UKPID MONOGRAPH TELLURIUM HEXAFLUORIDE WN Harrison PhD CChem MRSC SM Bradberry BSc MB MRCP S Meacham BSc JA Vale MD FRCP FRCPE FRCPG FFOM National Poisons Information Service (Birmingham Centre), West Midlands Poisons Unit, City Hospital NHS Trust, Dudley Road, Birmingham B18 7QH This monograph has been produced by staff of a National Poisons Information Service Centre in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Peer review group: Directors of the UK National Poisons Information Service. TELLURIUM HEXAFLUORIDE Toxbase summary Type of product Tellurium hexafluoride is a gas at room temperature and is used as a chemical reagent. Toxicity Acute poisoning is rare. Due to its gaseous nature, inhalation and topical exposure are most likely. Ingestion has not been reported. Features Topical - Irritant to skin and eyes. - May cause dermal discolouration. Inhalation - A garlic odour to the breath, sweat and urine is characteristic of tellurium exposure. - A metallic taste, nausea, loss of appetite, tiredness, reduced sweating and unspecified ECG changes have been reported. - May cause respiratory tract irritation, although reports of significant pulmonary toxicity are rare. Management Dermal 1. If possible the patient should remove soiled clothing and wash him/herself. 2. Wash contaminated hair and skin with soap and copious amounts of water. 3. Pay special attention to skin folds, fingernails and ears. Ocular 1. Immediately irrigate the affected eye thoroughly with tepid water or 0.9 per cent saline for at least 10-15 minutes. 2. Any particles lodged in the conjunctival recesses should be removed. 3. Continue irrigation with saline infusion using drip tubing. 4. Repeated instillation of local anaesthetic may reduce discomfort and help more thorough decontamination. 5. Corneal damage may be detected by instillation of fluorescein. 6. Patients with corneal damage and those whose symptoms do not resolve rapidly should be referred for ophthalmological assessment. Inhalation 1. Remove from exposure 2. Treat symptomatically and supportively. 3. If symptoms occur perform a chest X-ray, ECG, biochemical and haematological profiles. 4. Collect urine and blood for tellurium concentration measurements to confirm diagnosis although these assays are not widely available. Check with NPIS. 5. It has been suggested that ascorbic acid may reduce the garlic odour from tellurium intoxication (De Meio, 1947) but this has not been confirmed. 6. Dimercaprol increases tellurium toxicity and should not be used. References Blackadder ES, Manderson WG. Occupational absorption of tellurium: a report of two cases. Br J Ind Med 1975; 32: 59-61. De Meio RH. Tellurium. II. Effect of ascorbic acid on the tellurium breath. J Ind Hyg Toxicol 1947; 29: 393-5. Kron T, Hansen C, Werner E. Renal excretion of tellurium after peroral administration of tellurium in different forms to healthy human volunteers. J Trace Elem Electrolytes Health Dis 1991; 5: 239-44. Müller R, Zschiesche W, Steffen HM, Schaller KH. Tellurium-intoxication. Klin Wochenschr 1989; 67: 1152-5. Substance name Tellurium hexafluoride Origin of substance Prepared by direct fluorination of tellurium metal. (MERCK, 1996) Synonyms Tellurium fluoride (NIOSH, 1997) Chemical group A compound of tellurium, a group VI A element. Reference numbers CAS 7783-80-4 (DOSE, 1994) RTECS WY2800000 (RTECS, 1997) UN 2195 (DOSE, 1994) HAZCHEM CODE NIF Physicochemical properties Chemical structure TeF6 (DOSE, 1994) Molecular weight 241.59 (DOSE, 1994) Physical state at room temperature Gas (SAX'S, 1996) Colour Colourless (SAX'S, 1996) Odour Repulsive (SAX'S, 1996) Viscosity NIF pH NIF Solubility Slowly absorbed by water. (MERCK, 1996) Autoignition temperature NIF Chemical interactions Corrodes mercury. Hydrolyzed by aqueous potassium hydroxide. (MERCK, 