UKPID MONOGRAPH ALUMINIUM OXIDE SM Bradberry BSc MB MRCP ST Beer 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. ALUMINIUM OXIDE Toxbase summary Type of product Used as a component of paints and varnishes and in the manufacture of alloys, ceramics, glass, electrical insulators and resistors. Toxicity Significant toxicity has been reported only following chronic occupational inhalation. Features Topical - Aluminium contact sensitivity has been described but is extremely rare. Inhalation - There are no case reports relating to acute exposure. - Chronic occupational exposure causes conjunctivitis, pharyngitis, and nasal irritation. Occupational asthma has been reported in aluminium smelter workers but these individuals are exposed to several other potential allergens (including fluorides and sulphur dioxide). - Chronic aluminium oxide inhalation may cause pneumoconiosis with cough and exertional dyspnoea, diffuse reticulonodular shadowing on chest X-ray and a restrictive pattern of pulmonary function. In severe cases death may result from respiratory failure or corpulmonale. - There is evidence from controlled studies among aluminium workers that chronic aluminium oxide exposure with an increased body aluminium burden may be associated with neurocognitive dysfunction but not increased mortality. Management Topical 1. Remove from exposure. 2. Treat symptomatically. Inhalation 1. Remove from exposure. 2. Give supplemental oxygen by face-mask if there is evidence of respiratory distress. 3. Asthmatic symptoms respond to conventional measures. 4. In chronic exposure suspected pulmonary fibrosis should be investigated and managed conventionally. 5. Obtain blood and urine for aluminium concentration estimations in symptomatic patients. Discuss with NPIS as these analyses are not widely available. 6. Estimation of the aluminium content of CSF may be an important investigation in suspected aluminium-related dementia. 7. There is no established role for chelation therapy in chronic aluminium oxide poisoning. Discuss with NPIS. References Bast-Pettersen R, Drablos PA, Goffeng LO, Thomassen Y, Torres CG. Neuropsychological deficit among elderly workers in aluminum production. Am J Ind Med 1994; 25: 649-62. Jederlinic PJ, Abraham JL, Churg A, Himmelstein JS, Epler GR, Gaensler EA. Pulmonary fibrosis in aluminum oxide workers. Investigation of nine workers, with pathologic examination and microanalysis in three of them. Am Rev Respir Dis 1990; 142: 1179-84. Kongerud J, Boe J, Syseth V, Naalsund A, Magnus P. Aluminium potroom asthma: the Norwegian experience. Eur Resp J 1994; 7: 165-72. Nielsen J, Dahlqvist M, Welinder H, Thomassen Y, Alexandersson R, Skerfving S. Small airways function in aluminium and stainless steel welders. Int Arch Occup Environ Health 1993; 65: 101-5. Schwarz YA, Kivity S, Fischbein A, Ribak Y, Fireman E, Struhar D, Topilsky M, Greif J. Eosinophilic lung reaction to aluminium and hard metal. Chest 1994; 105: 1261-3. Sjögren B, Ljunggren KG, Almkvist O, Frech W, Basun H. A follow-up study of five cases of aluminosis. Int Arch Occup Environ Health 1996; 68: 161-4. Substance name Aluminium oxide Origin of substance Occurs naturally as minerals such as bauxite, corundum, diaspore and gibbsite. (CSDS, 1989) Synonyms Aluminium Aluminum Aluminium sesquioxide (CSDS, 1989) Alumina (DOSE, 1992) Chemical group A compound of aluminium, a group III metal. Reference numbers CAS 1344-28-1 (CSDS, 1989) RTECS BD1200000 (RTECS, 1996) UN NIF HAZCHEM CODE NIF Physicochemical properties Chemical structure Aluminium oxide, Al2O3 (DOSE, 1992) Molecular weight 101.96 (DOSE, 1992) Physical state at room temperature Solid (powder) (CSDS, 1989) Colour White (CSDS,1989) Odour NIF Viscosity NA pH NA Solubility Insoluble in water, practically insoluble in non-polar organic solvents, slowly soluble in aqueous alkaline solutions. (CSDS, 1989) Autoignition temperature NA Chemical interactions Aluminium oxide will react vigorously with vinyl acetate vapour, exothermically with halogenated carbon compounds (above 200°C), and exothermically, possibly explosively with oxygen difluoride. A mixture of aluminium oxide and sodium nitrite will react explosively, and ignition will occur if