UKPID MONOGRAPH SELENIUM HEXAFLUORIDE ST Beer BSc SM Bradberry BSc MB MRCP 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. SELENIUM HEXAFLUORIDE Toxbase summary Type of product Used as a gaseous electric insulator. Toxicity Selenium hexafluoride is a gas so toxicity is associated primarily with inhalation. Features Topical - Selenium compounds may produce local irritation, burning, erythema and pain. Inhalation Brief/minor inhalation: - Mucous membrane irritation with cough, coryzal symptoms and a bitter metallic taste. Moderate/substantial inhalation: - In addition to mucous membrane irritation there may be a garlic odour on the breath, hoarseness, dyspnoea, nausea, vomiting, headache and dizziness. - Chemical pneumonitis may complicate severe cases. - An inflammatory response with granuloma formation has been attributed to pulmonary selenium accumulation following chronic inhalation (Diskin et al, 1979). Management Topical 1. Irrigate with copious volumes of water. 2. Other symptomatic measures as required. Inhalation 1. Remove from exposure. 2. Establish a clear airway. 3. Administer supplemental oxygen as necessary. 4. Treat symptomatically. 5. Parenteral steroids may be considered if pulmonary oedema is present but there is no evidence that their use influences outcome; discuss with an NPIS physician. References Diskin CJ, Tomasso CL, Alper JC, Glaser ML, Fliegel SE. Long-term selenium exposure. Arch Intern Med 1979; 139: 824-26. Köppel C, Baudisch H, Beyer KH, Klöppel I, Schneider V. Fatal poisoning with selenium dioxide. Clin Toxicol 1986; 24: 21-35. Wilber CG. Toxicology of selenium: a review. Clin Toxicol 1980; 17: 171-230. Substance name Selenium hexafluoride Origin of substance Produced by passing gaseous fluorine over finely divided selenium in a copper vessel. (CSDS, 1991) Synonyms Selenium fluoride (CSDS, 1991) Chemical group A compound of selenium, a group VI A element. Reference numbers CAS 7783-79-1 (CSDS, 1991) RTECS VS 9450000 (RTECS, 1997) UN 2194 (CSDS, 1991) HAZCHEM CODE NIF Physicochemical properties Chemical structure SeF6 (DOSE, 1994) Molecular weight 192.95 (DOSE, 1994) Physical state at room temperature Gas (CSDS, 1991) Colour Colourless (CSDS, 1991) Odour NIF Viscosity NIF pH NIF Solubility Insoluble in water. (CSDS, 1991) Autoignition temperature NA Chemical interactions Selenium, nitrogen and hydrogen fluoride are produced following reaction with ammonia gas at 200°C. (MERCK, 1996) Major products of combustion When heated to high temperatures, may decompose to emit toxic fluoride and selenium fumes. (HSDB, 1997) Explosive limits NA Flammability Non-flammable (HAZARDTEXT, 1997) Boiling point -34.5°C (CSDS, 1991) Density 3.25 at -25°C (CSDS, 1991) Vapour pressure 8.68 x 103 Pa at -48.7°C (MERCK, 1996) Relative vapour density Vapour density 6.7 (HSDB, 1996) Flash point NA Reactivity Selenium hexafluoride hydrolyzes slowly in cold water. (HAZARDTEXT, 1997) Uses Selenium hexafluoride is used as a gaseous electric insulator and in transformers. (CSDS, 1991; HUNTER, 1994) Hazard/risk classification Selenium compounds, except cadmium sulphoselenide. Index no. 034-002-00-8 Risk phrases T; R23/25-33 - Toxic by inhalation and if swallowed. Danger of cumulative effects. Safety phrases S(1/2-)20/21-28-45- keep locked up and out of the reach of children. When using do not eat, drink or smoke. After contact with skin, wash immediately with plenty of .... (to be specified by the manufacturer). In case of accident or if you feel unwell, seek medical advice immediately (show label where possible). EEC no. NIF (CHIP2, 1994) INTRODUCTION AND EPIDEMIOLOGY The metalloid selenium occurs naturally in four oxidation states: elemental selenium (0), selenite (+4), selenide (-2) and selenate (+6). Selenium is an essential trace element with a narrow therapeutic index. It functions as an essential micronutrient at less than 1 ppm and is likely to exhibit metabolic toxic effects at systemic concentrations of 10 ppm (Oldfield, 1987). Selenium is closely related to sulphur in its chemical behaviour (Wilber, 1980). It is a component of selenocysteine, the active site of the antioxidant enzyme glutathione peroxidase and is required