UKPID MONOGRAPH ZIRCONIUM WN Harrison PhD CChem MRSC 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. ZIRCONIUM Toxbase summary Type of product Zirconium is used in a number of metal alloys, explosive primers and flash bulbs. Zirconium compounds have been used in deodorant and dermatitis treatments. Toxicity Most zirconium compounds have low systemic toxicity due to their poor solubility. However, some soluble compounds, such as zirconium tetrachloride, are irritants and may cause corrosive injury. In addition, skin and lung granulomas have been reported following repeated zirconium exposure. Features Dermal and inhalational exposure are reported most commonly. Dermal - Most zirconium compounds are considered inert to the skin. - Zirconium tetrachloride is irritant and may cause corrosive injury. - Development of granulomas has been reported following application of zirconium-containing deodorants and dermatitis treatments to broken skin. Ocular - Eye irritation, lacrimation, blurred vision and conjunctivitis may occur. - Some soluble compounds may cause corrosive damage. Inhalation - Most zirconium dusts and vapours will cause only mucosal irritation. - Some corrosive compounds may cause hoarseness, dyspnoea and, in severe cases, stridor due to laryngeal oedema. - Pulmonary oedema has been reported after exposure to zirconium tetrachloride (Cordasco and Stone, 1973) and may be delayed for up to 36 hours. - Pulmonary granulomas have been reported in workers chronically exposed to zirconium dusts (Bartter et al, 1991; Liippo et al, 1993). Ingestion - There are no reports of zirconium intoxication, although ingestion of a soluble salt may cause corrosive injury. Management Dermal 1. Irrigate with copious lukewarm water. 2. Zirconium-induced granulomas are managed most effectively by discontinuing exposure. Topical or systemic steroids may hasten resolution in severe cases. Ocular 1. Irrigate immediately with lukewarm water or preferably saline for at least 10 minutes. 2. Application of local anaesthetic may be required for pain relief and to overcome blepharospasm to allow thorough decontamination. 3. Ensure no particles remain lodged in the conjunctival recesses. 4. Corneal damage may be detected by the instillation of fluorescein. 5. If symptoms do not resolve rapidly or if there are abnormal examination findings, refer for an ophthalmological opinion. Inhalation 1. Remove from exposure and administer supplemental oxygen by face-mask if there is evidence of respiratory distress. 2. Intubation and assisted ventilation may be necessary. 3. Rarely tracheostomy may be required for life-threatening laryngeal oedema. 4. Corticosteroids in high dosage (prednisolone 60-80 mg/day) may be considered for laryngeal and pulmonary oedema but there is no confirmed evidence that they improve prognosis. 5. Chronic exposure may precipitate a pulmonary granulomatous reaction. Initial assessment involves chest X-ray and lung function tests. Specialist referral may be indicated. Ingestion 1. Ingestion of most common zirconium compounds will require symptomatic and supportive care as dictated by the patient's condition. 2. If corrosive injury is suspected management is as for acid ingestion (see Corrosives). References Anderson KD, Rouse TM, Randolph JG. A controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med 1990; 323: 637-40. Baler GR. Granulomas from topical zirconium in poison ivy dermatitis. Arch Dermatol 1965; 91: 145-8. Bartter T, Irwin RS, Abraham JL, Dascal A, Nash G, Himmelstein JS, Jederlinic PJ. Zirconium compound-induced pulmonary fibrosis. Arch Intern Med 1991; 151: 1197-201. Cordasco EM, Stone FD. Pulmonary edema of environmental origin. Chest 1973; 64: 182-5. Hadjimichael OC, Brubaker RE. Evaluation of an occupational respiratory exposure to a zirconium-containing dust. J Occup Med 1981; 23: 543-7. Jeng L-BB, Chen H-Y, Chen S-C, Hwang T-L, Jan Y-Y, Wang C-S, Chen M-F. Upper gastrointestinal tract ablation for