chlorine trifluoride is mixed with aluminium oxide. Aluminium oxide should be kept well away from water, and is incompatible with strong oxidizers and chlorinated rubber. (CSDS, 1989) Major products of combustion NIF Explosive limits NA Flammability Non-flammable (CSDS, 1989) Boiling point 2977°C (CSDS, 1989) Density 4.0 at 20°C/4°C (DOSE, 1992) Vapour pressure 133.3 Pa at 2158°C (CSDS, 1989) Relative vapour density NIF Flash point NA Reactivity NIF Uses Aluminium oxide is used as an adsorbant, desiccant, as a filler for paints and varnishes, and as a catalyst for organic reactions. Aluminium oxide is employed widely in the manufacture of alloys, ceramics, glass, electrical insulators and resistors. (CSDS, 1989; DOSE, 1992) Hazard/risk classification NIF INTRODUCTION AND EPIDEMIOLOGY Aluminium is the most abundant metal on earth, naturally occurring in rocks as bauxite (aluminium oxide), mica and feldspar (aluminosilicates). It is a light metal which is a good conductor of both heat and electricity. Aluminium oxide forms as a thin surface layer when aluminium is exposed to air, making it resistant to corrosion. Aluminium oxide is used as an industrial catalyst, adsorbant, desiccant, and as a filler for paints and varnishes. It is also employed widely in the manufacture of alloys, ceramics, glass, electrical insulators and resistors. Aluminium oxide is an insoluble aluminium compound which does not produce an acute toxic response. The presumed low toxicity of inhaled aluminium oxide led in the past to its use as a prophylactic agent against silicotic lung disease in miners but this practice was abandoned in the 1970's amid concern that chronic exposure may be harmful. Current important sources of occupational exposure via inhalation are aluminium smelting and welding. MECHANISM OF TOXICITY There is experimental evidence that aluminium inhibits bone mineralization partly by the deposition of aluminium at the osteoid/calcified-bone boundary thereby directly inhibiting calcium influx, and partly by aluminium accumulation in the parathyroid glands with suppression of parathyroid hormone secretion (Visser and Van de Vyver, 1985; Berland et al, 1988; Firling et al, 1994). Proposed mechanisms of aluminium-induced neurotoxicity include free-radical damage via enhanced lipid peroxidation, impaired glucose metabolism, effects on signal transduction and protein modification and alterations in the axonal transport and phosphorylation state of neurofilaments (Birchall and Chappell, 1988; Exley and Birchall, 1992; Erasmus et al, 1993; Winship, 1993; Haug et al, 1994; Joshi et al, 1994; Strong, 1994). It has also been suggested that low-level aluminium exposure may influence the body distribution of other essential metals with potential adverse metabolic effects (Röllin et al, 1991). TOXICOKINETICS Absorption In a healthy adult only approximately 15µg of the average daily dietary aluminium intake of 3-5mg is absorbed (Winship, 1992). The intestinal absorption of aluminium and its oxide is enhanced by citrate (which is found frequently in effervescent drug formulations) and reduced by silica. Since aluminium oxide is insoluble it is poorly absorbed following inhalation. Distribution Since aluminium oxide is insoluble some will be retained in the lung following inhalation. More than 90 per cent of that which is systematically absorbed is bound to transferrin which does not cross the blood-brain barrier readily. The remaining ten per cent is associated with low molecular weight complexes, such as citrate, which can accumulate in brain tissue. Systematically absorbed aluminium is stored mainly in bone (up to 40 per cent) and liver. Excretion Aluminium is excreted predominantly via the kidneys and therefore will accumulate in patients with renal failure (Alfrey, 1980). Following long-term occupational inhalation, aluminium oxide exposed workers with normal renal function may also accumulate aluminium. In two such cases the total body aluminium half-life was estimated as three years (Elinder et al, 1991). CLINICAL FEATURES: ACUTE EXPOSURE Aluminium oxide ingestion is rare and does not lead to significant toxicological problems; most exposures are via inhalation. No features following