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    UNITED NATIONS ENVIRONMENT PROGRAMME
    INTERNATIONAL LABOUR ORGANISATION
    WORLD HEALTH ORGANIZATION


    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY



    ENVIRONMENTAL HEALTH CRITERIA 194





    Aluminium






    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.


    Environmental Health Criteria  194


    First draft prepared by Dr H. Habs, Dr B. Simon and Professor K.U.
    Thiedemann (Fraunhofer Institute, Hoanover, Germany) and Mr P. Howe
    (Institute of Terrestrial Ecology, Monks Wood, United Kingdom)


    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization, and produced within the framework of the
    Inter-Organization Programme for the Sound Management of Chemicals.


    World Health Organization
    Geneva, 1997

         The International Programme on Chemical Safety (IPCS) is a joint
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    of the biological action of chemicals.

    WHO Library Cataloguing in Publication Data

    Aluminium

    (Environmental health criteria ; 194)

    1.Aluminium - toxicity             2.Aluminium - adverse effects
    3.Environmental exposure           I.Series

    ISBN 92 4 157194 2                 (NLM Classification: QV 65)
    ISSN 0250-863X

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    CONTENTS

    ENVIRONMENTAL HEALTH CRITERIA FOR ALUMINIUM

    1. SUMMARY AND CONCLUSIONS

         1.1. Identity, physical and chemical properties
         1.2. Analytical methods
         1.3. Sources of human and environmental exposure
         1.4. Environmental transport, distribution and transformation
         1.5. Environmental levels and human exposure
         1.6. Kinetics and metabolism
               1.6.1. Humans
               1.6.2. Animals
         1.7. Effects on laboratory mammals and  in vitro test systems
         1.8. Effects on humans
         1.9. Effects on other organisms in the laboratory and field
         1.10. Conclusions
               1.10.1. General population
               1.10.2. Subpopulations at special risk
               1.10.3. Occupationally exposed populations
               1.10.4. Environmental effects

    2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

         2.1. Identity
         2.2. Physical and chemical properties
               2.2.1. Aluminium metal
               2.2.2. Aluminium compounds
         2.3. Analytical methods
               2.3.1. Sampling and sample preparation
               2.3.2. Separation and concentration
               2.3.3. Detection and measurement
               2.3.4. Speciation analysis of aluminium in water

    3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         3.1. Natural occurrence
         3.2. Anthropogenic sources
               3.2.1. Production levels and processes
               3.2.2. Uses

    4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION

         4.1. Transport and distribution between media
               4.1.1. Air
               4.1.2. Freshwater
                       4.1.2.1   Dissolved aluminium
                       4.1.2.2   Aluminium adsorbed on particles
                       4.1.2.3   Aluminium in acidified waters

               4.1.3. Seawater
               4.1.4. Soil
               4.1.5. Vegetation and wildlife
         4.2. Biotransformation
               4.2.1. Biodegradation and abiotic degradation
               4.2.2. Bioaccumulation
                       4.2.2.1   Plants
                       4.2.2.2   Invertebrates
                       4.2.2.3   Fish
                       4.2.2.4   Birds

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         5.1. Environmental levels
               5.1.1. Air
               5.1.2. Precipitation
               5.1.3. Water
                       5.1.3.1   Freshwater
                       5.1.3.2   Seawater
               5.1.4. Soil and sediment
               5.1.5. Terrestrial and aquatic organisms
         5.2. Occupational exposure
         5.3. General population exposures
               5.3.1. Air
               5.3.2. Food and beverages
               5.3.3. Drinking-water
               5.3.4. Miscellaneous exposures
               5.3.5. Total human intake of aluminium from
                       all environmental pathways
               5.3.6. Aluminium uptake

    6. KINETICS AND METABOLISM IN LABORATORY ANIMALS

         6.1. Absorption
               6.1.1. Animal studies
                       6.1.1.1   Inhalation exposure
                       6.1.1.2   Oral administration
                       6.1.1.3   Dermal
               6.1.2. Studies in humans
                       6.1.2.1   Inhalation exposures
                       6.1.2.2   Oral administration
                       6.1.2.3   Dermal exposure
         6.2. Distribution
               6.2.1. Animal studies
               6.2.2. Human studies
                       6.2.2.1   Transport in blood
                       6.2.2.2   Plasma aluminium concentrations in humans
                       6.2.2.3   Tissue aluminium concentrations in humans

         6.3. Elimination and excretion
               6.3.1. Animal studies
               6.3.2. Human studies
                       6.3.2.1   Urinary excretion
                       6.3.2.2   Biliary excretion
         6.4. Biological indices of exposure, body burden and organ
               concentration

    7. EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

         7.1. Single exposure
         7.2. Short- and long-term exposure
               7.2.1. Oral administration
               7.2.2. Inhalation exposure
               7.2.3. Parenteral administration
         7.3. Reproductive and developmental toxicity
               7.3.1. Reproductive effects
               7.3.2. Developmental effects
         7.4. Mutagenicity and related end-points
               7.4.1. Interactions with DNA
               7.4.2. Mutations
               7.4.3. Chromosomal effects
         7.5. Carcinogenicity
         7.6. Neurotoxicity
               7.6.1. Impairments of cognitive and motor function
               7.6.2. Alterations in electrophysiological properties
               7.6.3. Metabolic effects in the nervous system
         7.7. Effects on bone
               7.7.1. Toxic effects of aluminium in the skeleton
               7.7.2. Dose response
         7.8. Effects on mineral metabolism

    8. EFFECTS ON HUMANS

         8.1. General population exposure
               8.1.1. Acute toxicity
               8.1.2. Effects of short-term exposure
               8.1.3. Neurotoxic effects
                       8.1.3.1   Aluminium and Alzheimer's disease (AD)
                       8.1.3.2   Epidemiological studies on AD and
                                 environmental aluminium levels
                       8.1.3.3   Epidemiological studies relating
                                 aluminium concentrations in water to
                                 cognitive dysfunction
                       8.1.3.4   Other neurological conditions in the
                                 general population
                       8.1.3.5   Conclusions regarding neurological
                                 effects of aluminium
               8.1.4. Allergic effects

         8.2. Occupational exposure
               8.2.1. Respiratory tract effects
                       8.2.1.1   Restrictive pulmonary disease
                       8.2.1.2   Obstructive pulmonary disease
               8.2.2. Central nervous system effects
         8.3. Cancer
         8.4.  Genotoxicity
         8.5. Reproductive toxicity
         8.6. Subpopulations at special risk
               8.6.1. Encephalopathy
               8.6.2. Osteomalacia
               8.6.3. Microcytic anaemia

    9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

         9.1. Laboratory experiments
               9.1.1. Microorganisms
                       9.1.1.1   Water
                       9.1.1.2   Soil
               9.1.2. Aquatic organisms
                       9.1.2.1   Plants
                       9.1.2.2   Invertebrates
                       9.1.2.3   Fish
                       9.1.2.4   Amphibians
               9.1.3. Terrestrial organisms
                       9.1.3.1   Plants
                       9.1.3.2   Invertebrates
                       9.1.3.3   Birds
         9.2. Field observations
               9.2.1. Microorganisms
               9.2.2. Aquatic organisms
                       9.2.2.1   Plants
                       9.2.2.2   Invertebrates
                       9.2.2.3   Vertebrates
               9.2.3. Terrestrial organisms
                       9.2.3.1   Plants
                       9.2.3.2   Invertebrates
                       9.2.3.3   Vertebrates

    10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT

         10.1. Health effects
               10.1.1. Exposure assessment
               10.1.2. Evaluation of animal data
               10.1.3. Evaluation of human data
         10.2. Evaluation of effects on the environment
               10.2.1. Exposure
               10.2.2. Effects

    11. CONCLUSIONS AND RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH
         AND THE ENVIRONMENT

         11.1. Conclusions
               11.1.1. Healthy general population
               11.1.2. Subpopulations at special risk
               11.1.3. Occupationally exposed populations
               11.1.4. Environmental risk
         11.2. Recommendations
               11.2.1. Public health protection
               11.2.2. Recommendations for protection of the environment

    12. FURTHER RESEARCH

         12.1. Bioavailability and kinetics
         12.2. Toxicological data
         12.3. Research on the relationship between aluminium exposure and
               Alzheimer's disease
         12.4. Occupational exposure

    13. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    REFERENCE

    RESUME ET CONCLUSIONS

    RESUMEN Y CONCLUSIONES
    

    NOTE TO READERS OF THE CRITERIA MONOGRAPHS

         Every effort has been made to present information in the criteria
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                                     * * *

         A detailed data profile and a legal file can be obtained from the
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                                     * * *

         This publication was made possible by grant number 5 U01
    ES02617-15 from the National Institute of Environmental Health
    Sciences, National Institutes of Health, USA, and by financial support
    from the European Commission.

    Environmental Health Criteria

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    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ALUMINIUM

     Members 

    Dr T.M. Florence, Centre for Environmental Health Sciences, Oyster
         Bay, New South Wales, Australia

    Dr M. Golub, California Regional Primate Research Center, University
         of California, Davis, California, USA

    Mr P. Howe, Institute of Terrestrial Ecology, Monks Wood, Abbots
         Ripton, Huntingdon, Cambridgeshire, United Kingdom
         ( Co-Rapporteur)

    Professor D.R. McLachlan ( Retired from: Centre for Research in 
         Neurogenerative Diseases, University of Toronto, Toronto,
         Ontario, Canada 

    Dr M. Moore, National Health and Medical Research Council, National
         Research Centre for Environmental Toxicology, Coopers Plains,
         Brisbane, Australia ( Chairman)

    Dr T.V. O'Donnell, University of Otago, Wellington South, New Zealand
         ( Vice-Chairman)

    Professor B. Rosseland, Norwegian Institute of Water Research  (NIVA),
         Oslo, Norway

    Dr B. Simon, Fraunhofer Institute, Hanover, Germany ( Co-Rapporteur)

    Dr B. Sjogren, Department of Occupational Medicine, Swedish National
         Institute for Working Life, Solna, Sweden

    Dr L. Smith, Disease Control Service, Public Health Branch, Ontario
         Ministry of Health, North York, Ontario, Canada

    Dr E. Storey, Royal Melbourne Hospital, Department of Pathology,
         University of Melbourne, Parkville, Victoria, Australia

    Dr H. Temmink, Department of Toxicology, Agricultural University,
         Wageningen, The Netherlands ( Vice-Chairman)

    Dr M.K. Ward, Department of Renal Medicine, Royal Victoria Infirmary,
         Newcastle-upon-Tyne, United Kingdom

    Dr M. Wilhelm, Health Institute, University of Dusseldorf, Dusseldorf,
         Germany

    Professor H.M. Wisniewski, New York State Institute for Basic 
         Research in Developmental Disabilities, Staten Island, New York,
         USA

    Professor P. Yao, Chinese Academy of Preventive Medicine,  Institute
         of Occupational Medicine, Ministry of Health, Beijing, China

     Observers 

    Dr K. Bentley, Environmental Health Assessment and Criteria, Human
         Services and Health, Woden, Australia

    Dr O.C. Bśckman, Norsk Hydro, Porsgrunn Research Centre, Porsgrunn,
         Norway

    Dr J. Borak, Occupational and Environmental Health, Jonathan Borak &
         Co., New Haven, Connecticut, USA

    Dr I. Calder, Occupational and Environmental Health, South Australian
         Health Commission, Adelaide, Australia

    Dr J.N. Fisher, ALCOA of Australia Ltd, Point Henry Works, Geelong,
         Victoria, Australia

    Mr D. Hughes, Environment, Mount Isa Mine Holdings, Brisbane,
         Australia

    Dr P. Imray, Environmental Health Branch, Queensland Health, Brisbane,
         Australia

    Ms M.E. Meek, Environmental Health Directorate, Health Canada,
         Tunney's Pasture, Ottawa, Ontario, Canada

    Dr N. Priest, AEA Technology, Harwell, Didcot, Oxfordshire, United
         Kingdom

    Dr D. Wilcox, Medical Section, Health Services, Sydney Water, Sydney,
         Australia

     Secretariat 

    Dr G.C. Becking, International Programme on Chemical Safety
         Inter-regional Research Unit, World Health Organization, Research
         Triangle Park, North Carolina, USA ( Secretary)

    Dr D. Johns, DPIE, Coal and Mineral Division, Canberra, Australia
         ( Temporary Adviser)

    Mr D. Wagner, Chemicals Safety Unit, Human Services and Health,
         Canberra, Australia ( Temporary Adviser)

    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ALUMINIUM

         A WHO Task Group on Environmental Health Criteria for Aluminium
    met in Brisbane, Australia, from 24 to 28 April 1995.  The meeting
    was sponsored by a consortium of Australian Commonwealth and State
    Governments through a national steering committee chaired by
    Dr K. Bentley, Director, Health and Environmental Policy, Department
    of Health and Family Services, Canberra.  The meeting was hosted and
    organized by the NHMRC National Research Centre for Environmental
    Toxicology (NRCET), Dr M. Moore, Director, being responsible for
    the arrangements.  Dr D. Lange, Chief Health Officer, welcomed
    participants on behalf of Queensland Health, and Professor L. Roy
    Webb, Vice-chancellor, Griffith University, welcomed them on behalf of
    NRCET.  Dr G.C. Becking, IPCS, welcomed the participants on behalf of
    Dr M. Mercier, Director of the IPCS and the three cooperating
    organizations (UNEP/ILO/WHO).  The Task Group reviewed and revised the
    draft criteria monograph and made an evaluation of the risks to human
    health and the environment from exposure to aluminium.

         The first draft was prepared under the coordination of Dr G.
    Rosner, Fraunhofer Institute of Toxicology and Aerosol Research,
    Germany, and Mr P. Howe, Institute of Terrestrial Ecology, Monks Wood,
    United Kingdom.  The draft reviewed by the Task Group, incorporating
    the comments received following review by the IPCS Contact Points, was
    prepared through the cooperative effort of the Fraunhofer Institute,
    Institute of Terrestrial Ecology and the Secretariat.

         Dr G.C. Becking (IPCS Central Unit, Inter-regional Research Unit)
    and Dr P.G. Jenkins (IPCS Central Unit, Geneva) were responsible for
    the overall scientific content and technical editing, respectively, of
    this monograph.

         The efforts of all who helped in the preparation and finalization
    of this publication are gratefully acknowledged.

    ABBREVIATIONS

    AD               Alzheimer's disease
    AIBD             aluminium-induced bone disease
    cAMP             cyclic adenosine monophosphate
    CI               confidence interval
    1,25-(OH)2-D3    1,25-dihydroxy-vitamin D3
    DOC              dissolved organic carbon
    EDTA             ethylenediaminetetraacetic acid
    i.p.             intraperitoneal
    i.v.             intravenous
    LOAEL            lowest-observed-adverse-effect level
    LOEL             lowest-observed-effect level
    LTP              long-term potentiation
    NFT              neurofibrillary tangle
    NIOSH            National Institute for Occupational Safety and
                     Health (USA)
    NOEC             no-observed-effect concentration
    NOEL             no-observed-effect level
    NTA              nitrilotriacetic acid
    OR               odds ratio
    PHF              paired helical filaments
    Pt               platinum unit (1 unit equals the colour produced by
                     lung chloroplatinate in 1 litre of water)
    PTH              parathyroid hormone
    s.c.             subcutaneous
    WAIS             Weschler Adult Intelligence Scale

    1.  SUMMARY AND CONCLUSIONS

    1.1  Identity, physical and chemical properties

         Aluminium is a silvery-white, ductile and malleable metal. It
    belongs to group IIIA of the Periodic Table, and in compounds it is
    usually found as AlIII. It forms about 8% of the earth's crust and is
    one of the most reactive of the common metals. Exposure to water,
    oxygen or other oxidants leads to the formation of a superficial
    coating of aluminium oxide, which provides the metal with a high
    resistance to corrosion. Aluminium oxide is soluble in mineral acids
    and strong alkalis but insoluble in water, whereas aluminium chloride,
    nitrate and sulfate are water soluble. Aluminium halogenides, hydride
    and lower aluminium alkyls react violently with water.

         Aluminium possesses high electrical and thermal conductivity, low
    density and great resistance to corrosion. It is often alloyed with
    other metals. Aluminium alloys are light, strong and readily machined
    into shapes.

    1.2  Analytical methods

         Various analytical methods have been developed to determine
    aluminium in biological and environmental samples. Graphite furnace
    - atomic-absorption spectrometry (GF-AAS) and inductively coupled
    plasma - atomic-emission spectrometry (ICP-AES) are the most
    frequently used methods. Contamination of the samples with aluminium
    from air, vessels or reagents during sampling and preparation is the
    main source of analytical error. Depending on sample pretreatment,
    separation and concentration procedures, detection limits are
    1.9-4 µg/litre in biological fluids and 0.005-0.5 µg/g dry weight in
    tissues using GF-AAS, and 5 µg/m3 in air and 3 µg/litre in water
    using ICP-AES.

    1.3  Sources of human and environmental exposure

         Aluminium is released to the environment both by natural
    processes and from anthropogenic sources. It is highly concentrated in
    soil-derived dusts from such activities as mining and agriculture, and
    in particulate matter from coal combustion. Aluminium silicates
    (clays), a major component of soils, contribute to the aluminium
    levels of dust. Natural processes far outweigh direct anthropogenic
    contributions to the environment. Mobilization of aluminium through
    human actions is mostly indirect and occurs as a result of emission of
    acidifying substances. In general, decreasing pH results in an
    increase in mobility and bioavailability for monomeric forms of
    aluminium. The most important raw material for the production of
    aluminium is bauxite, which contains up to 55% alumina (aluminium
    oxide). World bauxite production was 106 million tonnes in 1992.
    Aluminium metal has a vide variety of uses, including structural

    materials in construction, automobiles and aircraft, and the
    production of metal alloys. Aluminium compounds and materials also
    have a wide variety of uses, including production of glass, ceramics,
    rubber, wood preservatives, pharmaceuticals and waterproofing
    textiles. Natural aluminium minerals, especially bentonite and
    zeolite, are used in water purification, sugar refining, brewing and
    paper industries.

    1.4  Environmental transport, distribution and transformation

         Aluminium occurs ubiquitously in the environment in the form of
    silicates, oxides and hydroxides, combined with other elements such as
    sodium and fluorine and as complexes with organic matter. It is not
    found as a free metal because of its reactivity. It has only one
    oxidation state (+3) in nature; therefore, its transport and
    distribution in the environment depend only upon its coordination
    chemistry and the chemical-physical characteristics of the local
    environmental system. At pH values greater than 5.5, naturally
    occurring aluminium compounds exist predominantly in an undissolved
    form such as gibbsite (Al(OH)3) or as aluminosilicates, except in the
    presence of high amounts of dissolved organic material, which binds
    with aluminium and can lead to increased concentrations of dissolved
    aluminium in streams and lakes. Several factors influence aluminium
    mobility and subsequent transport within the environment. These
    include chemical speciation, hydrological flow paths, soil-water
    interactions, and the composition of the underlying geological
    materials. The solubility of aluminium in equilibrium with solid phase
    Al(OH)3 is highly dependent on pH and on complexing agents such as
    fluoride, silicate, phosphate and organic matter. The chemistry of
    inorganic aluminium in acid soil and stream water can be considered in
    terms of mineral solubility, ion exchange and water mixing processes.

         Upon acidification of soils, aluminium can be released into
    solution for transport to streams. Mobilization of aluminium by acid
    precipitation results in more aluminium being available for plant
    uptake.

    1.5  Environmental levels and human exposure

         Aluminium is a major constituent of a number of atmospheric
    components particularly in soil-derived dusts (both from natural
    sources and human activity) and particulates from coal combustion. In
    urban areas aluminium levels in street dust range from 3.7 to
    11.6 µg/kg. Airborne aluminium levels vary from 0.5 ng/m3 over
    Antarctica to more than 1000 ng/m3 in industrialized areas.

         Surface freshwater and soil water aluminium concentrations can
    vary substantially, being dependent on physico-chemical and geological
    factors. Aluminium can be suspended or dissolved. It can be bound with
    organic or inorganic ligands, or it can exist as a free aluminium ion.
    In natural waters aluminium exists in both monomeric and polymeric
    forms. Aluminium speciation is determined by pH and the concentrations
    of dissolved organic carbon (DOC), fluoride, sulfate, phosphate and
    suspended particulates. Dissolved aluminium concentrations for water
    in the circumneutral pH range are usually quite low, ranging from
    1.0 to 50 µg/litre. This rises to 500-1000 µg/litre in more acidic
    water. At the extreme acidity of water affected by acid mine drainage,
    dissolved aluminium concentrations of up to 90 mg/litre have been
    measured.

         Non-occupational human exposure to aluminium in the environment
    is primarily through ingestion of food and water. Of these, food is
    the principal contributor. The daily intake of aluminium from food and
    beverages in adults ranges between 2.5 and 13 mg. This is between 90
    and 95% of total intake. Drinking-water may contribute around 0.4 mg
    daily at present international guideline values, but is more likely
    to be around 0.2 mg/day. Pulmonary exposure may contribute up to
    0.04 mg/day. In some circumstances, such as occupational exposure and
    antacid use, the levels of exposure will be much greater. For example,
    > 500 mg of aluminium may be consumed in two average-sized antacid
    tablets. There are some difficulties in assessing uptake from these
    exposures because of analytical and sampling difficulties. Isotopic
    investigations with Al26 indicate that one of the most bioavailable
    forms of aluminium is the citrate and that there could be as much as
    1% absorption when aluminium is in this form. However, humans would
    absorb only 3% of their total daily uptake of aluminium from drinking-
    water, a relatively minor source compared to food.

    1.6  Kinetics and metabolism

    1.6.1  Humans

         Aluminium and its compounds appear to be poorly absorbed in
    humans, although the rate and extent of absorption have not been
    adequately studied. Concentrations of aluminium in blood and urine
    have been used as a readily available measure of aluminium uptake,
    increased urine levels having been observed among aluminium welders
    and aluminium flake-powder producers.

         The mechanism of gastrointestinal absorption of aluminium has not
    yet been fully elucidated. Variability results from the chemical
    properties of the element and the formation of various chemical
    species, which is dependent upon the pH, ionic strength, presence of
    competing elements (silicon), and the presence of complexing agents
    within the gastrointestinal tract (e.g., citrate).

         The biological behaviour and gastrointestinal absorption of
    aluminium in humans ingesting aluminium compounds has been studied by
    using the radioactive isotope Al26. Significant intersubject
    variability has been demonstrated. Measured fractional uptakes of 5 ×
    10-3 for aluminium as citrate, 1.04 × 10-4 for aluminium hydroxide
    and 1.36 × 10-3 for the hydroxide given with citrate were reported. A
    study of the fractional uptake of aluminium from drinking-water showed
    an uptake fraction of 2.35 × 10-3. It was concluded that members of
    the general population consuming 1.5 litres/day of drinking-water
    containing 100 µg aluminium/litre would absorb about 3% of their total
    daily intake of aluminium from this source depending upon the levels
    found in food and the frequency of antacid use.

         The proportion of plasma Al3+ normally bound to protein in
    humans may be as high as 70-90% in haemodialysis patients with
    moderately increased plasma aluminium. The highest levels of aluminium
    may be found in the lungs, where it may be present as inhaled
    insoluble particles.

         The urine is the most important route of aluminium excretion.
    After peroral administration of a single dose of aluminium, 83% was
    excreted in urine after 13 days and 1.8% in the faeces. The half-life
    of urinary concentration among welders exposed for more than 10 years
    was 6 months or longer. Among retired workers exposed to aluminium
    flake powders, the calculated half-lives were between 0.7 and 8 years.

    1.6.2  Animals

         Absorption via the gastrointestinal tract is usually less than
    1%. The main factors influencing absorption are solubility, pH and
    chemical species. Organic complexing compounds, notably citrate,
    increase absorption. The aluminium absorption may interact with
    calcium and iron transport systems. Dermal and inhalation absorption
    has not been studied in detail. Aluminium is distributed in most
    organs within the body with accumulation occurring mainly in bone at
    high dose levels. To a limited but as yet undetermined extent,
    aluminium passes the blood-brain barrier and is also distributed to
    the fetus. Aluminium is eliminated effectively by urine. Plasma half-
    life is about 1 h in rodents.

    1.7  Effects on laboratory mammals and in vitro test systems

         The acute toxicity of metallic aluminium and aluminium compounds
    is low, the reported oral LD50 values being in the range of several
    hundred to 1000 mg aluminium/kg body weight per day. However, the
    LC50 values for inhalation have not been identified.

         In short-term studies in which an adequate range of end-points
    was examined following exposure of rats, mice or dogs to various
    aluminium compounds (sodium aluminium phosphate, aluminium hydroxide,
    aluminium nitrate) in the diet or drinking-water, only minimal effects
    (decreases in body weight gain generally associated with decreases in
    food consumption or mild histopathological effects) have been observed
    at the highest administered doses (70 to 300 mg aluminium/kg body
    weight per day). Systemic effects following parenteral administration
    also included kidney dysfunction.

         Adequate inhalation studies were not identified. Following
    intratracheal administration of aluminium oxide, particle-associated
    fibrosis was observed, similar to that found in other studies on
    silica and coal dust.

         No overt fetotoxicity was noted, nor were general reproductive
    parameters noted after gavage treatment of rats with 13, 26 or 52 mg
    aluminium/kg body weight per day (as aluminium nitrate). However, a
    dose-dependent delay in the growth of offspring was noted with females
    administered 13 mg/kg and in male offspring at 26 mg/kg. The lowest-
    observed-adverse-effect level (LOAEL) for developmental effects
    (decreased ossification, increased incidence of vertebral and
    sternebrae terata and reduced fetal weight) was 13 mg/kg (aluminium
    nitrate). These effects were not observed at much higher doses of
    aluminium hydroxide. There were reductions in postnatal growth at
    13 mg/kg (aluminium nitrate), although maternal toxicity was not
    examined. In studies on brain development, grip strength was impaired
    in offspring of dams fed 100 mg aluminium/kg body weight as aluminium
    lactate in the diet, in the absence of maternal toxicity.

         There is no indication that aluminium is carcinogenic. It can
    form complexes with DNA and cross-link chromosomal proteins and DNA,
    but it has not been shown to be mutagenic in bacteria or induce
    mutation or transformation in mammalian cells  in vitro. Chromosomal
    aberrations have been observed in bone marrow cells of exposed mice
    and rats.

         There is considerable evidence that aluminium is neurotoxic in
    experimental animals, although there is considerable variation among
    species. In susceptible species, toxicity following parenteral
    administration is characterized by progressive neurological
    impairment, resulting in death with status epilepticus (LD50 =
    6 µg Al/g dry weight of brain). Morphologically, the progressive
    encephalopathy is associated with neurofibrillary pathology in
    large and medium size neurons predominantly in the spinal cord,
    brainstem and selected areas of the hippocampus. These tangles are
    morphologically and biochemically different from those that occur in

    Alzheimer's disease (AD). Behavioural impairment has been observed in
    the absence of overt encephalopathy or neurohistopathology in
    experimental animals exposed to soluble aluminium salts (e.g.,
    lactate, chloride) in the diet or drinking-water at doses of 50 mg
    aluminium/kg body weight per day or more.

         Osteomalacia, as it presents in man, is observed consistently in
    larger species (e.g., dogs and pigs) exposed to aluminium; a similar
    condition is observed in rodents. These effects appear to occur in all
    species, including humans, at aluminium levels of 100 to 200 µg/g bone
    ash.

    1.8  Effects on humans

         No acute pathogenic effects in the general population have been
    described after exposure to aluminium.

         In England, a population of about 20 000 individuals was exposed
    for at least 5 days to increased levels of aluminium sulfate,
    accidentally placed in a drinking-water facility. Case reports of
    nausea, vomiting, diarrhoea, mouth ulcers, skin ulcers, skin rashes
    and arthritic pain were noted. It was concluded that the symptoms were
    mostly mild and short-lived. No lasting effects on health could be
    attributed to the known exposures from aluminium in the drinking-
    water.

         It has been hypothesized that aluminium in the drinking-water is
    a risk factor for the development or acceleration of AD as well as for
    impaired cognitive function in the elderly. It has also been suggested
    that stamped fine aluminium powder and fume may be risk factors for
    impaired cognitive function and pulmonary disease in certain
    occupations.

         Some 20 epidemiological studies have been carried out to test the
    hypothesis that aluminium in drinking-water is a risk factor for AD,
    and two studies have evaluated the association between aluminiun in
    drinking-water and impaired cognitive function. Study designs ranged
    from ecological to case control. Eight studies in populations in
    Norway, Canada, France, Switzerland and England were considered
    of sufficiently high quality to meet the general criteria for
    exposure and outcome assessment and the adjustment for at least
    some confounding variables. Of the six studies that examined the
    relationship between aluminium in drinking-water and dementia or AD,
    three found a positive relationship but three did not. However, each
    of the studies had some deficiencies in the study design (e.g.,
    ecological exposure assessment, failure to consider aluminium exposure
    from all sources and to control for important confounders such as
    education, socioeconomic status and family history, the use of
    surrogate outcome measures for AD, and selection bias). In general,
    the relative rists determined were less than 2, with large confidence

    intervals, when the total aluminium concentration in drinking-water
    was 100 µg/litre or higher. Based on current knowledge on the
    pathogenesis of AD and the totality of evidence from these
    epidemiological studies, it was concluded that the present
    epidemiological evidence does not support a causal association between
    AD and aluminium in drinking-water.

         In addition to the epidemiological studies that examined the
    relationship between AD and aluminium in drinking-water, two studies
    examined cognitive dysfunction and AD in elderly populations in
    relation to the levels of aluminium in drinking-water. The results
    were again conflicting. One study of 800 male octogenarians consuming
    drinking-water with aluminium concentrations up to 98 µg/litre found
    no relationship. The second study used "any evidence of mental
    impairment" as an outcome measure and found a relative risk of 1.72 at
    aluminium concentrations greater than 85 µg/litre in 250 males. Such
    data are insufficient to show that aluminium is a cause of cognitive
    impairment in the elderly.

         Reports of impaired cognitive function related to aluminium
    exposure are conflicting. Most studies are on small populations, and
    the methodology used in these studies is open to question with respect
    to magnitude of effect reported, exposure assessment and confounding
    factors. In a comparative study of cognitive impairment in miners
    exposed to a powder containing 85% finely ground aluminium and 15%
    aluminium oxide (as prophylaxis against silica) and unexposed miners,
    the cognitive test scores and the proportion impaired in at least one
    test indicated a disadvantage for the exposed miners. A positive
    exposure-related trend of increased risk was noted.

         In all occupational studies reported, the magnitude of effects
    found, presence of confounding factors, problems with exposure
    assessment and the probability of mixed exposures all make the data
    insufficient to conclude that aluminium is a cause of cognitive
    impairment in workers exposed occupationally to aluminium.

         Neurological syndromes including impairment of cognitive
    function, motor dysfunction and peripheral neuropathy have been
    reported in limited studies of workers exposed to aluminium fume. A
    small population of aluminium welders who were compared with iron
    welders were reported to show a small decrement in repetitive motor
    function. When a questionnaire methodology was used in another study,
    an increase in neuropsychiatric symptoms was reported.

         Iatrogenic exposure in patients with chronic renal failure,
    exposed to aluminium-containing dialysis fluids and pharmaceutical
    products, may cause encephalopathy, vitamin-D-resistant osteomalacia
    and microcytic anaemia. These clinical syndromes can be prevented by
    reduction in exposure to aluminium.

         Premature infants, even where kidney impairment is not severe
    enough to cause raised blood creatinine levels, may develop increased
    tissue loading of aluminium, particularly in bone, when exposed to
    iatrogenic sources of aluminium. Where there is kidney failure,
    seizures and encephalopathy may occur.

         Although human exposure to aluminium is widespread, in only a few
    cases has hypersensitivity been reported following exposure to some
    aluminium compounds after dermal application or parenteral
    administration.

         Pulmonary fibrosis was reported in some workers exposed to very
    fine stamped aluminium powder in the manufacture of explosives and
    fireworks. Nearly all cases involved exposure to aluminium particles
    coated with mineral oil. That process is no longer used. Other cases
    of pulmonary fibrosis have related to mineral exposures to other
    agents such as silica and asbestos and cannot be attributed solely to
    aluminium.

         Irritant-induced asthma has been associated with inhalation
    of aluminium sulfate, aluminium fluoride, potassium aluminium
    tetrafluoride and with the complex environment of the potrooms during
    aluminium production.

         There is insufficient information to allow for classification of
    the cancer risk from human exposures to aluminium and its compounds.
    Animal studies do not indicate that aluminium or aluminium compounds
    are carcinogenic.

    1.9  Effects on other organisms in the laboratory and field

         Aquatic unicellular algae showed increased toxic effect at low
    pH, where bioavailability of aluminium is increased. They are more
    sensitive than other microorganisms, the majority of 19 lake species
    showing complete growth inhibition at 200 µg/litre total aluminium
    (pH 5.5). Selection of aluminium-tolerant strains is possible; green
    algae capable of growing in the presence of 48 mg/litre at pH 4.6 have
    been isolated.

         For aquatic invertebrates, LC50 values range from 0.48 mg/litre
    (polychaete) to 59.6 mg/litre (daphnid). For fish, 96-h LC50 values
    range from 0.095 mg/litre (American flagfish) to 235 mg/litre
    (mosquito fish). However, care must be taken when interpreting the
    results because of the significant effects of pH on the availability
    of aluminium. The wide range of LC50 values probably reflects
    variable availability. The addition of chelating agents, such as NTA
    and EDTA, reduces the acute toxicity of aluminium to fish.

         Responses to aluminium by macroinvertebrates are variable. In the
    normal pH range aluminium toxicity increases with decreasing pH;
    however, in very acidic waters aluminium can reduce the effects of
    acid stress. Some invertebrates are very resistant to acid stress and
    can be very numerous in acidic waters. Increased drift rate of
    invertebrates has been reported in streams suffering either pH or
    pH/aluminium stress; this is a common response to a variety of
    stressors. Lake invertebrates generally survived field exposure to
    aluminium but suffered as a result of phosphate reduction in
    oligotrophic conditions induced by precipitation with aluminium.

         Short- and long-term toxicity tests on fish have been carried out
    under a variety of conditions and, most importantly, at a range of pH
    values. The data show that significant effects have been observed at
    monomeric inorganic aluminium levels as low as 25 µg/litre. However,
    the complex relationship between acidity and aluminium bioavailability
    makes interpretation of the toxicity data more difficult. At very
    low pH (not normally found in natural waters) the hydrogen ion
    concentration appears to be the toxic factor, with the addition of
    aluminium tending to reduce toxicity. In the pH range 4.5 to 6.0
    aluminium in equilibrium exerts its maximum toxic effect. Toxicity has
    also been shown to increase with increasing pH levels in the alkaline
    pH region. The mechanism of aluminium toxicity to fish has been
    attributed to the inability of fish to maintain their osmoregulatory
    balance, as well as respiratory problems associated with precipitation
    of aluminium on the gill mucus. The former effect is associated with
    lower pH levels. These laboratory findings have been confirmed by
    field studies especially in areas under acid stress.

         Amphibian eggs and larvae are affected by acidity and aluminium,
    with interaction between the two factors. Reduced hatching, delayed
    hatching, delayed metamorphosis, metamorphosis at small size, and
    mortality have been reported in various species and at aluminium
    concentrations below 1 mg/litre.

         Exposure of roots of terrestrial plants to aluminium can cause
    diminished root growth, reduced uptake of plant nutrients and stunted
    plant development. Tolerance to aluminium has been demonstrated both
    in the laboratory and the field.

    1.10  Conclusions

    1.10.1  General population

         Hazards to neurological development and brain function from
    exposure to aluminium have been identified through animal studies.
    However, aluminium has not been demonstrated to pose a health risk to
    healthy, non-occupationally exposed humans.

         There is no evidence to support a primary causative role of
    aluminium in Alzheimer's disease (AD), and aluminium does not induce
    AD pathology  in vivo in any species, including humans.

         The hypothesis that exposure of the elderly population in some
    regions to elevated levels of aluminium in drinking-water may
    exacerbate or accelerate AD lacks adequate supporting data.

         The data in support of the hypothesis that particular exposures,
    either occupational or via drinking-water, may be associated with non-
    specific impaired cognitive function are also inadequate.

         There is insufficient health-related evidence to justify
    revisions to existing WHO Guidelines for aluminium exposure in
    healthy, non-occupationally exposed humans. As an example, there is an
    inadequate scientific basis for setting a health-based standard for
    aluminium in drinking-water.

    1.10.2  Subpopulations at special risk

         In people of all ages with impaired renal function, aluminium
    accumulation has been shown to cause the clinical syndrome of
    encephalopathy, vitamin-D-resistant osteomalacia and microcytic
    anaemia. The sources of aluminium are haemodialysis fluid and
    aluminium-containing pharmaceutical agents (e.g., phosphate binders).
    Intestinal absorption can be exacerbated by the use of citrate-
    containing products. Patients with renal failure are thus at risk of
    neurotoxicity from aluminium.

         Iatrogenic aluminium exposure poses a hazard to patients with
    chronic renal failure. Premature infants have higher body burdens of
    aluminium than other infants. Every effort should be made to limit
    such exposure in these groups.

    1.10.3  Occupationally exposed populations

         Workers having long-term, high-level exposure to fine aluminium
    particulates may be at increased risk of adverse health effects.
    However, there are insufficient data from which to develop with any
    degree of certainty occupational exposure limits with regards to the
    adverse effects of aluminium.

         Exposure to stamped pyrotechnic aluminium powder most often
    coated with mineral oil lubricants has caused pulmonary fibrosis
    (aluminosis), whereas exposure to other forms of aluminium has not
    been proven to cause pulmonary fibrosis. Most reported cases had
    exposure to other potentially fibrogenic agents.

         Irritant-induced asthma has been associated with inhalation of
    aluminium sulfate, aluminium fluoride or potassium aluminium
    tetrafluoride, and with the complex environment within the potrooms
    during aluminium production.

    1.10.4  Environmental effects

         Aluminium-bearing solid phases in the environment are relatively
    insoluble, particularly at circumneutral pH values, resulting in low
    concentrations of dissolved aluminium in most natural water.

         In acidic or poorly buffered environments subjected to strong
    acidifying inputs, concentrations of aluminium can increase to levels
    resulting in adverse effects on both aquatic organisms and terrestrial
    plants. However, there exist large species, strain and life history
    stage differences in sensitivity to this metal.

         The detrimental biological effects from elevated concentrations
    of inorganic monomeric aluminium can be mitigated in the presence of
    organic acids, fluorides, silicate and high levels of calcium and
    magnesium.

         There is a substantial reduction in species richness associated
    with the mobilization of the more toxic forms of aluminium in acid-
    stressed waters. This loss of species diversity is observed at all
    trophic levels.

    2.  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

         The element aluminium (Al) was first obtained in an impure form
    by Oersted in 1825, and pure aluminium was prepared by Woehler two
    years later. The name aluminium is derived from alum, which the
    ancient Greeks used as an astringent in medicine (Lide, 1991).

         Aluminium is the most abundant metallic element and constitutes
    8.13% of the earth's crust. Owing to its high reactivity, it is always
    found combined with other elements and does not occur in its pure
    state. Combined with oxygen, silicon, the alkali and alkaline-earth
    metals, and fluorine, and as hydroxides, sulfates and phosphates,
    aluminium appears in a wide variety of minerals (Frank et al., 1985;
    Hudson et al., 1985; Lide, 1991).

         Some aluminium compounds, synonyms and molecular formulae are
    listed in Table 1. The most abundant natural aluminium ores are shown
    in Table 2.

    2.1  Identity

         Pure aluminium is a silvery-white, malleable, ductile metal with
    the atomic number of 13 and the relative atomic mass of 26.98. With
    few exceptions aluminium is found in chemical compounds as AlIII.
    Aluminium occurs naturally as 27Al; eight radioactive isotopes are
    known, of which 26Al is the most stable with a half-life of 7.4 ×
    105 years (Frank et al., 1985).

    2.2  Physical and chemical properties

    2.2.1  Aluminium metal

         Elemental aluminium possesses many desirable characteristics and
    is therefore widely used in commerce (Sax & Lewis, 1987; Lide, 1991).
    Aluminium crystallizes in a face-centered cubic lattice that is stable
    from 4 K to melting point; the coordination number is 12, it is light
    and malleable, and thus is easily formed into a variety of shapes
    (Frank et al., 1985).