1996) Major products of combustion Fumes of fluoride and tellurium. (SAX'S, 1996) Explosive limits NA Flammability Nonflammable gas (NIOSH, 1997) Boiling point Sublimes at -38.9°C (SAX'S, 1996) Density 4.006 at -191°C (solid); 2.499 at -10°C (liquid) (SAX'S, 1996) Vapour pressure NIF Relative vapour density 8.3 (Air = 1 at boiling point of tellurium hexafluoride) (HSDB, 1997) Flash point NA Reactivity Hydrolyzed by water to telluric acid, H6TeO6. (MERCK, 1996) Uses A chemical reagent. Hazard/risk classification NIF INTRODUCTION Tellurium hexafluoride is a hexavalent compound of tellurium. It is a gas at room temperature and so exposure is mainly dermal, ocular and via inhalation. Tellurium exposure is characterized by a distinctive garlic odour which is due to formation of the hepatic metabolite dimethyl telluride. EPIDEMIOLOGY Tellurium hexafluoride poisoning is rare. Only occupational exposure has been reported (Blackadder and Manderson, 1975). MECHANISMS OF TOXICITY There are few data on the mechanism of toxicity of tellurium or its compounds. Animal studies suggest tellurium may affect the conversion of squalene to cholesterol so interfering with neurotransmission via demyelination (Gerhardsson et al, 1986). Impaired secretory nerve neurotransmission is the proposed mechanism of impaired saliva and sweat secretion in humans and of reduced gastric acid secretion in animals poisoned with tellurium (Shie and Deeds, 1920). There is some evidence that the aroma of fresh garlic is caused by a high tellurium content. This may contribute to garlic's cholesterol-lowering properties (Larner, 1995). In vitro studies demonstrate that tellurite (Te4+) ions can penetrate the erythrocyte membrane and, in the presence of reduced glutathione, form telluride (Te2+) which causes irreversible membrane damage and hence haemolysis (De Meio and O'Leary, 1975; Kurantsin- Mills et al, 1988). Tellurate (Te6+) ions do not penetrate the erythrocyte membrane. Haemolysis has been observed in animals poisoned with tellurium (Shie and Deeds, 1920) but not as a feature of tellurium intoxication in man. TOXICOKINETICS Absorption Two male research chemists developed characteristic features of systemic tellurium intoxication from inhalation of tellurium hexafluoride gas (Blackadder and Manderson, 1975). Tellurium dusts and fumes can be absorbed via the lung. Workers exposed to tellurium concentrations up to 0.1 mg/m3 had urine tellurium concentrations up to 0.06 mg/L (Steinberg et al, 1942). The mean (± SD) gastrointestinal absorption in healthy volunteers ingesting between 15 and 57 µg has been estimated as ten per cent (± 4 per cent) for elemental tellurium, 23 per cent (± 9 per cent) for tellurate and 21.5 per cent (no SD given) for tellurite (Kron et al, 1991). Ingestion of 0.5 µg tellurium oxide produced a garlic breath odour within 75 minutes which lasted for 30 hours (Reisert, 1884). Organometallic complexes of tellurium and soluble tellurium salts can be absorbed through the skin (Blackadder and Manderson, 1975). Distribution Tellurium is distributed widely with high concentrations particularly in kidneys, liver, bone, brain and testes (Meditext, 1997). Excretion Excretion is mainly renal although small amounts of tellurium are exhaled as dimethyl telluride which has a distinctive garlic odour which may persist for many days; Reisert (1884) reported garlic breath odour for 237 days following ingestion of 15 mg tellurium oxide. The susceptibility to this effect varies considerably between individuals and is exacerbated by alcohol consumption (Cerwenka and Cooper, 1961). CLINICAL FEATURES: ACUTE EXPOSURE Dermal exposure Blue-black patches in the webs of the fingers and streaks on the neck were observed in two postgraduate chemists who handled volatile tellurium esters. The