patients with extensive injury after ingestion of strong acid. Arch Surg 1994; 129: 1086-90. Liippo KK, Anttila SL, Taikina-Aho O, Ruokonen E-L, Toivonen ST, Tuomi T. Hypersensitivity pneumonitis and exposure to zirconium silicate in a young ceramic tile worker. Am Rev Respir Dis 1993; 148: 1089-92. Marcus RL, Turner S, Cherry NM. A study of lung function and chest radiographs in men exposed to zirconium compounds. Occup Med 1996; 46: 109-13. Romeo L, Cazzadori A, Bontempini L, Martini S. Interstitial lung granulomas as a possible consequence of exposure to zirconium dust. Med Lav 1994; 85: 219-22. Rubin L, Slepyan AH, Weber LF, Neuhauser I. Granulomas of the axillas caused by deodorants. JAMA 1956; 162: 953-5. Shelley WB, Hurley HJ. The allergic origin of zirconium deodorant granulomas. Br J Dermatol 1958; 70: 75-101. Skelton HG, Smith KJ, Johnson FB, Cooper CR, Tyler WF, Lupton GP. Zirconium granuloma resulting from an aluminium zirconium complex: a previously unrecognized agent in the development of hypersensitivity granulomas. J Am Acad Dermatol 1993; 28: 874-6. Zargar SA, Kochhar R, Nagi B, Mehta S, Mehta SK. Ingestion of corrosive acids. Spectrum of injury to upper gastrointestinal tract and natural history. Gastroenterology 1989; 97: 702-7. Substance name Zirconium Origin of substance Found in rare earth minerals, zircon, malacon, baddeleyite, zirkelite, eudialyte and in monazite sand. Invariably associated with hafnium. (MERCK, 1996) Synonyms Zircat (HAZARDTEXT, 1997) Chemical group A group IV B (d block) transition metal. Reference numbers CAS 7440-67-7 (DOSE, 1994) RTECS ZH7070000 (RTECS, 1997) UN 2858, 2009 (dry); 2008 (powder, dry); 1358 (powder, wetted) (DOSE, 1994) HAZCHEM NIF Physicochemical properties Chemical structure Zr (DOSE, 1994) Molecular weight 91.22 (DOSE, 1994) Physical state at room temperature Solid (MERCK, 1996) Colour A grey-white metal or a blue-black powder. (MERCK, 1996) Odour NIF Viscosity NA pH NIF Solubility Insoluble in hot or cold water. Slightly soluble in acids. Soluble in hydrogen fluoride and aqua regia. (HSDB, 1997) Autoignition temperature NIF Chemical interactions Zirconium reacts with hydrofluoric acid, aqua regia and hot phosphoric acid. Zirconium is slightly attacked by hot concentrated sulphuric acid or hydrochloric acid and avidly attacked by fused potassium hydroxide or nitrate. Treatment of zirconium powder with hydrogen fluoride solution (1 per cent) desensitizes it to electrostatic ignition. Zirconium dust may explode when mixed with alkali hydroxides, alkali metal chromates, dichromates, molybdates, sulphates, tungstates, borax, carbon tetrachloride, cupric oxide, lead, lead oxide, phosphorus, potassium chlorate, potassium nitrate and nitryl fluoride. (MEDITEXT, 1997; SAX'S, 1996; MERCK, 1996) Major products of combustion Zirconium oxide (SAX'S, 1996) Explosive limits 0.16 g/L in air (SAX'S, 1996) Flammability Highly flammable. Dust may ignite spontaneously. (SAX'S, 1996) Boiling point 3577°C (DOSE, 1994) Density 6.5 at 20°C (DOSE, 1994) Vapour pressure NIF Relative vapour density NIF Flash point NIF Reactivity When exposed to heat and flame, zirconium dust is a very dangerous fire hazard. A 10 to 70 per cent zirconium lead alloy will ignite if hit by a hammer. (MEDITEXT, 1997; SAX'S, 1996) Uses Pure zirconium (hafnium free) is used in structural materials in nuclear reactors. In constructing rayon spinnerets in lamp filaments and flash bulbs. In explosive primers. As weighting agents, in welding rod manufacture and sandblasting applications. In moulds and furnaces in the aluminium, brass, steel and glass industries. As a reflective surface on satellites. In deodorants. (MERCK, 1996; DOSE, 1994; PATTY, 1994) Hazard/risk classification Index no. Zirconium powder (pyrophoric) 040-001-00-3 Risk phases R15-17 - Contact with water liberates extremely flammable gases. Spontaneously flammable in air. Safety phases S7/8 - 43 - Keep container tightly closed and dry. In case of