         Owing to the high charge/radius ratio of Al3+ in aqueous
    solutions, the ion proteolyses part of the water envelope and forms
    hydroxo complexes. It can also complex with electron-rich species,
    such as fluoride and chloride. The chemical properties of aluminium
    resemble those of beryllium and silicon. Because of its amphoteric
    character, it reacts with mineral acids and strong alkalis (Sax &
    Lewis, 1987). Although aluminium is one of the most reactive of the
    common metals used commercially, it has excellent resistance to 

        Table 1.  Chemical names, synonyms and molecular formulae of elemental aluminium and aluminium compoundsa
                                                                                                                                              

    Chemical name                  CAS registry number  Synonyms                                         Formula
                                                                                                                                              

    Aluminium                      7429-90-5            Aluminium, metana                                Al

    Aluminium chloride             7446-70-0            Aluminium trichloride                            AlCl3

    Aluminium chlorohydrate        1327-41-9            Aluminium chlorohydroxide,                       AlCl(OH)5
                                   11097-68-0           aluminium chloride, basic,
                                   84861-98-3           chlorhydrol, polyaluminium chlorideb             Al2Cl(OH)52H2O

    Aluminium fluoride             7784-18-1            Aluminium trifluoride                            AlF3

    Aluminium lactate              18917-91-4           Aluctyl                                          Al(C3H5O3)3

    Aluminium oxidec               1302-74-5            alpha-Alumina, corundum                          Al2O3

    Aluminium oxide hydroxidec     14457-84-2           Diaspore                                         alpha-AlO(OH) or alpha-Al2O3H2O

    Aluminium oxide hydroxidec     1318-23-6            Boehmite                                         gamma-AlO(OH) or gamma-Al2O3H2O

    Aluminium oxide, trihydratec   20257-20-9           Bayerite, alpha-aluminium trihydroxide           alpha-Al(OH)3 or alpha-Al2O33H2O

    Aluminium oxide, trihydratec   13840-05-6           Nordstrandite, ß-aluminium trihydroxide          ß-Al(OH)3 or ß-Al2O33H2O

    Aluminium oxide, trihydratec   14762-49-3           Gibbsite, hydrargillite, gamma-aluminium         gamma-Al(OH)3 or gamma-Al2O33H2O
                                                        trihydroxide

    Nitric acid, aluminium salt    13473-90-0           Aluminium trinitrate, aluminium nitrate          Al(NO3)3
                                                                                                                                              
    Table 1.  (Con't)
                                                                                                                                              

    Chemical name                  CAS registry number  Synonyms                                         Formula
                                                                                                                                              

    Phosphoric acid,
    aluminium salt                 7784-30-7            Aluminium orthophosphate                         AlPO4

    Sodium aluminate               1302-42-7                                                             NaAlO2, Na2OAl2O3 or
                                                                                                         Na2Al2O4

    Sulfuric acid, aluminium salt  10043-01-3           Alum, aluminium trisulfate, cake alum            Al2(SO4)3

    Trimethylaluminiumb            75-24-1                                                               Al(CH3)3

    2-Propanol, aluminium saltb    555-31-7             Aluminium isopropoxide, aluminium                Al(OCH(CH3)2)3
                                                        isopropylate

    2-Butanol, aluminium saltb     2269-22-9            Aluminium sec-butoxide, aluminium                Al(OC4H9)3
                                                        butylate
                                                                                                                                              

    a    adapted from ATSDR (1992)
    b    Zietz (1985)
    c    Hudson et al. (1985)

    Table 2.  CAS chemical names and registry numbers, synonyms, trade names, content and molecular formula of aluminium oresa
                                                                                                                  

    Chemical name               CAS registry   Synonyms and trade         Composition         Formula
                                number              names
                                                                                                                  

    Aluminium magnesium         -            Magnesium aluminium          48.8% O             MgAl2(SiO4)2
    silicate                                 silicate                     21.4% Si
                                                                          20.6% Al
                                                                          9.3% Mg

    Aluminium silicate, hydrate -            Kaolinite                    40% Al2O3b          Al2Si2O5(OH)4 or
                                                                          46% SiO2            Al2O3SiO2H2O
                                                                          14% H2O

    Aluminium silicofluoride    -            Topaz                        71.2% F             2Al2O32Al(F,OH)33SiO2
                                                                          17.6% Si
                                                                          11.2% Al

    Ammonium aluminium          7784-26-1    Ammonium alum,               -                   NH4Al(SO4)212H2O or
    sulfate, hydrate                         ammonium                                         Al2O3(NH4)2O24HOH
                                             aluminium sulfate

    Bauxite                     1318-16-7    -                            30-75% Al2O3        -
                                                                          3-25% Fe2O3
                                                                          9-31% H2O
                                                                          2-9% SiO2
                                                                          1-3% TiO2
                                                                                                                  

    Table 2.  (Con't)
                                                                                                                  

    Chemical name               CAS registry   Synonyms and trade         Composition         Formula
                                number              names
                                                                                                                  

    Potassium aluminium         7784-24-9    Potash alum, potassium       37% Al2O3           K(AlO)3(SO4)212H2O or
    sulfate, hydrate                         aluminium sulfate            11% K2O             Al2(SO4)3K2SO424HOH
                                                                          39% SO3
                                                                          13% H2O

    Sodium aluminium            15096-52-3   Cryolite, greenland          -                   Na3AlF6 or 3NaFAlF3
    fluoride                                 spar, isestone

    Sodium aluminium            7784-28-3    Sodium alum, sodium          -                   NaAl(SO4)212H2O or
    sulfate, hydrate                         aluminium sulfate                                Al2(SO4)2Na2SO424HOH

    Sodium calcium              -            Anorthosite, soda-lime       26-35% Al2O3b       Na2OAl2O36SiO2 &
    silicoaluminate                          feldspar                     46-59% SiO2         CaOAl2O32SiO2
                                                                          8-18% CaO
                                                                          1-7% Na2O
                                                                                                                  

    a    From: Sax & Lewis (1987)
    b    US Bureau of Mines (1967)
        corrosion. Exposed to oxygen, water or other oxidants, a continuous
    film of aluminium oxide (Al2O3) grows rapidly on the nascent
    aluminium surface, providing the metal with a high resistance to
    corrosion. The oxide film dissolves in alkaline solutions with
    evolution of hydrogen and formation of soluble alkali-metal aluminates
    (Sax & Lewis, 1987).

         The oxide film on the solid metal is resistant to some acids
    (e.g., nitric acid), and prevents further chemical attack on the
    metal. However, the protective oxide film dissolves in some acids
    (e.g., hydrochloric or hot sulfuric acids) and also in alkaline
    solutions, exposing the metal to further reactions. At elevated
    temperatures, aluminium metal reacts with water (above 180°C),
    producing Al(OH)3 and H2, and with many metal oxides producing
    Al2O3 and the metal. This reaction is used to produce certain
    metals, for example, manganese and alloys (e.g., ferro-titanium).

         Finely divided aluminium dust can ignite and cause explosions
    (Wade & Banister, 1973; Frank et al., 1985).

         Many applications of aluminium and its alloys are based upon its
    inherent properties of high electrical and thermal conductivity, low
    density, and great resistance to corrosion. Pure aluminium is soft and
    lacks strength, but it can be alloyed with small amounts of Cu, Mg,
    Si, Mn and other elements to impart greater strength and a variety of
    other useful properties. Aluminium alloys are light, strong and
    readily worked into a variety of shapes (Frank et al., 1985; Lide,
    1991).

    2.2.2  Aluminium compounds

         The aluminium compounds of the greatest industrial importance are
    aluminium oxide, aluminium sulfate and aluminium silicate. Some
    physical and chemical data of aluminium and selected aluminium
    compounds are summarized in Table 3.

         Aluminium oxide is a white powder that is found as balls or
    lump of various mesh sizes. Owing to its amphoteric character, it is
    soluble in mineral acids and strong alkali. Aluminium oxide is
    found in different modifications. The hexagonally closest-packed
    alpha-modification "corundum" (alpha-Al2O3) is the most stable
    oxide. Emery is an abrasive containing corundum, and ruby and sapphire
    are impure crystalline varieties of gem quality (Hudson et al., 1985).
    Formation of aluminium oxide by dehydration of the hydroxides produces
    a series of alumina types still containing a small proportion of
    hydroxyl groups and retaining some chemical reactivity. All oxides
    produced at low temperatures are collectively referred to as
    transitional oxides. Those formed by dehydration below 600°C are known

        Table 3.  Physical and chemical properties of aluminium and some of its compoundsa
                                                                                                                                              

    Chemical name           Relative atomic/   Melting      Boiling        Relative density    Crystalline           Solubilityd
                            molecular mass     point (°C)   point (°C)     (g/cm3)b            form
                                                                                                                                              

    Aluminium               26.98              660          2450c          2.708               silver-white cubic    sol alkali, HCl, H2SO4;
                                                                                                                     insol H2O, HNO3e

    alpha-Aluminium         77.99              300 (-H2O)                  2.420               monoclinic, powder    sol acid; insol H2O,
    hydroxide (bayerite)                                                                                             alcohole

    Aluminium nitrate       213.00             74           135            -                   rhombic delinq.       sol H2O, alkali,
                                                            (decomposes)                                             acetone, HNO3

    Aluminium oxide         101.94             2072         2980           3.965 (25)          hexagonal             very sl sol benzene;
                                                                                                                     insol H2O

    gamma-Aluminium oxide   59.99              -            -              3.440               orthorhomic           sol acid; sl sol
    hydroxide (boehmite)                                                                                             alkali; insol H2O,
                                                                                                                     alcohole

    Aluminium phosphate     121.95             1500         -              2.566               rhombic platelets     sol acid, alkali; insol H2O

    Aluminium sulfate,      342.14             700          -              2.710               powder                sol H2O, dil acid; sl
    anhydrate                                  (decomposes)                                                          sol alkali

    Aluminium sulfate,      666.41             87           -              1.690 (17)          monoclinic            sol H2O, dil. acid; sl
    hydrate                                    (decomposes)                                                          sol alkali

    Aluminium               204.25             119          141            1.035 (20)          crystals              sol alcohol, benzene,
    isopropoxidee                                                                                                    chloroform
                                                                                                                                              
    a    Compiled from ATSDR (1992)
    b    Temperature is given in parentheses
    c    Sax & Lewis (1987)
    d    Sol = soluble; insol = insoluble; sl = slightly
    e    Lide (1991)
        as gamma-aluminas or activated aluminas, while the aluminas formed by
    dehydration at higher temperatures (900-1000°C), the rho-aluminas, are
    nearly anhydrous Al2O3 (Wade & Banister, 1973). At 1400°C all
    transitional alumina converts to alpha-alumina (Hudson et al., 1985).
    The structural and compositional differences among various forms of
    alumina are associated with differing particulate size, particulate
    surface area, surface reactivity and catalytic activity.

         Various forms of aluminium hydroxides are known. The best defined
    forms are the trihydroxides (Al(OH)3) and the oxide-hydroxides
    (AlO(OH)). Besides these well-defined crystalline forms, several other
    hydroxides have been described in the literature (Wefers & Bell,
    1972). The aluminium hydroxides found abundantly in nature are
    gibbsite (Al(OH)3), diaspore ś-(AlO(OH)), and boehmite
    alpha-(AlO(OH)). They all convert to aluminium oxide when heated
    (Hudson et al., 1985).

         Aluminium sulfate can exist with varying proportions of water,
    the common form being Al2(SO4)3Ę18H2O. It is almost insoluble
    in anhydrous alcohol, but readily soluble in water. Above 770°C
    decomposition to aluminium oxide is observed. Aluminium sulfate is
    mainly used in water treatment, dyeing, leather tanning and in the
    production of other aluminium compounds. Alums are crystalline double
    salts composed of aluminium, sulfate and a monovalent cation, such
    as potassium, sodium or ammonium, and have the general formula
    M+Al3+(SO4)2Ę12H2O. In aqueous solution, alums show all the
    chemical properties that their components show separately (Helmboldt
    et al., 1985).

         Clays are aluminium silicates. They have cation-exchange capacity
    and the amounts and types of clay minerals in a soil largely determine
    its physical properties and suitability for agriculture (Wild, 1988).

         Aluminium halogenides, hydrides and lower aluminium alkyls react
    violently with molecular oxygen, and are spontaneously inflammable in
    air and explosive with water. Industrially these compounds are used as
    co-catalysts for organometallic and organic synthesis, and as
    intermediates in various production processes (Stokinger, 1987;
    Budavari, 1989).

         Further compounds of industrial interest are aluminium antimonide
    (AlSb) and selenide (AlSe), which are employed in the semiconductor
    technology industry (Budavari, 1989). Aluminium phosphide (AlP) is
    used as a rodenticide and pesticide, but it is not discussed in this
    monograph since its biocidal activity is due to the phosphide moiety
    and not to the aluminium.

    2.3  Analytical methods

         Various methods for sampling, sample preparation and
    determination of aluminium in biological and environmental samples
    have been developed and described. An overview of standard methods is
    given in Table 4.

    2.3.1  Sampling and sample preparation

         Because of the ubiquitous distribution of aluminium in nature,
    care must be taken during sampling and sample preparation to avoid
    contamination. Most analytical errors are due to contamination of the
    sample with aluminium from air, vessels and reagents during sampling
    and preparation for analysis. To prevent aluminium contamination, the
    use of aluminium-free polyethylene, polypropylene, teflon or quartz
    materials is recommended. Containers and laboratory materials have to
    be washed with warm, dilute nitric acid and subsequently rinsed with
    de-ionized water prior to use (Andersen, 1987).

         Air is sampled with high volume samplers using low-ash cellulose
    or cellulose ester filters for particulate aluminium (NIOSH, 1984).
    Biological samples need to be preserved by cooling, freezing or
    lyophilization. Preservation with 10% formalin is not recommended
    because of a high risk of aluminium contamination (Bouman et al.,
    1986).

         Homogeneity of the samples is an absolute prerequisite for
    accurate analysis. To prepare samples for analysis, inorganic samples
    are usually dissolved in nitric acid or extracted with water.
    Solutions are filtered with a membrane filter and the particulate
    residue is analysed separately (Dunemann & Schwedt, 1984).

         Water (DIN, 1993) and urine should be acidified with HNO3 or HCl
    to pH < 2 to prevent adsorption effects and the precipitation of
    salts. This ensures that aluminium remains in solution. Water samples
    for speciation analysis should be stored, without acidification, in
    high-density polyethylene bottles (Berden et al., 1994; Fairman et
    al., 1994). Prior to analysis biological tissues must be homogenized
    and separated or extracted. Blood and urine samples may be separated
    by centrifugation and diluted, or, if appropriate, analysed directly
    without pretreatment.

        Table 4.  Analytical methods for aluminium and aluminium compoundsa
                                                                                                                                              

    Medium         Sample preparation                 Analytical method   Detection limit            Recovery    Reference
                                                                                                                                              

    Environmental
    samples

    Air            Sample collection on cellulose     FAAS                500 µg/m3 (100-litre       n.g.        NIOSH (1984)
                   filter, ashing with HNO3                               sample)
                   Sample collection on cellulose     ICP-AES             5 µg/m3 (500-litre         n.g.        NIOSH (1984)
                   filter, ashing with HNO3                               sample)

    Water          Reaction with sulfonitrazo DAF     Spectrophotometry   4 µg/litre                 n.g.        Ermolenko &
                                                                                                                 Dedkov (1988)
                   Reaction with Chromazurol S        Spectrophotometry   0.0005 µg/0.5 ml-          n.g.        Schwedt (1989)
                                                                          sample
                   Reaction with alizarin S           Spectrophotometry   10 µg/litre; 50 µg/litre   n.g.        DIN (1993)
                                                                          (after digestion)
                   Digestion with HNO3 and            ICP-AES             100 µg/litre               n.g.        DIN (1993)
                   H2O2
                   Filtration, digestion with HNO3,   Spectrophotometry   6-13 µg/litre range        98-100%     van Benschoten &
                   reaction with 8-hydroxyquinoline   ICP-AES             3 µg/litre limit detection             Edzwald (1990)

    Soil           Extraction with H2O, filtration,   GF-AAS                                         n.g.        Gardinier et
                   high-performance size exclusion                                                               al. (1987)
                   chromatography

    Soil           Extraction with H2O, filtration,   Spectrophotometry   0.005 µg (absolute)        n.g.        Dunemann &
                   gel chromatography, reaction                                                                  Schwedt (1984)
                   with Chromazurol

    Fly ash        Vacuum dried                       NAA                                            n.g.        Fleming &
                                                                                                                 Lindstrom (1987)
                                                                                                                                              

    Table 4.  (Con't)
                                                                                                                                              

    Medium         Sample preparation                 Analytical method   Detection limit            Recovery    Reference
                                                                                                                                              

    Rock, soil,    Dried, digestion with              ICP-AES             1-5 µg/litre               > 57%       Que Hee &
    paint,         HNO3/HCl                                                                                      Boyle (1988)
    citrus leaves

    Biological
    samples

    Serum          Centrifugation, dilution with      GF-AAS              14.3-150 µg/litre          97-102%     Bettinelli et
                   Mg(NO3)2                                               (analytical range)                     al. (1985)

    Plasma,        Centrifugation, dilution with      GF-AAS              4 µg/litre                 90-102%     Gardinier et
    serum          water                                                                                         al. (1981)

    Whole blood,   Dilution with Triton X-100         GF-AAS              1.9 µg/litre (serum),      n.g.        van der Voet
    plasma, serum                                                         1.8 µg/litre (plasma),                 et al. (1985)
                                                                          2.3 µg/litre (blood)

    Biological     Wet-digestion, complexation        NAA                 2.1 µg/litre (liver)       n.g.        Blotcky et
    tissue, urine  with Tiron, anion-exchange                             0.18 µg/ml (urine)                     al. (1992)
                   chromatography

    Urine, blood   Dilution with water                ICP-AES             6 µg/litre                 n.g.        Sanz-Medel et
                                                                                                                 al. (1987)
                   Dilution with water                ICP-AES             0.3 µg/litre               n.g.        Mauras &
                                                                                                                 Allain (1985)
                                                                                                                                              

    Table 4.  (Con't)
                                                                                                                                              

    Medium         Sample preparation                 Analytical method   Detection limit            Recovery    Reference
                                                                                                                                              

    Biological     Freeze dry, grind                  NAA                                            n.g.        Yukawa et
    tissues                                                                                                      al. (1980)
                   Dried, digestion with HNO3,        GF-AAS              0.5 µg/g dry tissue        80-117%     Bouman et
                   dilution with water                                                                           al. (1986)
                   Dried, digestion with HNO3,        AMS                 106 atoms 26Al             n.g.        Kobayashi et
                   cation-exchange                                                                               al. (1990)
                   chromatography
                   Digestion, high-performance        Spectrophotometry   7 µg/litre                 87-94%      Dean (1989)
                   ion-exchange chromatography,
                   reaction with Tiron

    Hair           Washed with 2-propanol,            GF-AAS              0.65 µg/g dry weight       84-105%     Chappuis et
                   digestion with HNO3                                                                           al. (1988)

    Body fluids    Dilution with HNO3/HCl             ICP-AES             1-5 µg/litre               > 57%       Que Hee &
                                                                                                                 Boyle (1988)

    Haemodialysis  Dilution with HNO3 and             GF-AAS              3 µg/litre                 93-108%     Andersen (1987)
    concentrates   Triton X-100                       (Zeeman-corrected)

    Haemodialysis  Reaction with ferron in            Phosphorimetry      5.4 µg/litre               n.g.        De La Campa
    fluids         CTAB                                                                                          et al. (1988)
                                                                                                                                              

    a    AMS = accelerator mass spectrometry; CTAB = cetyltriammonium bromide; EDTA = ethylenediaminetetraacetic acid; FAAS = flame
         atomic-absorption spectrophotometry; ferron = 7-iodo-8-quinolinol-5-sulfonic acid; GF-AAS = graphite furnace - atomic-absorption
         spectrophotometry; ICP-AES = inductively coupled plasma - atomic-emission spectrophotometry; NAA = neutron activation analysis;
         n.g. = not given; Tiron = 4,5-dihydroxy-1,3-benzenedisulfonic acid
             Free aluminium may be determined directly from the samples or the
    sample extracts. To determine insoluble aluminium compounds and
    organically bound species, the samples (organic matter, air-filters,
    water, soil, etc.) need to be subjected to wet ashing (digestion) or
    dry ashing. Wet ashing, i.e. heating with nitric acid under reflux, is
    suitable for most organic and biological samples. The residues are
    dissolved in acids before analysis (NIOSH, 1984; Kobayashi et al.,
    1990; DIN, 1993). After digestion, differentiation between free metal
    species and kinetically labile and stable complexes is not possible.

    2.3.2  Separation and concentration

         A fractionation procedure for aluminium species in water using an
    0.22 µm size filter has been proposed by van Benschoten & Edzwald
    (1990). Total reactive aluminium is determined in the unfiltered,
    acidified sample. Dissolved monomeric aluminium is analysed in the
    unfiltered sample without acidification. Analysis of total dissolved
    aluminium is performed after filtration and acidification of the
    sample. Dissolved organically bound aluminium is analysed after
    separation of the filtered sample on a column of cation exchange
    resin. The eluate is acidified and analysed colorimetrically. For the
    determination of dissolved organic monomeric aluminium, samples are
    passed through a cation exchange column and are analysed with no
    acidification.

         In order to carry out long-term characterization of the highly
    acute toxicity during the initial phase of aluminium polymerization in
    "mixing zones" (Rosseland et al., 1992),  in situ fractionation
    techniques such as ultrafiltration (Lydersen et al., 1987) are
    recommended (see section 9.1.2.3).

         For the extraction of aluminium bound to fulvic acids, soil
    samples may be extracted with copper chloride solution (Gardinier et
    al., 1987). The clean-up of aqueous extracts of soil samples can be
    performed by gel chromatography (Dunemann & Schwedt, 1984) or by size
    exclusion chromatography. These methods are very mild and thus
    suitable for the determination of labile aluminium species (Gardinier
    et al., 1987).

         Water samples may be concentrated by careful evaporation (DIN,
    1993). Macro quantities of aluminium can be separated from small
    amounts of interfering elements by precipitation of aluminium as
    its hydroxide or phosphate. Chelating agents, such as EDTA,
    8-hydroxyquinoline, and 2,2'-dihydroxyazobenzene, can be used to
    extract aluminium into an organic solvent (Alderman & Gitelman, 1980).

         Biological materials contain a variety of compounds that
    can severely interfere with aluminium determinations. Hence,
    chromatographic methods are often employed for sample purification.
    Biological tissue samples may be cleaned-up by cation-exchange

    chromatography after acid digestion (Dean, 1989; Kobayashi et al.,
    1990). Blotcky et al. (1992) proposed the chelating of aluminium prior
    to anion-exchange chromatography. Precolumn derivatization coupled
    with reversed-phase high performance liquid chromatography (RP-HPLC)
    is an effective method for the separation of the chelates of
    different interfering metal ions (Nagaosa et al., 1991). Solvent
    extraction of aluminium chelate complexes, e.g., 2,4-pentanedione and
    4-methyl-2-pentanone, has been described as a separation and pre-
    concentration step in the analysis of body fluids (Buratti et al.,
    1984).

    2.3.3  Detection and measurement

         Spectrophotometric methods for aluminium analysis are simple
    and quick, and are most often used for the determination of aluminium
    in water. Samples are treated with inorganic or organic reagents to
    form coloured soluble complexes that can be measured by absorption
    spectrometry. Disadvantages of these methods are the narrowness of
    the pH range of the reaction, the instability of the complexes, the
    low selectivity, and the low sensitivity (Bettinelli et al., 1985).
    The working range for the aluminium determination with chromazurol C
    is 25-1000 µg/litre (Schwedt, 1989), with alizarin S it is 10-500
    µg/litre (DIN, 1993), and with Tiron it is 7-5000 µg/litre (Dean,
    1989). Detection limits of 1 µg/litre can be achieved. Chromatographic
    separation of chelates of interfering metals increases the selectivity
    of spectrophotometric methods.

         De La Campa et al. (1988) and García et al. (1991) reported a
    room temperature phosphorimetric method for aluminium analysis.
    Aluminium reacts with 7-iodo-8-quinolinol-5-sulfonic acid (ferron) in
    cetyltrimethylammonium bromide micelles to form a highly
    phosphorescent complex. The method is used to determine aluminium in
    water and dialysis fluids. The given detection limits are 5.4 µg/litre
    and 2 µg/litre, respectively.

         Instrumental methods applied to the determination of aluminium
    include neutron activation, X-ray fluorescence, flame atomic-
    absorption spectrophotometry, inductively coupled plasma - atomic-
    emission spectrophotometry (ICP-AES) and graphite furnace - atomic-
    absorption spectrophotometry (GF-AAS). However, neither X-ray
    fluorescence nor flame absorption methods are sensitive enough to
    measure trace levels in biological samples (Bettinelli et al., 1985).
    The NIOSH procedure for aluminium analysis in air is applicable over a
    working range of 50-5000 µg per sample or 0.5-10 mg/m3 for a
    100-litre sample (NIOSH, 1984).

         Neutron activation analysis produces excellent results but the
    methods are time consuming and the facilities are not always readily
    available. The method is used for determining aluminium in fly ash
    (Fleming & Lindstrom, 1987) and biological tissues (Yukawa et al.,
    1980; Blotcky et al., 1992). After digestion and concentration of the
    biological samples, a detection limit of 2.1 µg/g was found for bovine
    liver (Blotcky et al. 1992).

         GF-AAS is the most frequently used technique to determine
    aluminium at low concentrations. Detection limits between 0.5 and 4
    µg/litre or µg/g are achieved with the analysis of various
    environmental and biological samples (Gardinier et al., 1981; van der
    Voet et al., 1985; Bettinelli et al., 1985; Andersen, 1987). Most
    liquid samples can be injected directly after dilution into GF-AAS.
    Dilution is necessary because most biological fluids have high salt
    contents (in the order of 30%) (Andersen, 1987). To prevent
    precipitation of aluminium and the formation of carbon residues, EDTA
    or Triton X can serve as diluents. Ammonia may be added to convert
    aluminium to aluminate and thus avoid loss of aluminium as its
    chloride (Gardinier et al., 1981). Triton X-100 is used to reduce the
    viscosity of the samples, and MgNO3 is added as a matrix modifier to
    improve the volatility of aluminium (Bettinelli et al., 1985).

         ICP-AES is used for the determination of aluminium in various
    biological and environmental samples, allowing the simultaneous
    determination of different elements at low levels of interference
    (Mauras & Allain, 1985; Sanz-Medel et al., 1987). The NIOSH method for
    aluminium determination in air samples is recommended for a working
    range of 5-2000 µg/m3 for a 500-litre sample (NIOSH, 1984). A
    detection limit of 1 µg/litre in biological and environmental samples
    has been reported by Que Hee & Boyle (1988). ICP can also be combined
    with a mass spectrometer to further increase the sensitivity of the
    method. As a multi-element detector for reversed-phase liquid
    chromatography, ICP-MS offers the ability to measure isotope ratios on
    eluting peaks and to remove troublesome matrices on-line (Thompson &
    Houk, 1986).

         For 26Al tracer experiments (Kobayashi et al. 1990), the
    application of accelerator mass spectrometry (AMS) has been described.
    The limit of detection is 106 atoms; thus the sensitivity of AMS is
    105 times greater than that of gamma-ray counting techniques.

         Aluminium concentrations in human brain can be investigated by
    laser multipoint microprobe mass analysis (LAMMA) using focussed laser
    ionization with time-of-flight mass spectrometry (Stern et al., 1986).
    27Al nuclear magnetic resonance (NMR) may be used to ascertain the
    coordination of aluminium in soil solutions (Schierl, 1985).
    Aluminium in natural water samples has been determined using
    reversed-phase liquid chromatography of the 8-quinolinol complex using
    spectrophotometric detection. A detection limit of 2 µg/litre was
    reported (Nagaose et al., 1991).

    2.3.4  Speciation analysis of aluminium in water

         Speciation analysis aims to distinguish and determine
    quantitatively different groups of physico-chemical species present
    in a water sample. All speciation methods, with the exception of
    potentiometric techniques and direct spectroscopic methods (e.g.,
    NMR), will alter the speciation of the sample during measurement. This
    may not be a disadvantage, particularly if, as is usual, the
    speciation analysis is being carried out in order to estimate the
    toxicity of the sample to aquatic biota. Toxicity itself is a dynamic
    process, and the interaction of aluminium species in water with a
    biomembrane (e.g., a fish gill) will change the aluminium species
    distribution in the solution close to the biomembrane. The best
    speciation probe is one that  reacts with aluminium in a water sample
    to a similar extent and at a similar rate to the reaction of a
    biomembrane with the aluminium in the samples.

         Speciation analysis of aluminium in a water sample is usually
    carried out after first filtering the sample through a 0.45 µm
    membrane filter to remove particulate matter. The filtrate can then be
    analysed for groups of species by several different techniques,
    including kinetic spectrophotometry (Parker & Bertsch, 1992a,b), ion
    exchange (Driscoll, 1984) and ion chromatography (Jones, 1991).
    Combinations of methods such as sample acidification, kinetic
    spectrophotometry and ion exchange are frequently used to determine a
    variety of species (Driscoll, 1984; Courtijn et al., 1990; van
    Benschoten & Edzwald, 1990). These speciation schemes provide
    information on various speciation groups, including total dissolved
    aluminium, acid-soluble aluminium, total monomeric aluminium, reactive
    monomeric aluminium, non-reactive monomeric aluminium, aluminium
    fluoride complexes, organic monomeric aluminium and inorganic
    monomeric aluminium. The terms "reactive" and "labile", as applied to
    aluminium species, are operationally defined and refer to species that
    react rapidly with an analytical probe such as a cation exchange resin
    or a chromogenic reagent.

         The aluminium species that are most toxic to aquatic organisms
    are believed to reside in the reactive monomeric inorganic aluminium
    fraction and to consist principally of aluminium hydroxy complexes
    (Helliwell et al., 1983; Fairman et al., 1994; Parent & Cambell,
    1994). Although the fluoro complex is toxic, it is less so than the
    aluminium hydroxy complexes (Helliwell et al., 1983).

    3.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    3.1  Natural occurrence

         Aluminium is released to the environment both by natural
    processes and from anthropogenic sources. Natural processes far
    outweigh the contribution of anthropogenic sources because aluminium
    is a major constituent of the earth's crust, making up about 8% of the
    earth's surface (Lantzy & Mackenzie, 1979). Anthropogenic releases
    are mostly indirect, for example, through emission of acidifying
    substances such as sulfur dioxide and nitrogen oxides to the
    atmosphere. These acidify rain and soil and contribute to dissolution
    of aluminium from the soil. The largest anthropogenic impact on
    aluminium movement in the environment is through enhanced wind and
    water erosion from cultivated land, notably when fallow. Aluminium is
    the third most abundant element. It does not occur naturally in the
    metallic, elemental state, but is widely distributed in the earth's
    crust in combination with oxygen, fluorine, silicon and other
    constituents. Aluminium occurs ubiquitously in silicates such as
    feldspars and micas, complexed with sodium and fluoride as cryolite,
    and in bauxite rock, which is composed of hydrous aluminium oxides,
    aluminium hydroxides and impurities such as free silica. In general,
    decreasing pH as a result of acid rain or the release of acid mine
    drainage results in increased mobility of the monomeric forms of
    aluminium (ATSDR, 1992). Chemical speciation in soil and water
    affecting the bioavailability of aluminium to organisms is discussed
    in chapter 4.

    3.2  Anthropogenic sources

         Direct anthropogenic releases of aluminium compounds are
    primarily to the atmosphere and are associated with industrial
    processes such as smelting. However, the use of aluminium and
    aluminium compounds in processing, packaging, storage of food products
    and as flocculants in the treatment of drinking-water may contribute
    to its presence in drinking-water and food stuffs (ATSDR, 1992).

    3.2.1  Production levels and processes

         The most important raw material for the production of aluminium
    is bauxite, which contains up to 55% alumina (aluminium oxide). The
    commercial deposits of bauxite are mainly gibbsite (Al2O3Ę3H2O) and
    boehmite (Al2O3ĘH2O). The bauxite is extracted by open-cast mining
    (Dinman, 1983).

         The production of the metal comprises two basic steps: refining
    and reduction. Refining involves the production of alumina from
    bauxite by the Bayer process in which bauxite is digested at high
    temperature and pressure in a strong solution of caustic soda. The
    resultant hydrate is crystallized and calcined to the oxide. Reduction
    involves the reduction of alumina to virgin aluminium metal by the
    Hall-Heroult electrolytic process using carbon electrodes and a
    cryolite flux (Dinman, 1983).

         World bauxite production was 106 million tonnes in 1992. A
    comparison of the quarterly average figures for 1993 and 1994 with
    this figure shows that production in major producing countries is
    remaining fairly constant (World Bureau of Metal Statistics, 1994).
    The total primary aluminium production for 1992 is summarized in Table
    5. The amount of aluminium recovered from purchased or tolled scrap in
    1992 was 14% of the total primary production figure. The total alumina
    production for 1992 is summarized in Table 6. The total alumina
    production figure includes 30 million tonnes for metallurgical uses
    and 3 million tonnes for non-metallurgical uses. The total figures for
    primary aluminium and alumina production have not changed greatly
    since 1988.

    3.2.2  Uses

         Aluminium metal has a wide variety of uses including structural
    material for construction, automobiles and aircraft, and the
    production of metal alloys. Other uses include die-cast motor parts,
    cooking utensils, decorations, road signs, fencing, beverage cans,
    food packaging, foil, corrosion-resistant chemical equipment, solid
    fuel rocket propellents and explosives, dental crowns, and denture
    materials. In the electrical industry aluminium is used for power
    lines, electrical conductors, insulated cables and wiring (ATSDR,
    1992).

    Table 5.  Primary aluminium production in 1992 (from: IPAI, 1993)
                                                         

         Geographical area       Thousands of tonnes
                                                         

         Africa                          617
         North America                  6016
         Latin America                  1949
         East and South Asia            1379
         Europe                         3319
         Oceania                        1483

         Total                        14 763
                                                         
    Table 6.  Alumina production in 1992 (from: IPAI, 1993)
                                                         

         Geographical area       Thousands of tonnes
                                                         

         Africa                          604
         North America                  5812
         Latin America                  7627
         East and South Asia            2360
         Europe                         5565
         Oceania                      11 803

         Total                        33 771
                                                         

         Aluminium compounds and materials also have a wide variety of
    uses, some of which are listed in Table 7. Aluminium powder is used in
    paints, protective coatings and fireworks. Natural aluminium minerals
    especially bentonite and zeolite are used in water purification, sugar
    refining, brewing and paper industries. Aluminium sulfate is used for
    water purification, as a mordant in dyeing, and in paper production.
    Other aluminium compounds are used as tanning agents in the leather
    industry, and as components of human and veterinary medicines, glues,
    disinfectants, and in toothpaste, styptic pencils, deodorants,
    antacids and food additives. Clays (aluminium silicates) are used as
    industrial raw materials (e.g., production of ceramics), and
    aluminates are constituents of cement. Alkyl aluminium products are
    used as catalysts for the production of low pressure polyethylene
    (ATSDR, 1992).

        Table 7.  Main uses of aluminium compoundsa
                                                                                  

    Aluminium compounds  Uses
                                                                                  

    alums                hardening agent and setting accelerator for gypsum
                         plaster, in tanning and dyeing, and (formerly) in styptic
                         pencils

    aluminas             in water treatment and as accelerator for concrete
                         solidification (high alumina cements)

    alkoxides            in varnishes, for textile impregnation, in cosmetics and
                         as an intermediate in pharmaceutical production

    borate               production of glass and ceramics

    carbonate            antacid

    chlorides            production of rubber, lubricants and wood preservatives,
                         and in cosmetics as an astringent; the anhydrous
                         product is used as a catalyst and raw material in the
                         chemical and petrochemical industries; active ingredient
                         in antiperspirants

    hydroxide            stomach antacid, other pharmaceuticals

    isopropoxide         used in the soap and paint industries; waterproofing
                         textiles

    phosphate            antacid

    silicate             component of dental cement; antacid, food additives

    sulfate              used in water purification as a flocculent, in paper
                         production, as a mordant in dyeing, and as a starting
                         material for the production of other aluminium
                         compounds

    trioxide             used as an absorbent, abrasive and refractory material

    sodium aluminium     food additives
    phosphate
                                                                                  

    a    From: Helmbolt et al. (1985); ATSDR (1992)
    
    4.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION AND TRANSFORMATION

    4.1  Transport and distribution between media

         Aluminium occurs ubiquitously in silicates such as feldspars and
    micas, complexed with sodium and fluoride as cryolite, and in bauxite
    rock composed of hydrous aluminium oxides, aluminium hydroxides, and
    impurities such as free silica (ATSDR, 1992). Aluminium is not
    found as a free metal because of its reactivity. It has only one
    oxidation state (+3); therefore, its transport and distribution in
    the environment depend upon its coordination chemistry and the
    characteristics of the local environmental system. Aluminium
    partitions between solid and liquid phases by reacting and complexing
    with water molecules and electron-rich anions, such as chloride,
    fluoride, sulfate, nitrate, phosphate and negatively charged
    functional groups on humic materials and clay.

         At a pH greater than 5.5, naturally occurring aluminium compounds
    exist predominantly in an undissolved form such as gibbsite (Al(OH)3)
    or as aluminosilicates, except in the presence of high amounts of
    dissolved organic material such as fulvic acid, which binds with
    aluminium and can cause an increase in dissolved aluminium
    concentrations in streams and lakes (ATSDR, 1992). Several processes
    influence aluminium mobility and its subsequent transport within the
    environment; these include chemical speciation, hydrological flow
    paths, other spatial and temporal factors related to soil-water
    interactions, and the composition of the underlying geological
    materials (Grant et al., 1990). Watersheds with shallow, acidic soils
    and poorly buffered surface waters mobilize aluminium when exposed to
    acidic deposition (Driscoll et al., 1988).

    4.1.1  Air

         Aluminium enters the atmosphere as a major constituent of a
    number of atmospheric particulates, such as soil-derived dusts from
    erosion and particulates from coal combustion (Grant et al., 1990).
    Eisenreich (1980) studied the atmospheric loading of aluminium to Lake
    Michigan, USA. It was found that aluminium was generally associated
    with large particles (> 2 µm diameter) and that these were deposited
    near the source. The total atmospheric loading of aluminium to the
    lake was calculated to be 0.86 kg/ha per year. The more industrialized
    area south of the lake contributes 75% of this total loading. Cambray
    et al. (1975) calculated the dry deposition flux of aluminium to the
    North Sea to be 51 000 tonnes/year. Ottley & Harrison (1993)
    calculated the flux to be 7 300 tonnes/year; they suggest that the
    lower estimate is due to more spatially appropriate and extensive air
    monitoring since 1975. Rahn (1981) calculated the input of aluminium
    from the atmosphere to the Arctic Ocean at 30 000 tonnes/year. The
    input was significantly less than those of oceanic and riverine inputs
    (140 000 and 110 000 tonnes/year, respectively).

         Guieu et al. (1991) compared atmospheric inputs with river inputs
    of aluminium for the Golfe du Lion, France. Atmospheric inputs were
    found to be 11% of total inputs of aluminium. Rainwater was analysed
    for aluminium and only 19% was found in the dissolved fraction
    (< 0.4 µm). Losno et al. (1993) monitored rainwater and snow for
    aluminium and found large variations in the solubility of aluminium.
    The variations seem to be largely due to pH, lower pH values
    increasing the solubility of aluminium. Thermodynamic calculations
    reveal that, at pH values higher than 5, equilibrium with gibbsite or
    an insoluble trivalent alkaline form of aluminium acts to limit
    solubility, whereas, at lower pH values, aluminium could be in
    equilibrium with a hydroxysulfate salt.

    4.1.2  Freshwater

    4.1.2.1  Dissolved aluminium

         In groundwater or surface water systems an equilibrium is formed
    that controls the extent to which aluminium dissolution can occur. The
    solubility of aluminium in equilibrium with solid phase Al(OH)3 is
    highly pH-dependent. Aquo complex Al(H2O)63+ predominates at low
    pH values (e.g., pH < 4), but as the pH of the solution increases
    (e.g., pH 4-6) and/or the temperature rises, the positive charge
    of aluminium forces hydrolysis of a water ligand producing the
    Al(OH)(H2O)52+ ion. The degree of hydrolysis increases as the
    solution pH increases, resulting in a series of Al-OH complexes such
    as Al(OH)2+, Al(OH)2+, Al(OH) 4 - (Schecher & Driscoll, 1987).
    Fluoride ions, being similar in size to hydroxyl ions, will readily
    substitute in these complexes. At pH < 5.5, molar concentrations of
    aluminium in certain areas exceed concentrations of fluoride ions and
    form low ligand number complexes. The concentration of Al-F complexes
    under those conditions is limited by the total concentration of
    fluoride ions. At pH > 7.0, Al-OH complexes predominate in waters
    that are low in dissolved organic matter and silicate. Under acidic
    conditions sulfate also forms complexes with aluminium. Even though
    sulfate concentrations are typically higher than those of fluoride in
    surface waters, Al-SO42- complexes are significant only at high
    sulfate concentrations and low pH values (Courtijn et al., 1987).