acute inhalation have been reported. CLINICAL FEATURES: CHRONIC EXPOSURE Ocular exposure In one study conjunctivitis was reported significantly more frequently among aluminium welders (n=25) than controls (Nielsen et al, 1993). Dermal exposure Dermal toxicity Thériault et al (1980) described an increased number of skin telangiestases on the upper torso of workers in an aluminium plant. There were no associated clinical features and the causative agent was thought to be a hydrocarbon or fluoride emitted from the aluminium electrolytic reactors (Thériault et al, 1980). There are reports of contact sensitivity to aluminium but this is extremely rare (Kotovirta et al, 1984). Inhalation Pulmonary toxicity Because metallic aluminium has an high affinity for oxygen, exposure to aluminium dust usually also involves exposure to aluminium oxide. Important sources of such exposure include aluminium smelting (among 'potroom' workers) and welders. In some industries sub-micron sized aluminium particles are coated with oil to prevent surface aluminium oxide formation. Removal of this protective coating in vivo however exposes the metal to powerful natural oxidizing agents and tissue damage may result (Dinman, 1987). Smokers are at greater risk of pulmonary complications from aluminium dust as they have a reduced ability to clear inhaled particles from the lungs. In a controlled study of respiratory symptoms among 25 aluminium welders Nielsen et al (1993) reported a significantly increased incidence of pharyngitis. Interestingly, employees exposed to aluminium/aluminium oxide for less than 2´ years were more likely to experience this symptom, possibly reflecting 'healthy worker' selection or the development of tolerance. Chronic exposure to stamped aluminium powder (aluminium flake), produced by grinding hard unmelted aluminium, may cause pneumoconiosis. Initial symptoms include dyspnoea and cough although in some patients the first clue to respiratory disease is the finding of widespread miliary nodules on chest X-ray (Sjögren et al, 1996a). A honeycomb pattern is observed on lung biopsy and lung function tests show a restrictive pattern (Jederlinic et al, 1990). Patients may develop progressive exertional dyspnoea terminating in respiratory failure or corpulmonale (Mitchell, 1959; Mitchell et al, 1961; Sjögren et al, 1996a). Spontaneous regression is rare and should prompt reconsideration of the diagnosis (Sjögren et al, 1996a). Aluminium oxide-induced pulmonary fibrosis may be associated with generalized debility and weight loss (Schwarz et al, 1994). Schwarz et al (1994) described a 51 year-old sand-blaster who presented with an eight month history of cough and dyspnoea. Chest X-ray showed diffuse bilateral reticulonodular opacities in the mid and lower zones and bronchoalveolar lavage (BAL) fluid analysis revealed a marked eosinophilia (61.6 per cent). Transbronchial biopsy was consistent with interstitial pneumonia (with a giant-cell infiltrate and dust-laden macrophages). Mineralogic assessment identified large amounts of aluminium silicate and "hard metal". There was symptomatic and radiological improvement and partial resolution of BAL eosinophilia (to ten per cent) following removal from exposure and three months oral steroid therapy (prednisolone 40mg daily). The authors proposed a multifactorial aetiology in this case involving aluminium, 'hard metal' and iron exposure plus idiopathic predisposition. In a controlled study of 14 potroom workers exposed to aluminium oxide for a mean period of 12.9 ± (SD) 9 years, analysis of bronchoalveolar lavage fluid demonstrated a mild alveolitis (as indicated by altered macrophage activity and increased alveolar capillary permeability) but no evidence of restrictive lung disease (Eklund et al, 1989). Occupational asthma has been reported in aluminium-smelter (potroom) workers (Kongerud et al, 1990; Saric and Marelja, 1991; Kongerud et al, 1992; Desjardins et al, 1994) but these individuals are exposed to several other allergens including fluorides and sulphur dioxide (Kongerud and Samuelsen, 1991; Syseth and Kongerud, 1992; Kongerud et al, 1992; Kongerud et al, 1994) which makes it difficult to identify a specific aetiological