fire, use (indicate in the space the precise type of fire fighting equipment). If water increases the risk add - Never use water. EEC no. 231 - 176 - 9 (CHIP2, 1994) INTRODUCTION Zirconium is a transition metal usually existing in valence state +4, although it can form compounds in the +3 and +2 states (PATTY/Beliles, 1994). It is believed to have low systemic toxicity due to the low solubility of many of its compounds (including the silicate, carbonate and oxide). Some soluble zirconium salts, such as zirconium tetrachloride, are irritants and may cause corrosive injury. Furthermore, zirconium may contain uranium and thorium presenting a potential radiation hazard to those exposed (Castello et al, 1992). EPIDEMIOLOGY Exposure to zirconium and its compounds is mainly as dust and fumes in the metallurgical industry. Although several studies have found no adverse health effects following occupational zirconium exposure (Hadjimichael and Brubaker, 1981; Marcus et al, 1996) a number of case reports have linked zirconium to respiratory disease (Bartter et al, 1991; Liippo et al, 1993; Romeo et al, 1994). The use of zirconium compounds in deodorants (Rubin et al, 1956; Anon.,1958; Obermayer, 1969) and dermatitis treatments (Baler, 1965) has led to the development of "allergic" granulomas; Shelley and Hurley (1958) reported 70 cases between 1956 and 1958. Exposure of bare feet to zirconium-rich clay in Ethiopia has been associated with non-filarial elephantiasis (Frommel et al, 1993). MECHANISMS OF TOXICITY In vitro studies demonstrate zirconium induces lymphocyte proliferation and may augment the T-cell mediated immune response to other agents via interaction with macrophages (Price and Skilleter, 1986). However, evidence that the development of lung granulomas in exposed individuals is a T- cell mediated delayed hypersensitivity response is inconclusive, unlike the case of beryllium hypersensitivity (Parkes, 1994). Some zirconium compounds, for example zirconium tetrachloride, have a direct irritant or corrosive effect on the skin, eyes and mucous membranes. TOXICOKINETICS Absorption Zirconium compounds are absorbed poorly following ingestion (PATTY/Beliles, 1994). The uptake of insoluble zirconium compounds following inhalation is low (PATTY/Beliles, 1994). Coal miners exposed to unstated zirconium concentrations had up to 14 ppm zirconium in heavily pigmented sections of lung and 22 ppm in pulmonary lymph nodes. Blood zirconium concentrations were up to 100 µg/L and urine concentrations up to 12 µg/L (PATTY/Beliles, 1994). Zirconium-induced skin granulomas are associated typically with areas of damaged skin indicating that absorption through intact skin is poor. Distribution Zirconium was found to be widely distributed in specimens from four autopsies of non-poisoned patients with particularly high concentrations in liver and body fat (Schroeder and Balassa, 1966). Excretion There are very little data available but most absorbed zirconium appears to be eliminated in bile with only small amounts appearing in urine (HSDB, 1997). CLINICAL FEATURES: ACUTE EXPOSURE Dermal exposure Most commonly used zirconium compounds are insoluble and considered inert to the skin, although some salts, such as zirconium tetrachloride, are skin irritants. The severity of injury will depend on concentration or extent of exposure. Development of axillary granulomas has been reported rarely following a single application of a zirconium-containing deodorant. However, prior sensitization, possibly from inhalation of zirconium compounds, is believed to have occured (Shelley and Hurley, 1958). Ocular exposure Ocular exposure to zirconium compounds may cause eye irritation, lacrimation, blurred vision and conjunctivitis. More severe damage may be expected following exposure to a corrosive salt such as zirconium tetrachloride. There are no clinical case data. Inhalation Most zirconium compounds cause only irritation when inhaled as dusts or vapours although