         The chemical speciation of aluminium in natural water regulates
    its mobility, bioavailability and toxicity. The concentration of
    aluminium in some natural water as a function of pH can be estimated
    by thermodynamic calculations. The actual geochemical mobility of
    aluminium is very complex and difficult to predict in areas affected
    by acid deposition, as non-equilibrium processes usually predominate
    during episodic events associated with aluminium release and transport
    (Bull & Hall, 1986; Lawrence et al., 1988; Seip et al., 1989).

         The chemistry of inorganic aluminium in acid soil and stream
    water can be considered in terms of mineral solubility, ion exchange
    and water mixing processes (Neal et al., 1990). The minerals that
    determine stream water Al3+ activity in acidic and acid-sensitive
    systems are kaoline (Al2Si2O5(OH)4), various forms of aluminium
    hydroxide (Al(OH)3), aluminium hydroxy sulfate (Al(OH)SO 4) and
    aluminium hydroxy silicate (Seip et al., 1984; Neal & Williams, 1988;
    Nealet al., 1990).

         Goenaga & Williams (1988) found that the concentrations of Al-F
    and Al-SO4 complexes in Welsh upland water were < 40 µg/litre and
    accounted for less than 20% of the inorganic aluminium at pH < 5.0.
    Organic complexes were significant (16 to 49 µg/litre) even in samples
    with a low total organic carbon content. Organic monomeric aluminium
    increased during high flows as total organic carbon (TOC) and free
    ionic aluminium concentrations increased. LaZerte (1984) analysed
    streams and lakes during spring snow melt in acidified catchments in
    Ontario, Canada (pH 4.1-6.9, and TOC 1-24 mg/litre). Very little
    polymeric and amorphous aluminium was found, and most of the inorganic
    monomeric fraction was in the fluoride complexes.

         Neal (1988) found that Plynlimon (Wales) stream water was
    saturated or over-saturated with respect to some crystalline form of
    Al(OH)3, and saturated or under-saturated with respect to amorphous
    Al(OH)3: the level of saturation became less as pH decreased. The
    solubility relationship for the kaolin mineral group is that at low pH
    the waters are saturated with respect to crystalline kaolin
    (kaolinite) and under-saturated with respect to poorly crystalline
    kaolin (low crystallinity hallyosite). At higher pH the waters become
    progressively more over-saturated with respect to crystalline forms
    and near to saturation with respect to poorly crystalline forms. It
    appears that at high pH the waters are in approximate equilibrium with
    amorphous Al(OH)3 whilst at low pH values the waters are in
    equilibrium with an aluminium hydroxy sulfate phase (equilibrium
    constant 10-4.9).

         Aluminium begins to polymerize when the pH of an acidic solution
    increases notably over pH 4.5. Polymerization implies that in the
    first step, two hydroxyls are shared by two aluminium atoms, e.g.,

         2 Al(OH)(H2O)52+ -> Al2(OH)2(H2O)84+ + 2 H2O

    Polymerization gradually proceeds to larger structures, eventually
    leading to the formation of the Al13 "polycation" (Hem & Robertson,
    1967; Parker & Bertsch, 1992a,b). As polymers coalesce, they increase
    in relative molecular mass, eventually becoming large enough to
    precipitate aluminium hydroxide from solution. As the precipitate ages
    the solubility decreases (Chow, 1992). Tipping et al. (1988b) found
    that if precipitation occurs at pH 4 to 6 it involves the formation of
    aluminium (oxy)hydroxide and not aluminosilicates or basic aluminium
    sulfates. The solubility of the (oxy)hydroxide was highly temperature

    dependent and decreased in the presence of sulfate and more
    particularly humate. Lükewille & van Breemen (1992) analysed
    precipitates from stream bottoms in the Senne area of northern Germany
    and found them to consist of amorphous aluminium hydroxide,
    co-precipitated with minor amounts of sulfate, phosphate and silica.

         Aluminium is predominantly cationic under acidic conditions and
    strongly binds with negatively charged organic functional groups such
    as fulvic acid and humic acid (Chow, 1992). Aluminium-humate complex
    formation has been modelled by several researchers. For example,
    Tipping et al. (1988a,c) developed a model using data collected from
    acidified streams in northern England and Scotland. This model
    describes the equilibria between humic acid substances, aluminium
    species, calcium ions and hydrogen ions under acidic conditions (pH <
    6) (Tipping et al., 1989a). Tipping & Backes (1988) reported on two
    models of aluminium-humic acid complexation. Reasonable results were
    obtained only at pH 4.0 to 5.0. Plankey & Patterson (1987) used a
    fluorescence technique to study the complex formation kinetics of
    aluminium with a single metal-free fulvic acid isolated from an
    Adirondack mountain soil (USA). At pH 3.0 to 4.5 two types of
    aluminium binding sites were identified.

    4.1.2.2  Aluminium adsorbed on particles

         Goenaga et al. (1987) collected stream water from tributaries of
    Llyn Brianne reservoir, Wales. Analysis of the freshwater samples
    showed total aluminium and monomeric aluminium concentrations to be
    positively correlated with suspended solid content. The levels of
    total (acid digestible) aluminium that were detected in filtrates of
    freshwater samples were affected by the pore diameter of the membrane
    filter used. Between 13% and 50% of this form of aluminium initially
    present in the sample could be removed by a 0.4 µm pore diameter
    membrane, depending on the level of suspended solid originally
    present. Goenaga & Williams (1988) calculated the amount of aluminium
    adsorbed onto suspended solids by measuring monomeric aluminium before
    and after separation of suspended solids by filtration (0.015 µm pore
    diameter). Adsorbed aluminium was low (< 20 µg/litre) during dry
    weather periods; however, the adsorbed fraction was very significant
    (> 40 µg/litre) for samples with high suspended solids (>
    20 mg/litre) collected from a Welsh upland area during a storm
    episode. Goenaga & Williams (1990) found that aluminium associated
    with particles > 0.015 µm was negligible (< 20 µg/litre) in spot
    samples with a suspended solid content of < 5 mg/litre but
    significant (< 200 µg/litre) for episode samples with high suspended
    solids (> 20 mg/litre); between 40% and 60% of the adsorbed aluminium
    was found to be associated with particles > 0.4 µm. Tipping et al.
    (1989b) studied the adsorption of aluminium in water from various
    acidified streams in northern England. The adsorption of aluminium by

    particles was found to increase with total aluminium, pH and particle
    concentration. Calculations using an adsorption equation, and taking
    competition by dissolved humic substances into account, suggest that
    adsorbed aluminium may commonly account for a significant proportion
    (> 10%) of total monomeric aluminium in such water.

    4.1.2.3  Aluminium in acidified waters

         Fisher et al. (1968) monitored aluminium concentrations in
    acidified streams of the Hubbard Brook Experimental Forest, New
    Hampshire, USA from 1964 to 1966. Annual loads of aluminium were
    calculated to be between 0.9 and 2.4 kg/ha for three streams. The
    acidic deposition at the Hubbard Brook ecosystem has induced a series
    of geochemical responses. Firstly, hydrogen ion acidity is neutralized
    by the dissolution of alumina primarily found in the soil zone.
    Secondly, hydrogen ion acidity and aluminium acidity are neutralized
    by the chemical weathering of silicate materials (Johnson et al.,
    1981). Hall et al. (1980) acidified a stream in the Hubbard Brook
    Experimental Forest. The pH of the control stream ranged from 5.7 to
    6.4 and in the acidified stream from 3.9 to 4.5. Dissolved aluminium
    increased significantly in the acidified stream water by an average of
    181%compared to the control stream. Lawrence et al. (1988) reported
    that at high elevations the increased stream flow was associated with
    reduced surface water acidity and decreased inorganic aluminium
    concentrations. At low elevations, increased stream flow was
    associated with increases in stream acidity and concentrations of
    inorganic aluminium. The contributions of flow from the more acidic
    upper region of the watershed during high-flow conditions appear to be
    the major hydrological influence on stream chemistry. In the acid-
    affected Experimental Forest system, acidity of low-order stream water
    was high due to elevated inputs of strong acids (sulfuric and nitric)
    relative to the releases of basic cations from soil. Concentrations of
    aluminium were also high and predominantly in labile (inorganic)
    monomeric form. For comparison, samples were collected from the
    Jamieson Creek watershed, British Columbia, Canada. For this watershed
    the low-order stream water was acidic due to low concentrations of
    basic cations coupled with the presence of organic acids.
    Concentrations of aluminium were relatively low and largely associated
    with organic solutes (Driscoll et al., 1988).

         Large temporal and spatial variations in aluminium concentration
    occur in Welsh stream water due to hydrological and land use controls.
    The most acidic streams have the highest aluminium concentration.
    Variations in stream and soil water aluminium concentrations in the
    order semi-natural moorland < conifer forested moorland < recently
    harvested forest can be explained by ion exchange reactions related to
    changes in the anion concentrations passing through the system and
    weathering (Neal et al., 1990). Lawrence et al. (1986) found that
    observed altitude trends in stream aluminium chemistry may be related
    to spatial variations in vegetation type and mineral soil depth.

    Mobilization of aluminium was studied in streams at the Hubbard Brook
    Experimental Forest, New Hampshire, USA. At the highest altitudes
    maximum densities of spruce and fir vegetation occur, and aluminium
    appears to be mobilized by transformations involving dissolved organic
    matter. At mid-altitudes hardwood vegetation predominates and the
    mechanism of aluminium mobilization shifts to dissolution by strong
    acids within the mineral soil. At the lowest altitudes relatively
    thick mineral soil seems to limit aluminium mobility resulting in low
    concentrations in stream water. During 1983 and 1984 an experimental
    watershed at Hubbard Brook was commercially whole-tree harvested.
    Whole-tree harvesting resulted in a large increase in stream nitrate
    concentrations, followed by a decrease in pH and concomitant increase
    in inorganic aluminium (Lawrence et al., 1987). Ormerod et al. (1989)
    studied the spatial patterns in aluminium and pH data from 113 Welsh
    catchments of contrasting land use. It was found that pH declined and
    aluminium increased significantly with increasing forest cover. The
    percentage contribution of labile aluminium to the total filterable
    concentration ranged from 39% to 90%, the highest levels being
    associated with streams draining forest. Neal et al. (1992) found that
    felling conifers led to decreases in pH and increases in aluminium
    concentrations in streams and soils at Plynlimon, Wales, for the first
    2 years. The major changes were found to occur during the winter storm
    flow periods. The trends were reversed after the first two years. The
    short-term effects (2-3 years) of forest harvesting on soil and stream
    water inorganic aluminium chemistry were predominantly controlled by
    the nitrogen dynamics of the site. A reduction in inorganic aluminium
    was observed concomitant with declines in nitrate and total inorganic
    anions. However, 4-5 years after harvesting, inorganic aluminium
    concentration in soil and stream water of Welsh and Cumbrian study
    sites was still greater than that expected in moorland catchments
    (Reynolds et al., 1992).

         Bird et al. (1990) compared the effects of a winter "rain on
    snow" episode with a summer storm episode on the pH and dissolved
    aluminium levels in a moorland stream and a conifer forest stream. The
    pre-episode conditions were broadly similar in both streams. In
    winter, following the snow melt, both moorland and forest stream
    showed reduced pH accompanied by increases in dissolved aluminium
    concentrations as buffering capacity provided by the calcium was
    exceeded by anions such as sulfate. The timing of flow changes was
    similar, but flush of solutes to the moorland stream was more rapid.
    Both streams had a similar buffering capacity, but the changes in the
    forest stream were much greater (pH reduction of 2 units and dissolved
    aluminium levels exceeding 1 mg/litre), reflecting a greater flux of
    anions. The surface run-off and reduced buffering capacity from frozen
    soils led to the changes in both streams. During the summer episode,
    again the forest stream showed a greater reduction in pH and higher
    increase in dissolved aluminium; however, the concentrations of
    sulfate were much lower in both streams and less aluminium was
    mobilized.

         Mach & Brezonik (1989) studied the biogeochemical cycling of
    aluminium in acidified and reference basins of Little Rock Lake,
    Wisconsin, USA. Background dissolved lake water aluminium
    concentrations were 7 µg/litre (0.4 µm pore-size). The acidified basin
    was acidified in a step-wise manner. Acidification to pH 5.1 resulted
    in a 45% elevation of dissolved aluminium levels (15.5 µg/litre) over
    reference basin levels (10.7 µg/litre). Analysis of suspended
    particulate matter collected from both basins revealed lower levels of
    particulate aluminium in the acidified basin, demonstrating that there
    is reduced affinity for particulate matter at the lower pH. Brezonik
    et al. (1990) studied the effects of acidification of Little Rock Lake
    on the dissolved concentrations of aluminium. Aluminium desorbed from
    sediments of the lake basin at pH 4 and below in laboratory studies.
    In littoral enclosures, dissolved aluminium was elevated above control
    levels at pH 4.5, and elevated levels were observed in pelagic
    enclosures at both pH 5.0 and 4.5. Dissolved aluminium levels remained
    constant in the acidified basin at pH 5.6 and 5.1 (16 µg/litre, while
    concentrations in the reference basin declined to 11 µg/litre during
    the study period. The authors stated that these levels of aluminium
    were low compared with other reported values because the lake was
    hydrologically isolated.

         Cosby et al. (1985) presented a mathematical model (MAGIC; Model
    Acidification of Groundwater In Catchments) that uses quantitative
    descriptions of soil chemical processes to estimate the long-term
    chemical changes that occur in soil, soil water and surface waters of
    catchments in response to changes in atmospheric deposition. The model
    is based on soil base cation exchange, dissolution of aluminium
    hydroxide and solution of carbon dioxide. The model uses "average" or
    lumped representations of these spatially distributed catchment
    processes. The long-term responses of the model are controlled by
    sulfate adsorption and primary weathering of base cations in the
    catchment soils. The model was applied to the Shenandoah National
    Park, Virginia, USA, and indicated that the alkalinity of surface
    waters had been reduced by as much as 50% over the last 140 years.

         Cosby et al. (1986) applied the MAGIC model to a sub-catchment in
    southwestern Scotland. Assuming that deposition rates are maintained
    in the future at 1984 levels, the model indicated that stream pH was
    likely to decline. Neal et al. (1986) reported that the model predicts
    increases in pH (reductions in acidity) with conifer deforestation.
    In the Welsh uplands the model simulates quite accurately the
    acidification of catchments (Whitehead et al., 1990). The model shows
    that atmospheric deposition is the primary cause of stream
    acidification with conifer afforestation enhancing stream acidity.
    Historical trends determined by the model indicate that acidification
    has been present since the turn of the century (Whitehead et al.,
    1988). Ormerod et al. (1990) compared the predicted effects of reduced
    acidic deposition and liming on stream acidification with actual
    treatments. The results indicate that liming and 90% reduction in
    sulfate deposition reduce concentrations of soluble aluminium to

    similar levels. However, calcium concentrations and pH were increased
    by liming to values that were high by comparison with conditions
    simulated under low acid deposition.

         A dynamic model has been developed that reproduces major trends
    in chemical and hydrological behaviour in Norwegian catchments.
    Christophersen & Seip (1982) reported that a simple two-reservoir
    model incorporating a small number of physically realistic processes
    accounts for the major short-term variations in stream water chemistry
    during the snow-free season at a 0.41 km2 catchment in coniferous
    forest on granite bedrock at Birkenes, Norway. The model incorporates
    both hydrolytic and sulfate sub-models, and a cation sub-model that
    includes hydrogen, aluminium, calcium and magnesium ions. Typical
    characteristics predicted by the model include positive correlations
    between hydrogen ions and aluminium concentrations and discharge, and
    negative correlations between these factors and the calcium and
    magnesium concentrations. Seip et al. (1989) attempted to model
    episodic changes in stream water chemistry of hydrogen and aluminium
    ions. However, only partial success was achieved. Trends were correct
    for hydrogen ions but there were discrepancies at peak heights. There
    were correct predictions for aluminium concentrations in the autumn
    but not in the spring.

    4.1.3  Seawater

         In contrast to fresh water, seawater (salinity > 32%) has a
    constant pH of approximately 8.2. Hydes (1977) found that bottom and
    suspended clay sediments probably act as a source of dissolved
    aluminium to seawater. However, removal below predictions of clay
    solubility is probably the result of biological activity.

         Hydes & Liss (1977) reported that approximately 30% of the
    dissolved aluminium entering the Conwy Estuary, Wales, appears to be
    removed during mixing with seawater. The removal occurs during the
    early stages of mixing and is virtually complete by the time the
    salinity reaches 8%. The authors concluded that the most likely
    mechanism involves the trapping of aluminium adsorbed onto the surface
    of fine clay particles entering with the freshwater as the particles
    are irreversibly coagulated on mixing with saline water.

         Mackenzie et al. (1978) measured the concentration of aluminium
    in a vertical hydrographic profile of the Mediterranean Sea. They
    found that the concentrations did not correspond to seasonal
    thermocline, nitrate minimum and an oxygen maximum, thus supporting
    the hypothesis that aluminium cycles in the oceans are associated with
    the activity of diatoms. Stoffyn (1979) stated that experimental
    evidence using the diatom  Skeletonema costatum supports the
    hypothesis that the concentration and distribution of dissolved
    aluminium in ocean water is controlled by biological activity in the

    surface waters. However, Hydes (1979) reported that the distribution
    of dissolved aluminium in open ocean waters is probably controlled by
    the solution of aluminium from atmospherically derived particles and
    bottom sediments balanced against scavenging by siliceous shells of
    dead organisms. Chou & Wollast (1989) studied eight vertical profiles
    of dissolved aluminium in the Mediterranean Sea. They found that
    dissolved aluminium is depleted in surface waters as compared with
    deep waters. The high concentrations of aluminium in deep water may
    result from fluxes from pore water in sediments to the overlying
    water. These authors suggested that aluminium is possibly removed by
    biological processes in the euphotic zone.

    4.1.4  Soil

         In soil, aluminium is released into solution for transport to
    streams upon acidification. The chemistry of inorganic aluminium in
    acid soil and, in particular, the solubility controls are very similar
    to those given in section 4.1.2 for fresh water (Furrer, 1993).
    However, the extrapolation of stream water chemistry to soil is
    difficult because of the complexity of hydrological pathways and
    chemical reactivity during water mixing (Neal, 1988).

         Water mixing processes may be important in determining the
    relationship between aluminium (inorganic) and hydrogen ions.
    Consequently there is a need to model how these species vary as a
    function of mixing so that comparisons can be made with field
    observation. In order to resolve the effects of mixing, a basic
    calculation is made to allow soil to mix and degas carbon dioxide in
    the stream. To do this it is assumed that pCO2 in soil/groundwater
    and the stream is 25 and 2 times the atmospheric value, respectively,
    and that bicarbonate principally controls the acid buffering (Neal et
    al., 1990).

         In soils, solid-phase aluminium occurs in the lattice structure
    of minerals, in inter-layer sites of expanding clay minerals, and in
    poorly ordered minerals (allophane and hydrous oxides) of variable
    composition. Natural acidification processes result in increasing
    solubility of aluminium. At moderately acidic levels (pH 5.5)
    aluminium appears as the exchangeable cation that dominates in the
    lower mineral horizons initially as poly-nuclear hydroxy ions but
    subsequently as the simple mono-nuclear ions. Aluminium ions displace
    calcium at permanent-charge exchange sites (Bache, 1980). The cation
    exchange system of acid soils provides a large reserve of ionic
    aluminium, which can be brought into solution when soluble salts
    percolate through soil. Ligands, such as fluoride and organic anions,
    which form aluminium complexes, combine with aluminium and maintain
    higher concentrations of aluminium than might be expected, especially
    at pH 5-7 (Bache, 1986). In soil the most soluble form of aluminium
    under acidic conditions is non-silicate organically bound aluminium,

    while the amorphous aluminium hydroxy forms are more soluble than the
    crystalline forms (ATSDR, 1992; Sjöström, 1994).

         Bloom et al. (1979) found that hydrolysis of organically bound
    aluminium is a major source of buffering in the pH range 4 to 5 for
    dilute salt suspensions of acid soils. The exchange of aluminium ions
    from organic matter exchange sites controls the relationship between
    pH and Al3+ activity in acid soils that have a low amount of
    permanent-charge cation exchange capacity relative to the quantity of
    organic matter. Walker et al. (1990) studied the influence of organic
    matter on the solubility of aluminium in organic soil horizons from
    different geographical regions of North America. The equilibrium
    solubility of aluminium was dependent on pH and the degree to which
    soil organic matter was saturated with aluminium. Soluble aluminium
    increased with decreasing pH and increased with increasing surface-
    bound aluminium at each pH level. Temperature dependence and rate
    studies suggested that aluminium solubility was governed by an ion-
    exchange reaction between H+ and aluminium and the organic matter.

         Litaor (1987) studied the aluminium chemistry in an alpine
    watershed, Front Range, Colorado, USA. It was found that the aluminium
    solubility in the interstitial water is complex and controlled by
    organic solutes, H4SiO4 and pH. However, neither pH nor sulfate
    concentrations correlated with aluminium concentrations. The chemical
    equilibrium of aluminium was controlled by amorphous aluminosilicate.

         The most important inorganic aluminium complexes are the
    mononuclear and to a lesser extent the polynuclear hydroxo species.
    The formation of these complexes is directly coupled to pH and also,
    to a lesser extent, to ionic strength. The hexa aqua-aluminium cation
    (Al(H2O)63+) predominates at low pH, whereas the mononuclear
    (Al(OH)2+) and dihydroxo-mononuclear species (Al(OH)2+) become
    important in the circumneutral pH range. The tetrahydroxo aluminium
    anion (aluminate, Al(OH)4-) is the predominant species at higher pH,
    and is responsible for the increasing solubility of aluminium above pH
    6.2. Polynuclear aluminium complexes can be the predominant species in
    solution over a wide pH range, although, being formed under non-
    equilibrium conditions, they are difficult to predict (Grant et al.,
    1990). Dahlgren & Ugolini (1989) collected leachates from subalpine
    spodosol located in the Cascade Range, Washington, USA. The ability of
    organic acids to complex aluminium in these subalpine soils increases
    from pH 3.8 to 5.0. Walker et al. (1988) found that adsorption of
    aluminium by aluminosilicate clay minerals, such as montmorillonite,
    kaolinite and vermiculite, is controlled by a simple electrostatic
    cation exchange involving outer sphere complexes. Adsorption to
    vermiculite may also be controlled by internal ion diffusion.

         Equilibrium constants (Ka) for the formation of an adsorbed
    aluminium clay complex were high (approx. 105) for the three minerals,
    suggesting that they play a significant role in controlling aluminium
    concentrations in soil solutions.

         Blume & Brümmer (1991) studied the influence of soil acidity on
    aluminium binding in sandy soils with a low humus content (< 2%).
    Binding was found to decrease steadily from very strong at pH 5.5-7.0
    to very weak at pH 2.5. The binding of aluminium was found to be
    increased by increasing the organic matter content. In loam or clay
    soils binding was increased compared with sandy soils at all levels of
    pH.

         Driscoll et al. (1989) studied the chemistry and transfer of
    aluminium in a forested watershed of the Adirondack region, New York,
    USA. The drainage waters from the watershed were highly acidic due to
    elevated inputs of both sulfuric and nitric acids compared with the
    release of basic cations. The conditions facilitated the mobilization
    of aluminium. Alumino-organic solutes were mainly released from the
    soil organic horizon with inorganic monomeric aluminium derived
    predominantly from the mineral soil and to a lesser extent from the
    soil organic horizon. Inorganic monomeric aluminium predominated in
    the drainage water. The deposition of organic monomeric aluminium in
    the stream bed coincided with the dissolved organic content retention
    whilst the deposition of inorganic monomeric aluminium appeared to be
    facilitated by nitrate retention.

         Nilsson & Bergkvist (1983) studied soil acidification and
    aluminium chemistry in three adjacent catchments on the Swedish west
    coast. The concentration of organic aluminium was linearly correlated
    with concentrations of carbon. The percentage of organic species in
    the dissolved aluminium decreased with increasing depth from > 90% in
    the upper layers to < 10% below 55 cm. The average concentration
    of total aluminium increased with increasing depth from 3.3 to
    9.8 µmole/litre at 5 cm to 95.3 to 115 µmole/litre below 55 cm.

         Atmospheric acid inputs have a strong impact on the aluminium
    chemistry of acidic sandy soils with low concentrations of basic
    cations. The base saturation of such soils is low and the rate of
    basic cation weathering does not increase with rate of acid input. Any
    additional acidic deposition is neutralized by aluminium. Dissolution
    of aluminium is the major acid sink in such soils, neutralizing 30% to
    95% of the total acid load (Mulder et al., 1989).

         Bergkvist (1987) studied the leaching of aluminium in a brown
    forest soil and a podzol with adjacent stands of spruce, beech and an
    open regeneration area in South Sweden using lysimeter techniques. The
    leaching of aluminium was greatest from the podzol. The solubility of

    aluminium increased suddenly within a small pH range (4.5-4.0) in the
    B horizon (15 to 55 cm). The concentration of aluminium in soil
    solution increased from 2 to 10 mg/litre when the pH decreased from
    4.4 to 4.2. Berggren et al. (1990) reported that forest soils of south
    Sweden are losing base cations, such as aluminium, owing to increased
    leaching rates following soil acidification. The processes controlling
    the mobilization of aluminium in podzols and cambisols of southern
    Sweden were investigated by Berggren (1992). Podzols in spruce and
    beech stands had a high release of organic compounds from the upper 5
    to 7 cm (O/Ah horizons), which resulted in high organic complexation
    of aluminium in soil solution at a depth of 15 cm (E horizon). Organic
    complexes were mainly adsorbed or precipitated at 20 to 40 cm (upper
    Bh horizon) and the overall transport of aluminium at 50 cm was
    governed by a pH-dependent dissolution of solid-phase aluminium. In
    the cambisols inorganic aluminium predominated at both 15 cm and 50 cm
    with solubility being closely related to solution pH. The results
    indicate that the relatively large organically bound solid-phase
    aluminium pools in both soil types give rise to the measured solution
    aluminium activities. The authors also found that aluminium in
    solution efficiently competed for exchange sites and played an
    important role in the mobilization of cadmium in these soils.

         In laboratory studies simulating snow melt leaching of forest
    soils, nitric acid leached more aluminium than did sulfuric acid
    from soil columns representative of high elevation forest soils
    and watersheds thought to be sensitive to acidification by acid
    precipitation. Increasing the nitric acid concentration 100-fold
    (pH 5 to 3) increased the total aluminium concentration in the
    leachate from 0.70 to 0.85 mmol/litre, while increasing the sulfuric
    acid had no effect. Similar experiments with albic and ochric mineral
    soil horizons revealed no difference between the acids and no effect
    of increasing acid concentrations (James & Riha, 1989).

         The acidity produced by soil nitrification is buffered by
    exchange with base cations. In acidified soils aluminium will be
    dissolved or the pH of the soil will decrease. Aluminium release from
    soil is also dependent on the sulfate supply and the capacity of the
    soil to provide aluminium hydroxides. The molar ratio between
    aluminium and nitrate is important in evaluating the effects of
    nitrification. During dry summers the release of aluminium ions may be
    entirely controlled by the acidification caused by nitrification
    (Gundersen & Rasmussen, 1990).

    4.1.5  Vegetation and wildlife

         Mobilization of aluminium by acid rain results in more aluminium
    being available to plants (ATSDR, 1992).

         Henriksen et al. (1988a) found during acidification experiments
    in Norwegian streams that the buffering capacity was 20 times higher
    than that associated with the water alone and a reduction of the pH to
    5 resulted in large releases of aluminium (up to 2500 µg/litre).
    The source of the buffering and the reservoir of aluminium was
    hypothesized to be dense growths of liverwort. A second experiment
    confirmed that liverworts are involved in the ion exchange of base
    cations and aluminium during acid episodes.

         Vogt et al. (1987) studied the aluminium concentrations of above-
    and below-ground tissues of a white fir ( Abies amabilis) stand in
    the Cascade mountains, Washington, USA. It was found that 97% of the
    total detrital cycling of aluminium was below ground. When compared
    with the other elements analysed, aluminium showed the highest
    proportion of total annual element pool circulated (82%). The large
    root biomasses of these stands allows large amounts of aluminium to be
    accumulated and immobilized. The high root turnover observed for these
    stands appears to be due to the root senescence occurring in response
    to high aluminium accumulation. However, there is little impact on
    short-term elemental cycling because the roots decay very slowly
    (99% decay = 456 years).

    4.2  Biotransformation

    4.2.1  Biodegradation and abiotic degradation

         Elemental aluminium does not degrade in the environment. In the
    trivalent oxidation state, it can complex with electron-rich species
    (ATSDR, 1992).

    4.2.1  Bioaccumulation

    4.2.2.1  Plants

         Plants differ in their ability to take up aluminium; some
    accumulate aluminium whereas others are able to immobilize it at the
    root surface (Roy et al., 1988). Exposure to aluminium in nutrient
    solution leads to accumulation, especially in the roots (Lee, 1972;
    Boxman et al., 1991).

         Aluminium taken up by roots is mainly found in the mucilage layer
    on the root tip surface (Horst et al., 1982) and in the walls of the
    epidermis and cortex cells (Huett & Menary, 1980). In the cell wall
    pectins, aluminium ions compete with calcium ions for the same
    absorption sites (Wagatsuma, 1983). Some aluminium is taken up in the
    cytoplasm and bound to nucleic acids and acid-soluble phosphates
    (Wagatsuma, 1983). Aluminium is translocated only to a small extent to
    shoots.

         The concentrations of aluminium in leaf tissue of a variety of
    plants growing on limestone soils in Sweden (pH around 8) were found
    to be similar to those in plants growing on an acid silicate (granite;
    pH 4.1-4.9) site, although the aluminium concentration in the topsoil
    solution was at least one order of magnitude lower in the limestone
    than in the acid silicate soils (Tyler, 1994).

    4.2.2.2  Invertebrates

         Ryther et al. (1979) cultured soft shell clams ( Mya arenaria),
    hard shell clams ( Mercenaria mercenaria), American oysters
    ( Crassostrea virginica) and sand worms ( Nereis virens) in tanks
    containing fly ash from a coal-burning power station. The fly ash
    contained a wide range of elements including aluminium at 105.8 g/kg.
    After a period of 4 months the sand worms and the edible parts of the
    clams and oyster were analysed. Aluminium concentrations were
    9645 mg/kg (dry weight) for the sand worms and 8218, 268 and
    1373 mg/kg for soft shell clams, hard shell clams and oysters,
    respectively.

         Crayfish ( Orconectes virilis) from a lake with an average total
    aluminium concentration of 36 µg/litre were placed in caged tubes
    spiked with 40 µg/litre total aluminium and transferred to a lake with
    background levels of 8 µg/litre total aluminium. Half of the tubes
    were acidified to pH 5.3 and the others remained at pH 6.7. None of
    the crayfish accumulated aluminium. Controls had lower aluminium
    concentrations in the hepatopancreas and abdominal muscle after 25 to
    27 days. Crayfish under acidified conditions retained aluminium in the
    hepatopancreas and not in the muscle whereas those at pH 6.7 retained
    aluminium in the muscle and not the hepatopancreas. The same authors
    also carried out a laboratory experiment with crayfish obtained
    from the original lake. Crayfish were maintained in a solution of
    500 µg/litre for 14 days. No tissues showed an increase in aluminium
    levels. However, crayfish transferred back to the original lake water
    for 16 days retained aluminium only in the carapace and gills (Malley
    et al., 1987).

         Havas (1985) exposed water fleas ( Daphnia magna) to total
    aluminium concentrations of 0.02, 0.32 and 1.02 mg/litre for 24 h.
    Bioconcentration was related to pH, the highest concentration factors
    occurring at pH 6.5 and the lowest at pH 4.5; there was no effect of
    increasing the calcium concentration from 2.5 to 12.5 mg/litre. Mean
    bioaccumulation factors ranged from 11 000 to 18 000 at pH 6.5, 3000
    to 9000 at pH 5.0, and 1200 to 4300 at pH 4.5.

         Frick & Herrmann (1990) studied the accumulation of aluminium
    by nymphs of the mayfly ( Heptagenia sulphurea) exposed to
    concentrations of 0.2 and 2 mg inorganic monomeric aluminium/litre at

    pH 4.5 for up to 4 weeks. The highest mean concentrations found in
    mayflies were 1.24 and 2.34 mg/g aluminium (dry weight) for the higher
    treatment groups, which did not undergo moulting. The major part of
    the aluminium was deposited on/in the exuviae of the nymphs, as
    aluminium determinations revealed a 70% decrease in content after
    moulting.

    4.2.2.3  Fish

         Cleveland et al. (1986) exposed brook trout ( Salvelinus 
     fontinalis) eggs, larvae and juveniles to 300 µg/litre total
    aluminium at three pH levels. At 30 days post-hatch for larvae and
    for an exposure period of 30 days for juveniles (37 to 67 days),
    significantly more aluminium was accumulated at pH 5.28 than at either
    pH 7.24 or 4.44. Aluminium levels at pH 5.28 were 398 and 112 mg/kg
    for the larvae and juveniles, respectively. At pH 7.24 residues were
    12 and 33 mg/kg, and at pH 4.44, 71 and 17 mg/kg, respectively.
    Cleveland et al. (1991) maintained brook trout in water containing
    200 µg/litre total aluminium at pH values of 5.0, 6.0 and 7.2 for 56
    days. Estimated steady state bioconcentration factors for aluminium,
    which were inversely related to pH, were 215 at pH 5.3, 123 at pH 6.1
    and 36 at pH 7.2. The estimated time to 90% steady state was 1.5 days
    at pH 5.3, 4.2 days at pH 6.1 and 1.7 days at pH 7.2. Elimination
    during the 28-day depuration phase was more rapid at pH 5.3 than at pH
    6.1 or 7.2. Karlsson-Norrgren et al. (1986b) found that brown trout
    ( Salmo trutta) accumulated significantly more aluminium in gill
    tissue at pH 5.5 than at pH 7.0 (60-160 µg/kg and 10-40 µg/kg dry
    weight, respectively) when exposed to 200-500 µg total
    aluminium/litre. Skogheim et al. (1984) found a gill aluminium
    accumulation of 70 to 341 µg/g fresh weight in dying Atlantic salmon
    ( Salmo salar) during an episodic fish kill in the river Ogna,
    Norway, at pH 5.4-5.5 and total aluminium and labile aluminium
    concentrations of 160 and 130 µg/litre, respectively.

         Segner et al. (1988) exposed young brown trout ( Salmo trutta)
    to total aluminium (230 µg/litre) at pH 5.0 in high calcium water at a
    temperature of 12°C for 5 days. Whole body aluminium concentrations
    were 230 mg/kg dry weight in aluminium-exposed fish, as compared to
    75 mg/kg (pH 5.0) and 44 mg/kg (pH 7.2) for fish in aluminium-free
    water.

         Wicklund Glynn et al. (1992) exposed minnows ( Phoxinus 
     phoxinus) to acidic water (pH 5.0) with and without total aluminium
    (150 µg/litre) at varying calcium (0, 0.07 and 2 mmol/litre) and humus
    (5 and 25 Pt) concentrations for 15 days. Aluminium concentrations in
    the gills were highest in the lower calcium level groups with or
    without humus. In the absence of calcium the median aluminium level in
    the gills was 109 mg/kg wet weight, and at 2 mmol/litre calcium the
    aluminium level was 50 mg/kg.

    4.2.2.4  Birds

         Carričre et al. (1986) fed ring doves ( Streptopelia risoria) on
    a diet containing 0.1% aluminium sulfate with reduced calcium and
    phosphorus (0.9% Ca; 0.5% P) for a period of 4 months. Analysis of
    the tissues of breeding adult doves revealed that there was no
    accumulation of aluminium in kidney, brain or male femurae; however,
    the femurae of female doves showed a significant increase from a mean
    of 7.42 mg/kg dry weight in controls to 15.87 mg/kg in treated birds.
    Juvenile doves fed on diets containing 500, 1000 and 1500 mg/kg
    aluminium sulfate did not accumulate aluminium in leg and wing bones
    but did show a significant tendency to accumulate in the sternum.

         Sparling (1991) fed black ducks ( Anas rubripes) and mallard
    ( Anas platyrhynchos) on a diet containing 200, 1000 or 5000 mg
    aluminium/kg with varying amounts of calcium (3600 and 15 100 mg/kg)
    and phosphorus (6200, 13 500 and 21 500 mg/kg) for a period of 10
    weeks. All of the diets produced a dose-related and significant
    increase in the aluminium content of the femur. Black ducks maintained
    on normal calcium and phosphorus levels showed femur aluminium
    concentrations of 5.42, 13.6 and 19.5 mg/kg after 10 weeks at the
    three dose levels, respectively. Mallard femurs contained aluminium
    levels of 9.49, 12.1 and 18 mg/kg, respectively.

    5.  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    5.1  Environmental levels

         Aluminium is ubiquitous in the environment and its chemistry is
    controlled by pH, mineralogical composition, and the quantity and
    qualitative nature of the organic constituents present. It is,
    therefore, difficult to provide generalized estimates of natural
    background concentrations (Grant et al., 1990). Aluminium is released
    to the environment by both natural processes and anthropogenic
    sources. It is a major constituent of the earth's crust, and natural
    mobilization of aluminium far outweighs the direct contribution from
    anthropogenic sources (Lantzy & Mackenzie, 1979). The concentrations
    of aluminium in the different environmental compartments are dependent
    on its speciation and mobilization (see section 4.1). Jones & Bennett
    (1985) summarized the data on aluminium concentrations in the
    environment and produced a list of representative values as follows:
    urban air 1000 ng/m3 (160-7000 ng/m3), rural air 200 ng/m3
    (150-325 ng/m3), agricultural soil 70 000 mg/kg (10 000-300 000
    mg/kg), fresh water (dissolved) 50 µg/litre (1-2250 µg/litre), ocean
    (dissolved) 2 µg/litre (1-5 µg/litre), and terrestrial plants
    100 mg/kg (50-600 mg/kg).

    5.1.1  Air

         Aluminium is a major constituent of a number of atmospheric
    components, being highly concentrated in soil-derived dusts and in
    particulates from coal combustion (Grant et al., 1990). The sources of
    soil-derived dust are both natural (Sorenson et al., 1974) and from
    human activity such as mining and agriculture (Eisenreich, 1980).
    Leharne et al. (1992) monitored street dust from the inner London
    area, United Kingdom, and found aluminium levels ranging from 3.7 to
    11.6 µg/kg. The largest sources of particle-borne aluminium are the
    flux of dust from soil and rock materials in the earth's crust and
    from volcanic eruptions (Lee & von Lehmden, 1973; Sorenson et al.,
    1974; Lantzy & Mackenzie, 1979). Atmospheric aluminium concentrations
    show widespread temporal and spatial variations. The concentrations of
    aluminium in air are summarized in Table 8 and range from 0.5 ng/m3
    over Antarctica to > 1000 ng/m3 in industrialized areas.