agent. Neuropsychiatric toxicity There is increasing speculation that Alzheimer's disease may be linked aetiologically to the accumulation of aluminium in the brain but this remains a highly contentious issue (Ebrahim, 1989; Petit, 1989; Murray et al, 1991; Crapper McLachlan, 1994; Munoz, 1994). Animal studies have demonstrated the ability of aluminium to induce the formation of neurofibrillary tangles (Klatzo et al, 1965), impair the learning ability of rats, and increase brain acetylcholinesterase activity in a similar way to that seen in Alzheimer's disease (Bilkei-Gorzó, 1993). Other workers have shown elevated aluminium concentrations in brain tissue from patients with Alzheimer's disease (Crapper et al, 1973) and laser microprobe studies have demonstrated aluminium accumulation in the neurofibrillary tangles of these patients (Good et al, 1992). There is conflicting evidence as to whether neuropsychiatric sequelae result from chronic aluminium oxide exposure. Gibbs (1981) reported no increased mortality from Alzheimer's disease in over 5000 men employed at an aluminium plant. Clinical examination of 23 workers in an aluminium factory found no neurological signs or symptoms although another man who had worked in the same plant for 13´ years died from rapidly progressive encephalopathy (McLaughlin et al, 1962). Autopsy showed no identifiable cause of death or histological abnormality in the brain but the brain aluminium content was reported to be 20 times higher than normal. Rifat et al (1990) found that although there was no increased incidence of neurological diagnoses in miners exposed between 1944 and 1979 to a mixture of powdered aluminium and aluminium oxide, exposed workers performed significantly less well on cognitive testing than unexposed controls; the likelihood of impairment increased with duration of exposure. Bast-Pettersen et al (1994) performed neuropsychological tests on 38 men who had worked for at least ten years in an aluminium production plant. Potroom workers had significantly raised urine aluminium concentrations compared to controls; the serum aluminium concentration was normal in all groups. Potroom workers also had a significantly increased incidence of subclinical tremor compared to controls with some evidence of impaired visuospatial organization. In another controlled study of 38 aluminium welders with a median exposure of 7065 hours, a significant dose-related deterioration in certain motor function tests (for example tapping with the non- dominant hand) was observed (Sjögren et al, 1996b). Aluminium exposed workers had urine aluminium concentrations (spot samples) approximately seven times higher than controls. Several uncontrolled studies (Sjögren et al, 1990; White et al, 1992; Hänninen et al, 1994) have reported subtle memory defects in aluminium workers. Hänninen et al (1994) demonstrated a negative association between short-term memory loss, learning and attention, and the urine aluminium concentration. White et al (1992) also found clinical evidence of incoordination in 84 per cent of the 25 workers examined. Sjögren et al (1994 and 1996a) described a 78 year-old man with a 47 year history of aluminium pneumoconiosis, mild extrapyramidal impairment and moderate dementia. His cerebrospinal fluid aluminium concentration was markedly raised to 259µg/L (normal <10µg/L) without a rise in the serum and urine aluminium concentrations and with no evidence of cerebrovascular disease. Conclusions Controlled studies among aluminium workers suggest that chronic aluminium/aluminium oxide exposure with an increased body aluminium burden may be associated with neurocognitive dysfunction but not an increased mortality. There is insufficient evidence, however, to implicate occupational aluminium oxide exposure in the aetiology of Alzheimer's disease. Bone toxicity Schmid et al (1995) observed increased plasma and urine aluminium concentrations (mean 9.7µg/L and 115.8µg/L respectively) among 32 aluminium production plant workers (corresponding values among 29 controls were 4.3µg/L and 15.5µg/L respectively). There was however no significant difference in lumbar spine bone mineral content (as measured by photon absorptiometry) between