for free radical detoxification in conjunction with vitamin E. Selenium is also a component of the deiodinase which catalyzes hepatic T4 to T3 conversion (Hofbauer et al, 1997). Although animal studies have suggested a potential role for selenium in the treatment of heavy metal poisoning and chemical carcinogenesis, there is insufficient evidence and experience to advocate any therapeutic use in man (Whanger, 1992). Two endemic diseases associated with selenium have been described in China. Chronic selenium intoxication with hair and nail loss, skin lesions and dental caries occurred in Enshi County, Hubei Province of China (Yang et al, 1983; Whanger, 1989) and was most severe in the 1960's. The major source of selenium in this case was thought to be selenium rich coal (containing up to 5000 µg selenium/g) used for heating and cooking. The second disease "Keshan" is a cardiomyopathy associated with low dietary selenium intake (less than 17 µg selenium/day) (Whanger, 1989; Parízek, 1990). "Kashin Beck" disease, an osteoarthropathy, has also been associated with selenium deficiency but this has not been confirmed (Whanger, 1989; Parízek, 1990). Selenium toxicity can be a common problem in livestock. Cattle ingesting large amounts of plants containing high selenium residues may develop "blind staggers", characterized by gastrointestinal stasis, partial blindness and paralysis. Chronic ingestion may result in "alkali disease" with emaciation, hair loss and hoof deformities. Selenium hexafluoride is a colourless gas which is insoluble in water. It is used in industry primarily as a gaseous electric insulator. Thus, the main route of exposure is inhalation, though skin contact may lead to features of poisoning. Exposure to selenium hexafluoride may also occur during production of selenium hydroxide and hydrofluoric acid (HSDB, 1997). There is evidence that selenium intake by man is declining globally and selenium deficiency is considered a greater clinical problem than selenium toxicity (Rayman, 1997). MECHANISM OF TOXICITY Selenium inactivates cellular oxidative processes by catalyzing oxidation of sulphydryl groups on co-factors such as glutathione. Sulphur and selenium are readily exchanged during amino acid metabolism resulting in selenium incorporation into amino acids such as cysteine. Selenium competes with sulphur for sites at which sulphur normally plays a role in cellular respiration (Schellman et al, 1986; Ahmed et al, 1990). In addition, mitosis is inhibited by selenium at metaphase. TOXICOKINETICS Absorption Selenium hexafluoride is absorbed by the lungs (Högberg and Alexander, 1986). As selenium hexafluoride is a gas and insoluble in water, gastrointestinal absorption does not occur to any significant extent. Distribution There are no specific data concerning the metabolism and distribution of selenium hexafluoride. There is evidence from human studies that selenium binds to plasma lipoproteins (Sandholm, 1975) and some is present in erythrocytes, partly as a component of glutathione peroxidase (Högberg and Alexander, 1986). Animal studies suggest that following exposure to many different selenium compounds, selenium accumulates in all major organs particularly the liver and kidneys (Glover, 1970; Civil and McDonald, 1978; Diskin et al, 1979). By contrast the lung appears to be an important target organ of systemic selenium toxicity in man. Diskin et al (1979) suggested blood-borne selenium made a significant contribution to high lung selenium concentrations resulting in pulmonary granuloma formation. Excretion Animal studies suggest that excretion of selenium compounds during short-term exposure occurs chiefly via the kidneys as methylated derivatives (such as the trimethylselenonium ion) with faecal excretion playing a minor role (Diskin et al, 1979; Högberg and Alexander, 1986; Wilber, 1980). After substantial or prolonged exposure it is likely that elimination of the hepatic selenium metabolite dimethylselenide in expired air is important; dimethylselenide has a characteristic garlic odour (Diskin et al, 1979; Högberg and Alexander, 1986; Magos et al, 1987). CLINICAL FEATURES: ACUTE EXPOSURE Specific data regarding the