SM Bradberry BSc MB MRCP
    ST Beer BSc

    National Poisons Information Service
    (Birmingham Centre),
    West Midlands Poisons Unit,
    City Hospital NHS Trust,
    Dudley Road,
    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


    Toxbase summary

    Type of product

    Used in the paper industry, in water purification, for tanning
    leather, fireproofing and water proofing cloth and in antiperspirants.


    Most cases occur in renal dialysis patients exposed to intravenous or
    intraperitoneal aluminium-containing dialysates.

    Mild gastrointestinal symptoms were reported in Camelford in 1988
    after residents drank water to which aluminium sulphate had
    inadvertently been added in substantial amount, but there were no
    confirmed on-going adverse sequelae.



         -    Irritant to the skin and eyes.


    Minor ingestions (dilute solutions):
         -    Burning in the mouth and throat, mild gastrointestinal

    Substantial ingestions:
         -    Nausea, vomiting, diarrhoea, abdominal pain, rarely
              haemorrhagic gastritis, circulatory collapse and multi-organ
         -    Increased aluminium absorption and retention in bone is
              reported following acute ingestion without apparent adverse

         -    Chronic exposure to aluminium sulphate in drinking water may
              be involved in the pathogenesis of Alzheimer's disease
              though this remains a highly contentious issue.


         -    Potential pulmonary irritant


         -    Aluminium sulphate used in water purification is a source of
              aluminium toxicity in haemodialysis patients and may cause
              "dialysis dementia". Aluminium toxicity in these
              circumstances may contribute also to renal osteodystrophy
              and a microcytic anaemia.



         -    Irrigate with copious volumes of lukewarm water.


    Minor ingestions (dilute solutions; mildly acidic or neutral):
    1.   Gastrointestinal decontamination is unnecessary.
    2.   Symptomatic and supportive measures only.

    Substantial ingestions (concentrated acid solutions):
    1.   Do not attempt gastric decontamination.
    2.   Secure cardiorespiratory stability.
    3.   Replace fluids and electrolytes if necessary.
    4.   Upper gastrointestinal endoscopy may be required.
    5.   Measure serum aluminium concentration in patients with clinical
    6.   Parenteral desferrioxamine may be considered if there is evidence
         of an increased aluminium body burden. Seek specialist advice
         from the NPIS.


         -    There is clinical evidence that desferrioxamine therapy can
              improve aluminium-induced encephalopathy, bone disease and
              anaemia in dialysis patients but seek specialist advice from
              the NPIS.


    Day JP, Ackrill P.
    The chemistry of desferrioxamine chelation for aluminum overload in
    renal dialysis patients.
    Ther Drug Monit 1993; 15: 598-601.

    Eastwood JB, Levin GE, Pazianas M, Taylor AP, Denton J, Freemont AJ.
    Aluminium deposition in bone after contamination of drinking water
    Lancet 1990; 336: 462-64.

    Lowermoor Incident Health Advisory Group; Department of Health.
    Water pollution at Lowermoor, North Cornwall. 2nd report.
    London: HMSO, 1991; 1-51.

    McLaughlin RS.
    Chemical burns of the human cornea.
    Am J Ophthalmol 1946; 29: 1355-62.

    Substance name

         Aluminium sulphate

    Origin of substance

         Naturally occurring, as the mineral alunogenite.
                                                 (DOSE, 1992)


         Cake alum
         Aluminium sesquisulphate
         Dialuminium trisulphate                 (CSDS, 1989)

    Chemical group

         Compound of aluminium, a group III metal
                                                 (CSDS, 1989)

    Reference numbers

         CAS            10043-01-3               (CSDS, 1989)
         RTECS          BD1700000                (RTECS, 1995)
         UN             NIF

    Physicochemical properties

    Chemical structure
         Aluminium sulphate, Al2 (SO4)3
                                                 (DOSE, 1992)
    Molecular weight
         342.15                                  (DOSE, 1992)

    Physical state at room temperature
         Solid (powder)                          (CSDS, 1989)

         White                                   (CSDS,1989)

         Odourless                               (HSDB, 1995)


         Aluminium sulphate has a natural pH of 2.
                                                 (Anonymous, 1989)

         Soluble in water: 313 g/L at 0C, 891 g/L at 100C.
                                                 (DOSE, 1992)

    Autoignition temperature

    Chemical interactions
         Sulphuric acid is formed on hydrolysis of aluminium sulphate. On
         heating, toxic sulphur oxide and aluminium oxide fumes are
         released.                               (CSDS, 1989)

    Major products of combustion

    Explosive limits

         May burn, but will not ignite.          (HSDB, 1995)