        Table 8.  Concentrations of aluminium in air
                                                                                   

    Area                Year           Particle       Aluminium      Reference
                                       size           concentration
                                       (µm) a          (ng/m3)
                                                                                   

    Antarctic           1970           NR             0.57           Zoller et al.
                                                      (0.32-0.81)    (1974)

    Arctic              1976-1978      NR             25             Rahn (1981)
    (Barrow, Alaska)

    Hawaii              1967           > 0.15         2-40           Hoffman et al.
                                                                     (1969)

    Atlantic Ocean                     NR             8-370          Duce et al.
                                                                     (1975)
                                       NR             95 (41-160)    Windom (1981)

    Atlantic Ocean                     NR             102-184        Windom (1981)
    near coast of USA

    North Sea           1988-1989      NR             294.5          Chester &
                                                      (21-887)       Bradshaw (1991)
                        1988-1989      NR             197            Ottley &
                                                      (17-903)       Harrison (1993)
                        1985-1986      NR             210            Kersten et al.
                                                      (64-600)       (1988)

    Baltic Sea          1985           NR             218            Häsänen et al.
                                                      (47-800)       (1990)

    Kiel Bight,         1981-1983      NR             394            Schneider (1987)
    Germany                                           (68-720)

    USA cities &        1975-1977      < 3.5          48-1983        Stevens et al.
    industrial areas                                                 (1978)
                        1975-1977      > 3.5          331-8678       Stevens et al.
                                                                     (1978)

    Buffalo,            1968-1969      NR             1000-8000      Pillay & Thomas
    New York, USA                                                    (1971)

    Southern Arizona    1974           NR             5700           Moyers et al.
    (urban)                                                          (1977)
                                                                                   

    Table 8.  (Con't)
                                                                                   

    Area                Year           Particle       Aluminium      Reference
                                       size           concentration
                                       (µm) a          (ng/m3)
                                                                                   


    Southern Arizona    1974           NR             1200           Moyers et al.
    (rural)                                                          (1977)

    Charleston,         1976           < 3.5          74             Lewis & Macias
    West Virginia                                                    (1980)
                        1976           > 3.5          1100           Lewis & Macias
                                                                     (1980)

    UK (non-urban       1972-1973      NR             27-640 ng/kg   Cawse (1974)
    sites)

    Birkenes,           1978-1979      NR             80             Amundsen et al.
    S. Norway                                                        (1992)
                        1985-1986      NR             73             Amundsen et al.
                                                                     (1992)
                                                                                   

    a    NR = not reported
    
         Amundsen et al. (1992) analysed air samples from Birkenes,
    southern Norway, for aluminium and found concentrations to be
    highest in the spring period from March to May. The authors
    concluded that this was due to soil dust from wind erosion and
    agricultural activities because soils in Europe are likely to be dry
    during this period. Windom (1981) measured aluminium concentrations of
    28 000 ng/m3 during a dust storm.

         Aluminium was found to be concentrated up to 2650 ng/m3 in the
    Baltimore harbour tunnel, a two-fold increase on the air intake levels
    (Ondov et al., 1982).

    5.1.2  Precipitation

         Aluminium has been measured in atmospheric precipitation in the
    USA at concentrations of up to 1200 µg/litre (Feth et al., 1964;
    Fisher et al., 1968; Norton, 1971).

         Feth et al. (1964) analysed snow samples from the northern Sierra
    Nevada, USA, in 1959. Aluminium was detected in 7 out of 8 samples at
    a mean concentration of 30 µg/litre. Ecker et al. (1990) measured
    aluminium in wet-deposited snow at several sites in Japan, both
    urban and rural. Mean aluminium concentrations ranged from 9.6 to
    25.8 µg/litre. Average aluminium concentrations of freshly deposited
    snow at Shiramine (a mountain site) were 2.4 µg/litre in the insoluble
    fraction (> 0.45 µm) and 15.0 µg/litre in the soluble fraction (<
    0.45 µm).

         Rainwater collected in southern central Florida, USA, between
    1967 and 1969 contained aluminium concentrations ranging from not
    detectable to 900 µg/litre (Dantzman & Breland, 1969). Guieu et al.
    (1991) monitored rainfall at 45 sites in the south of France and found
    mean aluminium concentrations of 487 µg/litre and 55 µg/litre in the
    particulate (> 0.4 µm) and dissolved fractions (< 0.4 µm),
    respectively. Cawse (1974) measured aluminium in rainfall and dry
    deposition from seven non-urban United Kingdom sites in 1972 and 1973.
    Aluminium concentrations ranged from 56 to 14 800 µg/litre for
    rainfall and from 3.9 to 42 µg/cm2 per year for dry deposition.
    Aluminium concentrations in rainfall, total and dry deposition were
    measured for Bagauda, Nigeria, in 1976. Aluminium concentrations were
    1700 µg/litre for rainfall and 220 and 145 µg/cm2 per year for total
    and dry deposition, respectively (Beavington & Cawse, 1979).

    5.1.3  Water

    5.1.3.1  Freshwater

         Surface freshwater aluminium concentrations can vary
    significantly, being dependent on the various physicochemical and
    mineralogical factors described in section 4.1. Aluminium can occur in
    a number of different forms in freshwater. It can be suspended or
    dissolved. It can be bound with organic or inorganic ligands, or it
    can exist as a free aluminium ion. It can exist as a monomer in
    natural water, but tends to polymerize with time (see section 2.3.4).
    Aluminium speciation is determined by pH, dissolved organic carbon
    (DOC), fluoride, sulfate, phosphate, silicate and suspended
    particulate matter. Dissolved aluminium concentrations for water in
    the circumneutral pH range are usually quite low, ranging from 1.0 to
    50 µg/litre, and rise to 500 to 1000 µg/litre in more acidic waters.
    At the extreme acidity of waters affected by acid mine drainage,
    dissolved aluminium concentrations of up to 90 mg/litre can be
    measured (Filipek et al., 1987). Aluminium can also be leached from
    landfill containing coal combustion ash and aluminium smelting wastes
    (Sorenson et al., 1974). The concentrations of aluminium in freshwater
    are summarized in Table 9.

        Table 9.  Concentrations of aluminium in freshwater
                                                                                                                                              

    Area                               Year           pH             Particle    Aluminium         Detection      Reference 
                                                                     size        concentration     limit
                                                                     (µm)        (µg/litre)        (µg/litre)
                                                                                                                                              

    Lake Gardsjon catchment,           1981           4.0-6.4        < 0.45      300-2500                         Lee (1985)
    Sweden

    Swedish lakes                      1980           5.7-8.8                    69 (10-243)       10             Borg (1987)

    Loch Ard Forest and                1979-1980      4.63           < 1.0       400                              Caines et al. (1985)
    Galloway streams, Scotland                        6.62           < 1.0       25                               Caines et al. (1985)

    Llyn Brianne catchment, Wales      1984-1985      4.6-5.3        < 0.45      120-430                          Goenaga & Williams (1990)
                                       1984-1985      4.87                       42 µEq/litre                     Whitehead et al. (1988)
                                       1984-1985      5.2                        18 µEq/litre                     Whitehead et al. (1988)
                                       1984-1985      6.9                        7 µEq/litre                      Whitehead et al. (1988)
    Rivers Esk and Duddon,
    Cumbria, UK
      (moderate flow)                  1983-1984      4.3-7.2                    20-940                           Bull & Hall (1986)
      (low flow)                       1983-1984      4.8-7.5                    5-245                            Bull & Hall (1986)

    Vosges mountain streams,           1990           6.96                       64                               Mersch et al. (1993)
    France                             1990           4.64-5.74                  185-351                          Mersch et al. (1993)

    Boglakes, NE Belgium               1984-1986      3.4-3.9        < 0.4       150-3770          20             Courtijn et al. (1987)
                                       1984-1985      3.4-3.9        > 0.4       3200-65 000                      Courtijn et al. (1987)
                                       1984-1986      6.0            < 0.4       < 20              20             Courtijn et al. (1987)
                                       1984-1985      6.0            > 0.4       78 100-145 100                   Courtijn et al. (1987)
                                                                                                                                              

    Table 9.  (Con't)
                                                                                                                                              

    Area                               Year           pH             Particle    Aluminium         Detection      Reference 
                                                                     size        concentration     limit
                                                                     (µm)        (µg/litre)        (µg/litre)
                                                                                                                                              

    Stream water, California, USA                                    < 0.45      15                7              Silvey (1967)

    St Lawrence river, USA             1974-1976      7.6-8.0        < 0.4       64                               Yeats & Bewers (1982)
                                       1974-1976      7.6-8.0        > 0.4       964                              Yeats & Bewers (1982)

    South central Florida, streams     1969                                      200-300                          Dantzman & Breland
                                                                                                                  (1969)

    Highway drains, Louisiana          1990                                      412 (250-1270)                   Madigosky et al. (1992)

    Northern California streams        1972                                      5-10                             Jones et al. (1974)

    Shield lakes, Ontario and          1982           4.4-7.1                    46-372                           Stokes et al. (1985)
    Quebec

    Zaire river                        1976           6.8            < 0.45      28-44                            van Bennekom & Jager
                                                                                                                  (1978)

    Niger river                        1976           6.7            < 0.45      3-6                              van Bennekom & Jager
                                                                                                                  (1978)

    Reservoirs, Madras, India          1991                                      14 (5-210)        2              Pitchai et al. (1992)

    Orange river, Vioolsdrif,          1958-1959      6.4-8.1                    36-1080                          de Villiers (1962)
    South Africa

    River Yodo, Japan                  1981-1990                                 10-1150                          Yagi et al. (1992)
                                                                                                                                              
             Aluminium occurs ubiquitously in natural waters. Aluminium levels
    in surface waters can be increased by intense urban and industrial
    activity (Eisenreich, 1980). Kopp & Kroner (1970) monitored rivers and
    lakes in the USA from 1962 to 1967 and detected aluminium in 31%
    of samples. Mean dissolved aluminium levels ranged from 11 to
    333 µg/litre, the highest levels of 2760 µg/litre being measured in
    the Missouri river. Aluminium was found to be predominantly in the
    suspended sediment fraction (> 0.45) with a mean concentration of
    3860 µg/litre (compared with the dissolved phase at 74 µg/litre).

         Filipek et al. (1987) reported that weathering of sulfide ores
    exposed to the atmosphere in inactive mines and tailings dumps
    released large quantities of sulfuric acid and metals such as
    aluminium (up to 90 mg/litre). Boult et al. (1994) measured aluminium
    in the Afon Goch, Anglesey, Wales, a stream polluted by mine drainage.
    Sampling sites with pH 2.40, 5.99 and 6.49 gave mean soluble aluminium
    concentrations (< 0.45 µm) of 55.56, 1.14 and 0.12 mg/litre,
    respectively; mean aluminium concentrations in the particulate phase
    (> 0.45 µm) were 0.31, 2.15 and 0.69 mg/litre, respectively. Koga
    (1967) sampled water discharged from Wairakei drill holes in 1965.
    Total aluminium concentrations in filtered water ranged from 0.023 to
    0.05 mg/litre. Zelenov (1965) found elevated levels (4913 mg/litre) of
    aluminium in water of a volcanic crater lake in Indonesia.

         The concentrations of dissolved aluminium in water vary with pH
    levels and the humic-derived acid content of the water (ATSDR, 1992).
    Watt et al. (1983) compared Nova Scotian river water samples from
    1954-1955 with those from 1980-1981 and found that significant
    decreases in the pH corresponded to significant increases in dissolved
    aluminium. High aluminium concentrations occur in surface waters when
    the pH is less than 5 (Sorenson et al., 1974; Filipek et al., 1987).
    In general, aluminium levels in surface waters at pH levels above 5.5
    will be less than 0.1 mg/litre (Sorenson et al., 1974). However, even
    at neutral pHs, higher aluminium levels have been detected where the
    humic acid content is high (ATSDR, 1992).

         In the Thousand Lake Survey in Norway (Henriksen et al., 1988b),
    90% of the lakes with pH below 5.4 had a concentration of inorganic
    monomeric aluminium above 60 µg/litre. Lakes with a pH of 4.6-4.8
    and 4.8-5.0 had concentrations of 146-170 and 101-135 µg/litre,
    respectively.

         Generally, the data indicate that total aluminium concentrations
    in surface waters are elevated during periods of high flow, following
    episodic storm events, and/or during spring snow melt. Many studies
    also reported corresponding increases in the labile or inorganic
    aluminium fraction during these periods (LaZerte, 1984; Bull & Hall,
    1986; Henriksen et al., 1988c; Lawrence et al., 1988).

         Jones et al. (1974) monitored streams in Northern California and
    found that samples collected during low flow periods contained
    aluminium concentrations of between 1 and 3 µg/litre, whereas those
    collected during moderate flow periods contained 10 µg/litre. Values
    of aluminium that were higher than expected were associated with storm
    run-off.

         Caines et al. (1985) monitored streams in the Loch Ard Forest
    and Galloway areas of Scotland during 1978, 1979 and 1980. The
    concentrations of aluminium were found to be very closely dependent on
    the hydrogen ion concentrations in the stream water. The maximum
    concentration of aluminium in a stream with an average pH of 6.62 was
    25 µg/litre, compared with almost 400 µg/litre in a stream with an
    average pH of 4.63. The seasonal variation that occurred in the most
    acid stream had a maximum of 394 µg/litre in February, which declined
    rapidly to 35 µg/litre in May, during 1980. The authors stated that
    the sharp decrease coincided with a period of low rainfall which
    resulted in a rise in stream pH and greatly reduced leaching of
    aluminium from the catchment.

         Bull & Hall (1986) measured aluminium in the rivers Esk and
    Duddon, Cumbria, United Kingdom, and their tributaries. The findings
    showed a relationship between inorganic aluminium and pH, while
    organic aluminium was generally low in these rivers. In general, lower
    pHs and higher aluminium concentrations occurred at higher river flow
    rates.

         Ecker et al. (1990) monitored aluminium in the first and last
    meltwater run-off from snowfields at Shiramine, a mountainous area in
    Japan. Average aluminium concentrations were non-detectable and
    445.6 µg/litre in the insoluble fraction (> 0 45 µm) of the first and
    last run-offs, respectively, and 25.0 and 19.9 µg/litre, respectively,
    in the soluble fraction (< 0.45 µm).

    5.1.3.2  Seawater

         The concentrations of aluminium in seawater are summarized in
    Table 10. The concentration of aluminium is dependent on the salinity
    of the water. Concentrations in open seawater are typically around
    1 to 2 µg/litre in the dissolved fraction (< 0.45 µm). Bruland (1983)
    stated that the concentration of aluminium in surface seawater in the
    open ocean reflects atmospheric input and scavenging processes; the
    concentration is low at high latitudes in the North Atlantic because
    of a low atmospheric input and a higher scavenging rate resulting from
    intensified biological activity in these waters. Aluminium is higher
    in surface waters of mid-latitudes due to the higher atmospheric input
    and lower scavenging rate in these oligotrophic waters.

        Table 10.  Concentrations of aluminium in seawater
                                                                                                                                              

    Area                     Year           Depth          Salinity       Particle    Aluminium              Reference
                                            (m)            (%)            size        concentration
                                                                          (µm)        (µg/litre)
                                                                                                                                              

    Open Atlantic Ocean      1980-1982                                                15.2 and               Kremling (1985)
                                                                                      25.4 nmol/kg

    North-East Atlantic      1982           < 150          35-37                      16-32 nmol/litre       Hydes (1983)
    Ocean                    1982           > 1000         35-37                      6-11 nmol/litre

    Atlantic Ocean near      1974           300-1100                                  0.3-4.26               Alberts et al. (1976)
    Carribean islands        1977-1978      0-2730         33-37                      0.51-2.41              Stoffyn & Mackenzie (1982)

    Atlantic Ocean near      1951-1952                                                0-10                   Simons et al. (1953)
    USA coast

    Gulf of Mexico                                                        > 0.45      2.0 (0.2-10.2)         Feely et al. (1971)
                             1951-1952                                                2-5                    Simons et al. (1953)

    Pacific Ocean near                                                    < 0.45      1                      Sackett & Arrhenius (1962)
    USA coast                                                             > 0.45      0.2-27                 Sackett & Arrhenius (1962)
                                            0.3                           < 0.45      9.8 (3.7-166)          Silvey (1967)

    Weddel Sea, Antarctica                                                < 0.45      1                      Sackett & Arrhenius (1962)
                                                                          > 0.45      4-120                  Sackett & Arrhenius (1962)

    North Sea                1988           6              34-35          < 0.4       10.2-49.2              Hydes & Kremling (1993)
                                                                                      nmol/litre

    Mediterranean Sea        1976-1977      0-1500         35-38                      1.0-4.8                Stoffyn & Mackenzie (1982)
                                                                                                                                              
        5.1.4  Soil and sediment

         Aluminium partitions from water to sediment and particulate
    matter especially at circumneutral pH. The concentrations of aluminium
    in sediment are summarized in Table 11. Mean aluminium concentrations
    range from 20 000 to 80 000 mg/kg. Subramanian et al. (1988) measured
    heavy metals in the bed sediments and particulate matter of the Ganges
    Estuary, India. Average aluminium concentrations were 56 526 mg/kg for
    bed sediments and 70 222 mg/kg for suspended sediments. Sanin et al.
    (1992) measured elements in the sediments of the river Goksu and the
    Tasucu Delta, Turkey. Mean aluminium concentrations ranged from
    20 700 to 26 800 mg/kg for the river and from 30 150 to 42 875 mg/kg
    for the delta. Benninger & Wells (1993) sampled sediment from the
    Neuse river estuary, North Carolina, USA, between 1982 and 1990.
    Aluminium concentrations ranged from 2.1 to 4.9 mmol/g, equivalent to
    10.7% to 25.0% aluminium oxide. Fileman et al. (1991) found a mean
    aluminium level of 2490 mg/kg in suspended particulate material from
    the Dogger Bank region of the central North Sea.

         Aluminium is one of the most abundant elements in soil and
    concentrations vary widely. Shacklette & Boerngen (1984) collated the
    aluminium concentrations measured by the US Geological Survey; levels
    ranged from 700 to 100 000 mg/kg with an average of 72 000 mg/kg.
    Beavington & Cawse (1979) analysed soil from Baguada, Nigeria, and
    found aluminium levels of 24 000 µg/g (dry weight).

    Table 11.  Concentrations of aluminium in sediment
                                                                        

    Area             Yeara      Aluminium               Reference
                                concentration (mg/kg)
                                                                        

    River Goksu,     NR         20 800 to 26 600        Sanin et al.
    Turkey                                              (1992)

    Tasucu Delta,    NR         30 150 to 42 875        Sanin et al.
    Turkey                                              (1992)

    Tadenac Lake,    1979       31 000 to 64 800        Wren et al.
    Ontario                                             (1983)

    Turkey Lakes,    1981-1982  31 000 to 56 300        Johnson et al.
    Ontario                                             (1986)

    Hamilton,        1986-1987  25 941 to 68 870        Irvine et al.
    Ontario                                             (1992)
    (urban run-off)

    Fontana Lake,    1978       36 400 to 84 600        Abernathy et al.
    North Carolina                                      (1984)
                                                                        

    a    NR = not reported

         Aluminium is found in soil interstitial water at levels similar
    to those reported for freshwater. Litaor (1987) measured a mean
    aluminium concentration of 24.8 µmole/litre for the interstitial water
    (pH 6.0) of soil from the Green Lakes Valley Front Range in Colorado,
    USA.

    5.1.5  Terrestrial and aquatic organisms

         Mason & MacDonald (1988) monitored aluminium levels in aquatic
    moss ( Fontinalis squamosa) from the River Mawddach catchment, Wales
    (polluted with drainage water from disused mines) in 1984 and 1985.
    Mean aluminium concentrations ranged from 1970 to 26 800 mg/kg (dry
    weight). Mersch et al. (1993) transplanted aquatic moss ( Amblystegium
    riparium) from a non-acidified stream to streams with pH values
    ranging from 4.64 to 5.74. The moss accumulated aluminium, those
    exposed to acidified streams containing aluminium ranging from 10 390
    to 12 700 µg/g (dry weight) and those in a control stream (pH 6.96)
    containing 7750 µg/g. Caines et al. (1985) collected aquatic
    liverworts ( Nardia compressa  and  Scapania undulata) from streams
    in the Loch Ard and Galloway areas of Scotland. Mean liverwort
    aluminium concentrations were 3148, 6166 and 8532 mg/kg (dry weight)
    from streams containing 195, 71 and 24 µg/litre, respectively.
    Bioconcentration of aluminium occurred in all streams; however,
    increased hydrogen ion concentrations were associated with decreased
    liverwort aluminium concentrations. Albers & Camardese (1993a)
    monitored aquatic plants from acidified and non-acidified constructed
    wetlands. Aluminium concentrations for bur-reed ( Sparganium
    americnum) and bladderwort ( Utricularia spp.) were 167 and 533 µg/g
    (dry weight), respectively, for acidified wetlands and 104 and
    487 µg/g for non-acidified wetlands. Duckweed ( Lemna spp.) and green
    algae ( Oedogonium spp.) contained 998 µg aluminium/g at the non-
    acidified sites; acidified wetlands did not contain duckweed or green
    algae. Bur-reed (Sparganium spp.), bladderwort and pondweed collected
    from sites in Maryland and Maine contained aluminium concentrations of
    74.6, 1740 and 296 µg/g, respectively. The accumulation of aluminium
    by these aquatic plants correlated poorly with the water concentration
    (Albers & Camardese, 1993b).

         Leinonen (1989) collected leaves of  Vaccinium myrtillus from
    untreated forest, clear-cut untilled forest and clear-cut tilled land
    in Kuru, southern Finland in 1987. Aluminium levels were significantly
    higher in the tilled area, with levels of approximately 140 mg/kg dry
    weight in untilled areas and 185 mg/kg in the tilled area. Moomaw et
    al. (1959) collected a wide selection of Hawaiian plant species from
    highly leached latosol soils of low pH and high aluminium content.
    Aluminium concentrations ranged from 59 to 16 000 mg/kg dry weight.
    Thirteen of the 23 species contained aluminium levels in excess of
    1000 mg/kg; the highest levels were found in the pteridophyte
     Polypodium phymatoides  and the dicotyledon  Melastoma malahathricum.
    Beavington & Cawse (1979) analysed sorghum grain from Bagauda,
    Nigeria, and found aluminium levels of 90 µg/g dry weight.

         Wyttenbach et al. (1985) collected needles of  Picea abies from
    around the city of Winterthur, Switzerland. The washed needles were
    analysed for a wide range of elements including aluminium. The mean
    aluminium content of the needles was 19 mg/kg (10-64 mg/kg). It was
    found that washing the needles had removed more than 80% of the
    aluminium residue. Landolt et al. (1989) sampled spruce needles from
    locations throughout Switzerland in 1983 to study the distribution of
    elements. The mean aluminium concentration was found to be 61.4 mg/kg
    with a range of 12.88 to 344.5 mg/kg. Häsänen & Huttunen (1989)
    measured the aluminium content of the annual rings of pine trees
    ( Pinus sylvestris). The mean concentration for the period 1920 to
    1980 was 4.2 mg/kg (3.4-5.1 mg/kg). In the areas associated with
    higher sulfur deposition there had been increases in aluminium uptake
    since 1950.

         Malley et al. (1987) collected crayfish ( Orconectes virilis)
    from a lake in northwestern Ontario containing a total aluminium
    concentration of 36 µg/litre. Mean aluminium concentrations in the
    crayfish were highest in the gut tissue (774 mg/kg) and there were
    levels of 65.2, 84.4 and 50.4 mg/kg in the carapace, green gland and
    ovary, respectively. Madigosky et al. (1991) monitored red swamp
    crayfish ( Procambarus clarkii) from roadside drainage ditches
    in Louisiana, USA. Aluminium concentrations ranged from 1.75
    to 981.50 mg/kg dry weight in the order abdominal muscle
    < hepatopancreas < exoskeleton < alimentary canal tissue. The
    crayfish contained significantly higher levels of aluminium than those
    found in control crayfish sampled from a commercial crayfish farm.
    Madigosky et al. (1992) collected crayfish during 1990 from a site
    near to a Louisiana highway intersection. Aluminium concentrations
    were 2409 and 2342 mg/kg for intestinal tissue and contents,
    respectively, while concentrations of 527 and 27 388 mg/kg were found
    for stomach tissue and contents, respectively. It was found that
    purging the crayfish in 1.5% sodium chloride for 6 h did not
    significantly reduce aluminium in the gut tissue. However, there was
    an increase in the water concentration of aluminium probably caused by
    its release from exterior tissue sites.

         Albers & Camardese (1993a) collected aquatic insects from both
    acidified and non-acidified constructed wetlands; aluminium
    concentrations were 94.3 and 158 µg/g (dry weight) for the two types
    of wetland, respectively. Albers & Camardese (1993b) analysed aquatic
    insects from sites in Maryland (224 µg/g) and in Maine (102 µg/g). The
    same authors analysed crayfish and snails from sites in Maryland and
    Maine in 1987. Whole body aluminium concentrations were found to be 66
    to 542 µg/g (dry weight) and 27 to 398 µg/g for the two species,
    respectively.

         Brumbaugh & Kane (1985) collected smallmouth bass ( Micropterus 
     dolomieui) from the Chatuge reservoir on the border between Georgia
    and North Carolina, USA. The reservoir receives run-off from poorly
    buffered, forested watersheds, and the average pH of the reservoir was
    6.3. Mean aluminium concentrations were 58 µg/g wet weight for gills
    and 3.0, 2.5, 1.5 and < 1.0 µg/g for the carcass, gut, liver, and
    kidney, respectively. Fish collected from the vicinity of a liquid
    waste site in North Carolina, USA contained mean aluminium levels
    ranging from 10.9 to 18.2 mg/kg (wet weight - based on whole gutted
    fish) (Loehle & Paller, 1990). Buergel & Soltero (1983) analysed
    plankton and fish ( Oncorhynchus mykiss) from a lake in Washington
    State, USA, that had been treated with aluminium sulfate to reduce
    high phosphorus concentrations. Total and dissolved aluminium in the
    lake water ranged from 0.16 to 0.75 mg/litre, and from 0.09 to
    0.42 mg/litre, respectively. Aluminium concentrations in plankton
    ranged from 6.53 to 49.81 mg/kg, while those in various fish tissues
    ranged from 0.07 to 6.25 mg/kg with the highest levels concentrated in
    the gills. The aluminium concentrations measured in the fish were not
    significantly different from those analysed in fish from untreated
    lakes. Berg & Burns (1985) compared the aluminium concentrations in
    fish tissues from a lake receiving water treatment plant sludge
    containing aluminium hydroxide with a control lake. Both lakes had pH
    values in the range 7.0 to 8.0. Dissolved aluminium was 0.1 mg/litre
    in the treated lake and < 0.1 mg/litre in the control lake. Aluminium
    was found in all tissues of all fish analysed. Liver, kidney and gill
    samples from channel catfish ( Ictalurus punctatus) taken from the
    polluted lake contained significantly more aluminium than those from
    the control lake. For catfish brain and muscle, and for all tissues
    from largemouth bass ( Micropterus salmoides) and gizzard shad
    ( Dorosoma cepedianum) there were no significant differences.
    Aluminium concentrations ranged from 60.8 to 1808.9 mg/kg; the highest
    concentrations were found in the liver and brain.

         Karlsson-Norrgren et al. (1986a) collected and analysed brown
    trout ( Salmo trutta) from two fish farms within acid-susceptible
    areas in Sweden using lime-treated waters. Preliming, the water had a
    pH of 4.6 to 4.7, with total and labile aluminium concentrations of
    390-516 and 270-300 µg/litre, respectively. The post-liming water
    quality (to the hatchery) was 208-261 µg/litre as total aluminium and
    12-80 µg/litre as labile aluminium. Trout from a third non-acidified
    location (pH 6.9; total aluminium levels in water 35 µg/litre) were
    also analysed. Aluminium concentrations ranged from 89.3 mg/kg (wet
    weight) for gills to 0.8 mg/kg for muscle in fish from acid-
    susceptible areas. Fish from the control area contained aluminium
    ranging from 2.6 mg/kg in the intestine to 0.6 mg/kg in muscle, while
    levels in the gills were 1.9 mg/kg.

         Hellou et al. (1992a) analysed muscle samples from the bluefin
    tuna ( Thunnus thynnus) collected off the cost of Newfoundland,
    Canada, in 1990. Aluminium concentrations ranged from 0.4 to 1.9 µg/g
    dry weight with a mean value of 1.0 µg/g. Hellou et al. (1992b) found

    aluminium concentrations of < 1 to 8 µg/g dry weight in muscle, liver
    and ovaries of cod ( Gadus morhua) sampled from several sites off the
    coast of Newfoundland during 1990 and 1991.

         Wren et al. (1983) analysed fish, bird and mammal muscle from
    Tadenac Lake (a Precambrian Shield lake), Ontario, Canada, and its
    surrounding area. The lake had a pH of 7.1 and contained 47 400 mg
    aluminium/kg in the sediment. Mean aluminium concentrations ranged
    from 1.7 to 2.8 mg/kg (wet weight) for fish and from 2.5 to 5.2 mg/kg
    for birds and mammals.

    5.2  Occupational exposure

         The levels of aluminium to which workers are exposed vary greatly
    according to the type of industry and whether adequate industrial
    hygiene practices are adhered to. Most studies have dealt with
    inhalation of aluminium-containing dust particles rather than
    aluminium  per se. Some, however, have utilized urinary aluminium
    determinations as an indicator of exposure (Sjögren et al., 1983;
    Gitelman et al., 1995). Utilizing such a technique for exposure is
    essential, since it is rare for a worker to be exposed solely to
    aluminium but rather to a mixture of aluminium-containing dusts and
    chemicals.

         Occupational exposure limits for aluminium fumes and dust have
    been developed in many countries. Time-weighted averages of 5 mg/m3
    (respirable dust) and 10 mg/m3 (total dust) have generally been
    accepted. However, an occupational exposure limit of 1 mg/m3
    calculated as aluminium has been proposed in Sweden regarding
    aluminium-containing respirable fumes (Sjögren & Ekinder, 1992).

         Given the minimal amount of data on actual aluminium levels in
    workplace air, it is difficult to estimate a daily exposure from the
    occupational setting. Based on a recent publication, aluminium process
    and production workers are generally exposed to less than 1 mg per 8-h
    shift, assuming 10 m3 inhaled per shift (Gitelman et al., 1995). It
    should be noted that, in some occupations and under less than optimal
    industrial hygiene practices, occupational exposures to aluminium
    could be higher. Welders performing metal-inert gas welding have been
    exposed to 4 mg/m3 (calculated as aluminium) and these particles are
    generally less than 1 µm (Sjögren & Ulfvarson, 1985; Sjögren et al.,
    1985). Assuming 10 m3 inhaled per shift, this implies an exposure of
    40 mg per shift.

         Occupational exposures have been reported as total dust or
    particulate matter: e.g., potroom workers, 1.67 mg/m3 (Kongerud &
    Samuelsen, 1991); production of abrasives, 0.2 to 44.6 mg aluminium
    oxide/m3 (Jederlinic et al., 1990); MIG welders, 10 mg/m3; TIG
    welders, 1 mg/m3; respirable particles with a mean aluminium content

    of 39% (Ulfvarson, 1981; Sjögren et al., 1985) and aluminium soldering
    of aluminium cables, 1.1 mg/m3 respirable dust decreasing to
    0.7 mg/m3 after installation of a vacuum collection system
    (Hjortsbert, 1994).

    5.3  General population exposures

    5.3.1  Air

         Pulmonary exposure to aluminium is determined by air
    concentration, particulate size and ventilatory volume. Air
    concentrations vary between low levels in rural settings
    (20-500 ng/m3) and higher levels in urban settings
    (1000-6000 ng/m3) (see Table 8). Particles larger than 5-10 µm
    diameter tend to be removed from inhaled air and penetrate poorly into
    the lungs. Humans living in an urban area with ambient aluminium
    concentrations of about 2000 ng/m3, particle size < 5 µm and a
    ventilatory volume of 20 m3/day would be exposed to 40 µg
    aluminium/day by inhalation.

    5.3.2  Food and beverages

         Since aluminium is a major component of the earth's crust, it is
    naturally present in varying amounts in most food-stuffs consumed. The
    actual concentration in food and beverages from various countries will
    vary widely depending upon the food product, the type of processing
    used and, in particular, the levels of aluminium-containing food
    additives permitted and the geographical area in which food crops are
    grown. In general, the foods highest in aluminium are those than
    contain aluminium additives (e.g., grain products (flour), processed
    dairy products, infant formulae, etc.). Foods naturally high in
    aluminium include baked potato (skin on), spinach, prune juice and tea
    (Pennington & Schoen, 1995).

         The preparation and storage of food in aluminium vessels, foil or
    cans, may increase the aluminium content, particularly in the case of
    foods that are acidic, salty or alkaline (Greger et al., 1985b; Nagy &
    Nikdel, 1986; Baxter et al., 1988). Preparing acidic foods such as
    tomatoes and rhubarb in aluminium pans was found to lead to a
    significant increase in the level of aluminium in the food (0.5 mg/kg
    wet weight raw tomatoes to 3.3 mg/kg wet weight cooked), whereas only
    a slight increase was noted in similarly prepared rice or potatoes
    (Greger et al., 1985b). Although individual foodstuffs may leach
    aluminium from the vessel, there are indications that aluminium from
    cookware represents only a small fraction of the total dietary intake
    (Kupchella & Syty, 1980; Savory et al., 1987).

         The total intake of aluminium from food and beverages (excluding
    drinking-water) in several countries is given in Table 12. All
    estimates are less than 15 mg/day, with the lower values probably
    reflecting a lower use of aluminium additives in the preparation of
    cereal grain products (bread, etc.) (UK MAFF, 1993).

        Table 12.  Estimated average dietary intake of aluminium in various countries
                                                                                     

    Country        Method of      Estimated intake of           Reference
                   samplinga      aluminium
                                  (mg/day)
                                                                                     

    Australia      MB             2.4 (male)                    NFA (1993)
                                  1.9 (female)

    Canada         MB             0.08-0.69b (infants)          Dabeka &
                                                                McKenzie (1992)

    Finland        TD             6.7                           Varo &
                                                                Koivistoinen (1980)

    Germany        MB             11.0 (males)                  Treptow &
                   MB             8.0 (females)                 Askar (1987)
                   DD             0.78 (5-8 years old)          Wilhelm et al.
                                                                (1995)

    Japan          TD             4.5                           Teraoka et al.
                                                                (1981)

    Netherlands    DD             3.1 (mean male and female)    Ellen et al. (1990)

    Sweden         DD             13.0 (female)                 Jorhem &
                                                                Haegglund (1992)

    Switzerland    DD             4.4                           Knutti &
                                                                Zimmerli (1985)

    UK             TD             0.03-0.05 (4-month infant)c   UK MAFF (1993)
                                  0.27-0.53 (4-month infant)d
                   TD             3.9

    USA            TD             0.7 (6-11 month old infant)   Pennington &
                                  6.5 (6 years old)             Schoen (1995)
                                  11.5 (14-16 year old male)
                                  7.1 (adult female)
                                  8.2 (adult male)
                                                                                     

    a    MB = Market basket survey; TD = Total diet study; DD = Duplicate diet study
    b    Range represents intake of an infant (0-1 month old) fed cow's milk to that
         for an infant (1-3 month old) fed exclusively soya-based formulae
    c    Range for infants fed cow's milk-based formulae
    d    Range for infants fed soya-based formulae
    
    5.3.3  Drinking-water

         Aluminium levels in drinking-water, whether distributed through
    household plumbing or as bottled water, vary according to the natural
    levels found in the source and whether aluminium flocculants were used
    during the purification process. An international drinking-water
    guideline for aluminium was based on aesthetic rather than health
    grounds (WHO, 1993).

         Results from extensive monitoring of drinking-water supplies have
    been obtained from Germany (Wilhelm & Idel, 1995), Ontario Canada
    (OMEE, 1995), and the United Kingdom (UK MAFF, 1993).

         In Germany, levels of aluminium in public water supplies averaged
    (median) 10 µg/litre in the western region while 2.7% of public
    supplies in the eastern region exceeded 200 µg/litre. It was estimated
    that 500 000 people were exposed to these high levels. Aluminium
    levels of up to 10 000 µg/litre were reported in drinking-water from
    private wells in areas where the soil had low buffering capacity and
    was subjected to high acidic stress (Mühlenberg, 1990; Wilhelm & Idel,
    1995).

         In a province-wide survey of the aluminium content of public
    water supplies in Ontario, Canada, approximately 75% of all average
    levels in 1993 and 1994 were less than 100 µg/litre, the present
    operational guideline for Ontario (OMEE, 1995). The range of average
    values was 40 to 851 µg/litre.

         A large monitoring programme in 1991 by the water companies in
    the United Kingdom (75 305 samples) reported that only 553 (0.7%)
    exceeded the United Kingdom aluminium standard of 200 µg/litre (UK
    MAFF, 1993). Drinking-water would add about 400 µg aluminium to the
    daily intake, assuming a consumption of 2 litres water daily at the
    aesthetic guideline value of 200 µg/litre (WHO, 1993). From the
    monitoring data discussed above and normal intakes of water, a more
    realistic intake would be at or below 200 µg/day from monitored
    municipal supplies.

    5.3.4  Miscellaneous exposures

         The use of antacids and buffered analgesics may result in large
    intakes of aluminium, far in excess of that normally consumed in food
    (Shore & Wyatt, 1983; Lione, 1983; Schenck et al., 1989). It has been
    estimated that daily doses of aluminium in antacids and buffered
    analgesics range from 840 to 5000 mg and 130 to 730 mg per day,
    respectively (Lione, 1983). These are approximately two to three
    orders of magnitude greater than normal dietary intakes (see Table 12)
    and well in excess of the recommended provisional tolerable weekly
    intake (PTWI) of 420 mg for a 60-kg adult (FAO/WHO, 1989).

         Aluminium compounds are widely used in the preparation of
    cosmetics, particularly in antiperspirants (Sorenson et al., 1974).
    However, there are no reliable data supporting dermal absorption from
    such products.

    5.3.5  Total human intake of aluminium from all environmental pathways

         In calculating total human exposures one must be aware of the
    quality of the sampling and analytical procedures, particularly when
    using data from earlier studies. Total intake of aluminium must
    consider all routes of exposure, i.e. inhalation, oral and dermal.

         For humans, non-occupationally exposed to aluminium, oral intake
    of aluminium represents the major route of exposure. As shown in Table
    12 the total daily intake of aluminium in adults ranges from 2.5 to
    13 mg/day, depending upon the country of origin as well as the age and
    sex of the subject. The variation reflects different dietary habits as
    well as the level of additives used in food processing. For infants
    (under 6 months) daily intakes range from 0.27 to 0.53 mg/day for
    those consuming soya-based formulae and 0.03 to 0.05 mg/day for
    infants consuming cow's milk formulae (UK MAFF, 1993). Similar values
    were reported from Canada (respectively, 0.08 and 0.69) (Dabeka &
    McKenzie, 1990). Aluminium intake from breast milk has been calculated
    to be < 0.04 mg/day (UK MAFF, 1993).

         In conclusion, the total intake of aluminium by the general
    population varies between 2.5 and 13 mg/day. In most countries over
    95% of this comes from food and less than 1% from airborne aluminium.
    As noted in section 5.3.4, these intakes can be increased greatly
    (10 to 100 times) through the use of aluminium-containing antacids and
    buffered analgesics. Total daily exposure to aluminium from all
    sources, other than medicines, and for all age groups has been shown
    to be less than the PTWI of 1 mg/kg per day (WHO, 1993).

    5.3.6  Aluminium uptake

         In view of the fact that over 95% of the normal daily intake of
    aluminium comes from food and water, uptake from the gastrointestinal
    tract will play a major role in determining tissue levels of the
    metal. The ratio of intake to uptake will be a major determinant in
    the risk of orally ingested aluminium to humans. Factors affecting
    gastrointestinal absorption of aluminium are discussed in section
    6.1.2.

         Recent studies of the bioavailability and uptake of aluminium in
    human volunteers have employed the radioactive isotope 26Al, which
    may be detected at very low masses, i.e. 5 × 10-15 g using accelerator
    mass spectrometry (AMS). The first of these was a study by Day et al.
    (1991), who measured the uptake of aluminium in one volunteer
    following the ingestion of 1.1 µg of the isotope in sodium citrate.
    For this study aluminium uptake was assessed by extrapolation from a

    single measurement of 26Al in blood plasma 6 h after administration.
    The fraction of absorbed aluminium was estimated to be 1%. Later, the
    same technique was employed by Day et al. (1994) to estimate aluminium
    uptake from orange juice (with or without added silicate) in control
    subjects and Downśs syndrome patients. For the normal subjects uptake
    factors ranging from 0.04 to 1.5 × 10-4 were calculated. The addition
    of silica reduced the uptake by a factor of about 7. In the Downśs
    syndrome patients, many of whom develop AD, uptake was approximately 5
    times higher than in controls (4.7 × 10-4 compared with 0.91 × 10-4).

         Most recently, human bioavailability studies have been undertaken
    by Priest (1994) using a more vigorous methodology, employing the
    collection of blood samples and total excreta for a period of up to a
    week after a single administration of the aluminium compound. The
    results obtained showed significant intersubject variability in the
    extent and timing of aluminium absorption and indicated that the
    method employed by Day et al. (1994) was of limited utility. Two main
    studies were undertaken. The first was a study of the uptake of
    aluminium, as aluminium citrate, aluminium hydroxide and aluminium
    hydroxide in the presence of citrate, from the gut following the
    administration of 100 mg aluminium by gastric tube (Priest, 1994). The
    measured fractional uptakes were as follows: 5 × 10-3 for aluminium
    as citrate; 1.04 × 10-4 for aluminium hydroxide; 1.36 × 10-3 for
    hydroxide in the presence of sodium citrate. This study demonstrated
    the greater bioavailability of the citrate complex and the ability of
    citrate to enhance the uptake of aluminium taken in another chemical
    form. The second study measured the fractional uptake of aluminium
    from drinking-water using a similar technique, but different
    volunteers (Priest et al., 1995a,b,c). The measured uptake fraction
    was 2.2 × 10-4. It was concluded that members of the public, drinking
    1.5 litres per day of water containing 100 µg aluminium/litre, would
    absorb from this source about 3% of their total daily aluminium
    uptake. This result suggests that drinking-water, under most
    circumstances, is likely to be a minor source of aluminium for humans.