pulmonary oedema has been reported following exposure to zirconium tetrachloride which is corrosive (Cordasco and Stone, 1973). Early features following corrosive inhalation include cough and retrosternal discomfort. Hoarseness, dyspnoea and, in severe cases, stridor due to laryngeal oedema may follow. Where pulmonary oedema ensues its onset may be delayed for up to 36 hours. Ingestion There are no reports of zirconium poisoning by ingestion. Most zirconium compounds are absorbed poorly from the gastrointestinal tract although some salts such as zirconium tetrachloride may cause corrosive injury. Gastrointestinal toxicity Common early features of corrosive ingestion include immediate pain in the mouth, pharynx and abdomen, intense thirst, vomiting, haematemesis and diarrhoea. Gastric and oesophageal perforation and chemical peritonitis may also occur. Late features include antral or pyloric stenosis, jejunal stricture formation, achlorhydria, protein-losing gastroenteropathy and gastric carcinoma. Pulmonary toxicity Features associated with corrosive ingestion include hoarseness, stridor, respiratory distress and, in severe cases, laryngeal or epiglottal oedema. Chemical pneumonitis and adult respiratory distress syndrome (ARDS) are recognized. Nephrotoxicity Renal failure secondary to acute tubular necrosis may complicate ingestion of a corrosive zirconium salt. Cardiovascular toxicity Circulatory collapse is likely in patients with extensive gastrointestinal burns. Haemotoxicity Disseminated intravascular coagulation and haemolysis may complicate concentrated corrosive ingestions. Injection Two individuals developed vertigo following intravenous administration of 50 mg zirconium malate (Hathaway et al, 1991). CLINICAL FEATURES: CHRONIC EXPOSURE Dermal The use of soluble zirconium salts, notably sodium zirconium lactate, in deodorants (Rubin et al, 1956; Anon.,1958; Shelley and Hurley, 1958) has been associated with the development of axillary granulomas. These appear as red-brown or flesh coloured, mildly or non-pruritic papules which may form linear streaks, often associated with shaving and restricted to areas of deodorant application. Histologically they resemble sarcoid granulomas with epithelioid and multinucleate giant cells. Onset of the lesions is usually delayed for days to weeks after exposure with complete recovery within six to twelve months if exposure ceases. A more recent report linked the use of an aluminium zirconium complex to granuloma formation (Skelton et al, 1993). A 27 year-old woman developed a right axillary mass after some two years use of an antiperspirant containing aluminium zirconium tetrachlorohydrex glycerine. A year after its development the mass became acutely inflamed and was excised. Histological examination showed typical features of zirconium-induced granulomas and chemical analysis confirmed the presence of zirconium. The use of the antiperspirant was discontinued and no recurrence was reported after one year (Skelton et al, 1993). Similar lesions were reported in a 15 year old girl following treatment of poison ivy dermatitis with four per cent zirconium oxide cream. No granulomas appeared on intact skin areas indicating dermal damage is necessary for zirconium penetration. Oral prednisone (dose not stated), topical fluocinolone and intralesional injection of triamcinolone (6 mg/mL) each cleared the lesions leaving only areas of pigmentation. However, there was a complete recurrence on cessation of treatment and untreated granulomas showed no evidence of improvement over 20 months (Baler, 1965). The author noted that although cutaneous reactions to zirconium seemed less common following exposure to insoluble (e.g. zirconium oxide) than soluble (e.g. zirconium lactate) salts, once initiated reactions to insoluble salts were more likely to persist due to prolonged retention in dermal tissue. The development of lymph node sclerosis, leading to non-filarial elephantiasis has been associated