discolouration was believed to be due to deposition of elemental tellurium in the dermis and subcutaneous tissue (Blackadder and Manderson, 1975). Ocular exposure Some tellurium compounds are irritant although there are no reports of ocular exposure to tellurium or its compounds producing adverse effects. Exposure to either hydrogen telluride or to shampoo containing tellurium oxide has not caused eye problems (Grant and Schuman, 1993). Inhalation No pulmonary features were reported when two postgraduate chemists were exposed to some 50 g tellurium hexafluoride gas which leaked from a cylinder into a small laboratory. The first individual developed a metallic taste, anorexia and tiredness and, after two days, an erythematous papular vesicular rash on the hands, arms and neck. This was diagnosed as contact dermatitis, possibly from wearing rubber gloves, although the ability of tellurium to inhibit sweating may have contributed. The second person affected experienced only a metallic taste and somnolence. Both patients developed a garlic odour to the breath, sweat and urine which persisted for several weeks (Blackadder and Manderson, 1975). Haematological and biochemical profiles and chest X-ray were normal. CLINICAL FEATURES: CHRONIC EXPOSURE There are no reports regarding chronic exposure to tellurium hexafluoride though features similar to those observed for other tellurium compounds may be expected. Inhalation Thirteen individuals working near the blast furnaces in a lead refinery were examined for signs of tellurium exposure (Shie and Deeds, 1920). The workers were believed to have been exposed to hydrogen telluride though no exposure data were given. Seven had a garlic odour to the breath, sweat and urine, and dryness and a metallic taste in the mouth. Five had "considerable inhibition of the sweat function" and three developed dry and itchy skin, anorexia, nausea, vomiting, depression and somnolence. A survey of ninety-eight workers exposed to 0.01-0.1 mg/m3 tellurium for 22 months revealed similar effects. The most common findings were a garlic odour of the breath (84 individuals), dryness of the mouth (32), a metallic taste (27) and garlic odour of the sweat (20). Other symptoms included somnolence (16), loss of appetite (9) and nausea (3). No evidence of sweat suppression was found. Urinalysis revealed increased tellurium concentrations (0.01 to greater than 0.06 mg/L) in the exposed group compared to controls. Symptoms occurred even in those with urine tellurium concentrations less than 0.01 mg/L, though the frequency increased at higher tellurium concentrations with somnolence and a garlic sweat odour occurring only in workers with a urine tellurium concentration greater than 0.01 mg/L (Steinberg et al, 1942). MANAGEMENT Dermal exposure If possible the patient should remove any contaminated clothing him/herself. Affected areas of skin should be washed with copious quantities of water. Ocular exposure Irrigate immediately with lukewarm water or preferably saline for at least 10-15 minutes. Specialist ophthalmological advice should be sought if any abnormality is detected or suspected on examination and in those whose symptoms do not resolve rapidly. Inhalation Immediate management involves removal from exposure, establishment of a clear airway and administration of supplemental oxygen if necessary. Other symptomatic and supportive measures should be dictated by the patients condition. Antidotes Animal studies Four guinea pigs were administered 5 mg intramuscular dimercaprol eight hours prior to the intramuscular injection of 75 mg tellurium oxide. A second group of four similarly poisoned guinea pigs received dimercaprol eight hours after tellurium oxide injection. Both groups then received dimercaprol 5 mg tds for 24 hours and 5 mg bd for a further 24 