    Boiling point
         The solid decomposes at 770C.          (HAZARDTEXT, 1995)

         1.61 at 25C                            (CSDS, 1989)

    Vapour pressure
         Essentially zero                        (HSDB, 1995)

    Relative vapour density

    Flash point



         Aluminium sulphate is used in the paper industry, for tanning
         leather and as a mordant in dyeing.
         Other uses include water purification and sewage treatment,
         fireproofing and waterproofing cloth, and as an ingredient of
         antiperspirants.                        (CSDS, 1989; DOSE, 1992)

    Hazard/risk classification



    Aluminium sulphate is relatively non toxic. In 1988, contamination of
    drinking water with aluminium sulphate led to a variety of acute
    symptoms (Lowermoor Incident Health Advisory Group, 1991) but there
    are no case reports of substantial ingestions in the last 30 years.

    Uraemic patients on long-term haemodialysis may have an increased
    aluminium load via intravenous exposure to high concentrations of
    aluminium sulphate in dialysis (usually tap) water (Ward et al, 1978;
    Alfrey, 1980), although this should now be avoidable by deionization
    or reverse osmosis of the water prior to use. 


    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 axunal 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).



    In a healthy adult only approximately 15 g of the average daily
    dietary aluminium intake of 3-5 mg is absorbed (Winship, 1992). The
    intestinal absorption of aluminium is enhanced by citrate which is
    found frequently in effervescent drug formulations.

    Main and Ward (1992) reported a reversible increase in the serum
    aluminium concentration from 67.5 to 499.5 g/L in a patient on
    haemodialysis taking oral aluminium hydroxide when she was also given
    an effervescent analgesic containing sodium citrate. Conversely the
    bioavailability of aluminium in aqueous solution is greatly reduced by
    silica, such that the toxicity of aluminium-containing phosphate
    binders may be reduced significantly by the co-administration of
    dissolved silica (Birchall, 1993).

    In dialysis patients with aluminium overload, endogenous silicon may
    serve a protective role in limiting tissue aluminium uptake (Fahal et
    al, 1994). There may also be implications for domestic water supplies
    if a high silicic acid concentration evades any hazards posed by
    aluminium sulphate in water (Birchall, 1993).


    More than 90 per cent of absorbed aluminium 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. In the body
    aluminium is stored mainly in bone and liver.


    Aluminium is excreted predominantly via the kidneys and therefore will
    accumulate in patients with renal failure (Alfrey, 1980). Preterm
    infants also have a limited ability to excrete aluminium and there are
    reports of accumulation in infants on long-term parenteral nutrition
    (Sedman et al, 1985). Tsou et al (1991) demonstrated significantly
    higher plasma aluminium concentrations (mean 37.2 g/L) in normal
    infants receiving oral aluminium-containing antacids for a prolonged
    period compared to controls but this was not associated with adverse
    clinical effects.


    Dermal exposure

    Topical aluminium sulphate is irritant to the skin (Royal Society of
    Chemistry, 1989; Meditext, 1995). Tohani et al (1991) reported a
    macular, pruritic rash in association with the accidental addition of
    aluminium sulphate to a water supply. The skin reaction may have been
    due to the leaching of other metals (especially nickel) from the
    domestic plumbing system due to the acidic pH of the water caused by
    the high aluminium sulphate concentration.

    Ocular exposure

    Ocular exposure to aluminium sulphate may cause corneal burns
    (McLaughlin, 1946).


    Acute aluminium sulphate ingestion causes primarily gastrointestinal
    upset though neuropsychological and musculoskeletal sequelae were also
    reported in those who drank water to which 20 tonnes of eight per cent
    aluminium sulphate had accidentally been added in Camelford, Cornwall
    in 1988 (see below). However, a group reviewing this incident
    concluded that although "early symptoms, such as gastrointestinal
    disturbances, rashes and mouth ulcers, could probably be attributed to
    the toxic effects of the incident....The research reported to us does
    not provide convincing evidence that harmful accumulation of aluminium
    has occurred, nor that there is greater prevalence of ill-health due
    to toxic effects of the water in the exposed population" (Lowermoor
    Incident Health Advisory Group, 1991).

    Gastrointestinal toxicity

    Following the Camelford incident a variety of acute symptoms were
    reported (Eastwood et al, 1990; Lowermoor Incident Health Advisory
    Group, 1991), mainly mild gastrointestinal disturbance and mouth
    ulcers (McMillan et al, 1993b). Water aluminium concentrations
    recorded at the time ranged from 30 to 620 mg/L (WHO recommended
    maximum aluminium concentration in drinking water is 200 g/L)
    (Eastwood et al, 1990; WHO, 1993). The low pH of the water also led to
    leaching of other metals, such as copper, from the distribution pipes
    so that those washing in the water developed green-discoloration of
    their hair.