with increased soil concentrations of zirconium and beryllium in Southwest Ethiopia (Frommel et al, 1993). The exposure of bare feet to zirconium rich soil is thought to be exacerbated by the corrosive nature of the clay particles. Inhalation Epidemiological studies of industrial exposure to zirconium compounds have found no evidence of impaired pulmonary function although individual cases of zirconium-induced lung disease have been reported. No zirconium-attributed abnormalities were reported in 22 workers exposed to fumes in a zirconium reduction plant for one to five years (Reed, 1956). A group of 32 male metal handfinishers exposed to zirconium dust for one to 17 years were examined for any adverse pulmonary function compared to a control group matched for age, sex, payroll status and smoking history. No significant difference in self-reported symptoms, chest X-rays or expiratory lung function tests were found (Hadjimichael and Brubaker, 1981). The pulmonary function of 178 men exposed to zirconium dust (mainly less than 10 mg/m3; maximum measured concentration 30.0 mg/m3) was monitored between 1975 and 1988 (Marcus et al, 1996). No abnormal chest X-ray findings (in 1975, 1978 and 1982) or impaired pulmonary function were found to have resulted from zirconium exposure. Conversely, Bartter et al (1991) described a 62 year-old man with apparent zirconium-induced pulmonary fibrosis. He was employed for 39 years at a lens grinding company where he was responsible for mixing a powder containing 90 per cent zirconium dioxide. He was a smoker and wore no respiratory protection during the course of his work. Over 25 years he became increasingly dyspnoeic, and was originally diagnosed with emphysema. Examination revealed clubbing of the fingers and toes with diffuse crackles and wheeze in both lungs. A series of X-rays taken between 1969 and 1988 showed progressive interstitial fibrosis with honeycombing in the lower zones bilaterally. Pulmonary function tests showed a restrictive picture with total lung capacity 56 per cent predicted, carbon monoxide diffusing capacity 37 per cent predicted and modest hypoxia (pO2 9.3 kPa; pCO2 normal). An open lung biopsy showed end-stage fibrosis and honeycombing but no granulomas. Polarizing light microscopy revealed a moderate number of birefringent particles. Further scanning electron microscope analysis revealed 69 x 106 particles/cm3, 60 x 106 of which contained zirconium oxide, zirconium silicate or zirconium aluminium silicate (normal < 1 x 106/cm3). Zirconium-specific proliferation studies on peripheral lymphocytes and pulmonary lymphocytes obtained via bronchoalveolar lavage were negative. The patient died of pneumonia with sepsis two years after initial examination (Bartter et al, 1991). Zirconium-induced hypersensitivity pneumonitis was considered the underlying cause of death in a 25 year old female ceramic tile worker (Liippo et al, 1993) who had a history of atopy. The patient had worked for 1.5 years as a glazier where she was exposed to 0.8-5.8 mg/m3 dust containing 10-30 per cent zirconium silicate. She previously had worked for two years as a sorter where dust concentrations were 0.5 - 2.6 mg/m3 and one month with special shaped ceramics where dust concentrations were as high as 8.6 mg/m3. At presentation she gave a two month history of dry cough and exertional breathlessness. Examination revealed crackles in both lungs with bilateral interstitial fibrosis and small discrete nodules on chest X-ray. Respiratory function was markedly decreased with FEV1 32 per cent predicted, FVC 34 per cent predicted and carbon monoxide diffusing capacity 36 per cent predicted. Oral prednisolone 1 mg/kg for nine months gave no improvement. An open lung biopsy was performed but was complicated by pneumothorax which precipitated acute right heart failure and fatal splenic rupture one week later. At autopsy the lungs showed features compatible with hypersensitivity pneumonitis with widespread