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, Sœyseth 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; Sœyseth 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
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See Also:
Toxicological Abbreviations