toxicity of selenium hexafluoride are scarce, and there are no human case reports. Dermal exposure Topical exposure to selenium compounds produces local irritation with pain, burning and erythema (Wilson, 1962; Fan and Kizer, 1990). Ocular exposure Selenium hexafluoride is an eye irritant. Ocular exposure to selenium dusts or fumes has produced "rose eye" characterized by swollen pink eyelids (Glover, 1970) and conjunctival burns within hours of exposure (Wilson, 1962). Inhalation It is known from animal studies that selenium hexafluoride is a pulmonary irritant (Proctor et al, 1978) and inhalation of other selenium compounds by man has caused pulmonary toxicity. The likelihood of systemic selenium uptake following selenium hexafluoride inhalation is likely to be only modest since it is insoluble in water. Pulmonary toxicity Selenium compounds may cause immediate irritation of the mucous membranes, hoarseness, coughing and coryzal symptoms (Motley et al, 1937; Wilson, 1962; Schecter et al, 1980; Fan and Kizer, 1990). An acute sore throat and mild bronchitis of two weeks duration were described in laboratory technicians following dimethylselenide exposure (Motley et al, 1937). A 24 year-old male who accidentally inhaled hydrogen selenide immediately developed cough and wheeze and was admitted to hospital 18 hours later with progressive dyspnoea. Examination and investigations revealed pneumomediastinum (but no other chest X-ray abnormalities), hypoxia (pO2 9.2 kPa) and a severe obstructive ventilatory defect. Substantial improvement ensued during the next five days with conventional therapy (Schecter et al, 1980). Workers exposed to selenium oxide fumes developed symptoms and signs of a chemical pneumonitis between 10 hours and three days later. Features included dyspnoea, cyanosis, chest pain and wheeze, with radiological evidence of bilateral consolidation (Wilson, 1962). Non-cardiogenic pulmonary oedema has been described particularly following inhalation of high concentrations of inorganic selenium compounds (such as hydrogen selenide or selenium dioxide) (Glover, 1970; Waldron and Scott, 1994). Gastrointestinal toxicity A bitter metallic taste, nausea and vomiting have followed inhalation of selenium compounds (Fan and Kizer, 1990). These features developed immediately following inhalation of selenium oxide fumes and temporarily resolved within three hours (Wilson, 1962). Several hours later the 28 affected workers complained of nausea, vomiting and diarrhoea in association with malaise, headache and pulmonary complications (Wilson, 1962). A garlic odour on the breath is widely reported in selenium poisoning (Carter, 1966; Civil and McDonald, 1978; Schellman et al, 1986) and may occur in acute inhalational selenosis (Fan and Kizer, 1990). Cardiovascular toxicity An undefined transient fall in blood pressure associated with tachycardia was reported among workers exposed to selenium oxide fumes during a fire (Wilson, 1962). Acute severe selenium poisoning by ingestion has been associated with circulatory collapse (Carter, 1966) but this has not been reported following inhalation. Transient T-wave inversion, Q-T interval prolongation (Civil and McDonald, 1978) and increased cardiac enzyme activities (Nantel et al, 1985) have also been reported in selenium poisoning but again only following ingestion. Nephrotoxicity Acute nephrotoxicity has not been reported following selenium hexafluoride (or other selenium salt) inhalation, although transient haematuria and proteinuria have complicated selenium ingestion (Nantel et al, 1985). Hepatotoxicity Transient increases in hepatic enzyme activities have complicated acute selenium ingestion but have not occurred following inhalation (Nantel et al, 1985). Neurotoxicity Headache, malaise and dizziness may accompany the respiratory features (Wilson, 1962; Fan and Kizer, 1990). Workers exposed to selenium have complained of lassitude and irritability resolving on removal from exposure (Glover, 1970). Ingestion Selenium hexafluoride is a gas at room temperature; there are no reports of ingestion. CLINICAL FEATURES: CHRONIC EXPOSURE Dermal exposure Skin irritation has been reported in workers exposed