interstitial lymphocytic inflammation, mild fibrosis and multiple noncaseating epithelioid granulomas with some multinucleate cells. Scanning electron microscopy revealed 1.3 x 109 zirconium silicate particles per gram dry weight of lung (Liippo et al, 1993). Zirconium-induced lung disease has been implicated also in a 29 year old male worker with suspected pneumoconiosis following eight years exposure to 1.1 mg/m3 inhalable dust containing zirconium silicate. Pulmonary function tests were normal though chest X-ray showed diffuse interstitial reticular opacities. A transbronchial biopsy revealed small interstitial granulomas which histologically contained epithelioid and giant cells with no central necrosis (Romeo et al, 1994). A recent review has concluded that while prolonged zirconium dust inhalation undoubtedly may cause a benign pneumoconiosis, there is insufficient evidence to confirm zirconium as a cause of a delayed (type IV) granulomatous hypersensitivity reaction as seen among beryllium workers (Parkes, 1994). Ingestion There are no reports of chronic ingestion of zirconium or its compounds. MANAGEMENT Dermal exposure Ensure adequate self protection before attempting treatment. If possible the patient should remove any contaminated clothing him/herself. Affected areas of skin should be washed with copious quantities of water. Pay special attention to skin folds, fingernails and ears. Burns should be treated conventionally as for thermal burns (e.g. silver sulphadiazine dressing). Surgery may be required for deep burns. Dermal granulomas usually clear spontaneously six to twelve months after removal from exposure (PATTY/Beliles, 1994; Obermayer, 1969), although they may remain for longer periods in individuals exposed to insoluble zirconium compounds (Baler, 1965). Topical and/or systemic steroids may hasten granuloma resolution. Ocular exposure Irrigate immediately with lukewarm water or preferably saline for at least 10-15 minutes. A local anaesthetic may be indicated for pain relief and to overcome blepharospasm. Specialist ophthalmic 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. Rarely mechanical ventilation may be required or tracheostomy if there is life-threatening laryngeal oedema. The administration of prednisolone 60-80 mg daily may be considered if laryngeal or pulmonary oedema are present but there is no confirmed evidence that their use alters prognosis. Discussion with a NPIS physician is recommended. Ingestion Decontamination Ingestion of most common zirconium compounds will require only symptomatic and supportive care as dictated by the patient's condition. However, if ingestion is of a corrosive salt a more aggressive approach may be required. Gastric aspiration/lavage following corrosive ingestion is contraindicated. There may be some benefit of attempting oral dilution with milk or water, if performed immediately, though this is controversial. Fluids should not be offered if the patient is not fully conscious, is unable to swallow or protect his/her own airway, has respiratory difficulty or severe abdominal pain. Possible complications of fluid administration include vomiting, aspiration, perforation of the gastrointestinal tract and worsening of oesophageal or gastric injuries. Supportive measures Airway support and analgesia should be provided as required. Treat shock with intravenous colloid/crystalloid and/or blood. Monitor biochemical and haematological profiles and acid/base status. Administer antibiotics for established infection only. Symptoms and signs are unreliable predictors of the extent of injury following corrosive ingestion (Zargar et al, 1989) and therefore in symptomatic patients panendoscopy should be carried out, ideally within 12-24 hours to gauge the severity of injury. Grade 0: Normal examination 1: Oedema, hyperaemia of mucosa 2a: Superficial, localized ulcerations, friability, blisters 2b: Grade 2a findings and circumferential ulcerations 3: Multiple, deep