the two groups. The authors concluded that occupational aluminium/aluminium oxide exposure did not adversely effect bone density (Schmid et al, 1995). MANAGEMENT Dermal exposure Dermal manifestations following topical aluminium oxide are rare. If suspected treatment is supportive with removal from exposure. Inhalation Patients with suspected occupational pulmonary toxicity should be removed from exposure, treated symptomatically and undergo a full assessment of respiratory function. Asthmatic symptoms respond to conventional measures although Saric and Marelja (1991) demonstrated persistent bronchial hyperresponsiveness among potroom workers with occupational asthma (n=30) several years (mean 3.7) following a change of occupation. Partial resolution of radiographic chest X-ray opacities has been reported following systemic corticosteroid therapy in an aluminium exposed worker with pulmonary fibrosis (Schwarz et al, 1994) but this is unusual. Antidotes Desferrioxamine (deferoxamine) Desferrioxamine forms a stable complex with aluminium and in animal studies it mobilises aluminium primarily from bone with subsequent urinary elimination of the chelate (Gómez et al, 1994; Yokel, 1994). It is absorbed poorly from the gastrointestinal tract and parenteral therapy is necessary. Theoretically 100mg desferrioxamine can bind 4.1mg aluminium (Winship, 1993). The desferrioxamine chelate is dialyzable and all published clinical studies of aluminium chelation using desferrioxamine involve patients with renal failure undergoing haemodialysis (Sulkova et al, 1991) or, less commonly, peritoneal dialysis (O'Brien et al, 1987) or haemofiltration (Sulkova et al, 1991). This is discussed in detail in the aluminium sulphate monograph. Sulkova et al (1991) suggested that desferrioxamine-induced aluminium clearance is greater following haemofiltration (mean serum aluminium concentration reduction 66 per cent for 36 filtrations, each a 60 per cent body weight volume exchange) than haemodialysis (mean serum aluminium concentration reduction 41 per cent for 28 five hour dialyses). Available clinical evidence suggests desferrioxamine therapy can improve aluminium-induced encephalopathy in chronic haemodialysis patients (Day and Ackrill, 1993) and parenteral desferrioxamine therapy may slow the rate of cognitive deterioration in patients with Alzheimer's disease (Crapper McLachlan et al, 1991; Crapper McLachlan et al, 1993) but there are no data relating to desferrioxamine therapy following aluminium oxide exposure. If aluminium-induced neurocognitive impairment is confirmed desferrioxamine therapy may have a role. Desferrioxamine and charcoal haemoperfusion Chang and Barre (1983) compared aluminium clearance by desferrioxamine plus charcoal haemoperfusion with desferrioxamine plus haemodialysis in 17 patients with chronic renal failure who were stable on standard haemodialysis. Neither method enhanced aluminium clearance without desferrioxamine but forty-eight hours after intravenous desferrioxamine charcoal haemoperfusion produced more effective aluminium clearance (mean 65.3 ± (SD) 11.2 mL/min; n=6) than haemodialysis (mean 44.6 ± (SD) 13.7mL/min; n=4). The authors proposed haemoperfusion plus desferrioxamine as an effective method of rapid aluminium elimination in aluminium intoxicated patients to be used in series with haemodialysis in patients with renal failure. There are no data involving patients with aluminium oxide toxicity. Indications In patients exposed to aluminium oxide desferrioxamine therapy could be considered in those with neurocognitive abnormalities associated with a confirmed increased body aluminium burden but there are no clinical data to support this. Treatment protocol for desferrioxamine This is based on experience with aluminium intoxicated haemodialysis patients and is usually a once weekly intravenous does of 40-80mg/kg. The dose can be reduced to 20-60mg/kg (as indicated by response and adverse effects) if treatment is to be continued for several months (Domingo, 1989). Canavese et al (1989) have suggested the therapeutic effectiveness of desferrioxamine may be exhausted after some two years therapy even if aluminium bone deposits persist after this