    Substantial ingestion of aluminium sulphate causes burning in the
    mouth and throat, gingival necrosis, nausea, vomiting, diarrhoea,
    abdominal pain and, in severe cases, haemorrhagic gastritis with
    circulatory collapse (Gosselin et al, 1984; Royal Society of
    Chemistry, 1989; Meditext, 1995).

    Spira (1933) reported dry mouth and throat, anorexia, nausea and
    vomiting, glossitis, stomatitis, gingivitis and hiccup (in addition to
    cutaneous and neurological symptoms) suspected to be caused by the
    ingestion of elemental aluminium plus "aluminized" tap water. There
    are, however, no case reports of substantial aluminium sulphate
    ingestion in the literature over at least the last 30 years.

    Dermal toxicity

    Spira (1933) believed that skin conditions including urticaria,
    telangiectasia, alopecia and palmar keratosis were caused by ingestion
    of elemental aluminium plus "aluminized" tap water but this was not

    Neuropsychological toxicity

    McMillan et al (1993b) reported "possible impairment of memory" in
    those who drank aluminium sulphate-contaminated water in Camelford.
    Serial neuropsychological assessments of 10 individuals between eight
    and 26 months after the incident showed mild cognitive impairment but
    a causal link with aluminium exposure could not be verified and in no
    patient was there evidence of residual aluminium in bone or plasma
    McMillan et al, 1993b).

    Retrospective psychological testing on 39 children from schools in the
    contaminated area showed no significant differences compared to
    unexposed children (McMillan et al, 1993a). Muscle twitching, limb
    paraesthesiae, arthralgia, neuralgia, giddiness, depression and
    lassitude have been attributed to the ingestion of elemental aluminium
    and aluminium contaminated tap water (Spira, 1933) but this was

    Musculoskeletal toxicity

    Some individuals who drank the aluminium sulphate-contaminated water
    in Camelford later complained of joint and muscle pains and fatigue
    (Anonymous, 1991; McMillan et al, 1993b).

    Bone toxicity

    Bone biopsies some six months after the Camelford incident from two
    individuals who drank the contaminated water showed increased
    aluminium staining in bone formed at a time compatible with exposure
    but normal bone aluminium concentrations overall, suggesting increased
    aluminium absorption and retention following acute ingestion without
    apparent adverse sequelae (Eastwood et al, 1990).


    Cumming et al (1982) reported four dialysis patients who developed
    anorexia, nausea, vomiting, abdominal pain, weight loss and malaise
    within three days of using a contaminated peritoneal dialysis fluid
    containing 620-1460 g/L aluminium.



    Pulmonary toxicity

    No evidence of respiratory disease was found in 25 workers engaged in
    the manufacture of aluminium sulphate from aluminium hydroxide where
    the aluminium concentration in factory air was kept below the
    permissible limit of 3 mg/m3 (Elo and Uksila, 1977).


    Neuropsychological toxicity

    Aluminium sulphate is widely used in water purification. This source
    has in the past contributed to aluminium toxicity in haemodialysis
    patients (see below) and may be involved in the pathogenesis of
    Alzheimer's disease via 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).

    Martyn et al (1989) and Neri and Hewitt (1991) reported a geographical
    relationship between Alzheimer's disease and the concentration of
    aluminium in drinking water but Wood et al (1988) found no significant
    difference in mental test score between hip fracture patients living
    in high versus low water aluminium areas.

    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-Gorz, 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).

    Harrington et al (1994) described Alzheimer's-disease-like
    pathological changes in the brains of renal dialysis patients in
    association with aluminium accumulation without clinical evidence of
    dialysis encephalopathy (see below).


    Neuropsychological toxicity

    'Dialysis dementia' involves the accumulation of aluminium, mainly in
    the brain, in patients on haemodialysis where the dialysis water
    contains significant amounts of aluminium sulphate (McDermott et al,
    1978). This should now be avoidable by reverse osmosis or deionization
    of dialysis water prior to use.

    Peritoneal dialysis solutions and haemofiltration and plasma exchange
    substitution fluids also may contain excessive aluminium although the
    incidence of toxicity from these preparations is small (Mion, 1985;
    Mousson et al, 1989).

    Elliott et al (1978a) reported a significant correlation between serum
    aluminium concentrations and the concentrations of aluminium in the
    water supply in eight patients on home dialysis with cases of dialysis
    dementia confined to regions with high water aluminium concentrations
    (>350 g/L).