ulceration, areas of necrosis (Zargar et al, 1989). Following corrosive acid ingestion endoscopic findings within the first 36 hours have been successfully used to guide management. In a series of 41 patients (Zargar et al, 1989) those with grade 0 to 1 burns were discharged within one or two days, those with grade 2a burns required only supportive care for a little longer, whereas those with 2b and 3 burns required nutritional support via jejunostomy feeding (total parenteral nutrition is an alternative). All patients with grade 0, 1 and 2a injury recovered without sequelae. Acute complications and death were confined to those with grade 3 burns although several patients with grade 2b burns developed oesophageal or gastric strictures. In view of the high morbidity associated with corrosive-induced upper gastrointestinal perforation and the high incidence of later complications requiring surgery, an aggressive surgical approach is recommended (Jeng et al, 1994). Surgery should therefore be considered: 1. If symptoms or signs of gastrointestinal tract perforation are evident at initial presentation. 2. When endoscopy reveals evidence of grade 3 burns with full- thickness necrosis (black, ulcerated mucosa) of the stomach or oesophagus. Corticosteroids In a controlled trial of steroid use among 60 children with oesophageal burns following corrosive ingestion (alkalis in the majority) the use of steroids (intravenous prednisolone 2 mg/kg within 24 hours and daily until oral intake was resumed then prednisolone 2.5 mg/kg orally daily for at least three weeks) did not influence outcome (Anderson et al, 1990). Smaller case series have also concluded that systemic corticosteroids confer no benefit following acid ingestion and may exacerbate or mask symptoms of pending perforation (Hawkins et al, 1980). MEDICAL SURVEILLANCE Ensure adequate ventilation and air concentrations below the occupational exposure standard. Appropriate respiratory and dermal protective equipment should be available. In particular, the exposure of broken skin to zirconium compounds must be avoided. People with respiratory disease should be identified prior to employment if inhalational exposure is likely. Normal zirconium concentrations in biological fluids NIF OCCUPATIONAL DATA Occupational exposure standard Short-term exposure limit (15 minute reference period) 3.8 mg/m3. Long term exposure limit 1.3 mg/m3 (8 hour TWA reference period) (Health and Safety Executive, 1997). OTHER TOXICOLOGICAL DATA Carcinogenicity There is no evidence regarding the carcinogenicity of zirconium in humans (REPROTEXT, 1997). However, there is an increased risk of gastric cancer following severe mucosal damage after corrosive ingestion. Reprotoxicity There is no conclusive evidence that zirconium is reprotoxic in man (REPROTEXT, 1997). Genotoxicity Salmonella typhimurium TA98, TA100, TA102, TA1537, TA2637 negative. When tested in combination with 9-aminoacridine, the mutation rate was higher than that for 9-aminoacridine alone (zirconium tetrachloride) (DOSE, 1994). Fish toxicity LC50 (96hr) fish (unspecified) bioassay >20 mg/L (DOSE, 1994). 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 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 Anonymous. Zirconium granulomas. Lancet 1958; 1: 1164-5. Anderson KD, Rouse TM, Randolph JG. A controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med 1990; 323: 637-40. Baler GR. Granulomas from topical zirconium in poison ivy dermatitis. Arch Dermatol 1965; 91: 145-48. Bartter T, Irwin RS, Abraham JL, Dascal A, Nash G, Himmelstein JS, Jederlinic PJ. Zirconium compound-induced pulmonary fibrosis. Arch Intern Med 1991; 151: 1197-1201. Castello G, Vigo F, Gallelli G, Beccaria AM. Determination of radioactive impurities in zirconium minerals used in the ceramic industry and risk analysis for exposed workers. Int J Environ Stud 1992; 42: 271-9. CHIP2/Chemicals (Hazard Information and Packaging for Supply) Regulations 1994. Health and