to selenium fumes (Glover, 1970). A selenium refiner, employed for 50 years, was noted to have red hair and fingernails following daily dermal contact with selenium (Diskin et al, 1979). Ocular exposure Conjunctivitis developed in a student exposed to hydrogen selenide gas once a week for a year (Alderman and Bergin, 1986). Inhalation Pulmonary toxicity A 71 year-old selenium refiner died from an acute myocardial infarction after 50 years employment. At post-mortem non-caseating pulmonary granulomas were noted in association with very high selenium concentrations in the peribronchial nodes and lung parenchyma (26 and 109 ppm respectively; normal values for peribronchial nodes 0.1 ppm, lungs 0.15-0.21 ppm). The authors proposed a selenium-induced inflammatory response. Normal tracheal selenium concentrations and the absence of alveolar changes suggested a significant contribution from blood-borne selenium (Diskin et al, 1979). Dimethylselenide, excreted by the lungs following chronic or substantial selenium exposure, is itself a primary respiratory tract irritant. "Rose cold" with sore throat, cough, coryzal symptoms and bronchitis is thought to occur secondary to pulmonary dimethylselenide excretion (Diskin et al, 1979). Gastrointestinal toxicity A 21 year-old student exposed to hydrogen selenide gas at least once a week for a year gave a six month history of diarrhoea and abdominal pain, a bitter taste and garlic breath. Six dental caries developed over the same period (Alderman and Bergin, 1986). Blood and urine selenium concentrations were not measured but symptoms resolved on removal from exposure. Dermal toxicity Red hair and fingernails were noted in association with abnormally high hair (213 ppm, normal 0.36-0.74 ppm) and nail (178 ppm, normal not reported) selenium concentrations in a worker exposed by inhalation to selenium fumes for 50 years (Diskin et al, 1979). Transverse fingernail ridges have been described following occupational hydrogen selenide gas inhalation over some 12 months (Alderman and Bergin, 1986). MANAGEMENT Dermal exposure Decontamination with copious lukewarm water is the priority. Glover (1983) suggested topical thiosulphate relieved selenium dioxide burns and pain caused by selenium dioxide trapped under the nails but there are no controlled data to substantiate this view. Ocular exposure Remove from exposure and irrigate with lukewarm water for at least 10 minutes. A topical anaesthetic may be required. Glover (1983) proposed that the stinging associated with "rose eye" may be relieved by the application of 10 per cent sodium thiosulphate ointment to the eyelids but there is insufficient evidence to advocate this routinely. Seek an ophthalmic opinion for those with persisting symptoms or abnormal examination findings. Inhalation Immediate management involves removal from exposure, establishment of a clear airway and administration of supplemental oxygen as necessary. Parenteral steroids may be considered if laryngeal or pulmonary oedema are present but there is no evidence that their use influences outcome. Mechanical ventilation may be required. Wilson (1962) suggested ammonia inhalation could relieve the burning associated with acute selenium inhalation but this recommendation is unsupported by other studies. Antidotes Animal studies Selenium-intoxicated (sodium selenite, 10 mg/kg intramuscularly) rats were administered intraperitoneal sodium calciumedetate, 0.5 g/kg, at intervals of 15, 30 and 60 minutes post selenium poisoning (n=30 in each group). Selenium poisoned rats given no antidote served as controls. The 30 day survival ratio was increased substantially (from 9/30 in controls to 20/30 in selenium-treated rats) only if the antidote was administered within 15 minutes of selenium intoxication. Treatment with sodium calciumedetate was of little benefit at 15 minutes post selenite poisoning at a dose of 12.5 mgSe/kg (Sivjakov and Braun, 1959). Paul et al (1989) investigated the effect of potential antidotes on sodium selenate (2.24 mg/kg subcutaneously)-induced weight loss. Groups of rats (n=4) were administered an antidote by intraperitoneal injection 15 minutes following selenium dosing. DMPS (sodium dimercaptopropanesulphonate) 60 mg/kg, DMSA (dimercaptosuccinic acid) 50.9 mg/kg and sodium calciumedetate 500 mg/kg had no protective effect and dimercaprol 15 mg/kg increased selenium-induced weight loss. Diethyldithiocarbamate (DDC) 70 mg/kg significantly (p<0.05) reduced weight loss but only for the first 48 hours post antidote administration. In further experiments, DDC 70 mg/kg reduced selenium-associated weight loss but did not affect tissue selenium distribution when administered 15 minutes, three hours or six hours after sodium [75Se]selenite (50 µCi, 17.4 µgSe/kg subcutaneously) (Paul et al, 1989). A protective effect of linseed oil in selenium-poisoned animals has been suggested via selenium binding to tissues in a less toxic form (Levander, 1972). Levander and Morris (1970) claimed that in rats fed a diet containing 10 ppm selenium, supplementation with methionine and vitamin E offered protection against selenium-induced macroscopic liver damage. The authors suggested that vitamin E and other fat-soluble antioxidants may make the methyl group of methionine more available for selenium detoxification with subsequent excretion via the lungs and kidneys (Levander and Morris, 1970). Diets high in choline or betaine supplements also have been claimed to offer protection against chronic selenosis (Klevay, 1976). Clinical studies Following ingestion of 22.3 mg/kg selenium (as sodium selenate), a 15 year-old female underwent gastric lavage within one hour then was treated with vitamin C 1 g intramuscularly, (4 g/day orally thereafter) and forced diuresis. Dimercaprol therapy was commenced: 150 mg qds on day one, 75 mg tds on day two, and 50 mg tds on day three. The 24 hour urine selenium concentration on day two was 680 µg/L (urine volume not stated). Dimercaprol did not enhance urine selenium elimination, though the patient recovered fully (Civil and McDonald, 1978). Antidotes: Conclusions and recommendations 1. Clarke et al (1996) suggest that no chelating agents have proven effective in removing significant amounts of selenium; we concur with this view. 2. Chelation therapy cannot currently be advocated in selenium poisoning. Haemoperfusion As the majority of blood selenium is located in erythrocytes or bound to plasma proteins (Köppel et al, 1986) haemoperfusion is unlikely to be effective. MEDICAL SURVEILLANCE The possibility of pulmonary toxicity should be considered in those occupationally exposed to selenium hexafluoride, especially in individuals with pre-existing respiratory disease (HSDB, 1997). Urinary selenium excretion is a useful indicator of recent exposure (Wilber, 1980) with 24 hour excretion a more reliable parameter than random samples (Robberecht and Deelstra, 1984; Alaejos and Romero, 1993). Dietary intake, age, sex, pregnancy, energy consumption, selenium status, and any underlying pathological conditions which may influence selenium excretion must be considered when interpreting results. Formation of metal-selenium complexes in heavy metal workers exposed, for example, to mercury, cadmium and lead will result in raised urinary selenium concentrations (Alaejos and Romero, 1993). Increased blood selenium concentrations may be observed following acute exposure (Högberg and Alexander, 1986). Whole blood concentrations remain elevated longer than serum concentrations since most blood selenium is located in alpha and beta globulins and erythrocytes (Alderman and Bergin, 1986; Clark, 1996). However, blood concentrations alone do not accurately reflect the total body selenium burden (Wilber, 1980). As a result of serum protein binding, serum selenium concentrations decrease less rapidly than urine selenium concentrations (Sánchez-Ocampo et al, 1996). Platelet glutathione peroxidase activity and hair selenium concentrations have been suggested as indicators of human selenium status (Högberg and Alexander, 1986). It must be noted, however, that selenium is added to many antidandruff shampoos and is adsorbed onto hair. Normal selenium concentrations in biological fluids Plasma: 70-130 µg/L. 24 hour urine excretion: less than 300 µg. OCCUPATIONAL DATA Occupational exposure standard Selenium and compounds: Long-term