    A larger study (Registration Committee of the European Dialysis and
    Transplant Association, 1980) of patients treated in 65 dialysis
    centres in Europe in 1976 and 1977 identified 150 cases of dialysis
    dementia with a clear association between the occurrence of dementia
    and dialysis with water which was not treated by deionization or
    reverse osmosis. Only 23 of 150 patients were still alive in 1978.
    Similar findings were reported by Davison et al (1982).

    Although the problem of aluminium contamination of dialysates has
    reduced in recent years, these patients may still accumulate aluminium
    via oral aluminium hydroxide given as a phosphate binder (Salusky et
    al, 1991). The contribution this makes to dialysis dementia is likely
    to be small (McDermott et al, 1978; Registration Committee of the
    European Dialysis and Transplant Association, 1980).

    It has been suggested (Hodge et al, 1981) that to ensure no aluminium
    uptake by dialysis patients, the dialysate aluminium concentration
    should not exceed 14 g/L. This corresponds to a maximum aluminium
    concentration in the water supply of 5 g/L since aluminium is present
    in significant quantity in the dialysate concentrate (Hodge et al,
    1981). The WHO recommended maximum aluminium concentration in drinking
    water is 200 g/L (WHO, 1993).

    Dialysis dementia is progressive and often fatal (Alfrey et al, 1976;
    Burks et al, 1976). In a review of 412 dialysis patients admitted to
    one renal unit since 1972, Garret et al (1988) described 38 cases. The
    mean time between onset of regular dialysis and development of
    symptoms was 40 months with speech difficulties, seizures and
    myoclonus the most common presenting features. Dyspraxia, involuntary
    movements, poor concentration, loss of short-term memory, confusion,
    depression and anxiety were also described and only nine patients were
    still alive at the conclusion of the study (Garret et al, 1988).

    The neurological consequences of aluminium intoxication may be
    exacerbated in patients with aluminium bone disease who sustain
    fractures, probably via increased bone aluminium mobilization
    (Davenport and Ahmad, 1988).

    There are reports of impaired cerebral function in haemodialysis
    patients who have an increased body burden of aluminium but no
    evidence of "dialysis dementia" (Altmann et al, 1989; Bolla et al,
    1992). Altmann et al (1989) found significant abnormalities of
    psychomotor function in 27 long-term haemodialysis patients who had
    only mildly raised serum aluminium concentrations (mean 59  (SEM) 9
    g/L, normal < 10 g/L).

    In another study, 23 haemodialysis patients accidentally exposed to
    aluminium for up to six months following failure of a reverse osmosis
    system had a mean serum aluminium concentration of 147.3  (SEM) 11.7
    g/L without apparent neuropsychiatric sequelae (Caramelo et al,

    Bone toxicity

    In patients with renal failure aluminium toxicity may contribute to
    renal osteodystrophy (Goyer et al, 1994). In a survey conducted by the
    European Dialysis and Transplant Association, 102 of 150 patients with
    dialysis dementia also had evidence of bone disease (Registration
    Committee of the European Dialysis and Transplant Association, 1980).

    Parkinson et al (1979) demonstrated a significant correlation
    (p = 0.01) between the mean aluminium content of the water supply and
    the incidence of fracturing dialysis osteodystrophy in 1293 patients
    undergoing intermittent haemodialysis and Ward et al (1978) reported
    significantly fewer cases of osteomalacia in patients maintained on
    regular haemodialysis in Newcastle when the dialysate water was
    deionised. Another study (Chan et al, 1990) found that the incidence

    of osteomalacic fractures in dialysis patients could not be explained
    by the aluminium concentration in dialysate alone and a significant
    contribution by oral aluminium hydroxide was suggested.

    Aluminium associated osteomalacic osteodystrophy is progressive and
    characterized by bone pain, a proximal myopathy and spontaneous
    fractures. In a review of skeletal surveys of 67 patients with
    end-stage renal failure Garrett et al (1986) found that moderate or
    severe fracturing osteodystrophy with greater than five fractures had
    a diagnostic specificity for aluminium intoxication of 100 per cent,
    provided trauma could be excluded.

    Investigations typically show normal or only slightly increased
    alkaline phosphatase activity, normal serum calcium and normal or
    slightly high serum phosphate concentrations with reduced circulating
    parathyroid hormone and increased bone and serum aluminium
    concentrations (Winship, 1992). It is resistant to treatment with
    vitamin D but improvement may follow desferrioxamine therapy as
    discussed below.