Safety Commission. Sudbury: Heath and Safety Executive, 1994. Cordasco EM, Stone FD. Pulmonary edema of environmental origin. Chest 1973; 64: 182-5. DOSE/Dictionary of substances and their effects. Vol 5. Cambridge: Royal Society of Chemistry, 1994. Frommel D, Ayranci B, Pfeifer HR, Sanchez A, Frommel A, Mengistu G. Podoconiosis in the Ethiopian rift valley. Role of beryllium and zirconium. Trop Geogr Med 1993; 45: 165-7. Hadjimichael OC, Brubaker RE. Evaluation of an occupational respiratory exposure to a zirconium-containing dust. J Occup Med 1981; 23: 543-7. Hathaway GJ, Proctor NH, Hughes JP, Fischman ML (eds). Chemical hazards of the workplace. 3rd ed. New York: Van Nostrand Reinhold, 1991. Hawkins DB, Demeter MJ, Barnett TE. Caustic ingestion: controversies in management. A review of 214 cases. Laryngoscope 1980; 90: 98-109. Hazardtext. In: Tomes plus. Environmental Health and Safety Series 1. Vol 33. Colorado: Micromedex, Inc., 1997. Health and Safety Executive EH40/97. Occupational exposure limits 1997. Sudbury: Health and Safety Executive, 1997. HSDB/Hazardous Substances Data Bank. In: Tomes plus. Environmental Health and Safety Series 1. Vol 32. National Library of Medicine, 1997. Jeng L-BB, Chen H-Y, Chen S-C, Hwang T-L, Jan Y-Y, Wang C-S, Chen M-F. Upper gastrointestinal tract ablation for patients with extensive injury after ingestion of strong acid. Arch Surg 1994; 129: 1086-90. Liippo KK, Anttila SL, Taikina-Aho O, Ruokonen E-L, Toivonen ST, Tuomi T. Hypersensitivity pneumonitis and exposure to zirconium silicate in a young ceramic tile worker. Am Rev Respir Dis 1993; 148: 1089-92. Marcus RL, Turner S, Cherry NM. A study of lung function and chest radiographs in men exposed to zirconium compounds. Occup Med 1996; 46: 109-13. Meditext. In: Tomes plus. Environmental Health and Safety Series 1. Vol 32. Colorado: Micromedex, Inc., 1997. MERCK/The Merck Index. Zirconium. In: Budavari S, ed. An encyclopedia of chemicals, drugs, and biologicals. 12th ed. New Jersey: Merck and Co., Inc., 1996; 1737. Obermayer ME. Chronic granulomatous inflammation in axillae: reaction to zirconium? Arch Dermatol 1969; 100: 505. PATTY/Beliles RP. The metals: zirconium. In: Clayton GD, Clayton FE, eds. Patty's industrial hygiene and toxicology. Vol 2. 4th ed. New York: John Wiley & Sons, Inc. 1994; 2342-52. Parkes WR. Non-fibrogenic ('inert') minerals and pneumoconiosis. In: Parkes WR, ed. Occupational lung disorders. 3rd ed. Oxford: Butterworth-Heinemann Ltd,1994; 253-84. Price RJ, Skilleter DN. Mitogenic effects of beryllium and zirconium salts on mouse splenocytes in vitro. Toxicol Letts 1986; 30: 89-95. Reed CE. A study of the effects on the lung of industrial exposure to zirconium dust. Arch Ind Health 1956; 13: 578-80. REPROTEXT. In: Tomes plus. Environmental Health and Safety Series 1. Vol 32. Colorado: Micromedex, Inc., 1997. Romeo L, Cazzadori A, Bontempini L, Martini S. Interstitial lung granulomas as a possible consequence of exposure to zirconium dust. Med Lav 1994; 85: 219-22. 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. Rubin L, Slepyan AH, Weber LF, Neuhauser I. Granulomas of the axillas caused by deodorants. JAMA 1956; 162: 953-5. SAX'S/Lewis RJ. Sax's dangerous properties of industrial materials. 9th ed. Vol 3. New York: Van Nostrand Reinhold, 1996. Schroeder HA, Balassa JJ. Abnormal trace metals in man: zirconium. J Chronic Dis 1966; 19: 573-86. Shelley WB, Hurley HJ. The allergic origin of zirconium deodorant granulomas. Br J Dermatol 1958; 70: 75-101. Skelton HG, Smith KJ, Johnson FB, Cooper CR, Tyler WF, Lupton GP. Zirconium granuloma resulting from an aluminium zirconium complex: a previously unrecognized agent in the development of hypersensitivity granulomas. J Am Acad Dermatol 1993; 28: 874-6. Zargar SA, Kochhar R, Nagi B, Mehta S, Mehta SK. Ingestion of corrosive acids. Spectrum of injury to upper gastrointestinal tract and natural history. Gastroenterology 1989; 97: 702-7.
See Also: Zirconium (ICSC)