P. McCord and S.J. Baylis, The origin of the names of elemental metals. JOM, 15 (1973) 531-534. International Commission for Radiological Protection, in W.S. Snyder, M.J. Cook, E.S. Nasset, L.R. Karkausen, G, Parvy Howells and I.H. Tipton (Eds.), Report of the Task Group on Reference Man, ICRP Rep. No. 23, Pergamon Press, Oxford, 1975, pp. 365-418.
EXPOSURE TO METALS RECENTLY COME INTO USE
91
3 U.H. Ferm and S.J. Carpenter, Teratogenic and embryopathic effects of indium, gallium and germanium. Toxicol. Appl. Pharmacol., 16 (1970) 166-170. 4 L. Fishbein, Toxicology of selenium and tellurium, in R.A. Goyer and M.A. Mehlman (Eds.), Toxicology of Trace Elements, Hemisphere, Washington, 1977, pp. 191-240. 5 E.J. Hamilton, N.J. Minski and J.J. Cleary, The concentration and distribution of some stable elements in healthy human tissues from United Kingdom. Sci. Tot. Environ., 1 (1972/73) 341-374. 6 P.F.E. Van Montfort, J. Agterdenbos and B.A.H.G., Jute, Determination of antimony and tellurium in human blood by microwave induced emission spectrometry, Anal. Chem., 51 (1979) 1552-1557. 7 J.R. Glover, Tellurium and compounds, in L. Parmeggiani (Ed.), Encyclopaedia of Occupational Health and Safety, 3rd edn, ILO, Geneva, 1983, pp. 2156-2157. 8 C. Gmelin, (1824): cited in Hunter D. (1955). 9 D. Hunter, The Diseases of Occupations. English University Press, London, 1955, pp. 436-438. 10 H.J. Einbrodt and S. Michels, Tellur, in E. Merian (Ed.), MetaUe in der Umwelt, Verlag Chemie, Weinheim, 1984, pp. 561-569. 11 A. Hamilton and H.L. Hardy, Industrial Toxicology. Science Group, Acton, 1974, pp. 173-174.