    Cardiovascular toxicity

    Elliott et al (1978b) proposed aluminium induced cardiotoxity (via
    inhibition of magnesium and ATP-dependent enzymes) as a contributing
    factor in the sudden death of five dialysis patients, four with
    dialysis encephalopathy and one non-encephalopathic patient whose
    serum aluminium concentration was 600 g/L.


    Aluminium intoxication may exacerbate the microcytic hypochromic
    anaemia of chronic renal failure via impaired iron utilization
    (Caramelo et al, 1995). This effect is at least partly reversible with
    desferrioxamine therapy as discussed below.

    Dermal toxicity

    Brown et al (1992) suggested aluminium overload as the cause of a
    widespread pruritic nodular rash (prurigo nodularis) in three patients
    on maintenance haemodialysis. The serum aluminium concentration,
    measured in two patients, was normal but complete resolution occurred
    in all cases following weekly treatment for some three months with one
    gram intravenous desferrioxamine.


    Dermal exposure

    Remove all soiled clothing, wash the exposed area thoroughly with
    copious amounts of water and treat symptomatically.

    Ocular exposure

    The affected eye should be irrigated with lukewarm water for not less
    than 15-30 minutes and any visible particles removed. Installation of
    local anaesthetic is usually necessary to enable adequate
    decontamination. An ophthalmic opinion should be obtained.


    The likelihood of adverse effects following aluminium sulphate
    ingestion depends on the pH of the solution. Although pure aluminium
    sulphate has a pH of 2 most cases will involve ingestion of dilute
    solutions causing no, or only mild, gastrointestinal upset.

    Ingestion of dilute solutions

    These cases will require only symptomatic and supportive measures.
    Gastrointestinal decontamination is unnecessary as gastrointestinal
    aluminium absorption is poor. Measurement of the serum aluminium
    concentration or the administration of desferrioxamine are not

    Ingestion of concentrated solutions

    Theoretically, ingestion of a concentrated aluminium sulphate solution
    will cause severe gastrointestinal corrosion and, if this is
    clinically suspected, gastric aspiration or lavage should not be
    attempted. Activated charcoal does not adsorb aluminium and the
    administration of ipecac is not advocated under any circumstances.

    Measures to secure cardiorespiratory stability are mandatory and
    clinical suspicion of oesophageal or gastric corrosion may require
    endoscopic examination. Corticosteriods are not indicated and their
    administration may mask signs of abdominal perforation.

    The serum aluminium concentration should be measured in patients with
    clinical features and parenteral desferrioxamine therapy should be
    considered if there is evidence of an increased aluminium body burden;
    such as increase is only likely to occur after chronic aluminium


    The patient should be removed from exposure, and those with evidence
    of respiratory distress should receive high flow oxygen by face-mask.
    Corticosteriods may be employed if laryngeal or pulmonary oedema are
    present and, theoretically endotracheal intubation or tracheostomy may
    be required although there are no such case reports in the literature.


    Most cases of aluminium intoxication following aluminium sulphate
    exposure occur in renal dialysis patients exposed to either
    intravenous or intraperitoneal aluminium-containing dialysates. The
    oral administration of aluminium containing phosphate binders may
    exacerbate aluminium accumulation in these circumstances.


    The prevention of aluminium intoxication in renal dialysis patients

    1.   Monitoring of the water aluminium concentration in the supply
         used to prepare the dialysate. The maximum EC admissible
         aluminium concentration in domestic water is 0.2 mg/L (Eastwood
         et al, 1990) but Hodge et al (1981) suggested a maximum water
         aluminium concentration of 5 g/L as the 'safe' limit for use in

    2.   Judicious use of aluminium-containing phosphate binding agents
         with the use of alternative preparations, such as calcium
         carbonate, where possible.

    3.   Monitoring the total body aluminium load. There is some
         disagreement regarding the role of plasma aluminium
         concentrations in the estimation of total body aluminium burden
         (Gilli et al, 1983; Seyfert et al, 1987; D'Haese et al, 1990) but
         it is likely to be a useful measurement provided it is undertaken
         by a qualified laboratory.

    4.   The definitive investigation for aluminium osteodystrophy is a
         bone biopsy (Seyfert et al, 1987). The desferrioxamine infusion
         test is a less invasive method of assessing body aluminium
         although its interpretation requires clarification (see 'Medical


    There is some evidence that parenteral desferrioxamine therapy slows
    the rate of cognitive deterioration in patients with Alzheimer's
    disease (Crapper McLachlan et al, 1991; Crapper McLachlan et al, 1993)
    but further studies are required.

    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 (Gmez et al, 1994; Yokel 1994). It
    is absorbed poorly from the gastrointestinal tract and parenteral
    therapy is necessary. Theoretically 100 mg 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 or, less commonly,
    peritoneal dialysis (O'Brien et al, 1987) or haemofiltration (Sulkova
    et al, 1991).