    6.  KINETICS AND METABOLISM IN LABORATORY ANIMALS

         Investigations into the kinetics of aluminium include estimation
    of typical toxicokinetic parameters as well as issues specifically
    related to the chemistry of aluminium and its compounds. Many studies
    have been performed at high-dose levels. Since there are indications
    that the toxicokinetics of aluminium are dose-dependent, these results
    should be interpreted cautiously with respect to their relevance to
    humans (Wilhelm et al., 1990). In addition, owing to large variations
    in experimental protocols employed, many data-sets are not comparable,
    making the interpretation of these data very difficult.

    6.1  Absorption

    6.1.1  Animal studies

    6.1.1.1  Inhalation exposure

         Reports of systematic studies of the pulmonary absorption of
    aluminium in experimental animals have not been identified. However,
    aluminium has been detected in organs other than the lung following
    some inhalation experiments.

         In rats and guinea-pigs exposed for 24 months to 0.25-25 mg/m3
    aluminium chlorohydrate, aluminium was present primarily in the lungs.
    The only other organs with significant concentrations of aluminium
    were the peribronchial lymph nodes in guinea-pigs and the adrenal
    glands in rats (Stone et al., 1979).

         In New Zealand rabbits exposed to 0.56 mg aluminium/m3 for
    5 months, there was a 2.5 fold increase in the aluminium content of
    the brain (10.1 mg/kg dry weight) compared to control (4.1 mg/kg dry
    weight) animals, while the concentration of aluminium in serum was
    only slightly increased (Röllin et al., 1991a).

    6.1.1.2  Oral administration

         The gastrointestinal tract is the most important port of entry.
    In addition, inhaled aluminium aerosols that are cleared from the
    surface of the mucous membranes of the respiratory tract by action of
    the mucociliary escalator are swallowed and thus may be absorbed from
    the gastrointestinal tract.

         Based on available data, absorption via the gastrointestinal
    tract in experimental animals is generally less than 1%. However,
    estimates of the proportion absorbed vary considerably, in part, as a
    result of the different conditions of exposure (i.e., use of citrate
    versus hydroxide salts, etc.) to various compounds (see Table 13).
    Values from balance studies are probably overestimates, since the
    amount of aluminium retained in the gut was probably calculated as
    absorbed aluminium. The

    rather high value obtained by Gupta et al. (1986) has not been
    confirmed. Some studies on aluminium uptake after oral administration
    of various compounds are summarized in Table 14 and Table 15, where
    uptake has been measured by blood aluminium levels or tissue levels.

         Results from studies on isolated intestinal organ systems
    support the findings of low absorption rates of aluminium from the
    gastrointestinal tract (Jäger et al., 1991). Also, although not
    directly applicable to the human situation, experiments where
    aluminium salts have been given to rats and mice by interperitoneal
    injection further support the low amount of aluminium absorbed from
    the gastrointestinal tract (Leblondel & Allain, 1980; Muller et al.,
    1992; Greger & Powers, 1992). For example, blood aluminium levels in
    rats given 10 mg aluminium chloride/kg body weight per day for 11 days
    were about 15 times greater than controls (20 µg/litre compared to
    300 µg/litre) (Muller et al., 1992). In contrast, in rats fed 0.1%
    aluminium chloride in the diet for up to 25 days there was only a 22%
    increase in blood aluminium levels (0.91 mg/litre compared to
    1.11 mg/litre) (Mayor et al., 1977).

         The mechanism of intestinal absorption of aluminium is fairly
    complex and not yet fully elucidated (van der Voet, 1992). This
    complexity results from the very particular chemical properties of the
    element, i.e. (1) great variability of solubility at different pH
    values, amphoteric character, and formation of various chemical
    species depending on the pH, the ionic strength and the presence of
    complexing agents in the intestine (Martin, 1992), and (2) the complex
    organisation of the mammalian digestive tract where the chyme passes
    through a sequence of chemical environments differing in pH, presence
    of secretory products, etc. In addition, the different parts of the
    intestine may be distinct with regard to their resorptive properties
    and may be influenced by variation in physiological conditions. There
    are indications that aluminium interacts with the gastrointestinal
    calcium transport system (Adler & Berlyne, 1985; Provan & Yokel, 1988)
    and with transferrin-mediated iron uptake (van der Voet & de Wolff,
    1987; Jäger et al., 1991). There is consistent evidence that
    absorption of aluminium increases in the presence of citrate (Slanina
    et al., 1986; Froment et al., 1989a,b). There are some data suggesting
    that uptake increases after fasting (Walton et al., 1994).

    6.1.1.3  Dermal

         Aluminium absorption via the skin in animals has not been
    studied.

        Table 13.  Gastrointestinal absorption of aluminium compoundsa
                                                                                                                                              

    Species  Dose                    Form                  f (%)b      Methodc     Remarks                             References
                                                                                                                                              

    Rat      8.1 mg/kg               AlCl3                 27          3                                               Gupta et al. (1986)

    Rat      1; 12 mg Al/kg          lactate               0.18        2                                               Wilhelm et al. (1992)

    Rat      1; 12 mg Al/kg          lactate               0.02        3                                               Wilhelm et al. (1992)

    Rat      35 mg Al/kg             sucralfate, lactate   0.015       2                                               Froment et al. (1989a)

    Rat      35 mg Al/kg             AlCl3                 0.037       2                                               Froment et al. (1989a)

    Rat      1.20 mmol Al/kg         lactate               0.037       2                                               Froment et al. (1989a)

    Rat      3.8 ng 26Al and                               0.02        2                                               Jouhanneau et al.
             63 ng 27Al in citrate                                                                                     (1993)
             and citrate-free                              0.02        2
             solutions

    Rat      1; 12 mg Al/kg          lactate               0.18        2                                               Wilhelm et al. (1992)

    Rat      1; 12 mg Al/kg          lactate               0.02        3                                               Wilhelm et al. (1992)

    Rat      35 mg Al/kg             sucralfate            0.015       2                                               Froment et al. (1989a,b)

    Rat      35 mg Al/kg             Al(OH)3               0.015       2                                               Froment et al. (1989a,b)

    Rat      35 mg Al/kg             AlCl3                 0.037       2                                               Froment et al. (1989a,b)
                                                                                                                                              

    Table 13.  (Con't)
                                                                                                                                              

    Species  Dose                    Form                  f (%)b      Methodc     Remarks                             References
                                                                                                                                              

    Rabbit   10.8, 540 mg            lactate               0.70-1.9    3           no significant influence            Yokel & McNamara
             Al/kg                                                                 of dose                             (1985)

    Rabbit   2.5-10 mmol/kg          various               0.3-2.2     3           absorption: soluble>insoluble;      Yokel & McNamara
                                                                                   minor differences between           (1989)
                                                                                   organic and inorganic forms;
                                                                                   best bioavailability, citrate;
                                                                                   minor influence of renal
                                                                                   impairment

    Sheep    1-2 g/day               Al2(SO4)3;            2-15        1           order of absorption:                Allen & Fontenot
                                     Al-citrate;                                   Al2(SO4)3>Al citrate>AlCl3          (1984)
                                     AlCl3
                                                                                                                                              

    a    Modified from: Wilhelm et al. (1990)
    b    f = mass Al absorbed + mass Al ingested
    c    1 = balance study; 2 = estimation based on urinary excretion; 3 = comparison of areas under plasma aluminium concentration after oral
         and intravenous application

    Table 14.  Tissue aluminium concentrations in experimental animals administered aluminium compounds orallya
                                                                                                                                              

    Species                     Treatment                       Bone                     Brain                    Reference
                                                                                                                                              

    Mouse (BALB/c,              AlCl3, gavage                   n.d.                     n.d.                     Cranmer et al. (1986)
    5-10/group)                 200 mg/kg per day
                                300 mg/kg per day

    Mouse (Swiss, 6/group)      Al lactate, 25 mg Al/kg         (5.3 mg/kg w.w.)         35.3 mg/kg w.w.          Golub et al. (1989)
                                (= control),
                                500 mg Al/kg diet               5.0 mg/kg w.w.           38.3 mg/kg w.w.
                                1000 mg Al/kg diet              6.5 mg/kg w.w.           108.7 mg/kg w.w.

    Rat (8 Wistar)              2835 mg Al/kg in feed,          femur                                             Ondreicka et al. (1966)
                                (as Al2(SO4)3), 24 days         (702 mg/kg w.w.)         (7.1 mg/kg w.w.)
                                                                912 mg/kg w.w.           10.8 mg/kg w.w.

    Rat (juvenile,              aluminium in water              n.d.                     n.d.                     Cann et al. (1979)
    male SD, 8/group)           (1) control
                                (2) 0.32 g Al/litre, 29 days
                                (3) low Ca2+ + Al

    Rat (male SD, 8/group)      100 mg Al/kg b.w.                                        cortex:                  Slanina et al. (1984)
                                6 d/w; by gavage                (0.36 mg/kg w.w.)        (0.013 mg/kg w.w.)
                                Al(OH)3 (9 weeks);              0.41 mg/kg w.w.          0.013 mg/kg w.w.
                                Al citrate (4 weeks);           x 40 increased           0.057 mg/kg w.w.
                                citric acid (4 weeks)           x 20 increased           0.028 mg/kg w.w.

    Rat (male SD, 7/group)      gavage; 3 d/w; 11 week          (0.22 mg/kg w.w.)        (0.016 mg/kg w.w.)       Slanina et al. (1985)
                                Al(OH)3                         0.89 mg/kg w.w.          0.012 mg/kg w.w.
                                Al citrate                      10.7 mg/kg w.w.          0.048 mg/kg w.w.
                                Al(OH)3 + citrate               26.6 mg/kg w.w.          0.092 mg/kg w.w.
                                                                                                                                              

    Table 14.  (Con't)
                                                                                                                                              

    Species                     Treatment                       Bone                     Brain                    Reference
                                                                                                                                              

    Rat (weanling, male         270 mg Al/kg diet, 18 days      tibia: (1.9 mg/kg w.w.)  (0.0 mg/kg w.w.)         Greger et al. (1985a)
    SD, 6/group)                Al(OH)3                         15.6 mg/kg w.w.          2.2 mg/kg w.w.
                                Al palmitate                    15.0 mg/kg w.w.          0.6 mg/kg w.w.
                                Al lactate                      13.0 mg/kg w.w.          1.6 mg/kg w.w.
                                AlPO4                           14.5 mg/kg w.w.          1.3 mg/kg w.w.

    Rat (weanling, male         Al(OH)3 in diet, 67 days        tibia: (4.04 mg/kg)      n.d.                     Greger et al. (1986)
    SD, 9/group)                257 mg Al/kg diet               11.3 mg/kg (3.13 mg/kg)
                                1075 mg Al/kg diet              10.4 mg/kg

    Rat (male SD, 10/group)     Al(NO3)3, in water, 4 w         (5.75 mg/kg w.w.)        (1.4 mg/kg w.w.)         Gómez et al. (1986)
                                375 mg/kg/d                     11.4 mg/kg w.w.          7.7 mg/kg w.w.
                                750 mg/kg/d                     8.5 mg/kg w.w.           10.1 mg/kg w.w.
                                1500 mg/kg/d                    17.7 mg/kg w.w.          7.9 mg/kg w.w.

    Rat (female SD,             Al(NO3)3, oral, 100 d           (17.15 mg/kg w.w.)       (< 0.5 mg/kg w.w.)       Domingo et al. (1987b)
    10/group)                   360 mg/kg w.w.                  75.08 mg/kg w.w.         4.93 mg/kg w.w.
                                720 mg/kg w.w.                  79.18 mg/kg w.w.         2.09 mg/kg w.w.
                                3600 mg/kg w.w.                 56.39 mg/kg w.w.         4.28 mg/kg w.w.

    Rat (SD, weanling           Al(OH)3, in feed, 10 d          femur: (6.8 mg/kg d.w.)  n.d.                     Chan et al. (1988)
    6/group)                    50-60 mg/kg b.w.                8.4 mg/kg d.w.

    Rat (male, weanling SD)     Al(OH)3, 28 d                   tibia:                   n.d.                     Ecelbarger & Greger
                                13 mg Al/kg diet                36 mmol/kg w.w.                                   (1991)
                                  + 5 mmol/kg citrate           36 mmol/kg w.w.
                                41 mg Al/kg diet                50 mmol/kg w.w.
                                  + 5 mmol/kg citrate           69 mmol/kg w.w.
                                                                                                                                              

    Table 14.  (Con't)
                                                                                                                                              

    Species                     Treatment                       Bone                     Brain                    Reference
                                                                                                                                              

    Rat (18 male,               Al(OH)3 in feed, 29 days    tibia: (28.9 mmol/kg w.w.)   n.d.                     Greger & Powers
    weanling SD)                0.39 µmol Al/g diet             52.6 mmol/kg w.w.                                 (1992)
                                aluminium + 4% citrate          74.4 mmol/kg w.w.
                                100 µmol Al/g diet              79.6 mmol/kg w.w.
                                  + 4% citrate

    Rabbit (female NZ,          inhalation exposure             (18.2 mg/kg d.w.)        (4.1 mg/kg d.w.)         Röllin et al. (1991a)
    8/group)                    0.56 mg Al/m3 as Al2O3          22.2 mg/kg d.w.          10.1 mg/kg d.w.
                                8 h/d; 5 d/w; 5 months

    Rabbit (male NZ,            50 g/kg AlCl3, in feed          (n.d.)                   cortex, gray matter:     Thornton et al.
    3-4/group)                  1 month                                                  (n.d.) 3.1 mg/kg d.w.    (1983)
                                ethanol                                                  1.3 mg/kg d.w.
                                aluminium + ethanol                                      3.0 mg/kg d.w.

    Dog                         Al(OH)3 in feed, 3 g/d;         n.d.                     cerebral cortex:         Arieff et al. (1979)
                                5 months                                                 0.77 mg/kg d.w.
                                                                                         2.4 mg/kg d.w.

    Cattle (steer, 6/group)     AlCl3 in feed, 84 d             (n.d.)                   (6.4 mg/kg w.w.)         Valdivia et al.
                                  300 mg/kg                                              7.6 mg/kg w.w.           (1978)
                                  600 mg/kg                                              5.5 mg/kg w.w.
                                 1200 mg/kg                                              7.7 mg/kg w.w.
                                                                                                                                              

         Values in parentheses are normal control values in unexposed animals; b.w. = body weight; d = day; d.w. = dry weight;
         n.d. = not detected; NZ = New Zealand; SD = Sprague-Dawley; w = week; w.w. = wet weight

    Table 15.  Blood aluminium concentrations in experimental animals exposed orally to aluminium compoundsa
                                                                                                                                              

    Species             Sample    Dose                          Duration       Compound            Aluminium concentration  Reference
                                                                                                   (control value)
                                                                                                                                              

    Rat (8 Wistar)      blood     2835 mg Al/kg feed            24 days        Al2(SO4)3           (6.5 mg/kg w.w.)         Ondreicka et al.
                                                                                                   10.8 mg/kg w.w.          (1966)

    Rat (male albino)   serum                                                  Al(OH)3             (0.24 mg/litre)          Berlyne et
                                  150 mg Al/kg/d, gavage                                           0.99 mg/litre            al. (1972)

    Rat (male SD,       serum                                                  AlCl3               (0.91 mg/litre)          Mayor et al.
    8/group)                      0.1% aluminium in feed                                           day 10: 1.12 mg/litre,   (1977)
                                                                                                   day 25: 1.09 mg/litre

    Rat (male SD,       blood                                   11 weeks                           (0.005 mg/kg w.w.)       Slanina et al.
    7/group)                      3 d/w, gavage                                Al(OH)3             0.009 mg/kg w.w.         (1985)
                                                                               Al citrate          0.014 mg/kg w.w.
                                                                               Al(OH)3 + citrate   0.039 mg/kg w.w.

    Rat (male SD,       blood                                                  Al(NO3)3            (3.7 mg/kg w.w.)         Gómez et al.
    10/group)                     375 mg/kg/d                                                      3.1 mg/kg w.w.           (1986)
                                  750 mg/kg/d                                                      2.5 mg/kg w.w.
                                  1500 mg/kg/d, in water                                           3.0 mg/kg w.w.

    Rat (female SD,     blood                                   100 days       Al(NO3)3            (< 0.5 mg/kg)            Domingo et al.
    10/group)                     360 mg/kg w.w.                                                   < 0.5 mg/kg              (1987b)
                                  720 mg/kg w.w.                                                   < 0.5 mg/kg
                                  3600 mg/kg w.w., oral                                            < 0.5 mg/kg

    Rat (18 male,       serum                                   29 days        Al(OH)3             (0.28 µmol/litre)        Greger &
    weanling SD)                  0.39 mmol Al/kg diet                                             0.98 µmol/litre          Powers (1992)
                                  aluminium + 4% citrate                                           1.15 µmol/litre
                                  100 mmol Al/kg diet
                                  + 4% citrate, in feed                                            1.09 µmol/litre
                                                                                                                                              
    Table 15.  (Con't)
                                                                                                                                              

    Species             Sample    Dose                          Duration       Compound            Aluminium concentration  Reference
                                                                                                   (control value)
                                                                                                                                              

    Rat (weanling       serum     160 mg Al/kg d, gavage,       10 days                            (18.8 µg/litre)          Santos et al.
    SD, 4/group)                  1,25-(OH)2-D3                                                    24.3 µg/litre            (1987)
                                  1,25-(OH)2-D3 + Al(OH)3                                          29.5 µg/litre
                                  1,25-(OH)2-D3 + Al citrate                                       16.3 µg/litre

    Rabbit (male        serum                                   1 month                            (5 µg/litre)             Thornton et al.
    NZ, 3-4/group)                50 g/kg in feed                              AlCl3               14 µg/litre              (1983)
                                                                               Al+ethanol          24 µg/litre

    Cattle (steer,      blood                                   84 days        AlCl3               (0.103 mg/litre)         Valdivia et al.
    6/group)                      300 mg/kg                                                        0.118 mg/litre           (1978)
                                  600 mg/kg                                                        0.100 mg/litre
                                  1200 mg/kg, in feed                                              0.120 mg/litre
                                                                                                                                              

    a    1,25-(OH)2-D3 = 1,25-dihydroxy-vitamin D3; d = day; NZ = New Zealand; SD = Sprague-Dawley; w = week; w.w. = wet weight
        6.1.2  Studies in humans

    6.1.2.1  Inhalation exposures

         Studies dealing with the absorption of aluminium compounds in
    humans usually use the blood aluminium concentration or the urinary
    aluminium excretion as a marker of uptake (Schaller & Valentin, 1984;
    Ganrot, 1986). However, part of the aluminium-containing particulates
    deposited in the respiratory tract is cleared from the organ by
    mucociliary action and, when swallowed, enters the digestive tract.
    This means that after inhalation exposure to aluminium compounds not
    all aluminium appearing in the systemic circulation or in the urine
    necessarily arises solely from absorption in the respiratory tract.

         "Insoluble" particulates may be slowly dissolved and thus enter
    the blood circulation. Owing to the chemical properties of aluminium,
    the absorption of aluminium metal or its compounds by the respiratory
    system depends on the aluminium species inhaled and the biological
    environment in the tissue compartment where they are deposited
    (Martin, 1992).

         There is evidence from a number of reports that even aluminium
    compounds that are almost insoluble in water are bioavailable when
    introduced into the respiratory system. For example, increased urinary
    concentrations have been observed in aluminium welders and aluminium
    flake and powder producers after exposure to relatively insoluble
    particulate matter and metallic fumes and dusts. The levels of tissue
    aluminium after inhalation exposures are given in Table 16. When
    comparing the analytical results given in these tables, one has to
    keep in mind, however, that the analytical precision of the aluminium
    determination has been hampered by the potential for contamination
    during sampling and processing in view of the ubiquitous presence of
    the element (Steinegger et al., 1990). Analytical techniques for
    determination of aluminium have been improved considerably during
    recent years (see Chapter 2).

    6.1.2.2  Oral administration

         In view of the fact that over 95% of the normal daily intake of
    aluminium comes from food and water, uptake from the gastrointestinal
    tract will play a major role in determining tissue levels of the
    metal.

         The mechanism of gastrointestinal absorption of aluminium is
    fairly complex and has not yet been fully elucidated (van der Voet,
    1992). This complexity results from (1) the unique chemical properties
    of the element, particularly its amphoteric character, leading to
    marked variability in solubility at different pH values and the
    formation of various chemical species in the gut depending on the pH,
    the ionic

    strength and the presence of complexing agents (Martin, 1992), and (2)
    the complex organization of the mammalian digestive tract where the
    chyme passes through a sequence of chemical environments differing
    greatly in pH, presence of secretory products, etc. In addition, the
    different parts of the intestine may be distinct with regard to their
    absorptive and resorptive properties with respect to aluminium.

         Aluminium species may be modified in the gut prior to absorption
    (Skalsky & Carchman, 1983; Ganrot, 1986; Martin, 1986, 1992).
    Quantitatively the intraluminal absorption depends upon the amount of
    the chemical species present in the gut lumen, in the blood, and in
    the interstitial fluid. Absorption is influenced by the presence of
    other complexing ligands (citrate, lactate, etc.) and competing ions
    (e.g., iron, silicon). Other factors proposed to influence absorption
    include: age; renal function; and iron and calcium status (Birchall,
    1991; van der Voet, 1992; Edwardson, 1993).

         To date, research concerning the intestinal absorption of
    aluminium in humans has been mainly guided by clinical problems and
    has used a variety of physiological states and chemical conditions.
    Owing to the large variations in experimental conditions, many results
    are not comparable and interpretation of their relevance to the health
    population becomes very difficult or impossible.

         Gastrointestinal absorption of aluminium in humans ingesting
    antacids or phosphate binders is well documented. Variable quantities
    of Al(OH)3 or Al2(CO3)3 given to volunteers or patients for
    different periods of time resulted in significant increases in plasma
    and/or urinary aluminium concentrations (Cam et al., 1976; Kaehny et
    al., 1977a; Recker et al., 1977; Gorsky et al., 1979; Mauras et al.,
    1982; Herzog et al., 1982; Greger & Baier, 1983a). Administration of
    the insoluble AlPO4 did not significantly alter blood and urinary
    aluminium levels (Kaehny et al., 1977a). The results of these studies
    are summarized in Tables 16 and 17. It must be emphasized, however,
    where compounds are poorly bioavailable, the expected incremental
    increase in the plasma aluminium level after exposure may be lower
    than can be detected against normal plasma aluminium levels.

         Recent studies of the bioavailability and uptake of aluminium in
    human volunteers have employed the radioactive isotope 26Al, which
    may be detected at very low concentrations (5 × 10-15 g) using
    accelerator mass spectrometry (AMS). The first of these was a study by
    Day et al. (1991) who measured the uptake of aluminium in one
    volunteer following the ingestion of 1.1 µg of the isotope in sodium
    citrate. For this study aluminium uptake was assessed by extrapolation
    from a single measurement of 26Al in blood plasma 6 h after 

        Table 16.  Blood and urine aluminium concentrations in humans after oral ingestion of aluminium compoundsa
                                                                                                                                              

    Subjects and                  Aluminium concentration     Aluminium concentration    Remarks                         Reference
    treatment                     in blood (µg/litre)         in urine (µg/litre)
                                                                                                                                              

    5 normal subjects,            not specified               not specified              Al absorption                   Cam et al.(1976)
    2 patients with CRF;
    Al(OH)3 antacids,                                                                    normal: 0.3-3.6 mmol/day
    86-91 mmol/day                                                                       CRF: 3.3-9.1 mmol/day

    Normal subjects,              not detected                (85.8 µg/day)                                              Recker et al. (1977)
    Al(OH)3, oral, 3.8 g                                      increased by 4-10 times
    Al/day for 3 days

    Normal subjects,              plasma:                     (8-16)                     cumulative increase in          Kaehny et al. (1977a)
    2.2 g Al for 3 days           (6-7)                                                  excretion (µg)
    Al(OH)3                       17                          176-325                    730 ± 487
    Al2(CO3)3                     14                          51-355                     567 ± 437
    Al(OH)2-aminoacetate          17                          243-726                    1430 ± 1157
    AlPO4                         9                           52-60                      123 ± 77

    Normal subjects               6.2 (serum)                 not detected                                               Marsden et al.
    CRF                           13.4 (serum)                                                                           (1979)
    CRF + Al                      34.1

    Normal subjects, antacids     plasma Al:                  urinary Al excretion:      Al balance positive during      Gorsky et al. (1979)
    taken orally, 23-313          2-fold increase             2- to 6-fold increase      Al administration
    mg/day for 18-30 days

    Al-hydrocarbonate             (before Al: 8.35)           (before Al: 6.35)          serum aluminium in dialysed     Mauras et al.
    (Lithiagel), oral, 1.84 g     3-day Al: 15.9              3-day Al: 430.8            patients treated with Aludrox:  (1982)
    Al/day; 5 days                5-day Al: 14.8              5-day Al: 262.5            6-254 µg/litre
                                  after 1 week Al: 8.0        after 1 week Al: 12.2
                                                                                                                                              

    Table 16.  (Con't)
                                                                                                                                              

    Subjects and                  Aluminium concentration     Aluminium concentration    Remarks                         Reference
    treatment                     in blood (µg/litre)         in urine (µg/litre)
                                                                                                                                              

    Al-supplemented diet          serum (before: 4)           urinary excretion:         normalized to creatinine        Greger & Baier
    control: 4.6 mg Al/day        control: 4                  control: 35-36 µg/day      control: 20 mg/kg               (1983a)
    test: 125 mg Al/day           test: 7                     test: 105-129 µg/day       test: 57-72 mg/kg

    12 subjects                   serum Al                                                                               Herzog et al.
    (normal young) given          placebo: 0.3-0.9            placebo: 1.0-3.0                                           (1982)
    280 nM Mg + 190 nM            test: 0.8-1.1               test: 3.6-20.2
    Al/day for 4 weeks

    CRF,                          (3.4 plasma)                                           no correlation with Al          Wilhelm et al.
    on home dialysis              37.7-68.7                                              concentration in hair           (1989)
    on CAPD                       33.9-45.0
                                                                                                                                              

    a    control values are given in parentheses
         CAPD = continuous ambulatory peritoneal dialysis; CRF = chronic renal failure

    Table 17.  Tissue aluminium concentrations (mg/kg) in humans exposed to aluminium compoundsa
                                                                                                                                              

    Subjects and          Bone              Muscle       Kidney      Liver       Lung           Brain           Remarks               Reference
    treatment
                                                                                                                                              

    Normal                n.d.              1.55 d.w.    2.02 d.w.   2.4 d.w.    122.5 d.w.     1.4 d.w.        adrenal: 4.8 d.w.     Tipton &
    adult                                                                                                       spleen: 3.7 d.w.      Cook
                                                                                                                duod.: 4.56 d.w.      (1963)
                                                                                                                jejun.: 2.84 d.w.
                                                                                                                ileum: 9.86 d.w.

    Healthy               hard water area:  0.5 w.w.     whole       2.6 w.w.    18.2 w.w.      whole brain:                          Hamilton
    human                 73.4 w.w.                      kidney:                                0.5 w.w.                              et al.
    controls              soft water area:               0.4 w.w.                               frontal lobe:                         (1973)
                          60 w.w.                        cortex:                                0.05 w.w.
                                                         0.4 w.w.                               basal ganglia:
                                                         medulla:                               0.07 w.w.
                                                         0.3 w.w.

    Normal males          < 15 d.w.         n.d.         11 d.w.     19 d.w.     230 d.w.       n.d.            spleen: (22 d.w.)     Teraoka
    Stonemason            n.d.              n.d.         16 d.w.     130 d.w.    2000 d.w.                      520 d.w.              (1981)
                                                                                                                heart: (11 d.w.)
                                                                                                                2.0 d.w.
                                                                                                                adrenal: (37 d.w.)
                                                                                                                n.d.

    Ball-mill room        30 w.w.           n.d.         n.d.        90 w.w.     upper lobe:    5 w.w.                                McLaughlin
    worker in                                                                    430 w.w.                                             et al.
    aluminium powder                                                             lower lobe:                                          (1962)
    factory                                                                      340 w.w.

    Surgical and          n.d.              no Al        n.d.        n.d.        n.d.           n.d.            no Al intake:         Cann et
    autopsy specimen                        intake:                                                             PT: 13 d.w.           al. (1979)
    (hyperparathyroidism)                   2.0 d.w.                                                            thy: 3.5 d.w.
                                            Al intake:                                                          Al intake:
                                            7.6 d.w.                                                            PT: 78 d.w.
                                                                                                                thy: 8.8 d.w.
                                                                                                                                              

    Table 17.  (Con't)
                                                                                                                                              

    Subjects and          Bone              Muscle       Kidney      Liver       Lung           Brain           Remarks               Reference
    treatment
                                                                                                                                              

    Normal controls:      10.6              23.6         17.5        15.8        97.2           11.9            spleen: 17.2          Flendrig
    uraemia, non-dial:    6.4               24.7         33.8        19.7        142.3          n.d.                   25.1           et al.
    uraemia, dial:        23.5              39.6         44.1        32.9        127.1          12.1                   37.9           (1976)
    DES:                  272.7             13.8         156.5       610.2       99.6           66.1                  454.5

    DES                   cortical bone:                 n.d.        n.d.        n.d.           grey matter:    brain white           Alfrey et
    normal control        (3.88)            (1.22)                                              (2.18)          matter: (2.00)        al.
    uraemia/dial          46.83             DES: 23.6                                           non-DES: 6.5    non-DES: 3.81         (1976)b
    uraemia/non-dial      8.4               non-DES:                                            DES: 24.98      DES: 5.59
                          trabecular        10.24
                          bone: (2.39)
                          98.48
                          37.4

    Iliac bone                              n.d.         n.d.        n.d.        n.d.           n.d.            correlation of        Ellis et
    (biopsy or                                                                                                  duration of           al.
    autopsy spec.)                                                                                              dialysis and          (1979)
    control               5.7 ash                                                                               bone Al
    uraemia, non-dial     13.6 ash
    dial                  151.8 ash
    dial + transpl        92 ash

    Patients                                             n.d.                                   grey matter:    spleen:               Alfrey
    healthy controls      3.3 d.w.          1.2 d.w.                 4.0 d.w.    56 d.w.        2.2 d.w.        3.8 d.w.              (1980)
    uraemia, non-dial     27 d.w.           2.6 d.w.                 25.5 d.w.   75 d.w.        4.1 d.w.        35 d.w.
    uraemia, dial         115 d.w.          9.1 d.w.                 160 d.w.    89 d.w.        8.5 d.w.        243 d.w.
    DES                   281 d.w.          15 d.w.                  301 d.w.    215 d.w.       24.5 d.w.       493 d.w.
                                                                                                                                              

    Table 17.  (Con't)
                                                                                                                                              

    Subjects and          Bone              Muscle       Kidney      Liver       Lung           Brain           Remarks               Reference
    treatment
                                                                                                                                              

    Uraemia + dial                          n.d.         n.d.        n.d.        n.d.           n.d.                                  Hodsman
    normal control        2.4 d.w.                                                                                                    et al.
    osteomalacia          175 d.w.                                                                                                    (1982)
    osteitis fibrosa      46 d.w.
    mixed lesions         81 d.w.
    mild lesions          67 d.w.

    Normal, necropsy      n.d.              n.d.         n.d.        n.d.        n.d.           cortex:                               Crapper
                                                                                                0.23-2.7 d.w.                         et al.
                                                                                                white matter:                         (1973)
                                                                                                0.6-1.1 d.w.

    Normal adult          n.d.              n.d.         n.d.        n.d.        n.d.           1.9 d.w.                              Crapper
    infant                                                                                      0.7 d.w.                              et al.
    fetus                                                                                       0.7 d.w.                              (1976)

    Normal controls       n.d.              n.d.         n.d.        n.d.        n.d.           2.5 d.w.        whole brain           McDermott
                                                                                                5.6 d.w.        hippocampus           et al.
                                                                                                2.4 d.w.        frontal cortex        (1979)
                                                                                                1.4 d.w.        temporal cortex
                                                                                                2.9 d.w.        parietal cortex
                                                                                                2.9 d.w.        occipital cortex
                                                                                                2.6 d.w.        cerebellum
                                                                                                1.5 d.w.        corpus callosum
                                                                                                4.1 d.w.        mininges
                                                                                                1.3 d.w.        isolated neurons

    Normal adult          n.d.              n.d.         n.d.        n.d.        n.d.           0.467 w.w.                            Markesbery
    normal infant                                                                               0.298 d.w.                            et al.
                                                                                                                                      (1981)
                                                                                                                                              

    Table 17.  (Con't)
                                                                                                                                              

    Subjects and          Bone              Muscle       Kidney      Liver       Lung           Brain           Remarks               Reference
    treatment
                                                                                                                                              

    Al welders (2)        (0.6-5 d.w.)      n.d.         n.d.        n.d.        n.d.           n.d.            also increased:       Elinder et
    welding fumes         18-29 d.w.                                                                            blood and             al. (1991)
                                                                                                                urinary Al
                                                                                                                concentration

    CRF,                                                                                                        no correlation        Wilhelm
    cumulative            (median values)                                                                       with Al               et al.
    oral Al intake:                                                                                             concentration         (1989)
    0 kg                  5.3                                                                                   in hair:
    < 0.25 kg             47.5                                                                                  control: 2.6
    0.25 to 0.5 kg        56.7                                                                                  dial: 1.6-5.5
    0.5 to 1.0 kg         62.6                                                                                                        
    1.0 to 5.0 kg         133.4

    Controls              18.8 w.w.         n.d.         n.d.        n.d.        n.d.           n.d.            no differences        Burnel et
    (surgical                                                                                                   between cortical      al. (1982)
    specimens)                                                                                                  and medullary
    CRF                   6-130 w.w.                                                                            bone;
    (biopsies;                                                                                                  no correlation
    intake of                                                                                                   with age
    variable
    amounts of Al)
                                                                                                                                              

    a    Normal control values are given in parentheses
         DES  = dialysis encephalopathy syndrome;                         dial= on haemodialysis;
         w.w. = wet weight;                                               non-dial= not on haemodialysis;
         d.w. = dry weight;                                               transpl= transplantation;
         n.d. = no data;                                                  PT= parathyroid gland;
         ARF  = acute renal failure;                                      thy= thyroid gland
         CRF  = chronic renal failure;
    b    All concentrations expressed as mg Al/kg fat-free solid
        administration. Day estimated the fraction of absorbed aluminium to be
    1%. Later, the same technique was employed by Day et al. (1994) to
    estimate aluminium uptake from orange juice (with or without added
    silicate) in control subjects and patients with Downśs syndrome.
    Results were expressed as the gastrointestinal absorption factor
    (F1), defined as the ratio of mass of aluminium absorbed to mass of
    aluminium ingested. For the normal subjects uptake factors ranging
    from 0.04 to 1.5 × 10-4 were calculated. The addition of silica
    reduced the uptake by a factor of about 7. In the Downśs syndrome
    patients uptake was apparently 5 times higher than in controls (4.7 ×
    10-4 compared to an average of 0.91 × 10-4 in controls).

         Most recently, human bioavailability studies have been undertaken
    by Priest and his co-workers using a methodology employing the
    collection of blood samples and total excreta for a period of up to a
    week after a single administration of aluminium compound. The results
    of these experiments showed significant intersubject variability in
    the extent and timing of aluminium absorption, indicating the
    shortcomings of the methods employed by Day et al. (1991, 1994). Two
    main studies were undertaken. The first was a study of the uptake from
    the gut of aluminium, as aluminium citrate, aluminium hydroxide, and
    aluminium hydroxide in the presence of citrate, following the
    administration of 100 mg aluminium by gastric tube (Priest, 1994). The
    absorption fractions obtained were as follows: 5 × 10-3 for aluminium
    as citrate; 1.04 × 10-4 for aluminium hydroxide; and 1.36 × 10-3 for
    hydroxide in the presence of sodium citrate. This study demonstrated
    the greater bioavailability of the citrate complex and the ability of
    citrate to enhance the uptake of aluminium taken in another chemical
    form. The second study measured the fractional uptake of aluminium
    from drinking-water using a similar technique, but different
    volunteers (Priest et al., 1995a). The measured uptake fraction was
    2.2 × 10-4. It was concluded that members of the public, drinking
    1.5 litres/day of water containing 100 µg of aluminium/litre, would
    absorb about 3% of their total daily aluminium uptake from this
    source. This result suggests that drinking-water, under most
    circumstances, is likely to be a minor source of aluminium for humans.

    6.1.2.3  Dermal exposure

         There is no direct evidence that aluminium is absorbed through
    the intact skin of humans.

    6.2  Distribution

    6.2.1  Animal studies

         After absorption aluminium is bound in the plasma primarily to
    transferrin and, to a lesser extent, also to albumin (Trapp, 1983;
    Bertholf et al., 1984; Martin, 1986). There are indications that
    aluminium binding to protein is dose-dependent, with low binding rates

    at unexposed plasma levels (Höhr et al., 1989; Wilhelm et al., 1990).
    Aluminium distribution depends on the animal species used, route of
    administration and the aluminium compound administered. Volumes of
    distribution for aluminium have been estimated only following
    parenteral administration (Wilhelm et al., 1990) and are thus not
    relevant to the exposure of the general population. After a single
    dose of aluminium lactate (1 mg/kg body weight) in rats, no tissue
    uptake could be detected, whereas at 12 000 mg/kg body weight the only
    significant increase in tissue aluminium occurred in bone (Wilhelm et
    al., 1992). In other oral studies summarized in Table 17, more or less
    significant increases in tissue levels after aluminium ingestion were
    found, these increases generally being dose-dependent. In animals
    receiving aluminium, increases in tissue levels were most marked in
    bone.

         It has to be considered that at high-dose levels aluminium is
    toxic to the tissue of the gastrointestinal tract, thus inducing
    pathological changes that might be followed by increased uptake (Jäger
    et al., 1991). Gut tissue pathology has not been investigated in most
    distribution studies.

         Two studies have reported on aluminium accumulation following
    administration in drinking-water. Fulton et al. (1989) administered 0,
    0.1, 2.0 or 100 mg/litre Al(OH)3 or AlCl3 (equivalent to 0, 0.01,
    0.2 or 5.5 mg Al/kg body weight per day) in drinking-water containing
    acetate or citrate at various pH levels to Sprague-Dawley rats
    (6 rats per group) for 10 weeks. In the highest-dose group, aluminium
    accumulated in intestinal cells but not in other tissues investigated.
    The effect was more pronounced when citrate was added and when water
    with an acidic pH was used.

         In a recent study, Walton et al. (1995) administered to eight
    fasted adult rats by gavage 4 ml of aluminium-free drinking-water
    containing 1.0 µg 27Al and 70 becquerel (0.1 µg) 26Al. Two
    experimental animals had brain 26Al/27Al ratios similar to the two
    controls while the remaining six animals had ratios of 26Al/27Al in
    brain tissue that were substantially higher than background. However,
    the variation between animals was marked (148 ± 19 to 5220 ± 208).

         Studies in mice (Golub et al., 1993), rats (Muller et al., 1992)
    and rabbits (Yokel, 1984) indicate that aluminium is not readily
    transferred from the dam to offspring via nursing.

         Studies in mice (Golub et al., 1993) and rabbits (Yokel, 1985)
    indicate that aluminium compounds that are bioavailable and therefore
    available to the dam also reach the fetus. However, a study in rats
    reported elevated levels of aluminium in maternal tissue, but not in
    the fetus, after exposure to aluminium lactate in the diet during

    gestation (Muller et al., 1993). Limited data in mice (Cranmer et al.,
    1986) and rabbits (Yokel, 1985) show higher concentrations of
    aluminium in the placenta than in maternal or fetal tissues after
    administration of aluminium to dams.

    6.2.2  Human studies

    6.2.2.1  Transport in blood

         The extent to which plasma aluminium is normally bound to
    proteins may be as high as 70 to 90% in haemodialysis patients with
    moderately increased plasma aluminium levels (25 to 200 µg/litre).