time. Adverse effects of desferrioxamine Side-effects of long-term treatment with desferrioxamine include hypotension, gastrointestinal upset, porphyria cutanea tarda-like lesions, transient visual disturbances (McCarthy et al, 1990), posterior cataracts, ototoxicity (Domingo, 1989) and an increased potential for septicaemia, especially Yersinia sepsis (Boyce et al, 1985). Some dialysis patients with aluminium encephalopathy develop worsening of neurological symptoms within hours of desferrioxamine treatment which may be due to desferrioxamine alone or in combination with a rising plasma aluminium concentration (McCauley and Sorkin, 1989). There are several reports of desferrioxamine-associated systemic fungal infection (mucormycosis) in dialysis patients (Goodill and Abuelo, 1987; Windus et al, 1987). An international registry of this potentially fatal complication has been established (Boelaert et al, 1991) although a causal link between desferrioxamine and fungal infection in these patients has not been confirmed (Vlasveld and van Asbeck, 1991). Other chelating agents The practical problems of desferrioxamine administration and its side effects have prompted a search for an alternative aluminium chelator although as yet none has been confirmed (Domingo, 1989; Main and Ward, 1992; Yokel, 1994). Uncontrolled clinical studies with d-penicillamine and dimercaprol in dialysis encephalopathy were unsuccessful (Yokel, 1994) and although in animal studies parenteral citric acid is effective (Domingo et al, 1988), evidence in man that oral citrate enhances gastrointestinal aluminium absorption means the problems of parenteral administration persist. Rats treated with intraperitoneal aluminium (as the chloride) 2mg/kg daily, four days per week for four weeks, followed by 40mg/kg intraperitoneal ethylenediamine-N,N'-di(2-hydroxyphenyl acetic acid) (EDDHA) showed significantly increased (p<0.05) urine aluminium excretion but no reduction in tissue aluminium concentrations (Graff et al, 1995). In a recent clinical trial Kontoghiorghes et al (1994) demonstrated that the administration of oral 1,2-dimethyl-3-hydroxypyrid-4-one in a dose of 40-60 mg/kg to six haemodialysis patients resulted in rapid aluminium mobilization. The plasma aluminium concentration peaked at one hour post chelation therapy and returned to baseline in most cases within seven hours. The aluminium chelate was readily dialysable during both haemodialysis and continuous ambulatory peritoneal dialysis. Haemodialysis Sulkova et al (1991) reported no aluminium elimination during four haemodialyses without prior desferrioxamine administration. Peritoneal dialysis Aluminium is removed in small amounts by peritoneal dialysis (O'Brien et al, 1987) and elimination is enhanced by desferrioxamine. In a 32 year-old man with aluminium osteodystrophy O'Brien et al (1987) reported an aluminium clearance of 2.5mL/min with continuous ambulatory peritoneal dialysis (CAPD) alone. CAPD plus intravenous desferrioxamine (six grams once a week) gave an aluminium clearance of 4.2mL/min compared to a clearance of 3.1mL/min when the same cumulative desferrioxamine dose was given into the peritoneal cavity. Haemofiltration During four haemofiltrations (each with a 60 per cent body weight volume exchange) Sulkova et al (1991) reported a mean 15 per cent fall in the serum aluminium concentration compared to a mean 66 per cent reduction (36 haemofiltrations) in patients pre-treated with desferrioxamine (see above). Haemoperfusion Chang and Barre (1983) demonstrated that haemoperfusion enhances aluminium elimination only in the presence of desferrioxamine. Protein(transferrin)-bound aluminium is not dialyzable (Day and Ackrill, 1993). Enhancing elimination: Conclusions and recommendations There is currently insufficient data to advocate chelation therapy or extracorporal methods of enhancing elimination in aluminium oxide poisoning. Most cases involve pulmonary complications following inhalational exposure and should be managed conventionally. The role of chelating agents in the management of neuropsychiatric sequelae remains to be determined. MEDICAL SURVEILLANCE Monitoring airborne aluminium concentrations and periodic assessment of