    Following intravenous desferrioxamine administration the
    concentrations of protein (mainly transferrin)-bound and erythrocyte
    aluminium remain relatively constant as chelatable aluminium is
    mobilized from bone (Day and Ackrill, 1993). The
    aluminium-desferrioxamine chelate concentration reaches a maximum
    12-24 hours post infusion (Day and Ackrill, 1993) producing a rise in
    the total plasma aluminium concentration which persists until the next
    dialysis. The administration of desferrioxamine shortly before
    dialysis will reduce this effect (Douthat et al, 1994). In the longer
    term, a fall in the erythrocyte aluminium concentration is observed as
    red cells are formed from bone marrow with a lower aluminium load (Day
    and Ackrill, 1993).

    In chronic renal failure patients treated with 1 gram intravenous
    desferrioxamine, Sulkova et al (1991) observed a mean 41 per cent
    decrease in the serum aluminium concentration during 28 five hour
    haemodialyses (aluminium clearance 28 mL/min during each dialysis)
    compared to a mean 66 per cent reduction in the serum aluminium
    concentration during 36 sessions of haemofiltration (volume exchange
    60 per cent of body weight and calculated aluminium clearance 42
    mmol/L in the 60th minute of each filtration). The authors concluded
    haemofiltration is superior to haemodialysis in enhancing aluminium
    elimination using desferrioxamine.

    In another study O'Brien et al (1987) calculated aluminium clearance
    rates in a 32 year-old male with aluminium osteomalacia following a
    change from haemodialysis to chronic ambulatory peritoneal dialysis
    (CAPD). CAPD plus intravenous desferrioxamine (six grams once a week)
    gave an aluminium clearance of 4.2 mL/min compared to a clearance of
    3.1 mL/min when the same cumulative dose of desferrioxamine was given
    into the peritoneal cavity and an aluminium clearance of 2.5 mL/min
    with CAPD alone.

    Indications for desferrioxamine therapy

    There is clinical evidence that desferrioxamine therapy can improve
    aluminium-induced encephalopathy, bone disease and anaemia in dialysis
    patients (Day and Ackrill, 1993). Its use should be considered,
    therefore, in these patients in the following circumstances:

    1.   When features are present compatible with dialysis encephalopathy
         in the absence of an alternative neurological diagnosis.

    2.   Where a desferrioxamine infusion test indicates an increased body
         aluminium load. As discussed below (see Medical Surveillance)
         there are some problems with the interpretation of this test.
         Milliner et al (1984) found that a 200 g/L increase above

         baseline in the plasma aluminium concentration following 40 mg/kg
         intravenous desferrioxamine provided 50 per cent specificity for
         a diagnosis of aluminium osteodystrophy with the diagnostic
         specificity improving to 71 per cent with an increase above
         baseline in the plasma aluminium concentration of 300 g/L.

    3.   Where there is clinical evidence of aluminium-related bone
         disease. This is usually associated with a 'positive'
         desferrioxamine infusion test.

    4.   Possibly in the presence of severe, transfusion-dependant anaemia
         even in the absence of characteristic clinical or analytical
         features of aluminium overload (Praga et al, 1987).

    5.   In the presence of an increased "baseline" serum aluminium
         concentration. D'Haese et al (1990) suggested that a serum
         aluminium concentration in excess of 60 g/L reliably indicated
         aluminium overload.

    Desferrioxamine and dialysis encephalopathy

    McCarthy et al (1990) treated 28 dialysis patients suffering from
    aluminium toxicity with long-term (mean 11.0 months) intravenous
    desferrioxamine, initially at a mean dose of 41.7 mg/kg body weight
    once weekly, increasing to a maximum dose of 60 mg/kg as tolerated.
    After five to seven months of treatment serum aluminium concentrations
    decreased from a mean of 401 g/L to 245 g/L. Four patients, who had
    advanced dementia before treatment, died during the study period. With
    desferrioxamine treatment seven of 28 patients showed neurological
    improvement and 25 patients showed improved or stable muscle strength
    and overall functional capacity. The authors concluded that whilst
    long-term desferrioxamine therapy can be important in the treatment of
    patients with significant aluminium exposure it should be employed
    only when symptoms demand treatment and when patients can be monitored
    regularly for desferrioxamine toxicity (McCarthy et al, 1990).