         Studies using 26Al (Day et al., 1994) have shown that one day
    after injection, 99% of aluminium in blood is present in the plasma
    fraction and 1% in the erythrocytes. By contrast, 880 days after
    injection, 14% was associated with the erythrocyte fraction,
    indicating the probable incorporation of aluminium into the
    erythrocytes during erythropoiesis. One day after injection, 80% of
    the plasma fraction was found to be associated with transferrin, 10%
    with albumin, 5% with low molecular weight proteins (5000-50 000
    molecular weight) and about 4% with a lower molecular weight fraction.
    No details of the plasma speciation at 880 days were given. Priest et
    al. (1996) found that only about 50% of injected aluminium was
    recoverable from blood at 15 min after injection. It was suggested
    that aluminium may pass through blood vessel walls to establish an
    equilibrium between aluminium in blood and aluminium in the
    extravascular tissue fluids. In contrast, the same study showed that
    gallium remained in the blood. This and other observations suggested
    that gallium is an inappropriate surrogate for aluminium in
    bioavailability and kinetic studies (Priest et al., 1991).

    6.2.2.2  Plasma aluminium concentrations in humans

         The role of aluminium in the etiology of dialysis-related
    disorders such as encephalopathy, vitamin-D-resistant osteomalacia,
    and normochromic microcytic anaemia has drawn attention to the
    possible mechanisms of aluminium uptake through the parenteral and
    intestinal routes.

         Normal human plasma or serum aluminium values reported vary
    largely, mainly due to methodological problems in the analytical
    technique and with sample contamination. Ganrot (1986) emphasized this
    in his extensive review.

         As methods have improved, suggested reference values for plasma
    levels have been revised downwards, and it was suggested by Nieboer et
    al. (1995) that the actual value in normal subjects lies in the range
    of 0.04 to 0.07 µmol/litre (1.1 to 1.9 µg/litre).

         Seasonal variations in serum aluminium concentrations in patients
    with moderate chronic renal failure were observed by Nordal et al.
    (1988), with peak levels occurring in the autumn. These variations
    were presumed to be related to an increased gastrointestinal
    absorption due to waterborne factors.

         The data summarized in Tables 16 and 17 indicate that, as is the
    case with experimental animals, the aluminium concentrations in human
    blood and selected tissues are increased after ingestion or inhalation
    of aluminium compounds.

    6.2.2.3  Tissue aluminium concentrations in humans

    (a)   Normal concentrations

         The available data relating to the aluminium concentrations found
    in various human tissues are summarized in Table 17. It should be
    noted that the measurement of tissue concentrations is difficult. In
    particular, where the average concentrations for a tissue have been
    reconstructed, by extrapolation, from the analysis of small samples of
    the tissues concerned, they may be significantly affected by lack of
    homogeneity in the distribution of the metal in the organ and will
    also amplify errors due to sample contamination. In this respect the
    reconstruction of average bone concentrations is particularly
    difficult, given that small samples of bone collected from disparate
    skeletal sites will contain very different levels of aluminium as a
    result of the different amounts of bone surface to which the metal
    binds. Owing to the above difficulties it is commonly prudent to
    ignore measurements that indicate very high levels of aluminium in a
    particular tissue without additional biological data to explain the
    findings. This approach has been taken by a Canadian group (Nieboer et
    al., 1995), which based its conclusions on the lowest levels
    consistently reported for the tissues considered (bone and brain). It
    was concluded that normal levels of aluminium in bone are in the order
    of 1-3 µg/g (wet weight) and that background levels in brain tissue
    (mostly in the grey matter) are around 1-3 µg/g (dry weight) or <
    0.5 µg/g (wet weight), based on the lowest levels consistently
    reported. The authors also showed that the bone and brain aluminium
    levels are significantly elevated in patients with renal failure who
    are treated with either aluminium-containing phosphate scavengers or
    who received total parenteral nutrition with aluminium-contaminated
    intravenous nutrient solutions.

         With respect to other tissues, measurements suggest that the
    highest levels of aluminium are found in the lung (56-215 mg/kg dry
    weight) (Alfrey et al., 1980), presumably as inhaled, undissolved,
    aluminium-containing particles. Similarly, inhaled particles may
    relocate in the regional (hilar) lymph nodes and in the organs
    comprising the reticulo-endothelial system, i.e. liver, spleen and

    bone marrow. This may explain some or, in the case of the lymph nodes,
    most of the aluminium present in these organs. For example, Teraoka
    (1981) reported the levels of aluminium in the lungs and reticulo-
    endothelial organs of a stone mason dying from silicosis and
    corpulmonale: lungs (2 g/kg dry weight); hilar lymph nodes (3.2 g/kg
    dry weight); spleen (520 mg/kg dry weight) and liver (130 mg/kg dry
    weight). Excluding particulate aluminium, it is likely that of all the
    extrapulmonary tissues only the skeleton contains significant levels
    of aluminium. This is the conclusion of Priest (1993), who based his
    conclusion on a theoretical consideration of ion size of Al3+,
    supported by measurements of the distribution of the sources of 26Al
    gamma-emission in a human volunteer at earlier times after injection
    (using the same techniques gallium uptake in the liver was estimated
    to be about 30%). The possibility that at later times liver levels
    build up would be consistent with rather high levels for this tissue
    (Flendrig et al., 1976) and with the observation of Day et al. (1994)
    that some aluminium is taken up by red blood cells - considering the
    role of the liver in the breakdown of old red blood cells.

    (b)   Concentrations after aluminium exposure

         Data on the tissue burden of aluminium-exposed humans are mostly
    derived from patients with chronic uraemia as well from occupationally
    exposed workers. In these patients, the aluminium intake may come from
    more than one source and is difficult to follow.

         More than 40 years after exposure, the cerebrospinal fluid of an
    aluminium powder worker exposed heavily during 1944-1946 contained 250
    µg aluminium/litre. Aluminium-associated pulmonary fibrosis
    (aluminosis) was diagnosed in 1946 (Sjögren et al., 1994a,b). The
    normal value for cerebrospinal fluid is less than 10 µg/litre.

         In two heavily exposed aluminium welders, bone aluminium
    concentrations were 18 mg/kg dry weight and 29 mg/kg dry weight,
    clearly above the reference range for the investigators (0.6-5 mg/kg
    dry weight) (Elinder et al., 1991). In a worker producing fine
    aluminium powder, who developed encephalopathy and pulmonary fibrosis
    after 13.5 years of work, the aluminium concentration in lung and
    brain was increased 20-fold and in the liver 122-fold (McLaughlin et
    al., 1962).

         In patients with impaired renal function, a wide range of tissue
    aluminium concentrations have been reported (bone, 8.4-281 mg/kg;
    muscle, 2-23.6 mg/kg; brain, 2.2-25 mg/kg; Table 16). This wide range
    reflects the variable exposure to aluminium-containing phosphate-
    binding pharmaceutical agents and the duration of haemodialysis. The
    increased tissue concentrations are associated with the clinical
    syndromes of encephalopathy, osteomalacia and microcytic anaemia.
    Channon et al.

    (1988) reported a positive correlation between the dose of aluminium-
    containing phosphate-binding pharmaceutical agent prescribed and bone
    aluminium content, but no correlation with the serum aluminium
    concentration for the 6 months preceding bone biopsy.

         In a worker exposed to aluminium dust and powder in a ball-mill
    room for 13.5 years, the aluminium concentration in lung and brain was
    increased 20 times and that of the liver 122 times over the normal
    value (Table 16). Teraoka (1981) published data indicating that
    aluminium concentrations were increased in the lungs (2000 mg/kg dry
    weight), hilar lymph nodes (3200 mg/kg dry weight), spleen (520 mg/kg
    dry weight), and liver (130 mg/kg dry weight) in a stone-mason dying
    from silicosis. The average organ concentrations in normal unexposed
    control males were 230, 2000, 22 and 19 mg/kg, respectively
    (Table 16).

    6.3  Elimination and excretion

    6.3.1  Animal studies

         In animals aluminium is eliminated effectively by urine.
    Following single intravenous doses of up to 100 µg/kg body weight in
    rats, aluminium was quantitatively recovered from urine (Wilhelm et
    al., 1992). It is difficult to obtain an accurate half-life for low
    oral doses, since the rate of aluminium absorption is low. Data on
    plasma half-life and on renal clearance have been mainly obtained from
    parenteral administration generally using high doses of aluminium
    (Wilhelm et al., 1990). It seems that at doses comparable with human
    exposure the plasma half-life is less than 1 h.

         Based on stop-flow experiments conducted in pigs, Monteagudo et
    al. (1988) concluded that aluminium excretion occurs in the distal
    tubule of the kidney and is situated close to the sites of maximal
    calcium and sodium ion reabsorption.

    6.3.2  Human studies

    6.3.2.1  Urinary excretion

         The biokinetics of aluminium in man has been evaluated by Priest
    and his co-workers (Priest et al., 1991, 1995b, 1996; Talbot et al.,
    1995) using 26Al injected into human volunteers. These authors
    described the pattern of urinary excretion of the isotope following
    its intravenous injection as citrate, the effect of excretion on body
    retention and the relationship between aluminium levels in blood and
    in urine/faeces. In a first study using a single volunteer (Priest et
    al., 1991, 1995b, 1996), the authors confirmed that aluminium is
    overwhelmingly excreted by the urinary route and that most blood
    aluminium is cleared to excretion. More than half of the 26Al had

    left the blood within 15 min and the decline continued, leaving < 1%
    in the blood after 2 days. Total excretion up to 13 days was 83%
    (urine) and 1.8% (faeces), leaving 15% in the body. After 4 months
    more than 90% was excreted. With increasing time the rate of urinary
    excretion, as indicated by the fraction of retained aluminium (Rt),
    decreased with time (t) according to the power function:

         Rt = 35.4 t-0.32(t > 1)

         At 1178 days after injection about 4% remained in the body; an
    estimated 94% had been excreted by the urinary route and 2% in the
    faeces. Faecal excretion most likely represented aluminium that had
    entered the gastrointestinal tract in bile. The power function
    calculated for the fraction of aluminium excreted by the urinary route
    (Ut) at time (t) after intake was:

         Ut = 0.47 t-1.36

         The excretory clearance rate (ECR) from whole blood (in kg/day)
    during the first two weeks after injection was expressed as:

         ECR = 42 t-0.14

         In a second study (Talbot et al., 1995) of shorter duration, but
    using six male volunteers, inter-subject variability was examined.
    This showed significant inter-subject variation in the pattern of
    aluminium excretion. For example, after 5 days an average of
    71.8% ± 7.3% (SD) of the injected activity had been excreted in urine
    (range 62.4-82.9%). Of this total, an average of 59.1% was excreted in
    the first day, 7.2% in day two, 2.6% in day three, 1.7% in day four
    and 1.1% in the fifth day. In the same period an average of 1.2% was
    excreted in the faeces. With respect to blood clearance to urine, the
    study showed a gradual decrease in the fraction of blood aluminium
    excreted per unit time, indicating a changing speciation of aluminium
    in the blood. Overall, the results of the study were wholly consistent
    with those generated in the single volunteer study, with the first
    volunteer showing aluminium biokinetics in the middle of the range of
    results generated by the multi-volunteer study.

         Sjögren et al. (1985) studied previously unexposed volunteers and
    individuals previously exposed to welding fumes containing aluminium
    at their workplaces for different periods of time. All subjects were
    exposed to welding fumes containing aluminium during a working day for
    about 8 h. In previously unexposed individuals urinary aluminium
    concentration after exposure was increased but decreased to pre-
    exposure levels after a few days. The half-life of the first phase of
    excretion was approximately 8 h. In welders exposed for less than 2
    years in the aluminium concentration decreased during the weekend, the

    half-life being about 9 days. In welders exposed for more than 10
    years urinary concentration did not change despite cessation of
    exposure. In these welders, the urine half-life was more than 6 months
    (Sjögren et al., 1988).

         Elinder et al. (1991) analysed urinary, blood and bone aluminium
    content in two aluminium welders exposed to welding fumes for more
    than 20 years. The urinary values varied from 107 to 351 µg
    aluminium/litre. The daily urinary aluminium elimination was estimated
    to be 0.06% of the estimated body burden (on the basis of bone
    aluminium content), which corresponds to a half-life of about 3 years.

         Ljunggren et al. (1991) studied workers occupationally exposed to
    aluminium flake powder after acute exposure and after periods of non-
    exposure of varying length. The calculated half-life during 4-5 weeks
    of exposure-free vacations was 6.8 weeks. In workers retired (for 6
    months to 14 years) after exposure periods of 9 to 50 years, the
    calculated half-life varied between 0.7 and 7.9 years, depending on
    the length of the exposure-free period.

    6.3.2.2  Biliary excretion

         There is insufficient information to comment on biliary excretion
    of aluminium in humans.

    6.4  Biological indices of exposure, body burden and organ
         concentration

         Aluminium levels in blood and urine have been used to determine
    exposure levels. However, this relation is relatively weak. Blood
    aluminium levels are a poor indicator of tissue stores, rather
    indicating acute intake or rate of tissue store mobilization. In
    patients with impaired renal function, blood and urine levels are poor
    indicators of tissue levels.

         High occupational exposure levels seem to be reflected better by
    urine levels than by blood levels, but the quantitative relation is
    not well established. Balance studies by current methodologies are not
    possible. Increased blood and urine concentrations have been observed
    in several groups of occupationally exposed workers and a quantitative
    relationship between the amount inhaled and the urinary aluminium
    concentration has been suggested (Sjögren et al., 1983).

         A linear relationship has been observed between the air levels of
    aluminium exposure, the number of exposure years and the post-shift
    urine level in aluminium welders (Sjögren et al., 1988):

         UAl = 41.7 × AAl + 6.7 × E ś 4.6

    where  UAl = urine aluminium level (µg/litre)
           AAl = air aluminium level (mg/m3)
           E     = years of exposure

         Owing to intra-individual variation, this equation can only be
    used for groups, not individuals. There have been no adequate
    investigations of the relation between air levels of exposure and
    urine or blood levels in workers apart from welders.

         No information exists regarding the use of biological exposure
    indices in general populations.

    7.  EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS

    7.1  Single exposure

         The acute toxicity is influenced by the solubility and
    bioavailability of the aluminium compounds administered. Aluminium
    compounds are only poorly absorbed after exposure by the
    gastrointestinal, respiratory and dermal routes. The acute toxicity of
    aluminium metal and aluminium compounds is relatively low. No LC50
    has been identified in inhalation studies.

         Lethal doses of soluble aluminium compounds, such as AlCl3,
    Al(NO3)3 and Al2(SO4)3, have been determined by the oral or
    parenteral routes. Some LD50 values are given in Table 18.

        Table 18.  LD50 values for various aluminium compounds
                                                                                                 

    Compound         Species             Route of              LD50         Reference
                                         administration    (mg Al/kg b.w.)
                                                                                                 

    AlCl3            mouse (male         oral (gavage)           770          Ondreicka
    Al2(SO4)3        Dobrá Voda)                                 980          et al. (1966)

    Al(NO3)3         mouse (Swiss;       oral (gavage)           286          Llobet et al.
                     20/sex)             i.p.                    133          (1987)
    AlCl3                                oral (gavage)           222
                                         i.p.                    105
    Al2(SO4)3                            oral (gavage)         > 730
                                         i.p.                     40
    AlBr3                                oral (gavage)           164
                                         i.p.                    108

    Al(NO3)3         rat (Sprague-       oral (gavage)           261          Llobet et al.
                     Dawley, 20/sex)     i.p.                     65          (1987)
    AlCl3                                oral (gavage)           370
                                         i.p.                     81
    Al2(SO4)3                            oral (gavage)         > 730
                                         i.p.                     25
    AlBr3                                oral (gavage)           162
                                         i.p.                     82
                                                                                                 
    
    7.2  Short- and long-term exposure

    7.2.1  Oral administration

         Available data on the toxicity of aluminium compounds following
    repeated oral administration are presented in Table 19. Few of
    the studies reviewed are adequate to serve as a basis for the
    determination of effect levels, since many were designed to address
    principally aspects such as effect of citrate and decrements in kidney
    function on the body burden of aluminium; a very limited range of
    toxicological end-points was also examined in these studies
    (Ecelbarger & Greger, 1991; Greger & Powers, 1992).

         There have been several repeated dose toxicity studies in which a
    wide range of end-points, including clinical signs, food and water
    consumption, growth, haematological and serum analyses, tissue and
    plasma concentrations of aluminium, histopathology, has been examined
    following oral exposure to various aluminium compounds. There were no
    treatment-related effects in rats fed up to 288 mg Al/kg body weight
    per day as sodium aluminium phosphate or 302 mg Al/kg body weight per
    day as aluminium hydroxide in the diet for 28 days (Hicks et al.,
    1987). In a subchronic study in which aluminium nitrate was
    administered in drinking-water to rats, the only effect observed was a
    significant decrease in body weight gain associated with a decrease in
    food consumption at 261 mg Al/kg body weight per day. (NOEL = 52 mg
    Al/kg body weight per day) (Domingo et al., 1987b).

         When small groups of Beagle dogs were given sodium aluminium
    phosphate for 6 months in the diet, there were no treatment-related
    effects except for a decrease in food consumption not associated with
    a decrease in body weight (NOEL = approximately 70 mg Al/kg body
    weight) (Katz et al., 1984). Similarly, in small groups of Beagle dogs
    administered up to 80 mg Al/kg body weight per day as sodium aluminium
    phosphate for 26 weeks, the only treatment-related effect was a sharp,
    transient decrease in food consumption and concomitant decrease in
    body weight in males (LOEL = 75 to 80 mg Al/kg body weight per day;
    Pettersen et al., 1990).

        Table 19.  Toxicity of aluminium compounds after repeated oral administration
                                                                                                                                              

    Protocol descriptiona                   End-points examined                Results                                                Reference
                                                                                                                                              

    5-10 male rats (Weizman strain)         clinical signs, histopathology     periorbital bleeding in 3 of 5 animals at 350          Berlyne
    per group;                              (appears to have been              mg/kg body weight per day Al2(SO4); tissue and         et al.
    Al2(SO4)3 (200 or 350 mg Al/kg          limited to animals that            serum levels highest in nephrectomized animals;        (1972)
    body weight per day in drinking         died during study), tissue         clinical signs of toxicity and death in all groups
    water), AlC13 (250 mg Al/kg             concentrations                     of nephrectomized animals; comments: protocol and
    body weight per day in drinking                                            results poorly documented; inadequate for
    water), Al(OH3) (150 mg Al/kg                                              establishment of effect levels
    body weight per day by gavage)
    for an unspecified period; groups
    of animals that were 5/6
    nephrectomized similarly exposed

    Controls: 56 male Sprague-Dawley        aluminium concentrations in        five of these measures (concentrations in tibia,       Greger &
    rats 10.5 mg Al/kg exposed groups       tibia, liver, kidney and serum;    liver, and serum and urinary excretion with and        Powers
    16 animals, ingesting: aluminium        serum aluminium concentrations     without DFO treatment); were highly correlated         (1992)
    hydroxide, 1079 mg Al/kg diet           after DFO; urinary                 with oral exposure; changes induced by DFO were
    (29 days) or 1012 mg Al/kg diet         aluminium excretion with and       very small; ingestion of citrate had small but
    plus 4% citrate (29 days), 2688         without DFO treatment; body        significant effects on aluminium retention; rats
    mg/kg and 4% citrate (12 or 29          and organ weight gain and          fed citrate weighed less (not associated with
    days); 24 h prior to sacrifice,         haematological status              differences in intake of feed) and had significantly
    all animals injected i.p. with                                             enlarged kidneys and livers and significantly smaller
    desferrioxamine (DFO) or buffer                                            tibias; haematocrits were inversely correlated to
                                                                               tissue concentrations of aluminium - more evident
                                                                               with oral than parenteral exposure; hepatic iron
                                                                               was elevated with the citrate-containing diets but
                                                                               was only weakly correlated with hepatic aluminium
                                                                               concentrations;
                                                                                                                                              

    Table 19.  (Con't)
                                                                                                                                              

    Protocol descriptiona                   End-points examined                Results                                                Reference
                                                                                                                                              

                                                                               comments: comparisons of aluminium exposure in         Greger &
                                                                               tibias and sera of rats exposed parenterally and       Powers
                                                                               orally indicated that 0.01 to 0.04% of dietary         (1992)
                                                                               aluminium was absorbed; inadequate for establishment
                                                                               of effect levels owing to limited range of end-points
                                                                               examined; primarily an investigation to monitor
                                                                               aluminium body burdens

    Administration to groups of 6 rats      tissue concentrations of           ingestion of citrate increased retention of aluminium  Ecelbarger
    exposed in a 2x2x2x2 factorial          aluminium; body and                in bone of rats fed 1000 mg Al/kg diet and increased   & Greger
    design of diets containing 13 or        organ weight changes               apparent absorption of zinc; when dietary calcium      (1991)
    1112 mg Al/kg as aluminium                                                 intake was increased from 67 to 250 mmol/kg diet,
    hydroxide, citrate (0 or 5.2 mmol/kg                                       aluminium concentrations in bone were reduced without
    diet) and calcium (2.7 or 10.0 g/kg                                        a change in growth of rats; reduction in kidney
    diet) for 30 days; groups of 6 rats                                        function (by removal of one kidney), which was
    exposed in a 4x2 factorial design                                          insufficient to alter growth, increased aluminium
    to 14 or 904 mg Al/kg diet and one                                         retention in bone by 13% in rats fed aluminium; rats
    of 4 levels of citrate (0, 10, 21 or                                       fed aluminium retained only 0.01 to 0.5% as much as
    31 mmol/kg diet) for 28 days;                                              those injected; comments:authors concluded that
    groups of 7 rats exposed in 2x2x2                                          tissue concentrations and, presumably, toxicity can
    factorial design to 9 or 1044 mg                                           be altered by moderate changes in diet and kidney
    Al/kg diet and citrate (0 or                                               function even though overall retention of orally
    21 mmole/kg diet) sham-operated                                            administered aluminium is low, inadequate for
    or with one kidney removed for                                             establishment of effect levels owing to limited
    28 days                                                                    range of end-points examined; designed primarily to
                                                                               investigate effect of dietary citrate, calcium
                                                                               and decreases in kidney function on absorption
                                                                               of aluminium
                                                                                                                                              

    Table 19.  (Con't)
                                                                                                                                              

    Protocol descriptiona                   End-points examined                Results                                                Reference
                                                                                                                                              

    Groups of 10 female Sprague-            clinical signs, food and water     no effects on any end-points examined except for       Gómez
    Dawley receiving 1, 26, 52 or           consumption, growth,               mild histopathological changes in the spleen and       et al.
    104 mg Al/kg body weight per            haematological and serum           liver of high dose group (hyperaemia in the red pulp   (1986)
    day as Al(NO3)3 in drinking             analyses, tissue and plasma        of the spleen and liver; periportal lymphomonocytic
    water for 28 days                       concentrations of aluminium,       infiltrate in the liver); dose-dependent accumulation
                                            histopathology                     of aluminium in spleen, heart and gastrointestinal
                                                                               tract; comments: well-conducted repeated dose
                                                                               toxicity in which a wide range of end-points was
                                                                               examined, though short term; NOEL = 52 mg Al/kg
                                                                               body weight per day; LOEL = 104 mg Al/kg body
                                                                               weight per day (aluminium nitrate)

    Groups of female Sprague-Dawley         clinical signs, food and water     significant decrease in body weight gain at highest    Domingo
    rats receiving 0, 26, 52 or 261 mg      consumption, organ and body        dose associated with decrease in food consumption;     et al.
    Al/kg body weight per day as            weights, haematological and        no dose-dependent accumulation of aluminium in         (1987b)
    Al(NO3)3 in drinking-water for          serum analyses, tissue and         tissues; comments: well-conducted repeated dose
    100 days                                plasma concentrations of           toxicity in which a wide range of end-points;
                                            aluminium, histopathology          LOEL = 261 mg Al/kg body weight per day; NOEL =
                                                                               52 mg Al/kg body weight per day for subchronic
                                                                               period of exposure

    Groups of Beagle dogs (4/sex)           clinical signs, food and water     statistically significant decreases in food            Katz et
    administered 0, 0.3, 1.0 or 3.0%        consumption, organ and body        consumption in females but no associated decrease      al.
    sodium aluminium phosphate in           weights, haematological and        in body weight; no other treatment-related effects;    (1984)
    the diet for 6 months (118, 317         serum analyses, urinalysis,        comments: range of end-points examined; subchronic
    and 1034 mg/kg body weight per          ophthalmological examinations,     period of exposure for dogs; small group sizes;
    day in males and 112, 361 and           tissue and plasma                  NOEL = 1087 mg/kg body weight per day (approximately
    1087 mg/kg body weight per day          concentrations of aluminium,       70 mg Al/kg body weight per day)
    in females                              histopathology
                                                                                                                                              

    Table 19.  (Con't)
                                                                                                                                              

    Protocol descriptiona                   End-points examined                Results                                                Reference
                                                                                                                                              

    Groups of Beagle dogs (4/sex)           clinical signs, food and water     sharp, transient decrease in food consumption and      Pettersen
    administered 0, 10, 22 to 27 or         consumption, organ and body        concomitant decrease in body weight in high-dose       et al.
    75 to 80 mg Al/kg body weight           weights, haematological and        males; in same group, decrease in testes weight and    (1990)
    per day as sodium aluminium             serum analyses, urinalysis,        histopathological changes in the liver and kidney
    phosphate in the diet for               ophthalmological examinations,     considered to be secondary to decreased food
    26 weeks                                tissue and plasma                  consumption; slight increase in concentration of
                                            concentrations of aluminium,       aluminium in the brain in high-dose females but not
                                            histopathology                     males; comments: wide range of end-points examined;
                                                                               subchronic period of exposure for dogs; small group
                                                                               sizes; minimal toxicity at the highest dose;
                                                                               LOEL = 75 to 80 mg Al/kg body weight per day

    Groups of 25 male Sprague-Dawley
    rats fed control diets or
    30 000 mg/kg
    KASAL I (6% aluminium-sodium            clinical signs, food and water     no treatment-related effects or significant            Hicks et
    aluminium phosphate), 7000 or           consumption, organ and body        deposition of aluminium in bone; comments: wide        al.
    30 000 mg/kg KASAL II (13%              weights, haematology and           range of end-points examined; short-term exposure;     (1987)
    aluminium-sodium aluminium              clinical chemistry urinalysis,     no effects at 141 mg Al/kg body weight per day
    phosphate) or 14 470 mg/kg              ophthalmological examinations,     KASAL I; NOEL for KASAL II = 288 mg Al/kg body
    aluminium hydroxide for 28 days         concentrations of                  weight per day; no effects at 302 mg Al/kg body
    (5, 141, 67, 288, 302 mg Al/kg          aluminium in the femur,            weight per day aluminium hydroxide
    body weight per day, respectively)      histopathology
                                                                                                                                              

    Table 19.  (Con't)
                                                                                                                                              

    Protocol descriptiona                   End-points examined                Results                                                Reference
                                                                                                                                              

    Groups of 15 albino male rats           histopathological examination      dose-related cytotoxic effect in the liver -           Roy et
    administered aluminium sulfate          of heart, liver, kidney,           cytoplasmic degeneration at 17 to 29 mg Al/kg body     al.
    (0, 17, 22, 29, 43, 86 and              brain, testes, stomach and         weight with multifocal degeneration and fibrous        (1991b)
    172 mg Al/kg body weight) and           femur                              tissue proliferation at higher doses. Dose-related
    potassium aluminium sulfate                                                effects in the kidney at 17 mg Al/kg body weight
    (43 mg Al/kg body weight, 29 mg                                            per day as aluminium sulfate, slight swelling of
    Al/kg body weight) in deionized                                            the tubules. With increased dose, increased swelling
    water for 21 days; 5 rats killed                                           and degeneration of the cortical tubules.
    weekly                                                                     Degeneration of the nerve cell at 29 and 43 mg Al/kg
                                                                               body weight per day aluminium sulfate and
                                                                               potassium aluminium sulfate, respectively, which
                                                                               was more severe at higher doses. Some evidence of
                                                                               spermatological cell decrease at doses of 43 mg Al/kg
                                                                               body weight per day and above. Multifocal degeneration
                                                                               and decalcification at 43 mg Al/kg body weight
                                                                               per day and above for both salts, which increased with
                                                                               increasing dose; degeneration of calcified bone and
                                                                               irregularity of osteoblasts in animals exposed to 86
                                                                               and 171 mg Al/kg body weight as aluminium sulfate.
                                                                               Hyperplasia and ulceration of stomach at highest doses.
                                                                               Comments: difficult to verify reported effect levels
                                                                               based on limited information presented in paper.
                                                                                                                                              

    a    Strain, number of animals/group and vehicle specified, where available; doses reported as mg/kg body weight, unless specified
             In a study that was not well reported, mild histopathological
    effects on the kidney and liver of rats, which increased in severity
    with dose, were reported at doses as low as 17.2 mg Al/kg body weight
    (as aluminium sulfate) administered by gavage for 21 days (Roy et al.,
    1991b). Data presented in the report were inadequate to verify the
    reported effect levels.

    7.2.2  Inhalation exposure

         Many inhalation/intra-tracheal instillation studies have
    been conducted using aluminium compounds, including chloride,
    chlorohydrate, oxyhydrate and oxides (Stacy et al., 1959; Corrin,
    1963; Christie et al., 1963; Gross et al., 1973; Drew et al., 1974;
    Steinhagen et al., 1978; Stone et al., 1979; Finelli et al., 1981;
    Thompson et al., 1986). However, in the case of the inhalation
    studies, little data is available concerning exposure conditions and
    the size of the ambient aerosol, and some studies were of relatively
    short duration compared with the life-span of the animal employed.
    Consequently, although no toxic effects were reported in nearly all
    cases, it is not possible to assess how much, if any, of the compound
    was deposited in the lungs of the experimental animal, and the time-
    span of the experiment may have been too short to demonstrate delayed
    effects. The only inhalation study that demonstrated an effect was
    that of Finelli et al. (1981) who described increased lung size. Where
    aluminium oxide particles were administered by intra-tracheal
    instillation, fibrosis has been consistently reported (Stacy et al.,
    1959; Corrin, 1963). Dinman (1988) described this disease as "alumina-
    related pulmonary disease". However, such fibrosis is a common
    consequence of the inhalation of many particles, including silica and
    coal; it is unlikely to be related to aluminium  per se, but rather
    to the physical properties of the particle inhaled.

    7.2.3  Parenteral administration

         Aluminium compounds were found to possess an increased toxicity
    when administered parenterally rather than orally. The effect depends
    on the dose, the aluminium compound used and the particular animal
    model. It can vary from death to behavioural alteration (loss of
    memory), loss of weight or minor changes in aluminium accumulation in
    bone. A LOAEL of approximately 1 mg/kg body weight per day can be
    obtained by this route for osteomalacia or for deterioration of renal
    function (Chan et al., 1983; Henry et al., 1984; Quarles et al., 1985;
    Bräunlich et al., 1986). Partially nephrectomized animals exhibited
    greater susceptibility to aluminium (Ittel et al., 1992).

    7.3  Reproductive and developmental toxicity

    7.3.1  Reproductive effects

         The limited number of studies are not able to provide adequate
    information on reproductive toxicity (Domingo, 1995). Of these, few
    provide direct and complete evaluations of reproduction.

         Domingo et al. (1987a) administered aluminium nitrate at 0, 13,
    26 or 52 mg Al/kg body weight per day by intubation to male rats for
    60 days prior to mating and to virgin females treated for 14 days
    prior to mating. The same doses were administered by gavage to
    pregnant animals from 14 days gestation to 21 days of lactation in a
    separate study (Domingo et al., 1987c). Domingo et al. (1987a)
    reported no reproductive effects on fertility (number of litters
    produced), litter size, or intrauterine or postnatal offspring
    mortality. Numbers of corpus lutea on day 13 of gestation were
    significantly lower at 52 mg Al/kg body weight per day. However a
    dose-dependant delay in the growth of the pups was observed in all
    treatment groups; female offspring were affected at 13 mg Al/kg body
    weight per day and males at 26 and 52 mg Al/kg body weight per day.
    Because of the design of the study by Domingo et al. (1987a) it is not
    clear whether the postnatal growth effects in offspring represented
    general toxicity to male or female parents, or represented specific
    effects on reproduction or development. However, the reported LOAEL
    for adverse effects in females in this study was 13 mg Al/kg body
    weight per day.

         Dosing of pregnant animals from 14 days gestation to 21 days
    lactation with 13, 26 or 52 mg Al/kg body weight per day did not
    produce overt fetotoxicity (Domingo et al., 1987c), but growth of
    offspring was significantly delayed (body weight, body length and tail
    length) from birth to weaning.

    7.3.2  Developmental effects

         Details of the study designs of oral or gavage dosing studies of
    developmental toxicity are given in Table 20. Aluminium chloride
    administered i.p. to rats (Benett et al., 1975) or i.v. to mice (Wide,
    1984) during embryogenesis produced a syndrome characterized by
    delayed and incomplete ossification of skull and vertebrae, skeletal
    variations and malformations, internal haemorrhage and reduced fetal
    growth. Abnormal digits were also noted in rats. Administration of
    aluminium chloride in the diet with accompanying parathyroid hormone
    (PTH) injection (McCormack et al., 1979) also produced reduced
    skeletal ossification and increased incidence of skeletal variations.
    Maternal toxicity in the study of Benett et al. (1975) included
    reduced weight gain, hepatic granulomas and necrosis and maternal
    death at the highest dose levels (100 and 200 mg Al/kg per day).
    Resorption and embryolethality were seen primarily at highly

    maternally toxic doses (200 mg Al/kg per day). Maternal monitoring and
    reduced gestational weight gain were not seen at the LOAEL for
    developmental toxicity (75 mg Al/kg per day; day 9-13 of gestation).
    At this dose mean fetal weight and crown rump were reduced, and the
    number of resorptions increased. The use of i.p. administration makes
    it difficult to interpret these results with regards to human health
    effects.

         The severity of developmental aluminium toxicity by the oral
    route is highly dependent on the form of aluminium and the presence of
    organic chelators that influence bioavailability, as demonstrated in a
    series of studies by Domingo (1995) using gavage administration during
    embryogenesis. Aluminium nitrate (nonahydrate) produced developmental
    effects in rats (Paternain et al., 1988) similar to the effects seen
    after i.p. injections (Benett et al., 1975), including skeletal
    variations, poor ossification, haemorrhage, oligodactyly and some soft
    tissue malformations. Aluminium hydroxide did not produce either
    maternal or developmental toxicity when it was administered by gavage
    during embryogenesis to rats (Gómez et al., 1990) or mice (Domingo et
    al., 1989). When aluminium hydroxide was administered with ascorbate
    (Colomina et al., 1994), no maternal or developmental toxicity was
    seen in mice in spite of elevated maternal tissue concentrations of
    aluminium, whereas aluminium hydroxide given with citrate produced
    maternal and fetal toxicity in rats (Gómez et al., 1991). Aluminium
    hydroxide given with lactate was not toxic, but aluminium lactate
    administration produced developmental toxicity, in mice including poor
    ossification, skeletal variations and cleft palate (Colomina et al.,
    1992).

         In summary, developmental toxicology syndromes described above
    commonly included growth retardation, such as lower fetal weights and
    length (Bennet et al., 1975; Paternain et al., 1988; Gómez et al.,
    1990; Colomina et al., 1992). A study using s.c. administration of
    aluminium lactate did not demonstrate any developmental effects other
    than lower fetal length (Golub et al., 1987). Postnatal growth
    retardation has also been demonstrated in rats exposed in late
    gestation to aluminium nitrate (Domingo, 1987c) and in rabbits treated
    postnatally with aluminium lactate s.c. (Yokel, 1984). Reduced bone
    formation demonstrated when postnatal aluminium lactate was
    administered subcutaneously in rabbits (Yokel, 1987) supports the
    importance of bone as a target organ for developmental effects of
    aluminium.

        Table 20.  Developmental toxicity after oral administration of aluminium saltsa
                                                                                                                                              

    Species                Route of application     Compound               Dose                            Duration            Reference
                                                                                                                                              

    Mouse (Swiss,          oral (gavage)            Al(OH)3                66.5, 133, 266 mg/kg            gest. day 6-15      Domingo et al.
    20/group)                                                              b.w./day                                            (1989)

    Mouse (BALB/c,         oral (gavage)            AlCl3                  oral: 200, 300 mg/kg            gest. day 7-16      Cranmer et al.
    6-7 mice/group)                                                        b.w./day                                            (1986)

    Mouse (Swiss           oral (feed)              Al lactate             500, 1000 mg Al/kg diet         gest. day 0 to day  Golub et al.
    Webster, 15/group)                                                                                     21 p.p.             (1987)

    Mouse (16 Swiss        oral (feed)              Al lactate             25, 500, 1000 mg Al/kg diet     gest. day 0, until  Donald et al.
    Webster)                                                                                               weaning             (1989)

    Mouse (Swiss albino    oral (gavage)            Al(OH)3                57.5 mg/kg b.w./day             gest. day 6-15      Colomina et
    CD-1, 10-13/group)                              Al lactate             166 mg/kg/day                                       al. (1992)
                                                    Al(OH)3 + lactic acid  627 mg/kg/day

    Mouse (Swiss           oral (feed)              Al lactate             25, 1000 mg/kg diet/day         gest. day 0 - day   Golub et al.
    Webster)                                                                                               20 p.p.             (1992)

    Mouse (CBA)            oral (water)             Al2(SO4)3              750 mg/litre                    gest. day 10-17     Clayton et al.
                                                                                                                               (1992)

    Rat (Sprague-Dawley)   oral (feed)              AlCl3                  50 mg/kg b.w.                   gest. day 6-19      McCormack
                                                                                                                               et al. (1979)

    Rat (Wistar, 14/group) oral (feed)              Al lactate             100, 200, 300 mg Al/kg b.w.     gest. day 8 to      Bernuzzi et al.
                                                                                                           parturition         (1986, 1989a,b)

    Rat (Sprague-Dawley)   oral (gavage)            Al(NO3)3               180, 360, 720 mg/kg day         gest. day 14-21     Domingo et al.
                                                                                                                               (1987a)
                                                                                                                                              

    Table 20.  (Con't)
                                                                                                                                              

    Species                Route of application     Compound               Dose                            Duration            Reference
                                                                                                                                              

    Rat (Sprague-Dawley,   oral (gavage)            Al(NO3)3               180, 360, 720 mg/kg b.w.        gest. day 6-14      Paternain et
    10/group)                                                                                                                  al. (1988)

    Rat (Sprague-Dawley,   oral (gavage)            Al(OH)3                384 mg/kg/day                   gest. day 6-15      Gómez et al.
    15-19/group)                                    Al citrate             1064 mg/kg/day                                      (1991)
                                                    Al(OH)3 + citric acid

    Rat (Wistar,           oral (gavage)            Al(OH)3                192, 384, 768 mg/kg/day         gest. day 6-15      Gómez et al.
    18-19/group)                                                                                                               (1990)

    Rat (Wistar,           oral (feed)              Al lactate             400 mg Al/kg diet               gest. day 1-7       Muller et al.
    6-9/group)                                                                                             gest. day 1-14      (1990)
                                                                                                           gest. day 1-20
                                                                                                                                              

    a    b.w. = body weight; gest. = gestational; p.p. = postpartum
             Effects of aluminium exposures on brain development have also
    been studied in mice (Donald et al., 1989; Golub et al., 1992, 1994,
    1995; Clayton et al., 1992) and rats (Bernuzzi et al., 1986, 1989a,b;
    Muller et al., 1990; Cherroret et al., 1992) by the oral route, and in
    rabbits (Yokel, 1984, 1985, 1987) using subcutaneous injections.
    Effects recorded in immature animals in more than one study in rats
    and mice included impaired performance of reflexes and simple
    behaviours (e.g., righting reflex, grasping, negative geotaxis, rod
    climbing). Other effects included footsplay and temperature
    sensitivity (tail withdrawal); (Donald et al., 1989; Golub et al.,
    1992) and auditory startle (Golub et al., 1994). Postnatal mortality
    and growth were also affected at the higher doses in only some of
    these studies. Studies of cognitive parameters in immature animals are
    limited to evaluation of classical conditioning of the nictating
    membrane response in rabbits. No effect of aluminium was seen after
    postnatal subcutaneous injection of aluminium lactate (Yokel, 1987);
    both enhancement and impairment of conditioning were seen after
    exposure during gestation to aluminium lactate, depending on the dose
    (Yokel, 1985).