hours. There was 100 per cent mortality in the two dimercaprol administered groups (n=8) within 48 hours (and all animals showed pronounced haematuria) whereas the 48 hour survival rate in control animals (n=4) administered tellurium oxide alone was 75 per cent. A single guinea pig administered only intramuscular dimercaprol 5 mg every eight hours for 24 hours remained healthy. The weights of the animals were not stated (Armdur, 1958). Clinical studies Three men exposed to tellurium fumes developed a strong garlic breath odour and were treated with 2.5 mg/kg dimercaprol intramuscularly every four hours for 24 hours, every six hours for a further 24 hours and then daily for six days. Each patient reported accentuation of the garlic odour following the injection and the odour disappeared one to four days after the cessation of treatment. There was no evidence of enhanced tellurium elimination with therapy (Amdur, 1947). Ascorbic acid Animal studies The reduction in garlic odour from rabbits and guinea pigs intoxicated with tellurium following administration of ascorbic acid (route not described) has been reported. The proposed mechanism is reduction of ionized to elemental tellurium with decreased dimethyl telluride formation (De Meio, 1947). Intramuscular ascorbic acid 25 mg tds for 24 hours then 25 mg bd for a further 24 hours did not increase the one week survival of guinea pigs injected intramuscularly with 75 mg tellurium oxide compared to controls (Amdur, 1958). Clinical studies Workers exposed to tellurium dust were treated with 8-10 mg/kg ascorbic acid (route not stated) one to three times daily. A reduction in garlic breath odour was noted which recurred on cessation of treatment (De Meio, 1947). A 37 year old woman who ingested an unknown amount of tellurium was treated with ascorbic acid 200 mg daily (route not stated). She recovered fully though a garlic odour of the breath persisted from some ten months (Müller et al, 1989). Antidotes: Conclusions and recommendations 1. Animal studies suggest dimercaprol increases tellurium toxicity and, as there is no evidence that it enhances tellurium elimination, it should not be employed. 2. Ascorbic acid may decrease the extent of garlic odour in persons with tellurium intoxication although this has not been confirmed in controlled studies. MEDICAL SURVEILLANCE The most obvious indication of tellurium exposure is a garlic odour to the breath, which occurs in association with urine tellurium concentrations greater than 1 µg/L (Gerhardsson et al, 1986). This clinical indication of tellurium exposure may be masked in those with badly smelling breath (i.e. bronchiectasis, grossly carious teeth, severe gingivitis) (Gerhardsson et al, 1986). Normal concentrations in biological fluids The "upper normal limits" for tellurium in non-occupationally exposed individuals have been reported as 1.0 µg/L in serum and 1.0 µg/L in urine (Müller et al, 1989). OCCUPATIONAL DATA Occupational exposure standard Tellurium and compounds, except hydrogen telluride. Long-term exposure limit 0.1 µg/m3 (as Te) (Health and Safety Executive, 1997). OTHER TOXICOLOGICAL DATA Carcinogenicity There are no data on the possible carcinogenic effects of tellurium hexafluoride in humans. Reprotoxicity Pregnant rats fed diets containing 500 to 3500 ppm tellurium gave birth to hydrocephalic (non-obstructive) offspring, the incidence of hydrocephalus being proportional to the tellurium dose (Duckett, 1970). The mechanism of this effect is not known. There are no data on the possible reproductive effects of tellurium hexafluoride in humans. Genotoxicity An increase in the incidence of chromosome breakage was found when in vitro human leukocytes were treated for 48 hours with 1.2 x 10-8 mol/L sodium tellurite and 2.4 x 10-7 mol/L ammonium tellurite (Paton