exposure limit (8 hour TWA reference period) 0.1 mg/m3 (Health and Safety Executive, 1997). OTHER TOXICOLOGICAL DATA Carcinogenicity There is no conclusive evidence to link exposure to selenium compounds with an increased incidence of cancer in humans. Some epidemiological studies have proposed an inverse relationship between blood selenium concentrations and cancer mortality (Wilber, 1980). Gerhardsson et al (1986) stated "selenium might have a protective effect in occupational exposure against at least certain carcinogens causing lung cancer". Willett and Stampfer (1988) discuss the possible protective effect of selenium but conclude that insufficient evidence exists to recommend dietary selenium supplementation in humans. Reprotoxicity There are no reprotoxicity data regarding selenium hexafluoride exposure. Selenium is essential for reproduction and is selectively maintained in the testes during selenium deficiency (Reprotext, 1997). Selenium salts have been found to cross the placenta and selenium is normally excreted in breast milk (Reprotox, 1997). Robertson (1970) reported a cluster of spontaneous abortions among laboratory staff occupationally exposed to selenium where it was used as a culture medium component. However, it is not clear what other chemicals these staff were exposed to chronically. Genotoxicity There is experimental evidence of selenium genotoxicity mediated via active oxygen species formation (Kitahara et al, 1995). Fish toxicity NIF EC Directive on Drinking Water Quality 80/778/EEC Selenium: maximum admissible concentration 10 µg/L (DOSE, 1994). WHO Guidelines for Drinking Water Quality Guideline value 10 µg/L, as selenium (WHO, 1993). AUTHORS ST Beer BSc SM Bradberry BSc MB MRCP 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 Ahmed KE, Adam SEI, Idrill OF, Wahbi AA. Experimental selenium poisoning in Nubian goats. Vet Hum Toxicol 1990; 32: 249-51. Alaejos MS, Romero CD. Urinary selenium concentrations. Clin Chem 1993; 39: 2040-52. Alderman LC, Bergin JJ. Hydrogen selenide poisoning: An illustrative case with review of the literature. Arch Environ Health 1986; 41: 354-8. Carter RF. Acute selenium poisoning. Med J Aust 1966; 1: 525-8. CHIP2/Chemicals (Hazard Information and Packaging for Supply) Regulations 1994. Health and Safety Commission. Sudbury: Health and Safety Executive, 1994. Civil IDS, McDonald MJA. Acute selenium poisoning: Case report. N Z Med J 1978; 87: 354-6. Clark RF, Strukle E, Williams SR, Manoguerra AS. Selenium poisoning from a nutritional supplement. JAMA 1996; 275: 1087-8. CSDS/Chemical Safety Data Sheets. Vol 4a. Cambridge: Royal Society of Chemistry, 1991. Diskin CJ, Tomasso CL, Alper JC, Glaser ML, Fliegel SE. Long-term selenium exposure. Arch Intern Med 1979; 139: 824-6. DOSE/Dictionary of substances and their effects. Vol 7. Cambridge: The Royal Society of Chemistry, 1994. Fan AM, Kizer KW. Selenium - Nutritional, toxicologic, and clinical aspects. West J Med 1990; 153: 160-7. Gerhardsson L, Brune D, Nordberg GF, Wester PO. Selenium and other trace elements in lung tissue in smelter workers relationship to the occurrence of lung cancer. Acta Pharmacol Toxicol 1986; 59: 256-9. Glover JR. Selenium and its industrial toxicology. Ind Med 1970; 39: 50-4. Glover GR. Selenium and compounds. In: Parmeggiani L, ed. Encyclopedia of Occupational Health and Safety. Vol 2. Geneva: International Labour Office, 1983; 2017-8. Hazardtext. In: Tomes plus. Environmental Health and Safety Series I. Vol 32. Colorado: Micromedex, Inc., 1997. Health and Safety Executive. EH40/97. Occupational exposure limits 1997. Sudbury: Health and Safety Executive, 1997. Hofbauer LC, Spitzweg C, Magerstädt RA, Heufelder AE. Selenium-induced thyroid dysfunction. Postgrad Med J 1997; 73: 103-4. Högberg J, Alexander J. Selenium. In: Friberg L, Nordberg GF, Vouk VB, eds. Handbook on the toxicology of metals. Vol 2. 2nd ed. Amsterdam: Elsevier Science Publishers, 1986; 482-520. HSDB/Hazardous Substances Data Bank. In: Tomes plus. Environmental Health and Safety Series I. Vol 32. National Library of Medicine, 1997. HUNTER/Hunter's Diseases of Occupations. 