    A 44 year-old man treated with home dialysis (with deionized water)
    for four years and oral aluminium hydroxide 2850 mg daily for four
    months, developed severe short-term memory loss and myoclonic jerks
    (Arze et al, 1981). The serum aluminium concentration was 84 g/L.
    Symptomatic improvement followed the additional use of a reverse
    osmosis unit with reduction in the dialysate aluminium concentration
    from 6-109 g/L to 1-12 g/L but no aluminium was eliminated during
    dialysis. Two to six grams intravenous desferrioxamine once weekly for
    six months removed 259mg aluminium with considerable improvement on
    psychometric testing and no myoclonus at the end of this time.

    In another report (Payton et al, 1984) a patient with aluminium
    encephalopathy on CAPD improved substantially following two months
    treatment with intraperitoneal desferrioxamine (500-750 mg added to
    each two litre bag of dialysate). There was a significant (p<0.001)
    increase in the post-dialysis dialysate aluminium concentration during
    desferrioxamine treatment with an initial increase (from 189 g/L to

    224 g/L) then progressive decrease (to 27 g/L) in the serum
    aluminium concentration.

    Desferrioxamine and aluminium bone disease

    In 32 patients desferrioxamine therapy controlled progression of
    dialysis-associated aluminium osteodystrophy with bone scans in 21
    cases reverting to normal or showing a pattern typical of
    hyperparathyroidism (Botella et al, 1984). Charhon et al (1986)
    reported similar findings with intravenous desferrioxamine (3-6 grams
    once a week for 5-11 months) leading to dramatic clinical improvement
    in the bone disease of three haemodialysed patients.

    Desferrioxamine and dialysis-associated anaemia

    A three month course of desferrioxamine (30 mg/kg iv three times a
    week) significantly improved the microcytic anaemia of 15
    haemodialysis patients who had only modestly raised serum aluminium
    concentrations (5-125 g/L) and no neurological symptoms of aluminium
    toxicity (Altmann et al, 1988).

    Praga et al (1987) reported significant reduction in the transfusion
    requirement of seven anaemic haemodialysis patients following
    desferrioxamine therapy (two grams intravenously after each
    haemodialysis session for six months) even though none had either
    clinical or analytical characteristic features of aluminium

    Treatment protocol for desferrioxamine

    In patients with an indication for desferrioxamine therapy 40-80 mg/kg
    should be administered, usually intravenously, once a week. The dose
    can be reduced to 20-60 mg/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 septicaema, 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,

    There are several reports of desferrioxamine-associated systemic
    fungal infection (mucormycosis) in dialysis patients (Goodill and
    Abuelo, 1987; Windus et al, 1987) and 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).

    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) 13.7 mL/min; n=4). The authors
    proposed haemoperfusion plus desferrioxamine as a effective method of
    rapid aluminium elimination in intoxicated patients to be used in
    series with haemodialysis in patients with renal failure.

    Other chelating agents

    The practical problems of desferrioxamine administration and its side
    effects have prompted a search for an alternative aluminium chelator.
    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

    Although as yet there is no confirmed alternative to desferrioxamine
    (Domingo, 1989; Main and Ward, 1992; Yokel, 1994), 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.

    Haemoperfusion, haemodialysis and haemofiltration

    Chang and Barre (1983) demonstrated that haemoperfusion and
    haemodialysis only enhance aluminium elimination in the presence of
    desferrioxamine and that under these circumstances haemoperfusion is
    more effective than haemodialysis (see above). Protein-bound aluminium
    is not dialyzable (Day and Ackrill, 1993). Sulkova et al (1991) also
    observed no aluminium elimination during four sessions of
    haemodialysis in patients with known aluminium accumulation who were
    not pre-treated with intravenous desferrioxamine. The same authors

    reported a 15 per cent fall in the mean serum aluminium concentration
    during four haemofiltrations without desferrioxamine therapy.


    Chronic renal failure patients

    As discussed above, patients with chronic renal failure are at
    increased risk of aluminium toxicity from "tapwater" dialysate and
    possibly also oral aluminium-containing phosphate binders.


    Sedman et al (1985) found significantly increased plasma (p<0.0001),
    urine (p<0.01) and bone (p<0.0001) aluminium concentrations in 18-23
    premature infants receiving parenteral nutrition. Aluminium
    accumulation in these circumstances reflects a combination of
    aluminium contamination of the intravenous fluid and impaired renal
    aluminium excretion.

    Ten infants with normal renal function who had received oral aluminium
    containing antacids for at least one week had significantly higher
    plasma aluminium concentrations (mean 37.2  (SEM) 7.13 g/L compared
    to controls (4.13  0.66 g/L) (p<0.005) without signs of toxicity
    (Tsou et al, 1991).