and Allison, 1972). Fish Toxicity NIF EC Directive on Drinking Water Quality 80/778/EEC NIF WHO Guidelines for Drinking Water Quality NIF AUTHORS WN Harrison PhD CChem MRSC SM Bradberry BSc MB MRCP S Meacham BSc JA Vale MD FRCP FRCPE FRCPG FFOM National Poisons Information Service (Birmingham Centre), West Midlands Poisons Unit, City Hospital NHS Trust, Dudley Road, Birmingham B18 7QH UK This monograph was produced by the staff of the Birmingham Centre of the National Poisons Information Service in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Date of last revision 28/1/98 REFERENCES Amdur ML. Tellurium. Accidental exposure and treatment with BAL in oil. Occup Med 1947; 3: 386-91. Amdur ML. Tellurium oxide: an animal study in acute toxicity. Arch Ind Health 1958; 17: 665-7. Blackadder ES, Manderson WG. Occupational absorption of tellurium: a report of two cases. Br J Ind Med 1975; 32: 59-61. Cerwenka EA, Cooper WC. Toxicology of selenium and tellurium and their compounds. Arch Environ Health 1961; 3: 189-200. De Meio RH. Tellurium. II. Effect of ascorbic acid on the tellurium breath. J Ind Hyg Toxicol 1947; 29: 393-5. De Meio RH, O'Leary DJ. Hemolysis by tellurium compounds: Telluride and tellurate, effect on reduced glutathione. J Am Osteopath Assoc 1975; 75: 430-1. DOSE/Dictionary of substances and their effects. Vol 7. Cambridge: Royal Society of Chemistry, 1994. Duckett S Fetal encephalopathy following ingestion of tellurium. Experientia 1970; 26: 1239-41. Gerhardsson L, Glover JR, Nordberg GF, Vouk V. Tellurium. In: Friberg L, Nordberg GF, Vouk VB, eds. Handbook on the toxicology of metals. Vol 2. 2nd ed. Amsterdam: Elsevier Science Publishers, 1986; 532-48. Grant WM, Schuman JS. Toxicology of the eye. 4th ed. Illinois: Charles C Thomas, 1993. Health and Safety Executive. EH40/97: Occupational exposure limits 1997. Sudbury: HSE Books, 1997. HSDB/Hazardous Substances Data Bank. In: Tomes plus. Environmental Health and Safety Series 1. Vol 32. National Library of Medicine, 1997. Kron T, Hansen C, Werner E. Renal excretion of tellurium after peroral administration of tellurium in different forms to healthy human volunteers. J Trace Elem Electrolytes Health Dis 1991; 5: 239-44. Kurantsin-Mills J, Klug RK, Lessin LS. Irreversible erythrocyte volume expansion induced by tellurite. Br J Haematol 1988; 70: 369-74. Larner AJ. How does garlic exert its hypocholesterolaemic action? The tellurium hypothesis. Med Hypotheses 1995; 44: 295-7. MEDITEXT. In: Tomes plus. Environmental Health and Safety Series 1. Vol 32. Colorado: Micromedex, Inc., 1997. MERCK/The Merck Index. Tellurium hexafluoride. In: Budavari S, ed. An encyclopedia of chemicals, drugs, and biologicals. 12th ed. New Jersey: Merck and Co., Inc., 1996; 1560. Müller R, Zschiesche W, Steffen HM, Schaller KH. Tellurium-intoxication. Klin Wochenschr 1989; 67: 1152-5. NIOSH/NIOSH Pocket Guide. In: Tomes plus. Environmental Health and Safety Series 1. Vol 32. National Institute for Occupational Safety and Health (NIOSH), 1997. Paton GR, Allison AC. Chromosome damage in human cell cultures induced by metal salts. Mutat Res 1972; 16: 332-6. Reisert W. The so-called bismuth breath. Am J Pharm 1884; 56: 177-80. RTECS/Registry of Toxic Effects of Chemical Substances. In: Tomes plus. Environmental Health and Safety Series 1. Vol 32. National Institute for Occupational Safety and Health (NIOSH), 1997. SAX'S/Lewis RJ. Sax's dangerous properties of industrial materials. 9th ed. Vol 3. New York: Van Nostrand Reinhold, 1996. Shie MD, Deeds FE. The importance of tellurium as a health hazard in industry - a preliminary report. Public Health Rep 1920; 35: 939-54. Steinberg HH, Massari SC, Miner AC, Rink R. Industrial exposure to tellurium: atmosphere studies and clinical evaluation. J Ind Hyg Toxicol 1942; 24: 183-92.