         Adult rats and mice have also been evaluated for brain function
    after developmental exposures. Reduced grip strength and startle
    responsiveness were found to persist up to 150 days of age in mice
    (Golub et al., 1995). No effect was found on a light avoidance task in
    rats after gestational (Bernuzzi et al., 1989b) or postnatal exposure
    (Cherroret et al., 1992). Radial maze learning/performance was also
    unaffected by postnatal exposure (Cherroret et al., 1992). No effects
    on delayed alternation or discrimination reversals were recorded in
    mice after dietary exposure during gestation and lactation (Golub et
    al., 1995).

         The lowest-observed-adverse-effect level (LOAEL) for
    developmental effects after oral dosing was 13 mg Al/kg body weight
    per day by oral gavage of aluminium nitrate (Paternian et al., 1988).
    A dose-response relationship was noted with the highest dose of this
    extremely soluble aluminium salts (52 mg Al/kg body weight)
    representing 1/5 the LD50 (see Table 18). At 13 mg Al/kg per day,
    decreased ossification of skull bones, increased incidence of
    vertebral and sternebrae, and reduced fetal weight and tail length
    were reported with higher incidence of these effects at the higher
    doses (26 and 52 mg Al/kg body weight). Maternal toxicity (reduced
    weight gain during pregnancy) was reported to occur in a dose-
    dependent manner. No developmental toxicity was noted using much
    higher doses of aluminium hydroxide (266 mg Al/kg per day) in a
    similarly designed study (Gómez et al., 1990).

         After administration of aluminium lactate in the diet of mice and
    rats a LOAEL of 100 mg Al/kg body weight per day was reported (Donald
    et al., 1989; Bernuzzi et al., 1989a,b).

         The effect reported at 100 mg Al/kg per day by Bernuzzi et al.
    (1989a,b) in rats was impaired grip strength in the 6-day-old
    offspring of dams fed aluminium lactate in diet throughout gestation.
    Dose response was indicated in this study; at higher doses (200 and
    400 mg Al/kg per day) impaired grip strength was reported along with
    impaired righting reflex and locomotor coordination. No effects on
    maternal or offspring weight were reported at 100 mg Al/kg although
    they occurred at the higher doses. Litters were not culled to a
    standard size at birth in this study. The litter was used as the unit
    of statistical analysis to avoid litter effect.

         The effects reported at 100 mg Al/kg per day by Donald et al.
    (1989) in mice were increased landing foot splay, increased hindlimb
    grip strength and decreased temperature sensitivity in 21-day-old
    offspring of mice fed aluminium lactate in the diet throughout
    gestation and lactation. There was no effect on negative geotaxis or
    startle reflexes in the offspring. Dose response was not indicated in
    this study; similar effects were reported at a higher dose (200 mg
    Al/kg). No effects on maternal or offspring weights were found at
    either dose. It is not stated whether litters were culled to a
    standard number at birth. To address litter effects, litter was nested
    under treatment group in the statistical analysis. In this study,
    daily aluminium intake was estimated based on food intake at the
    beginning of pregnancy.

    7.4  Mutagenicity and related end-points

    7.4.1  Interactions with DNA

         A number of observations indicate that aluminium is able to form
    complexes with DNA and can cross-link chromosomal proteins and DNA. In
    thermal denaturation, circular dichroism and fluorescence studies,
    Karlik et al. (1980) found that aluminium had a stabilizing effect
    upon the DNA double helix at a pH > 6, while at lower pH levels,
    binding of aluminium de-stabilized the DNA double helix. A recent
    investigation of NMR spectra and circular dichroism of DNA-aluminium
    complexes indicated that Al3+ binds to the phosphate oxygen while
    hydroxylated aluminium-species probably prefer other sites such as DNA
    bases (Rao & Divakar, 1993).

         Cross-linking of various cytoplasmic proteins to DNA was
    investigated in live Novikoff ascites hepatoma cells exposed to
    aluminium  in vitro (Wedrychowski et al., 1986). Cross-linking agents
    frequently produce clastogenic effects, owing to conformational
    distortions that prohibit proper replication of the DNA. More recently
    it was shown that AlF4- stimulates the glycation of the histone H1
    in the proximity of its nucleotide-binding site, thus interfering with
    nucleoside triphosphate hydrolysis by H1 and with nucleotide
    modulation of H1 DNA binding (Tarkka et al., 1993).

         In addition, it has been shown that micro-molar levels of
    aluminium reduce 3H-thymidine incorporation in a transformed cell
    line (UMR 106-01) by impeding the cell cycle progression (Blair et
    al., 1989). More specifically, aluminium was shown to inhibit the
    ADP-ribosylation, a mechanism important for DNA repair,  in vivo and
     in vitro (Crapper McLachlan et al., 1983).

    7.4.2  Mutations

         The rec-assay using  Bacillus subtilis strains failed to show
    mutagenic activity for Al2O3, AlCl3 or Al2(SO4)3 at
    concentrations of 1-10 mM (Nishioka, 1975; Kada et al., 1980;
    Kanematsu et al., 1980; Léonard & Gerber, 1988; Bhamra & Costa,
    1992). No reverse mutations were observed in the Ames test using
     Salmonella typhimurium strain TA102 with AlCl3 (concentration
    range 10-100 nM per plate; Marzin & Phi, 1985). No morphological
    transformations were seen in Syrian hamster embryo cells after
    application of aluminium salts (no further specification) (Di Paolo &
    Casto, 1979). No induction of forward mutations were observed at the
    thymidine kinase locus in L5178Y mouse lymphoma assay with AlCl3 when
    tested at concentrations up to 625 µg AlCl3/ml (Oberly et al., 1982).

    7.4.3  Chromosomal effects

         A significant increase of chromatid-type aberrations (including
    gaps, breaks, translocation and ring formations), with non-random
    distribution over the chromosome complement, was found in bone marrow
    cells from mice that were dosed interperitoneally with AlCl3 (Manna &
    Das, 1972). Prolonged treatment of rats with Al2(SO4)3 or
    KAl(SO4)2 caused a dose-dependent inhibition of dividing cells (bone
    marrow) and an increase in chromosomal aberrations (Roy et al.,
    1991a). Chromosomal aberrations were also induced in peritoneal cells
    from rats, mice and Chinese hamsters (Bhamra & Costa, 1992) as well as
    in human leukocyte cultures (Roy et al., 1990). Aluminium caused a
    concentration-dependent bimodal change in the number of sister
    chromatid exchange in cultured human lymphocytes and increased the
    unscheduled DNA synthesis in cultured human astrocytes (De Boni et
    al., 1980).

    7.5  Carcinogenicity

         Based on limited early studies, there is little indication that
    aluminium is carcinogenic (Leonard & Gerber, 1988; Bhamra & Costa,
    1992). Some studies indicated that inhalation of aluminium-containing
    fibres and particles may induce carcinomas in the lung. However, in
    these cases it is likely that the toxicity reflects the physical
    properties of the particles/fibres (3.5 µm median diameter).
    Similarly, aluminium implanted subcutaneously has induced soft tissue

    carcinomas at the site of implantation, but in these cases also the
    effects are probably related to a chronic foreign body reaction rather
    than to the aluminium ion itself (Stanton, 1974; Pigott & Ishmael,
    1981; Pigott et al., 1981; Krueger et al., 1984).

    7.6  Neurotoxicity

         Considerable evidence indicates that aluminium is neurotoxic to
    experimental animals, but species variation exists. In susceptible
    animals, the toxicity is characterized by progressive neurological
    impairment resulting in death associated with status epilepticus.
    Morphologically, the progressive encephalopathy is associated with
    neurofibrillary pathology in large and medium size neurons
    predominantly in the spinal cord, brain stem, and selected areas of
    cortex (hippocampus and cingulate gyrus). However the nature of the
    accumulated fibrils at the light microscopic level and under the
    electron microscope differ from those found in AD. The tangles are not
    birefringent and are composed of 10 nm neurofilaments. The proteins
    involved in the aluminium-induced neurofibrillary tangles also differ
    from those found in the human diseases (see section 8.1.3.1). However,
    aluminium is the only known trace element capable of inducing this
    type of mylo-encephalopathy in susceptible animals (rabbit, cat,
    guinea-pig, ferret). The epileptogenic property of aluminium, in
    contrast to the progressive encephalopathy, occurs in all species
    studied (e.g., primates, rodents, fish). Routes of administration of
    aluminium sufficient to induce the encephalopathy include intrathecal
    intracerebral and subcutaneous injections. There have been no reports
    of progressive encephalopathy or epilepsy when aluminium compounds
    were given orally.

         The brain aluminium concentration necessary to achieve LD50 in
    rabbits is about 6 µg aluminium/g dry weight (Crapper McLachlan et
    al., 1989; McLachlan & Massiah, 1992). The normal brain aluminium
    concentration in healthy rabbits is approximately 1.1 µg/dry weight.

    7.6.1  Impairments of cognitive and motor function

         Cats and adult or infant rabbits given intracerebral injections
    of soluble aluminium compounds revealed a progressive impairment in
    learning and memory performance after an asymptomatic period of 8 to
    10 days (Crapper & Dalton, 1973a,b; Petit et al., 1980; Rabe et al.,
    1982; Solomon et al., 1990). Repeated subcutaneous injections of
    aluminium in rabbits affected classical conditioning (Yokel, 1983).

         The intracisternal injection of a single or repeated low doses of
    metallic aluminium in rabbits resulted in altered motor function
    (Wisniewski et al., 1982; Bugiani & Ghetti, 1982; Strong et al., 1991;
    Strong & Garruto, 1991b). The animals developed progressive myelopathy

    and topographically specific motor neuron degeneration. They exhibited
    myoclonic jerks and muscular weakness. Histopathologically a
    neurofibrillary degeneration with swelling of the proximal axonal
    processes of anterior horn neurons was present. The authors proposed
    these preparations as possible models of human amyotrophic lateral
    sclerosis.

         Behavioural impairment has been reported in laboratory animals
    exposed to aluminium in the diet or drinking-water in the absence of
    overt encephalopathy or neurohistopathology. Both rats (Commissaris et
    al., 1982; Thorne et al., 1987; Connor et al., 1988) and mice
    (Yen-Koo, 1992) have demonstrated such impairments at doses exceeding
    200 mg Al/kg body weight. While significant alterations in acquisition
    and retention of learned behaviour were documented, the possible role
    of organ damage (kidney, liver, immunological) due to aluminium was
    incompletely evaluated.

    7.6.2  Alterations in electrophysiological properties

         The progressive encephalopathy and morphological alterations are
    also associated with electrophysiological changes. The epileptic
    seizures are associated with slowing of the EEG and epileptic
    activity. The mechanisms that evoke the neuronal hyperexcitability
    have not yet been completely elucidated but may involve altered
    membrane electrotonic properties, K+ conductance, and synaptic
    processes (Franceschetti et al., 1990). Associative long-term
    potentiation (LTP), describes strengthening of a previously weak
    synaptic input by concomitant activation of a strong synaptic input.
    LTP can last up to several weeks and has been used as a model for the
    hippocampal contribution to memory. LTP was not sustained normally in
    hippocampal slices from rabbits exposed to intracranial injections of
    aluminium about 7 days prior to sacrifice. The occurrence of this
    electrophysiological alteration corresponds to the onset of
    behavioural changes but is not necessarily accompanied by
    neurofibrillary pathology in the hippocampal neurons exhibiting
    impaired LTP. The loss of LTP can be partially reversed by an increase
    in the calcium concentration in the bath (Farnell et al., 1985;
    Crapper McLachlan & Farnell, 1986).

         In summary, aluminium exposure has been used as an animal model
    for the study of epilepsy, information processing, cognitive
    dysfunction and motor neuron disease.

    7.6.3  Metabolic effects in the nervous system

         Considerable experimental evidence implicates aluminium in
    alterations in the second messenger systems of cAMP and G proteins
    (Steinweis & Gilman, 1982; Johnson & Jope, 1987; Johnson et al., 1990,
    1992). An increased cAMP concentration in brain tissue is a

    prerequisite for an increase in the phosphorylation of proteins. An
    elevation of protein kinase C activity and in the basal activity of
    cAMP-dependent protein kinase resulted in hyperphosphorylation of 12
    proteins in rats chronically treated with aluminium (Johnson et al.,
    1990). In rats chronically treated with low oral doses of aluminium,
    hyperphosphorylation of MAP-2 was increased by 150% and the
    neurofilament H subunit by 150-200%, while the phosphorylation of
    several other proteins including tau was not different from that of
    control rats (Johnson et al., 1990; Jope & Johnson, 1992). It was
    suggested that abnormal phosphorylation may impair the axonal
    transport of cytoskeletal proteins.

         Ohtawa et al. (1983) showed that Al3+ binding to ferritin
    reduced the binding of Fe2+ in rats fed aluminium. The free
    intracellular Fe 2+ augmented the peroxidation of membrane lipids.
    Lipid peroxidation in kidney, lung, liver and spleen were not
    affected. The increased lipid peroxidation is at least, in part, due
    to inhibition of superoxide dismutase in the brain but not in other
    organ systems. An increase in lipid peroxidation was also shown in
    chickens fed with aluminium sulfate (Chainy et al., 1993). It is
    presumed that an increase in lipid peroxidation may be part of the
    mechanisms underlying aluminium neurotoxicity.

         Aluminium is not equally distributed among chromatin fractions
    within the nucleus in control and aluminium-treated preparations.
    Concentrations of aluminium on highly condensed, non-transcribed
    chromatin are 15 to 20 times higher than those on active, decondensed
    chromatin (Crapper et al., 1980). Several experimental models have
    demonstrated that aluminium inhibits RNA synthesis and therefore may
    have an effect on gene expression.

         Transient change in the blood-brain barrier to [14C]sucrose have
    been observed following low-dose intraperitoneal injection of
    aluminium compounds (Kim et al., 1986). Intraperitoneal administration
    of aluminium compounds increased the permeability of the blood-brain
    barrier for a number of peptide and steroid hormones, such as
    prolactin, growth hormone, luteinizing hormone, thyroxine and
    cortisol. The greatest increase in penetration was observed for
    thyroxine, which is transported by a carrier-mediated mechanism (Banks
    & Kastin, 1985). From further studies on other transport systems, it
    was suggested that aluminium selectively alters the transport systems
    of the blood-brain barrier (Banks et al., 1988a; Vorbrodt et al.,
    1994).

    7.7  Effects on bone

         The skeleton is the principal site of aluminium deposition in the
    body. Aluminium deposited in this organ is important both because of
    its toxic effects on bone tissues and because the deposits act as a

    reservoir. Aluminium continues to be released from this reservoir to
    the blood stream for a long time after intake as a consequence of bone
    turnover, commonly referred to as bone remodelling.

         Within the skeleton aluminium, in common with most other
    polyvalent metal ions, deposits on bone surfaces within a very thin
    layer (van de Vyver & Visser, 1990). How metal ions deposit in this
    way is unclear, but three modes of uptake have been suggested.
    Firstly, the metal may become trapped within the hydration shell of
    the bone mineral crystal, secondly, it may become incorporated into
    new bone crystals as they form at sites of bone accretion, and,
    finally, they may become bound by acidic organic components of the
    bone matrix, such as phosphoproteins (Priest, 1990). Subsequently,
    much of the aluminium may remain on surfaces until it back-exchanges
    into tissue fluids or may become locked into the bone matrix. "Locked
    in" ions may then become buried to form volume deposits below bone
    surfaces, as a result of bone accretion, or may be released by the
    bone resorption process. Resorbed aluminium first enters osteoclasts
    and macrophages and then returns to tissue fluids, including blood,
    for recycling or excretion. The burial and resorption processes take
    many years in man, where only a minority of surfaces show remodelling
    activity, but occur rapidly in most experimental animals. As the rate
    of bone turnover is largely under hormonal control, it follows that
    hormones also regulate the retention by and release from the skeleton
    of the more permanent deposits of aluminium. In this respect the most
    important hormones are calcitonin and parathyroid hormone (PTH), which
    act to increase either the rate of bone formation or the rate of bone
    resorption in response to serum levels of calcium.

    7.7.1  Toxic effects of aluminium in the skeleton

         Excess deposits of aluminium in the skeleton may result in a
    syndrome commonly referred to as "aluminium-induced bone disease"
    (AIBD). This has been reviewed by Goodman (1986, 1990), van de Vyver &
    Visser (1990) and Quarles (1991). A summary of some of the animal
    models used to study osteomalacia induced by aluminium is given in
    Table 21. It should be noted that all models utilize intraperitoneal
    or intravenous routes of administration, making it impossible to
    extrapolate to the risk in humans exposed to aluminium primarily by
    the oral route. AIBD presents as a moderate to severe low bone
    turnover osteomalacia, which is often insensitive to the vitamin D
    complexes that reverse the osteomalacia of rickets. It may also result
    in the de-coupling of the bone resorption and bone accretion processes
    producing an excess volume of structurally incompetent bone (neo-
    osteogenesis) and in disturbances in the normal processes of
    endochondral ossification in the long-bone metaphyses. In osteomalacic
    bones, osteoid (the unmineralized bone matrix) fails to mineralize or
    is increased (Goodman et al., 1984a,b; Sedman et al., 1987; Quarles et

    al., 1988), tetracycline markers of bone mineralization are not
    incorporated (Ellis et al., 1979) and bone resorption is reduced,
    resulting in an increase in the volume of unmineralized bone.
    Associated with these changes is a reduction in the number of
    osteoblasts (bone-forming cells) (Robertson et al., 1983) and a
    reduction in the level of circulatory osteocalcin produced by these
    cells. If osteomalacic bones are stained for aluminium then the metal
    may be demonstrated as being present at the mineralized bone/osteoid
    interface. Where present it would seem that the aluminium inhibits the
    mineralization of osteoid, this amounting to a complete block in
    severe cases. However, the mechanism for this block is unknown.
    Goodman (1990) has suggested that it results from an impairment of the
    movement of calcium and phosphate ions from the tissue fluids to the
    face of the forming hydroxyapatite bone-mineral crystals.

         Aluminium, like some other metals, e.g., strontium, when present
    in bone crystals reduces the ability of the osteoclast (the bone
    resorbing cells) to resorb the mineral. As expected, reduced bone
    turnover may result in a reduced level of calcium in blood
    (hypocalcaemia), which, in turn, might be expected to produce changes
    in the levels of bone-active hormones in the circulation. In
    particular aluminium-induced hypocalcaemia would be expected to result
    in increased production of parathyroid hormone (PTH), in an attempt to
    stimulate bone resorption and restore normal blood calcium levels.
    However, the available evidence suggests that this does not occur and
    that the levels of circulating PTH are normal or even reduced (Goodman
    et al., 1984a). Rodriguez et al. (1990) found that PTH is able to
    stimulate osteoblasts in the presence of aluminium, but that it cannot
    improve mineralization. Similarly, there is also much evidence to
    suggest that fluoride (a potent stimulator of osteoblast numbers)
    interacts with aluminium in the skeleton by antagonizing the
    aluminium-induced reduction in osteoblast numbers, but does not
    ameliorate the aluminium-induced decrease in mineralization (Ittel et
    al., 1992).

         Of the available animal models, only the larger species, e.g.,
    dogs and pigs, consistently show osteomalacia as it presents in man
    (Goodman, 1990). In rodents bone remodelling is an unimportant feature
    of normal bone turnover (bone growth continues throughout life), and
    in these animals aluminium does not produce classical osteomalacia,
    although the changes in bone accretion, mineralization and resorption
    seen in the larger species are also seen in rats and mice. In these
    species, the disturbances seen in the ossification and resorption of
    bone under the growth cartilages may indicate a risk of similar
    occurrences in aluminium-contaminated children. Animal studies have
    shown that osteomalacia in trabecular bone is induced faster than in
    cortical bone, a result of the lower bone turnover in the latter
    (Goodman et al., 1984a,b).

        Table 21.  Experimental animal models of aluminium-induced osteomalaciaa
                                                                                                                                              

    Species        Route of      Compound  Dose           Duration of           Al concentration  Histomorphometry              Reference
                   application                            treatment             in boneb
                                                                                                                                              

    Rat (20        i.p.          AlCl3     0.27-2.7 mg    once daily; 5 days/   (15.4 µg/g),      n.d.                          Ellis et
    Wistar)                                Al/day         week; 48-85 days      109.3-176 µg/g                                  al. (1979)

    Rat            i.p.          AlCl3     N (control),   once daily; 5 days/   n.d.              % osteoid: N: 6.6;            Robertson
                                                          week; 90-120 days                       LD: 7.8; HD: 1.8;             et al.
                                           LD: 0.1 mg                                             osteoid width (µm): N: 3.3;   (1983)
                                           Al/day;                                                LD: 3.7; HD: 14.9;
                                           HD: 1.0 mg                                             tetracycline uptake:
                                           Al/day                                                 irregular, attenuated in HD

    Rat (74        i.p.          AlCl3     1.5 mg Al/kg   5 days/week;          55 mg/kg d.w.                                   Alfrey et
    male SD)                               b.w. per day   35-79 days                                                            al. (1985)

    Rat            i.p.          Al,       2 mg/day       5 days/week,          not specified     decreased bone formation      Goodman
    (weanling,                   elemental                4 weeks                                 and osteoid maturation        et al.
    male H,                                                                                       in Al-treated animals         (1984b)
    10/group)

    Rat            i.p.          Al,       2 mg/day       5 days/week,          not specified     formation of periosteal bone  Goodman
    (weanling                    elemental                44 days                                 and matrix reduced            (1984)
    male H,
    10/group)

    Rat (male      i.p.          AlCl3     1.5 mg Al/kg   5 days/week,          control:          osteoid width (µm): normal:   Chan et al.
    W, 23)                                 day;           9 weeks               1.8 mg/kg d.w.;   3.5; Al-treated: 3.0          (1983)
                                                                                Al-treated:
                                                                                47.0 mg/kg d.w.
                                                                                                                                              

    Table 21.  (Con't)
                                                                                                                                              

    Species        Route of      Compound  Dose           Duration of           Al concentration  Histomorphometry              Reference
                   application                            treatment             in boneb
                                                                                                                                              

    Rat (male      i.p.          AlCl3     10 mg/kg       5 days/week           3, 6, 9 weeks,    9 w: trabecular and           Ott et al.
    H, 18/group)                           per day                              3 weeks recovery  endosteal bone formation      (1987)
    weanling,                                                                                     decreased;
    adult                                                                                         periosteal bone formation
                                                                                                  normal, recovery to
                                                                                                  normal level

    Dog            i.v.          AlCl3     1 mg/kg b.w.   3 times weekly        control: 10.5     % osteoid surface:            Quarles
    (Beagle,                                              3 weeks               mg/kg d.w.        control: 35.6%                et al.
    6/group)                                                                    Al-treated: 73.6  Al-treated: 35.8%             (1985)
                                                                                mg/kg d.w.

    Dog (6         i.v.          AlCl3     1 mg Al/kg     3-5 weeks             (1.3 mg/kg),      % osteoid: (2.8)b 7.0         Goodman
    female                                 b.w. per day                         94 mg/kg d.w.     osteoid width: (5.7)b 8.0     et al.
    mongrel)                                                                                      poor tetracycline uptake      (1984a)

    Dog            i.v.          AlCl3     0.75 mg Al/kg  5 days/week,          (7.4 mg/kg d.w.)  number of osteoblasts         Galceran
    (female                                b.w.           3 months              202.6 mg/kg d.w.  8-fold decreased              et al.
    mongrel,                                                                                                                    (1987)
    7/group)

    Dog            i.v.          AlCl3     0.75 mg Al/kg  3 days/week,          (2.2 µg/g)        low dose, 8 weeks; reduced    Quarles
    (18 male                               b.w.           16 weeks              low dose,         bone resorption and           et al.
    Beagles)                                                                    8 weeks:          osteoblastic surfaces; low    (1988)
                                           1.2 mg Al/kg                         65.8 mg/kg low    turnover: low dose, 16 weeks;
                                           b.w.                                 dose, 16 weeks:   increased trabecular number;
                                                                                161.7 mg/kg       uncoupled bone formation
                                                                                                                                              

    Table 21.  (Con't)
                                                                                                                                              

    Species        Route of      Compound  Dose           Duration of           Al concentration  Histomorphometry              Reference
                   application                            treatment             in boneb
                                                                                                                                              

                                                                                high dose,        high dose, 8 and 16 weeks:
                                                                                8 weeks:          uncoupled bone formation
                                                                                125.2 mg/kg
                                                                                high dose,
                                                                                16 weeks:
                                                                                152.2 mg/kg

    Dog            i.v.          AlCl3     1.25 mg/kg     3 days/week:          (4.2 ng/litre)    sham op. + Al bone volume,    Quarles
    (8 male                                b.w. per day   8 weeks               sham op. + Al:    tabecular number increased    et al.
    Beagles),                                                                   147 ng/litre                                    (1989)
    normal

    Piglets        i.v.          AlCl3     1.5 mg/kg      8 weeks               (1.6 mg/kg d.w.)  osteoid seam width, osteoid   Sedman
    (8 Yorkshire)                          per day                              241 mg/kg d.w.    volume, mineralization lag    et al.
                                                                                                  time: increased; reduction of (1987)
                                                                                                  active bone forming surface
                                                                                                                                              

    a    b.w = body weight; d.w. = dry weight; H = Holtzman; i.p. = intraperitoneally; i.v. = intravenous; n.d. = no data; SD = Sprague-Dawley;
         W = Wistar; N = control; LD = low dose; HD = high dose; op = operation
    b    Control values are given in parentheses
             Neo-osteogenesis, resulting in large increases in the volume of
    trabecular bone, following aluminium administration has been observed
    in a number of animal studies (Galceran et al., 1987; Quarles et al.,
    1988, 1990) and has even been suggested as a possible treatment for
    post-menopausal osteoporosis in women. In these studies a dose and
    time-dependent effect was seen, lower levels of aluminium suppressing
    bone formation but higher doses for long periods of time resulting in
    an increased bone volume. Under such conditions it is likely that bone
    apposition has become uncoupled from bone resorption processes - a
    pathological change.

    7.7.2  Dose response

         As indicated above, the extent of pathological changes in bone
    produced by aluminium after parenteral administration is dose-
    dependent (Goodman, 1986), being barely perceptible at low doses, but
    marked or severe at high doses. However, dose response will be much
    affected by the period of aluminium accumulation, so that a single
    high intake of aluminium may produce transient changes that are more
    marked than in the case of higher accumulations over a long period. In
    general, the available evidence suggests that, as in humans, bone
    aluminium levels in the order of 100-200 µg/kg bone ash are required
    to produce these changes. The study of Ellis et al. (1979) showed that
    levels of aluminium in bone in the order of 100 µg/g bone ash produced
    few bone changes in rats, but that higher levels produced marked
    changes in the rat metaphysis and osteomalacic changes, these being
    most marked in rats with excess aluminium levels of about 200 µg/g
    bone ash. The authors found that osteotoxic doses of aluminium were
    similar in humans and rats. Longer term studies in dogs (see Table 21)
    show that low exposures to aluminium for short times produced few
    morphological changes in bone, but that similar or higher dose levels
    for a longer period did result in observable changes. Uncoupled bone
    formation (neo-osteogenesis) was produced after 16 weeks at a final
    bone aluminium level of 170 µg/g dry weight (Quarles et al., 1988). An
    earlier study by the same authors showed no observable bone changes
    after 9 weeks at a final bone aluminium content of 70 µg/g dry weight
    (Quarles et al., 1985). Similarly, human aluminium levels of this
    order are unlikely to result in osteomalacia.

    7.8  Effects on mineral metabolism

         Oral application of AlCl3 (300 to 1200 mg/kg diet) to cattle for
    84 days did not change plasma or tissue levels of calcium, phosphorus,
    magnesium or iron, although increased levels of zinc were seen in
    liver and kidney (Valdivia et al., 1978). In sheep (20 lambs) fed a
    diet supplemented with AlCl3 (2000 mg/kg for 56 days), Valdivia et
    al. (1982) observed a reduction of the apparent calcium absorption and
    lower plasma/serum phosphate levels. The ingestion of moderate
    concentrations of aluminium (aluminium lactate, aluminium palmitate, 

    aluminium phosphate, aluminium hydroxide; 5-272 µg Al/g diet) also had
    no effect on tissue calcium, magnesium or iron levels in male Sprague-
    Dawley rats (Greger et al., 1985a). Small effects were seen on tissue
    levels of phosphorus, zinc and copper. In rats receiving high
    intraperitoneal doses of aluminium (AlCl3, 2.7 mg Al/day) repeatedly
    for 10 days, the calcium concentration was increased in brain, liver
    and spleen, but not in the heart, and serum calcium levels were not
    significantly affected (Burnatowska-Hledin & Mayor, 1984). No changes
    in plasma magnesium levels were seen in this study.

         Reduced plasma magnesium concentrations were observed in cows
    (Kappel et al., 1983; Allen et al., 1986) and sheep (Valdivia et al.,
    1982) after feeding a diet supplemented with various amounts of
    aluminium chloride, sulfate or citrate. In sheep (24 lambs) fed an
    aluminium-rich diet (1450 µg/g), the magnesium content of kidney and
    bone was reduced (Rosa et al., 1982).

         From their experiments in dogs (female mongrel) receiving i.v.
    injections of AlCl3 (1 mg Al/kg body weight, 5 days/week, for 3-5
    weeks), Henry et al. (1984) concluded that the increased serum calcium
    concentration was due to an increased liberation from bone.

         In cows fed a diet supplemented with aluminium citrate
    (1730 mg Al/kg dry weight for 56 days), serum and urinary calcium
    concentrations were increased (Allen et al., 1986).

         The effect of vitamin D and its metabolites on calcium metabolism
    following aluminium intoxication was studied by Hodsman et al. (1984)
    and by Henry & Norman (1985). In vitamin-D-deficient rats receiving
    repeated intraperitoneal injections of AlCl3 (9.25 mg aluminium for
    33 days), serum calcium levels were increased regardless of the
    vitamin D status of the animals (Hodsman et al., 1984). Treatment of
    chickens with AlCl3 (5 mg Al/kg body weight intraperitoneally for 5
    days) partially blocked the intestinal calcium absorption response to
    vitamin D in vitamin-D-deficient animals, although serum calcium
    levels were elevated (Henry & Norman, 1985). No consistent effects of
    aluminium on the bone calcium mobilization response to vitamin D or
    1,25(OH)2D3 were noted. The authors concluded that the ability of
    the intestine to respond normally to 1,25(OH)2D3 may be compromised
    by the aluminium application.

         A depression of the serum phosphate level was also observed in
    vitamin-D-deficient rats receiving repeated intraperitoneal injections
    of AlCl3 (9.25 mg aluminium for 33 days; Hodsman et al., 1984).

         Aluminium forms complexes with fluoride, which are considerably
    more stable than the respective Fe3+ complexes. Ingestion of
    relatively small amounts of aluminium decreases the fluoride
    concentration available in the intestinal lumen by complexation and 

    thus fluoride absorption from the intestine. Fluoride and AlF4-
    stimulate the enzyme adenylate cyclase (Sternweis & Gilman, 1982).
    This effect presumably proceeds by complexation of Al3+ that is
    present as a contaminant of the substrate ATP, thus raising the
    effective ATP concentration (Martin, 1986).

         Aluminium exerts its protective effect from fluorine toxicosis,
    which has been reported in hens (Hahn & Guenter, 1986), turkeys (Cakir
    et al., 1977) and sheep (Saia et al., 1977), also by formation of a
    stable complex between Al3+ and F-, thus increasing the fecal
    fluoride excretion.

    8.  EFFECTS ON HUMANS

    8.1  General population exposure

         Aluminium is a potential neurotoxic agent in humans (Steinegger
    et al., 1990). Humans have highly efficient natural barriers to limit
    aluminium concentration within the central nervous system except under
    specific conditions such as renal failure. Encephalopathy attributed
    to aluminium intoxication in patients receiving treatment for chronic
    renal failure is discussed in section 8.3.1.

    8.1.1  Acute toxicity

         There is little indication that aluminium is acutely toxic by
    oral exposure despite its widespread occurrence in foods, drinking-
    water and many antacid preparations.

    8.1.2  Effects of short-term exposure

         In 1988 a population of perhaps 20 000 local residents and
    numerous tourists were exposed for 5 days or more to unknown levels of
    aluminium sulfate, subsequent to 20 tonnes of concentrated aluminium
    sulfate being accidentally placed in the Lowermoor water treatment
    plants in Camelford, England. The drinking-water also contained
    elevated concentrations of lead and copper, which leached from the
    plumbing systems due to increased water acidity. In view of the
    anecdotal reports of nausea, mouth ulcers, skin rashes and increased
    arthritic pain, some lasting for months after the exposure, the
    Cornwall District Health Authority convened a Health Advisory Group
    which prepared an official report on the incident (Clayton, 1989). The
    report described the exposure scenario and made conclusions based on
    expert knowledge of aluminium toxicity and interviews with local
    residences and tourists claiming long-lasting adverse health effects.
    No one was exposed to levels of aluminium over 100 mg/litre since such
    water is unpalatable. Levels between 10 and 50 mg/litre were found for
    only 1-3 days and water levels for the next month were above 0.2 mg/
    litre but below 1 mg/litre. The report concluded that such exposures
    should not pose a hazard to human health. Furthermore, the report
    concluded that there is no evidence to support the causation by the
    levels of aluminium, zinc, lead and sulfate of joint and muscle pain,
    memory loss, hypersensitivity or gastrointestinal disorders reported
    by residents and tourists some months after the incident. The report
    stated: "In our view it is not possible to attribute the very real
    current health complaints to the toxic effects of the incident, except
    insofar as they are the consequence of the sustained anxiety naturally
    felt by many people". Other reports, such as that of McMillan et al.
    (1993), despite containing major scientific deficiencies, do not
    provide evidence contrary to this conclusion.

    8.1.3  Neurotoxic effects

    8.1.3.1  Aluminium and Alzheimer's disease (AD)

         It has been suggested that aluminium exposure is a risk factor
    for the development or acceleration of onset of Alzheimer's disease
    (AD) in humans (Crapper McLachlan, 1986; Crapper McLachlan et al.,
    1989). The precise pathogenic role of aluminium in AD is judged
    controversial and remains to be defined (Wisniewski & Wen, 1992;
    Wischik et al., 1992; Edwardson, 1992).

    The purported association is based on six points:

    1.   The experimental induction of neurofibrillary changes in the
    neurons of certain species of animals, which suffer a unique
    progressive neurological impairment after parenteral administration of
    aluminium salts (see chapter 7). However, these neurofibrillary
    changes differ from those seen in AD in staining properties and
    ultrastructural and biochemical composition (Wisniewski & Wen, 1992).

    2.   The presence of elevated aluminium levels in bulk grey matter of
    AD-affected brains, which have been found by most investigators using
    various techniques, including graphite furnace atomic absorption
    spectroscopy (Crapper et al., 1973, 1976), neutron activation
    techniques, and inductively coupled mass spectroscopy. However, some
    investigators using the same techniques have failed to find elevated
    aluminium levels in the brains of patients with AD (McDermott et al.,
    1979; Jacobs et al., 1989).

    3.   The reported detection of aluminium in the amyloid core of
    classical plaques, neurofibrillary tangles and neuronal nuclei
    affected by neurofibrillary pathology in AD. Increased aluminium
    levels have been found within the neurofibrillary tangles of AD using
    laser microprobe mass spectrometry (LMMS) (Good et al., 1992).
    However, using the same technology, others have been unable to
    replicate these results (Lovell et al., 1993). These techniques are
    difficult. There may be technical reasons for the disparity in the
    results, or some of the differences may relate to aluminium
    contamination of fixatives and stains (Landsberg et al., 1992). AD
    patients may have an altered blood-brain barrier that allows excess
    aluminium to accumulate in the brain (Wisniewski & Kozlowski, 1982;
    Liss & Thornton, 1986; Banks et al., 1988b), although this may in turn
    be secondary to deposition of amyloid fibrils in the walls of large
    and small cerebral vessels (amyloid angiopathy) (Wisniewski et al.,
    1992). If it is accepted that aluminium levels are raised in classical
    plaques and neurofibrillary tangles in AD, it has been proposed that
    this may be a secondary phenomenon rather than the primary etiological
    agent.

    4.   Epidemiological studies showing an association between aluminium
    intake in drinking-water and an increase in the prevalence of AD. The
    methodology and interpretation of these studies is still under debate,
    and is considered further in section 8.1.3.2.

    5.   The reported decrease in the rate of disease progression in
    clinically diagnosed AD patients in one, single-blind, oral-versus-
    placebo controlled trial of desferrioxamine, a trivalent ion chelator
    administered by intramuscular injection (McLachlan et al., 1992).
    However, this study has been criticized on three grounds: a)
    desferrioxamine also chelates iron, which has been linked to free
    radical damage in AD (Andorn et al., 1990; Crapper McLachlan et al.,
    1991); b) desferrioxamine may have acted through an anti-inflammatory
    effect in this (at least partly) inflammatory disease (Crapper
    McLachlan et al., 1991); c) the absence of a double-blind placebo
    controlled design may have resulted in differential treatment of
    patients in the active arm (Wisniewski & Rabe, 1992).

    6.   The reported interactions of aluminium with ś-amyloid protein
    (the major component of AD plaques) and with purified paired helical
    filament tau protein (the major component of neurofibrillary tangles,
    NFTs). The neurotoxicity of ś-amyloid and the formation of plaque
    deposits is dependent on its aggregation, which has been found to be
    promoted by low millimolar concentrations of aluminium, iron and zinc
    (Mantyh et al., 1993). However, this pattern of results has been
    attributed to iodination-induced alteration of the ś-protein structure
    by Bush et al. (1994), who reported that zinc is a much more potent
    metallic ion aggregator of native ś-protein than aluminium, being
    active at low micromolar concentrations.  In vitro studies have
    failed to induce Alzheimer-type paired helical filaments (PHFs) in any
    cellular system. However, human neuroblastoma cells in tissue culture,
    exposed to aluminium, exhibit epitopes found in AD tangles. Mesco et
    al. (1991) reported aluminium induction of the well-known Alz50
    epitope-recognizing NFT, and Guy et al. (1991) reported the
    development of an epitope, recognized by an antibody staining for NFT
    and neuropil threads. Alz50 expression is also observed in
    experimental aluminium encephalopathy. Shin et al. (1994) have found
    that aluminium binds to and stabilizes paired helical filament tau,
    both  in vitro and  in vivo. Although aluminium-stabilized PHF tau
    induced co-deposition of ś-protein  in vivo, the relevance of these
    recent unconfirmed findings to AD is as yet unclear.

         It seems likely that the causation and pathogenesis of AD is
    multi-factorial (i.e. it may be regarded as a syndrome rather than a
    disease) and that genetic factors and environmental factors each
    contribute to a greater or lesser extent in the individual case.
    Recent genetic studies show that in a small proportion of dominant
    familial cases, a single point mutation near or in the ś-protein
    segment of the amyloid precursor protein is necessary to cause the
    disease - a situation of great theoretical importance despite its
    rarity (Goate et al., 1991).

         Other familial AD pedigrees have been linked to a locus on
    chromosome 14 (St. George-Hyslop et al., 1992; van Broeckhoven et al.,
    1992). Apo-E allele status is also a major risk factor, the presence
    of one E4 allele conveying a relative risk of about 3 (Saunders et
    al., 1993). Other environmental risk factors include low educational
    and socio-economic status, and head injury (van Duijin et al., 1991).
    It is against this knowledge base that the possible contribution of
    aluminium to AD must be evaluated.

    8.1.3.2  Epidemiological studies on AD and environmental aluminium
             levels

         Many studies have examined risk factors for AD. Among the many
    case control studies that have been carried out, head trauma, family
    history, thyroid status, maternal age, child with Down syndrome all
    stand out as important risk factors (van Duijn et al., 1991).
    Aluminium exposure as a single risk factor began to be examined in the
    early 1980s, when reports of the increased level of aluminium in
    brains of AD patients suggested that this might also be a factor. The
    availability of water-borne aluminium measurements in many public
    water supplies and of readily available vital statistics made the
    study of this exposure relatively accessible.

         Studies that examine the relationship between aluminium in
    drinking-water and AD have been carried out in five separate
    populations: Norway (Flaten, 1990), Ontario, Canada (Neri & Hewitt,
    1991; McLachlan, 1996), France (Michel et al., 1991; Jaqmin et al.,
    1994), Switzerland (Wettstein et al., 1991) and England (Martyn et
    al., 1989). These are summarized in Table 22. Several studies examined
    the water aluminium-AD relationship in the course of investigating
    other associations (Wood et al., 1988; Frecker, 1991). In addition,
    exposure from aluminium-containing antiperspirants (Graves et al.,
    1990) and aluminium-containing antacids (Flaten et al., 1991) have
    also been explored as risk factors for dementia and/or AD.