8th ed. Raffle PAB, Adams PH, Baxter PJ, Lee WR, eds. UK: Edward Arnold, 1994. Kitahara J, Seko Y, Imura N, Utsumi H, Hamada A. DNA strand breakage and lipid peroxidation as possible mechanisms of selenium toxicity. In: Sarkar B, ed. Genetic response to metals. New York: Marcel Dekker Inc, 1995; 121-9. Klevay LM. Pharmacology and toxicology of heavy metals: Selenium. Pharmacol Ther 1976; 1: 211-22. Köppel C, Baudisch H, Beyer KH, Klöppel I, Schneider V. Fatal poisoning with selenium dioxide. Clin Toxicol 1986; 24: 21-35. Levander OA. Metabolic interrelationships and adaptations in selenium toxicity. Ann NY Acad Sci 1972; 192: 181-92. Levander OA, Morris VC. Interactions of methionine, vitamin E, and antioxidants in selenium toxicity in the rat. J Nutr 1970; 100: 1111-8. Magos L, Tandon SK, Webb M, Snowden R. The effects of treatment with selenite before and after the administration of [75Se]selenite on the exhalation of [75Se]dimethylselenide. Toxicol Lett 1987; 36: 167-72. MERCK/The Merck Index. Selenium hexafluoride. In: Budavari S, ed. An encyclopedia of chemicals, drugs and biologicals. 12th ed. New Jersey: Merck and Co., Inc., 1996; 1449. Motley HL, Ellis MM, Ellis MD. Acute sore throats following exposure to selenium. JAMA 1937; 109: 1718-9. Nantel AJ, Brown M, Dery P, Lefebvre M. Acute poisoning by selenious acid. Vet Hum Toxicol 1985; 27: 531-3. Oldfield JE. The two faces of selenium. J Nutr 1987; 117: 2002-8. Parízek J. Health effects of dietary selenium. Food Chem Toxicol 1990; 28: 763-5. Paul M, Mason R, Edwards R. Effect of potential antidotes on the acute toxicity, tissue disposition and elimination of selenium in rats. Res Commun Chem Pathol Pharmacol 1989; 66: 441-50. Proctor NH, Hughes JP, Fischman ML. Chemical hazards of the workplace. 2nd ed. Philadelphia: JB Lippincott Company, 1978. Rayman MP. Dietary selenium: time to act. Br Med J 1997; 314: 387-8. Reprotext. In: Tomes plus. Environmental Health and Safety Series I. Vol 32. Colorado: Micromedex, Inc., 1997. Reprotox. In: Tomes plus. Environmental Health and Safety Series I. Vol 32. Washington DC: Fabro S, Scialli AR. Reproductive Toxicology Center, Columbia Hospital for Women, 1997. Robberecht HJ, Deelstra HA. Selenium in human urine: concentration levels and medical implications. Clin Chim Acta 1984; 136: 107-20. Robertson DSF. Selenium - a possible teratogen? Lancet 1970; 1: 518-9. RTECS/Registry of Toxic Effects of Chemical Substances. In: Tomes plus. Environmental Health and Safety Series I. Vol 32. National Institute for Occupational Safety and Health (NIOSH), 1997. Sánchez-Ocampo A, Torres-Pérez J, Jiménez-Reyes M. Selenium levels in the serum of workers at a rubber tire repair shop. Am Ind Hyg Assoc J 1996; 57: 72-75. Sandholm M. Function of erythrocytes in attaching Selenite-Se onto specific plasma proteins. Acta Pharmacol Toxicol 1975; 36: 321-7. Schecter A, Shanske W, Stenzler A, Quintilian H, Steinberg H. Acute hydrogen selenide inhalation. Chest 1980; 77: 554-5. Schellmann B, Raithel HJ, Schaller KH. Acute fatal selenium poisoning. Toxicological and occupational medical aspects. Arch Toxicol 1986; 59: 61-3. Sivjakov KI, Braun HA. The treatment of acute selenium, cadmium and tungsten intoxication in rats with calcium disodium ethylenediaminetetraacetate. Toxicol Appl Pharmacol 1959; 1: 602-8. Waldron HA, Scott A. Metals. In: Raffle PAB, Adams PH, Baxter PJ, Lee WR, eds. Hunter's Diseases of Occupations. 8th ed. London: Edward Arnold, 1994; 90-138. Whanger PD. Selenium in the treatment of heavy metal poisoning and chemical carcinogenesis. J Trace Elem Electrolytes Health Dis 1992; 6: 209-21. Whanger PD. China, a country with both selenium deficiency and toxicity: some thoughts and impressions. J Nutr 1989; 119: 1236-9. WHO. Guidelines for drinking-water quality. 2nd ed. Vol 1. Recommendations. Geneva: World Health Organization, 1993. Wilber CG. Toxicology of selenium: a review. Clin Toxicol 1980; 17: 171-230. Willett WC, Stampfer MJ. Selenium and cancer. Whether selenium protects against cancer is still unknown. Br Med J 1988; 297: 573-4. Wilson HM. Selenium oxide poisoning. N C Med J 1962; 23: 73-75. Yang G, Wang S, Zhou R, Sun S. Endemic selenium intoxication of humans in China. Am J Clin Nutr 1983; 37: 872-81.