respiratory function are important surveillance measures in the aluminium industry. Aluminium toxicity should be particularly sought in those who develop unexplained respiratory or neuropsychiatric symptoms. Measurement of blood and urine aluminium concentrations are of some value but close attention must be paid to avoiding sample contamination and consideration given to the potential effect of aluminium-containing medications (House, 1992). Grouped data are preferable to individual results. The interpretation of urine aluminium concentrations is complicated by the fact that the kinetics of urine aluminium excretion varies depending on the form of aluminium involved (Pierre et al, 1995). Aluminium is evenly distributed between plasma and blood cells so that plasma and whole blood aluminium concentrations have similar value in assessing toxicity (van der Voet and de Wolff, 1985). Thirteen workers exposed to aluminium flake ('atomised' aluminium solid) had significantly higher mean urine (203.6µg/L) and blood (12.4µg/L) aluminium concentrations compared to controls (median urine and blood concentrations 2.4µg/L and less than 2.7µg/L respectively) although the higher values in exposed workers were not related to duration of exposure time (Ljunggren et al, 1991). In the same study the mean urine and blood aluminium concentrations among ten retired workers were 20.0µg/L and 3.0µg/L respectively. Gitelman et al (1995) observed a strong association between grouped urine aluminium concentrations and airborne occupational exposure but emphasised that individual measurements were not reliable. In a study comparing 84 aluminium smelter workers with 48 controls, significantly higher mean urine aluminium concentrations were observed in workers exposed to airborne aluminium concentrations higher than 0.35mg/m3 (TLV = 10mg/m3) (Röllin et al, 1996). Urine aluminium monitoring was not useful at lower aluminium exposures, probably because a smaller proportion of the total airborne metal was in the respirable fraction. Serum aluminium concentrations were less valuable than urinary aluminium as a biological indicator of exposure. Estimation of the aluminium content of cerebrospinal fluid may be important in the investigation of aluminium-related dementia (Sjögren et al, 1994; Sjögren et al, 1996a). Hair analysis is a poor indicator of aluminium exposure (Wilhelm et al, 1989). AT RISK GROUPS Preterm infants have a limited ability to excrete aluminium. OCCUPATIONAL DATA Occupational exposure standard Long term exposure limit (8 hour TWA reference period) total inhalable dust 10 mg/m3, respirable dust 5mg/m3 (Health and Safety Executive, 1995). OTHER TOXICOLOGICAL DATA Carcinogenicity Workers involved in aluminium production may be at increased risk of developing lung cancer but mortality figures are difficult to interpret, especially when comprehensive occupational and smoking histories are not available (Andersen et al, 1982). Moreover, these workers are exposed to a number of established carcinogens including asbestos, chromium and polycyclic aromatic hydrocarbons (Dufresne et al, 1996). Higher than expected mortality from other cancers, including lymphoreticular and genitourinary malignancies have also been reported (Gibbs, 1981; Rockette and Arena, 1983) but again concomitant exposure to polycyclic aromatic hydrocarbons is likely to be involved (Thériault et al, 1984; Spinelli et al, 1991). In 521 workers exposed to aluminium oxide in an abrasive manufacturing plant and followed up between 1958 and 1983 Edling et al (1987) found no significantly increased cancer morbidity or mortality. Reprotoxicity NIF Genotoxicity Bacillus subtilis H17 (rec+), M45 (rec-) negative DNA damage (DOSE, 1992). Fish toxicity NIF EEC Directive on Drinking Water Quality 80/778/EEC Aluminium: Guide level 0.05mg/L, maximum admissible concentration 0.2g/L (DOSE, 1992). WHO Guidelines for Drinking Water Quality No health-based guideline value is recommended (WHO,1993). AUTHORS SM Bradberry BSc MB MRCP ST Beer 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 17/1/97 REFERENCES Alfrey AC. Aluminum metabolism in uremia. Neurotoxicology 1980; 1: 43-53. 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