    The aluminium content of cow's milk and soy milk are considerably
    higher (10-20 and 100 fold respectively) than human breast milk which
    has an aluminium concentration of 5-20 g/L and this may contribute to
    aluminium intoxication in premature infants with renal failure (Bishop
    et al, 1989). Freundlich et al (1985) reported two infants with
    congenital uraemia and aluminium toxicity where the source of excess
    aluminium was believed to be a powdered milk formulation.


    Aluminium toxicity should be considered in those exposed
    occupationally to aluminium dust who develop respiratory or
    neuropsychiatric symptoms and in patients with renal failure who may
    be at risk of aluminium retention. Useful indicators of exposure
    include the 24 hour urine aluminium excretion (normal range < 15
    g/24 hours) and the blood aluminium concentration (normal range < 10
    g/L). 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).

    In 71 dialysis patients D'Haese et al (1990) demonstrated that a serum
    aluminium concentration of 60 g/L or greater identified
    aluminium-related bone disease with 82 per cent sensitivity and 86 per
    cent specificity. However, Gilli et al (1983) suggested serum
    aluminium concentrations were unlikely to reflect total aluminium
    accumulation in uraemic patients and Seyfert et al (1987) suggested
    plasma aluminium concentrations were not reliable in the diagnosis of

    aluminium-related bone disease. This author emphasised the importance
    of bone biopsy as the definitive investigation for aluminium
    osteomalacia and advocated the 'desferrioxamine test' as a useful
    diagnostic tool.

    Desferrioxamine infusion test

    The desferrioxamine infusion test involves the intravenous
    administration, to renal failure patients with suspected aluminium
    toxicity, of a standard desferrioxamine dose (usually 20-40 mg/kg) and
    comparison of the peak post-infusion plasma aluminium concentration
    with the "baseline" concentration, as an indication of the total body
    aluminium burden (Day and Ackrill, 1993).

    Ackrill et al (1980) suggested that an increase in the serum aluminium
    concentration of at least 200 g/L was required following a
    desferrioxamine test dose if a significant amount of aluminium was to
    be removed by desferrioxamine during dialysis. The interpretation of
    this test has not yet been standardized and its predictive value in
    the assessment of aluminium bone disease requires clarification.
    Furthermore, the investigation is not without risk.

    Ravelli et al (1990) reported acute visual disturbances in 13 of 15
    patients given a standard desferrioxamine test with persisting
    symptoms in four patients some six months later. It recently has been
    suggested that a lower test dose of desferrioxamine can reduce
    toxicity without loss of diagnostic efficacy (Yaqoob et al, 1991).

    Hair analysis (Wilhelm et al, 1989) and individual spot urine
    concentrations (Gitelman et al, 1995) are poor indicators of aluminium
    exposure. Furthermore, the kinetics of urine aluminium excretion
    varies depending on the form of aluminium involved (Pierre et al,
    1995). Estimation of the aluminium content of cerebrospinal fluid may
    be important in the investigation of aluminium-related dementia
    (Sjgren et al, 1994).


    Occupational exposure standard

    Aluminium salts, soluble: Long-term exposure limit (8 hour TWA
    reference period 2 mg/m3 (Health and Safety Executive, 1995).



    There is no evidence that aluminium salts are carcinogenic in man
    (Leonard and Gerber, 1988).


    Pregnant rats given oral aluminium hydroxide 192-768 mg/kg/day on
    gestational days 6-15 showed no maternal or foetal developmental
    toxicity (Gomez et al, 1990). There was no evidence of adverse effects
    in pregnancy following the accidental contamination of drinking water
    with aluminium sulphate in Camelford, Cornwall in 1988 (Golding et al,


     Bacillus subtilis H17 (rec+) M45 (rec-) negative DNA damage.

     In vitro human lymphocyte cells (72 hr) 20 g/mL induced chromosomal
    aberrations in cells from male and female subjects, while the
    frequency of translocations and dicentrics was low.

    Oral rat (prolonged exposure) induced dose-dependent inhibition of
    dividing cells and increased chromosomal aberrations, not influenced
    by duration of exposure (DOSE, 1992).

    Fish toxicity

    LC50 goldfish (12-96 hr) 100 mg/L (DOSE, 1992).

    EEC Directive on Drinking Water Quality 80/778/EEC

    Aluminium: Guide level 0.05 mg/L, maximum admissible concentration 0.2

    Sulphate: Guide level 25 mg/L, maximum admissible concentration 250
    mg/L (DOSE, 1992).


    SM Bradberry BSc MB MRCP
    ST Beer BSc

    National Poisons Information Service (Birmingham Centre),
    West Midlands Poisons Unit,
    City Hospital NHS Trust,
    Dudley Road,
    B18 7QH

    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


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