         Each of the studies that relate aluminium in drinking-water to
    AD can be assessed systematically for comparability of exposed and
    control groups, precision of exposure assessment and outcome
    definition. Ideally, exposed and control groups should be controlled
    for age, sex, socio-economic status and other variables that can
    confound results (e.g., education, family history, etc.). Exposure
    should include concentration and duration for each member of the study
    group and include a dose range which can be used to assess dose-
    response relationships. The outcome should be measured preferably by
    standard criteria, not by surrogates (e.g., dementia for AD), and
    latency should be incorporated into the analysis (Smith, 1995).

        Table 22.  Summary of epidemiological studies of aluminium in drinking-water and dementia or Alzheimer's disease (AD)a
                                                                                                                                              

    Type of study   Exposure measure of               Outcome measure/                      Results                             Reference
                    aluminum intake                   data source                           RR
                                                                                                                                              

    Ecological      aluminum in drinking-water        mention of dementia                   AD only                             Flaten
                    (concurrent)                      ICD9 290, 290.1 (dementia)                                                (1990)
                    4 seasonal samples                342.0 (Parkinson's disease)           Al         Males    Females
                                                      348.0 (ALS); sex-adjusted             < 0.05     1.00     1.00
                                                      death certificate                     0.05-0.2   1.15     1.19
                                                                                            > 0.2      1.32     1.42
                                                                                            PD and ALS - no gradient

    Morbidity       aluminum in finished drinking-    dementia by diagnostic category       all males and females               Martyn et
    prevalence      water; historical                 (not standard)                        RR 1.3-1.5, no dose-response        al. (1989)
                                                      CT scan center records                < 65 males and females
                                                      age-sex-adjusted                      1.4-1.7b, dose response

    Morbidity       finished drinking-water           "cases" were hospital discharges      RR from OR, gradient for AD         Neri &
    prevalence      aluminum; historical              with Dx of AD (ICD9 331.0),                                               Hewitt
    case control                                      presenile dementia (ICD9 290).        Al                RR from OR        (1991)
                                                      age/sex/residence-matched             < 0.01            1.00
                                                      controls with other Dx                0.01-0.099        1.13
                                                                                            0.10-0.199        1.26
                                                      HMRI data base - Ontario              > 0.2             1.46

    Morbidity       aluminum in finished drinking-    mnemic skills in octogenerarians      no difference in mean scores of     Wettstein
    prevalence      water; residence >15 years        urinary and serum Al                  tests for cognitive function        et al.
                                                                                                                                (1991)
                                                                                                                                              

    Table 22.  (Con't)
                                                                                                                                              

    Type of study   Exposure measure of               Outcome measure/                      Results                             Reference
                    aluminum intake                   data source                           RR
                                                                                                                                              

    Morbidity       urinary aluminum and serum        sample of 800 residents in high       slightly higher serum aluminium     Wettstein
                    aluminum; historical and          & low aluminum areas 10 AD            in AD in low aluminium areas;       et al.
                    concurrent                        patients & controls in each area      similar urinary excretion in AD     (1991)
                                                                                            and controls
                                                      age, sex, education
                                                                                            hypothesis of association not
                                                      population based                      supported

    Morbidity       aluminum in drinking-water;       cognitive function in sample of       probable AD - gradient-adjusted     Michel
    prevalence      historical                        > 65 years by test battery            for age, education, residence       et al.
                                                      (DSM III)                                                                 (1991)
                                                                                            RR 4.53/100 µg/litre aluminium
                                                      population-based (2792); age, sex,    (NSS); RR corrected to NS with
                                                      education, ses, Al in water - many    current aluminium measurement
                                                      sources for the data

    Case control    aluminium in drinking-water;      pathological; confirmation of         RR 1.7 aluminium > 100 µg/litre     McLachlan
                    residence-weighted                diagnosis in all cases and controls   RR 2.5 aluminium > 100 µg/litre     et al.
                    historical                        no age-sex-education adjustment       based adjustment for 10-year        (1996)
                                                                                            weighted exposure history

    Morbidity       aluminum in water, pH,            cognitive function                    calcium protective                  Jacqmin
    prevalence      calcium                                                                 RR = 1.2 with pH < 7.3              et al.
    case control                                                                            NS /all other pH values             (1994)
                                                                                                                                              

    a    AD = Alzheimer's disease; PD = Parkinson's disease; RR = relative; OR = odds ratio; NS = not significant; ses = socioeconomic status
    b    Significant (P < 0.05) of highest exposure only
             In addition, a variety of study designs from least powerful to
    most powerful will allow a progressive assessment of the relationship
    under study (e.g., ecological, cross-sectional, case control, cohort).
    Nearly 20 studies that examine the relationship between AD and
    drinking-water aluminium levels have been published.

         Studies in five populations using different design are of
    sufficient quality and meet the general criteria for exposure and
    outcome assessment and for the adjustment of at least some confounding
    factors (e.g., age and sex) in order to be used here to evaluate the
    relationship between water-borne aluminium and AD.

         Results of four studies are consistent for a positive
    relationship between water-borne aluminium and AD (Martyn et al.,
    1989; Neri & Hewitt, 1990; Flaten et al., 1991; McLachlan et al.,
    1996). Three found a "dose-response" relationship (McLachlan, 1989;
    Flaten, 1990; Neri & Hewitt, 1991) and one found a significant
    relationship between high and low aluminium exposure (Martyn et al.,
    1989). Adjustment for sex was performed in two of these studies
    (Martyn et al., 1989; Flaten, 1990). One study (McLachlan et al.,
    1996) did not adjust for age, sex or any other confounding factor but
    did correct for "during life" exposure.

         With regard to exposure assessment, all of the positive studies
    used ecological assessment of exposure but from only one source, the
    public water supply. Total exposure to aluminium was not determined.
    It is therefore impossible to determine if the relationship observed
    is due to water aluminium alone without explicit adjustment for, and
    information about, other sources of aluminium intake.

         Studies that showed no association between water aluminium and AD
    (Wettstein et al., 1991; Michel et al., 1991) were more precise in
    their outcome measure. However, the water aluminium levels were very
    low and corresponded to the water aluminium levels found as the lowest
    concentrations of the studies that showed a positive association.

         Initial results reported by Michel et al. (1991) in the Bordeaux
    cohort study showed a high, though not significant, risk (4.5) for
    exposure to water aluminium levels greater than 0.10 mg/litre when
    10- to 15-year historical analyses of water were used. When current
    analyses of water were used, the relationship disappeared (Jacqmin et
    al., 1994). However, other relationships appeared, such as the
    increase in risk of cognitive impairment when the pH was below 7.3, a
    decrease in risk with a pH greater than 7.3, and no elevated risk when
    pH was not considered. An inverse relationship was found between
    cognitive impairment and calcium concentration (Jacqmin et al., 1994).

         The initial observation of elevated risk for cognitive impairment
    with a set of numbers that were possibly random (Flaten, 1990) and the
    changes in risk level with other water quality parameters such as
    calcium and pH are difficult to interpret and require further
    evaluation.

         Studies with more precise outcome and exposure measures would be
    expected to show the highest relative risks or odds ratios.

         McLachlan et al. (1996) examined the relationship between
    autopsy-confirmed AD and aluminium in drinking-water. The odds ratio
    of exposure to water above 100 µg/litre was calculated for confirmed
    cases of AD and a combination of AD and other neuropathology, compared
    to controls. Cases and controls were obtained from brains donated to a
    tissue bank supported by lay organizations. Control neuropathology
    included normal brains and brains with non-AD neuropathology. The
    aluminium level in water was obtained from a data bank of water
    measurements for public water supplies. A next-of-kin interview was
    used to refine exposure by weighing for length of residence by
    assigning exposure to residence not to place of death.

         The odds ratio of exposure to water with an aluminium
    concentration of > 100 µg/litre for AD alone compared to controls
    was 1.7 (1.2-2.5). The use of weighted exposure measures (residential
    group levels of aluminium in water) increased the odds ratios for the
    same comparison groups to 2.5 or more.

         The use of pathologically confirmed outcome measures and of
    accurate exposure measures brings added strength to the studies
    examining the relationship between aluminium and AD. Notwithstanding,
    this study is subject to selection bias of the sample (voluntary
    donation to a tissue bank), the possibility of misclassification of
    the ecological measure of exposure and a failure to account for
    confounding factors.

         The study of McLachlan et al. (1996) does show the highest
    relative risks of any of these studies. However, this study suffers
    from lack of adjustment for very important known risk factors, such as
    age, sex, education and socioeconomic status.

    8.1.3.3  Epidemiological studies relating aluminium concentrations in
             water to cognitive dysfunction

         Wettstein et al. (1991) looked for a relationship between water
    aluminium levels up to 98 µg/litre and cognitive function in a male
    population (800 men) of octogenarians but found none (OR = 0.92)
    (CI = 0.66-1.29).

         Forbes et al. (1994) examined a cohort of 2000 men followed since
    1959 in a longitudinal study of ageing. The outcome measure examined
    was "any evidence of mental impairment" as measured by skills of daily
    living assessment. In the survivors of the cohort for whom information
    was available (290 individuals), exposure was linked to the level of
    aluminium in their drinking-water obtained from the Ontario Canada
    Drinking Water Surveillance database. In an analysis that considered
    fluoride and aluminium in drinking-water, the odds ratio after
    exposure to water with high aluminium and low fluoride levels was 3.98
    [CI = 1.72-9.19]. In a multi-variate analysis, which adjusted for a
    variety of confounding factors, the adjusted odds ratio for high
    aluminium level (> 85 µg/litre) was 1.72 (1.08-2.75).

    8.1.3.4  Other neurological conditions in the general population

         Other severe neurological diseases, such as amyotrophic lateral
    sclerosis, Parkinsonism and the dementia complex of Guam, have been
    related to aluminium accumulation in the brain (Gajdusek & Salazar,
    1982; Perl et al., 1982; Garruto et al., 1984). However, the role of
    aluminium in these conditions is still under considerable scientific
    debate.

    8.1.3.5  Conclusions regarding neurological effects of aluminium

         The positive relationship between aluminium in drinking-water and
    AD, which has been demonstrated in several epidemiological studies,
    cannot be totally dismissed. However, strong reservations about
    inferring a causal relationship are warranted in view of the failure
    of studies to account for demonstrated confounding factors and for
    aluminium intake from all sources.

         Taken together, the relative risks for AD from exposure to
    aluminium in drinking-water at levels above 100 µg/litre as determined
    in these studies are low. But, because the risk estimates are
    imprecise for a variety of methodological reasons, a population-
    attributable risk cannot be calculated with precision. Such
    predictions may, however, be useful in making decisions about the need
    to control the exposure to aluminium in the general population.

         In light of the above studies, which consider water-borne
    aluminium as the sole risk factor, and the recent findings that water
    accounts for less than 5% of daily uptake of aluminium, it is
    difficult to reconcile a presumable impact on cognition. Several lines
    of investigation should be pursued to elucidate further the nature of
    the relationship found in these studies (see Chapter 12).

    8.1.4  Allergic effects

         Although human exposure to aluminium is widespread,
    hypersensitivity has been reported following exposure to some
    aluminium compounds in only a few cases, either after dermal
    application or parenteral administration.

         A case of contact sensitivity to aluminium was reported in
    Sweden. The patient had regularly been using an aluminium chloride
    roll-on antiperspirant and developed an itchy dermatitis in the
    axillae. Patch-tests with aluminium chloride were positive (Fischer &
    Rystedt, 1982). Contact allergy to aluminium also occurred in a
    patient hyposensitized with aluminium-precipitated grass pollen
    (Clemmensen & Knudsen, 1980). Two cases of contact allergy to
    aluminium after use of topical medications containing aluminium
    acetotartrate have been reported (Meding et al., 1984).

         Childhood immunization with an aluminium-bound vaccine can lead
    to delayed hypersensitivity to aluminium. Children who had had
    previous injections with these vaccines showed positive patch-tests to
    aluminium chloride (Böhler-Sommeregger & Lindemayr, 1986; Veien et
    al., 1986).

         In Denmark a follow-up study was made of 202 children (age
    6-15 years) who had received hyposensitization therapy with various
    aluminium-containing extracts (subcutaneous application) for
    an average of 3 years. One to three years after cessation of
    hyposensitization, 4% (13 children) still had severely pruriginous
    treatment-resistant subcutaneous nodules in their forearm (application
    site). Six of these 13 children were patch-tested and four reacted
    positively on aluminium chloride administration (Frost et al., 1985).

    8.2  Occupational exposure

         This section deals with the effects observed in occupations where
    workers are exposed to aluminium metal and aluminium compounds. Where
    exposures are to mixed dusts and/or chemical mixtures, one cannot
    infer causality between aluminium exposure and effects from studies on
    such workers.

    8.2.1  Respiratory tract effects

         Respiratory disorders among workers in the aluminium industry
    have been reviewed in detail (Dinman, 1988b; Abramson et al., 1989).

    8.2.1.1  Restrictive pulmonary disease

         Historically, pulmonary fibrosis has been associated with various
    jobs within the aluminium industry. Shaver's disease (described in the
    1940s) was a form of silicosis associated with the production of

    corundum abrasives (Shaver & Riddell, 1947). Another historically
    important occupational exposure associated with pulmonary fibrosis was
    experienced by "pyro powder" workers, who were exposed to very fine
    stamped aluminium powder (generally < 1 µm), including that used in
    the manufacture of explosives and fireworks (Doese, 1938; Meyer &
    Kasper, 1942; Mitchell et al., 1961; Jordan, 1961; McLaughlin et al.,
    1962; Gross et al., 1970). In that process, oils and solvents were
    used to coat particles to prevent naturally occurring oxidation, and
    nearly all cases of fibrosis were reported in workers exposed to
    mineral-oil-coated particles. That process is no longer used (Dinman,
    1988a) and only one case has been reported since 1960 (McLaughlin et
    al., 1962). This syndrome indicates the potential pulmonary effect of
    non-oxidized aluminium metal, but such exposures do not occur in
    nature.

         In a report of nine cases of workers exposed to aluminium oxide
    (mean duration of exposure 25 years), abnormal chest roentgenograms
    were described, as well as pathological lung functions in three of the
    cases (Jederlinic et al., 1990). Biopsies were taken from these three
    patients and analysed by electron microscopy and microprobe analysis.
    Interstitial fibrosis was the main histological finding. Metals
    occurred in amounts several orders of magnitude above background
    levels and the majority was aluminium oxide. The authors stated that
    aluminium oxide was the most likely cause for the development of
    interstitial fibrosis in these workers and that asbestos could be
    ruled out. Exposure to a "mixed dust", including free silica, also
    seemed to be a possible explanation.

         With the exception of this exposure, pathological findings
    associated with aluminium exposure listed in Table 23 refers to mixed
    exposures, and cannot be solely attributed to aluminium. Other
    exposures, such as to silica or other metals, must be considered.

    8.2.1.2  Obstructive pulmonary disease

    a)    Asthma

         A potentially persistent form of occupational asthma related to
    primary aluminium smelting (pot room asthma) has been reported over
    the past 35 years; reversible symptoms, airflow limitation and
    increased bronchial responsiveness have been described (O'Donnell et
    al., 1989). The likely causes are irritant airborne particulate and
    fumes contributed by cryolite (sodium aluminium fluoride), gaseous
    hydrogen fluoride and other agents that may be adsorbed onto
    aluminium. A close relationship in aluminium potroom workers between
    levels of exposure to fluoride, which may be one of a number of

        Table 23.  Clinical and pathological pulmonary findings in aluminium-exposed workersa
                                                                                                                                              

    Exposure              Clinical effects                Pathological changes                 Confounding exposures             Reference
                                                                                                                                              

    Aluminium powder      cough, DOE, abnormal            pulmonary alveolar proteinosis       iron, kaolinite, mica, rutile,    Miller et al.
    grinder for 6 years   X-ray, restrictive PFTs                                              calcium at biopsy                 (1984)

    Polisher for          cough, DOE                      bronchogenic cancer; diffuse         stainless steel, chromium,        de Vuyst et
    24 years                                              interstitial fibrosis                nickel, cigarettes (45 packet-    al. (1986)
                                                                                               years), silica (biopsy)

    Catalyst fabrication  cough, DOE, mild restriction    non-caseating granuloma;             iron, copper, zinc, nickel,       de Vuyst et
                          no clinical evidence            T-lymphocyte alveolitis              chromium, manganese, cobalt,      al. (1987)
                          of sarcoid                                                           molybdenum, vanadium,
                                                                                               palladium, silica, nobellium
                                                                                               on biopsy; cigarettes

    Welding fumes         mild ventilatory restriction    diffuse and focal fibrosis;          iron, cigarettes                  Vallyathan
                                                          pigmented content of macrophages                                       et al. (1982)

    Welding fumes,        X-ray interstitial pattern;     interstitial granuloma,              smoker, no TB                     Chen et
    intermittent welder   dyspnoea                        macrophages, foreign body giant                                        al. (1978)
    (1965-1970)                                           cells, crystals, EDA indicated
                                                          aluminium crystals

    Welder for 16 years   dyspnoea, X-ray bilateral,      lung biopsy, diffuse chronic         ex-smoker                         Herbert et
                          hazy basal infiltrates,         interstitial pneumonia,                                                al. (1982)
                          reduced TLC (3.5/6.8)           predominantly desquamative
                                                                                                                                              

         DOE = dyspnoea on exertion; TLC = total lung capacity (measured/predicted (6.8 litres)); EDA = energy dispersive analysis;
         PFT = pulmonary function test; TB = tuberculosis
        general inhalant irritants, and the work-related asthmatic symptoms
    has been shown (Kongerud et al., 1990; Kongerud, 1991). A positive
    association between plasma levels of fluoride and increased bronchial
    responsiveness has also been reported (Söyseth et al., 1994).

         A similar occupational asthma ascribed to irritant particulate
    has also been described among workers following technical failure in
    plants producing aluminium fluoride and aluminium sulfate (Simonsson
    et al., 1985) and in solderers working with potassium aluminium
    tetrafluoride flux (Hjortsbert et al., 1994).

    b)    Chronic bronchitis

         Aluminium production and processing may lead to high levels of
    workplace exposure to dusts and particulate.

         In Italy the possible association of aluminium exposure and
    pneumoconiosis was investigated (Saia et al., 1981). Chronic
    bronchitis symptoms were found in 39% of the 119 exposed workers and
    in 13% of the 119 control subjects. The X-ray findings showed one kind
    of pneumoconiosis with small irregular opacities or accentuation of
    broncopulmonary markings in 29% of the exposed workers and in 15% of
    the controls.

         A case study of 2086 employees at the Arkansas operations of a
    large aluminium production company was performed (Townsend et al.,
    1985). The study indicated that long-term high accumulative dust
    exposure was associated with decreased levels of pulmonary function in
    active workers at a bauxite refinery and aluminium-based chemical
    products plant. A follow-up study of this cohort (Townsend et al.,
    1985) supported the conclusion regarding respiratory effects of dust
    in the workplace related to lung function.

         In a cross-sectional study (Sjögren & Ulfvarson, 1985) on 64
    aluminium welders and 64 age-matched controls (non-welding industrial
    workers), an increased prevalence of chronic bronchitis was observed
    but there were no effects on pulmonary function. The prevalence of
    chronic bronchitis among aluminium welders was similar to that of
    welders working with stainless steel or iron.

    8.2.2  Central nervous system effects

         A number of neurological effects have been associated with
    occupational exposure to aluminium, including impairment of cognitive
    function, motor dysfunction and peripheral neuropathy.

         Welders exposed to aluminium fumes for about 13 years had
    significantly more neuropsychiatric symptoms (ascertained from
    positive answers in a questionnaire) than railway track welders not
    exposed to aluminium (Sjögren et al., 1990). Despite the potential
    bias associated with the questionnaire methodology used in this study,
    a dose-response effect was seen.

         In a further study (Sjögren et al., 1994b) 38 aluminium-exposed
    welders (median urinary aluminium level, 22 µg/litre; median exposure
    time, 4.5 years) were compared with a group of 39 iron-exposed
    welders. Small decrements in the speed of repetitive motor functions
    were found, but there were no differences in other neurophysiological
    or neuropsychological parameters.

         A mixture of finely ground aluminium (85%) and aluminium oxide
    (15%) powder was used between 1944 and 1979 as a prophylactic against
    silicosis. Underground gold and uranium miners were exposed to an
    aluminium dust concentration of 20 000-34 000 particles/ml air
    (approximately 30 mg/m3) in their changing room before each shift for
    10 min (Rifat et al., 1990). Exposure to aluminium powder in the
    cohort ranged from 6 months to 36 years. A yearly deposition in each
    miner of about 375 mg of aluminium powder has been calculated.

         From the 29 000 underground miners examined in provincial chest
    clinics between 1955 and 1979, a sampling frame was constructed
    containing a cohort of 6604. Two samples were drawn from this cohort.
    One sample consisted of 369 exposed and 369 unexposed matched miners
    adjusted for age and year of their first mining experience in Ontario,
    Canada, and total mining time. The second sample consisted of 678
    randomly drawn miners in equal numbers from the exposed and unexposed
    populations. Between 1988 and 1989, miners who could be traced were
    interviewed and psychometric testing was performed. Cognitive test
    scores and proportions impaired in at least one test indicated a
    disadvantage for exposed miners. A positive exposure-related trend in
    increased risk was described.

         A group of 87 workers (average age 40.7 years) from an aluminium
    foundry exposed to workplace aluminium concentrations ranging between
    4.6 and 11.5 mg/m3 air, with an exposure time of at least 6 years,
    was studied by Hosovski et al. (1990). Sixty non-exposed workers
    matched for age, job, seniority and social status served as control.
    Psychomotor and psychometric tests were performed, except on workers
    who consumed alcohol or who had taken psychotropic drugs within a
    month prior to the test. A significant difference in complex reaction
    time, oculomotor coordination and the sum of manipulative tests was
    noted in exposed workers compared to controls. In the Weschler Adult
    Intelligence Scale (WAIS), the most significant differences were found
    in the memory subtest.

         In contrast, Bast-Petersen et al. (1994) did not find any
    impairments in small groups of foundry workers (8) or potroom workers
    (14) in a broad battery of psychometric tests. A cluster of aluminium
    potroom workers exposed to unhooded pots for 4 or more years displayed
    an increased incidence of impairment of cognitive function and/or
    defects in motor control. However, insufficient biochemical
    investigations were undertaken to determine whether aluminium or other
    potential neurotoxins were the causative agent (Longstreth et al.,
    1985; White et al., 1992).

         In a case where a man was exposed to ultrafine aluminium powder
    for 13.5 years in the ballmill area of an aluminium factory, the
    individual died following a rapidly progressive encephalopathy, and
    his brain was found to contain elevated aluminium levels (McLaughlin
    et al., 1962).

    8.3  Cancer

         There is insufficient information to allow for the classification
    of the cancer risk from human exposures to aluminium and its
    compounds.

    8.4  Genotoxicity

         In an abstract, Haugen et al. (1983) reported no increase in the
    number of sister chromatid exchanges in peripheral blood lymphocytes
    of workers employed in an aluminium factory. There have been no
    reports concerning genetic effects of aluminium in humans following
    oral exposure to aluminium.

    8.5  Reproductive toxicity

         There is no information regarding reproductive toxicity in humans
    following exposure to aluminium.

    8.6  Subpopulations at special risk

         Aluminium intoxication developed over weeks or months in patients
    with chronic renal failure when dialysis fluids or parenteral
    solutions contained aluminium (Alfrey et al., 1972; Klein, 1991), or
    when the main source was aluminium-containing oral phosphate binders.
    In patients suffering from renal failure, increases in serum and
    tissue aluminium concentration were observed. The increased aluminium
    content in brains of patients with renal failure seems to be the major
    etiological factor in the development of the neurological syndrome
    termed either dialysis encephalopathy or dialysis dementia. The
    development of a specific form of osteomalacia and of microcytic,
    hypochromic anaemia is also attributed to aluminium (Ward, 1991).

         Aluminium intoxication is caused by using haemodialysis fluids
    made from tap water without removal of the aluminium (Elliot et al.,
    1978). After the introduction of water treatment with a combination of
    filtration, softening, carbon absorption, reverse osmosis and
    de-ionization, these clinical syndromes were prevented. Nephrologists
    limit the exposure to aluminium from dialysis fluids and drugs. This
    follows the introduction of guidelines in the USA, Canada, Japan and
    the EEC. As a consequence, in most dialysis centres the dialysis
    fluids are monitored and the aluminium level is kept below
    0.4 µmol/litre (10 µg/litre). Aluminium-free phosphate-binding agents
    such as calcium carbonate are preferably used for oral medication. The
    same clinical syndromes have been described in patients with renal
    impairments, including premature infants who have not been dialyzed,
    and are a consequence of aluminium accumulation from aluminium-
    containing pharmaceutical products and parenteral solutions (Finberg
    et al., 1986).

    8.6.1  Encephalopathy

         Dialysis encephalopathy is a complication of prolonged
    haemodialysis first described in 1972 (Alfrey et al., 1972). The main
    symptoms are speech disorder followed by the development of dementia,
    convulsions and myoclonus. The mean duration of dialysis was 48 months
    and the dialysis fluids were made with untreated tap water. Elevated
    aluminium contents were found in the brain, muscle and bone tissues
    of the affected patients. The same findings were reported from
    other dialysis centres in Europe and the USA. Many outbreaks of
    encephalopathy have been described in association with the use of
    dialysis fluids containing a high concentration of aluminium, usually
    above 200 µg/litre (Flendrig et al., 1976; McDermott et al., 1978;
    Alfrey, 1978).

         In a study with 55 patients suffering from dialysis
    encephalopathy in six dialysis centres using a uniform clinical
    classification, the incidence of dialysis encephalopathy rose
    significantly with increasing cumulative exposure to aluminium via the
    dialysate (Schreeder et al., 1983).

         Epidemiological studies of dialysis centres in England showed
    that encephalopathy was almost non-existent in those centres using
    water with aluminium concentrations less than 50 µg/litre to prepare
    dialysis fluids. The incidence of encephalopathy rose progressively
    with higher water concentrations of aluminium. The Registration
    Committee of the European Dialysis and Transplant Association made a
    European survey, which showed clusters of encephalopathy in certain
    areas of Britain, Spain, Greece and Scandinavia. In Britain, 92% of
    the patients in these areas had been treated with dialysis fluids made
    from softened tap water (Kerr & Ward, 1988). No signs of overt
    aluminium toxicity were observed in 27 long-term haemodialysis
    patients on dialysis fluids containing low aluminium concentrations
    (Altmann et al., 1989) and these subjects had only mildly elevated

    serum aluminium levels. However, defects in several tests of
    psychomotor function, including digit coding, were found.

    8.6.2  Osteomalacia

         Osteomalacia has also been observed in patients with chronic
    renal failure, exposed to aluminium in dialysis fluids, or in infants
    with renal failure treated with aluminium hydroxide to control
    hyperphosphataemia (Ward et al., 1978; Andreoli et al., 1984). Bone
    pain, myopathy, pathological fractures and poor response to vitamin D
    therapy are the characteristic symptoms of osteomalacia, accompanied
    by radiological changes, including partial and complete non-healing
    fractures, osteopenia, and reduction in calcified bone area (Simpson
    et al., 1973). When aluminium was removed from fluids used for
    dialysis, the incidence of osteomalacia diminished. The level without
    undue risk was estimated to be 30 µg/litre or less (Platts et al.,
    1984). The aluminium content of the bone is increased in patients with
    renal disease, treated by haemodialysis, and this aluminium may remain
    in the bone even after successful renal transplantation (Ellis et al.,
    1979). The aluminium in patients with osteomalacia was found to be
    mainly localized at the interface between the osteoid and the
    calcified matrix (Cournot-Witmer et al., 1981). Vitamin-D-resistant
    osteomalacia due to aluminium is a progressive metabolic bone disease.
    The mechanism for the disordered bone formation remains to be
    clarified.

    8.6.3  Microcytic anaemia

         In a study of ten aluminium-intoxicated dialysis patients,
    microcytic anaemia was observed. The disease was reversible after
    deionization of the dialysis water (Touam et al., 1983). The mechanism
    by which an excess of aluminium induces microcytic anaemia remains to
    be clarified (Wills & Savory, 1983, 1989).

    9.  EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

    9.1  Laboratory experiments

    9.1.1  Microorganisms

         Den Dooren de Jong (1971) inoculated a medium containing
    aluminium chloride (10-4 mol/litre) with three  Azobacter strains.
    After incubation for 1 to 2 days, the aluminium had produced an
    inhibition zone of 14 mm with increased pigmentation at the edges. The
    inhibition zone, when compared with that produced by other metals, was
    found to indicate intermediate toxicity.

    9.1.1.1  Water

         Sheets (1957) studied the effect of shock loadings of aluminium
    sulfate on the biochemical oxygen demand of sewage sludge and found
    that a concentration of 18 mg/litre caused a 50% reduction.

         Panasenkov (1987) found that aluminium sulfate at concentrations
    of 0.1 and 1 mg/litre had no effect on the heterotrophic fixation of
    14CO2 or the number of saprophytes of a natural bacterial coenosis.
    However, at 10 mg/litre aluminium sulfate reduced these two parameters
    by 50% and 60%, respectively.

         Dobbs et al. (1989) studied the effect of complexation on the
    toxicity of aluminium using the Microtox system based on measurement
    of the light output of a luminescent bacterium. Aluminium citrate
    complexes were essentially non-toxic up to levels of at least
    25 mg Al/litre. The one-hour EC50, defined as a 50% reduction in
    light output, was 300 µg/litre in the absence of citrate. Complexation
    by fluoride was complicated by a toxic response to fluoride itself.
    Correction for this effect still revealed an appreciable toxicity of
    aluminium fluoride complexes. The toxic response in the presence of 9
    and 36 mg/litre fulvic acid was reduced by 24% and 61%, respectively.
    Hoke et al. (1992) reported 15-min EC50 values (Microtox tests) for
    aluminium chloride (as aluminium) of 5.57 and 3.31 mg/litre for
    solutions osmotically adjusted with 22% sodium chloride and 20.4%
    sucrose, respectively.

    9.1.1.2  Soil

         Zwarun et al. (1971) found the soil bacterium  Bacillus sp. to
    be resistant to aluminium. Increasing acidity from pH 6.6 to pH 4.5
    reduced the number of surviving cells suspended for 3 h in an acetate
    buffer. Addition of 80 mg Al/litre produced no further reduction, even
    though the cell walls were saturated with aluminium. Zwarun & Thomas
    (1973) exposed the soil bacterium  Pseudomonas stutzeri to acidic

    conditions at aluminium concentrations of 1, 10 and 80 mg/litre for
    3 h. Increasing the acidity reduced the number of surviving cells. The
    addition of aluminium (10 mg/litre) at pH 4.5 significantly reduced
    the survival rate of cells, and 80 mg/litre was lethal.

         Thompson & Medve (1984) studied the effects of aluminium
    (0-500 µg/ml) on the growth of the ectomycorrhizal fungi  Cenococcum 
     graniforme, Suillus luteus, Thelephora terrestris, and three
    isolates of  Pisolithus tinctorius (all four species are commonly
    found on spoil tips).  T. terrestris was the most sensitive species
    showing no growth at aluminium concentrations > 150 µg/ml, whereas
     S. luteus was the most tolerant, being unaffected at aluminium
    concentrations < 350 µg/ml. The other species showed reduced growth
    at all aluminium concentrations. However, the results obtained were
    not consistent with field observations.

         The severity of the incidence of the fungal disease potato scab
    was reduced by the addition of aluminium (Mizuno & Yoshida, 1993).

    9.1.2  Aquatic organisms

    9.1.2.1  Plants

         Algal assays are often carried out in culture media containing
    high concentrations of nutrients, including phosphate. These nutrients
    ameliorate the toxicity of aluminium, and limit the application of the
    results to natural waters. For example, in culture medium the green
    alga  Chlorella pyrenoidosa successfully grew at concentrations of
    up to 12 mg total aluminium/litre at pH 4.6, but an aluminium
    concentration of 24 mg/litre was toxic. By selecting those algae which
    tolerated high levels of aluminium, the authors were able to develop
    algal cultures that grew at up to 48 mg/litre (Foy & Gerloff, 1972).
    However, Helliwell et al. (1983) found that maximum toxicity of
    aluminium to algal growth was achieved at pH 5.8 to 6.2, 5 µg labile
    Al/litre significantly inhibiting the growth of the alga  Chlorella 
     pyrenoidosa in a synthetic hard water. The assay showed that
    toxicity is a function of the labile, rather than the total,
    aluminium. It was found that Al (OH)2+ was the aluminium species
    most toxic to the alga. Similar results were reported by Parent &
    Campbell (1994), although they found that polymerized aluminium
    species were also toxic.

         Bringmann & Kühn (1959) found a toxic threshold of 1.5 to
    2 mg/litre aluminium chloride for the green alga  Scenedesmus 
     quadricauda. Rueter et al. (1987) found that a concentration of
    60 µmol aluminium/litre at pH 5.7 is required to produce any
    inhibitory effect on the growth rate of the  S. quadricauda. In an
    experiment studying the effect of both copper and aluminium on the
    growth of  Scenedesmus it was found that the majority of the toxic
    action was due to indirect chemical interactions that result in higher
    cupric ion activities.

         Hörnström et al. (1984) studied the effects of aluminium on 19
    freshwater algal species in lake water at pH 5.5. The biotests showed
    that 13 of the species, including all of the desmoids and diatoms,
    experienced complete growth inhibition at 200 µg/litre. In fact, two
    of the four diatom species ( Nitschia actinastroides and  Synedra 
     nana) showed 47% inhibition at 100 µg/litre. The most insensitive
    group was the Chrysophyceae, where three out of five species were
    unaffected at 400 µg/litre.

         Lindemann et al. (1990) studied the impact of aluminium
    (4-220 µmol/litre) on green algae ( Scenedesmus sp. and  Chlorella 
    sp.) isolated from acidic and alkaline headwater streams in a semi-
    continuous culture media at pH 5. The threshold for inhibition was
    found to be less than 4 µmol aluminium/litre when the aluminium was
    added to the medium abruptly. When the aluminium was added gradually
    there was a lag period, which can be explained by the formation of
    polymeric aluminium hydroxy compounds and the precipitation of
    aluminium hydroxides and phosphates; this reduces the amount of
    aluminium bioavailable to the algae. Folsom et al. (1986) studied
    the toxicity of aluminium (0, 10, 25 and 50 mg/litre) to the acid-
    tolerant green alga  Chlorella saccarophila at pH 3.0 and found a
    concentration-dependent growth inhibition. Addition of the fast-
    exchange ions Ca2+, Mg2+, Na+ and K+ (150 mg/litre) caused some
    reversal of the toxic effects of aluminium.

         Exley et al. (1993) studied the effect of aluminium on the
    freshwater diatom  Navicula pelliculosa and the amelioration of this
    toxicity with silicon. An aluminium concentration of 10 µmol/litre
    significantly inhibited diatom growth at all but the highest silicic
    acid concentration (100 µmol/litre). The mechanism of action was found
    to be independent of a direct effect on cell biomass, chlorophyll
     a content per cell or the protein content of each cell. The toxicity
    of aluminium was mitigated by increasing the nominal phosphorus
    concentration from 1 to 10 µmol/litre. Further growth experiments
    were carried out on the non-silicon-requiring green alga  Chlorella 
     vulgaris. The rate of growth was significantly inhibited at
    48 µmol/litre. The inhibitory effects were again removed at the
    highest silicic acid concentration. The authors concluded that the
    mechanism of aluminium toxicity was a reduction in the bioavailability
    of phosphorus.

         Genter & Amyot (1994) exposed freshwater benthic algal
    populations to aluminium concentrations of 50, 100 and 500 µg Al/litre
    (as aluminium sulfate) at pH 4.8 in artificial streams. During the
    28-day test, aluminium in acidified water inhibited the abundance of
    diatoms and cyanobacteria (blue-green algae) more than the acidity
    alone. Aluminium decreased chlorophyll abundance beyond the effects of
    acidity alone at 500 µg/litre.

         Nalewajko & Paul (1985) studied the effect of aluminium on
    phytoplankton collected from a circumneutral and an acid-stressed
    lake. Addition of aluminium (50 µg/litre) caused significant decreases
    in microbial phosphate uptake and photosynthesis. The effects were
    more pronounced at pH 5.2-6.9 (lake water pH range) than at pH 4.5,
    there being larger decreases in phytoplankton from the acid-stressed
    lake. The authors reported that the toxicity was due to both the
    precipitation of phosphate as particles after addition of aluminium
    and the direct effect of aluminium.

         Stanley (1974) grew the aquatic angiosperm Eurasian milfoil
    ( Myriophyllum spicatum) in solutions of aluminium for 32 days. There
    was a 50% inhibition of root dry weight, shoot dry weight, root length
    and shoot length at aluminium concentrations of 2.5, 7.6, 5.1 and
    12.7 mg/litre, respectively.

    9.1.2.2  Invertebrates

    a)    Acute toxicity

         The acute toxicity of aluminium to aquatic invertebrates is
    summarized in Table 24; 48-h and 96-h LC50 values range from
    0.48 mg/litre (polychaete) to 59.6 mg/litre (daphnid). However, care
    must be taken when interpreting the results because of the significant
    effects of pH on the availability of aluminium.

         Bringmann & Kühn (1959) found no effect on  Daphnia magna 
    immobilization at aluminium chloride concentrations of up to
    1000 mg/litre over a 48 h exposure period at pH 7.5.

         Havens (1990) exposed two acid-sensitive cladocerans ( Daphnia 
     galeata and  D. retrocurva) and one acid-tolerant cladoceran
    ( Bosmina longirostris) to aluminium concentrations of 200 µg/litre
    at pH 5.0 for 24 h. The exposure consistently resulted in nearly 100%
    mortality for  D. galeata and  D. retrocurva, but mortality rates
    for  B. longirostris were not significantly different from those of
    controls (2-6%). Haematoxylin staining procedures revealed that the
    daphnids showed marked aluminium binding at the maxillary glands (the
    site of ion exchange), whereas  B. longirostris showed no noticeable
    aluminium binding.

         Havas & Hutchinson (1982) studied the tolerance of crustaceans,
    collected from acid (pH 2.8) and alkaline (pH 8.2) tundra ponds, to
    low pH and elevated levels of aluminium. When adjusted to pH 4.5,
    water from acid ponds was more toxic than water from alkaline ponds,
    probably due to elevated concentrations of aluminium (up to 20 mg
    Al/litre). Removal of heavy metals and aluminium by co-precipitation
    significantly reduced the toxicity of adjusted pond

        Table 24.  Toxicity of aluminium (LC50) to aquatic invertebrates
                                                                                                                                              

    Organism       Size/age    Stat/flowa   Temperature    Hardnessb      pH        Salt           Duration     LC50c            Reference
                                            (°C)           (mg/litre)                              (h)          (mg/litre)
                                                                                                                                              

    Bivalve                    stat         20-25                         3.5                      96           > 1.0 m          Mackie
    Pisidium                   stat         20-25                         4.5                      96           > 0.4 m          (1989)
    casertanum

    Bivalve                    stat         20-25                         3.5                      96           > 1.0 m          Mackie
    Pisidium                   stat         20-25                         4.5                      96           > 0.4 m          (1989)
    compressum

    Gastropod                  stat         20-25                         3.5                      96           > 1.0 m          Mackie
    Amnicola                   stat         20-25                         4.5                      96           > 0.4 m          (1989)
    limosa

    Hyallela                   stat         20-25                         3.5                      96           > 1.0 m          Mackie
    azteca                     stat         20-25                         4.5                      96           > 0.4 m          (1989)

    Enallagma sp.              stat         20-25                         3.5                      96           > 1.0 m          Mackie
                               stat         20-25                         4.5                      96           > 0.4 m          (1989)

    Polychaete                 stat         20-25                         7.6-8.0   chloride       96           > 2.0 n          Petrich &
    Neanthes                                                                                                                     Reish
    arenaceodentata                                                                                                              (1979)

    Polychaete                 stat                                       7.6-8.0   chloride       96           2.0 n            Petrich &
    Polychaete                 stat                                       7.6-8.0   chloride       96           0.48 n           Reish (1979)
    Ctenodrilus
    serratus

    Copepod        adult       stat            20          7d             8.0       chloride       96           10               Bengtsson
    Nitocra                                                                                                     (7.5-13.4)       (1978)
    spinipes
                                                                                                                                              

    Table 24.  (Con't)
                                                                                                                                              

    Organism       Size/age    Stat/flowa   Temperature    Hardnessb      pH        Salt           Duration     LC50c            Reference
                                            (°C)           (mg/litre)                              (h)          (mg/litre)
                                                                                                                                              

    Water flea     < 24 h      stat         17-19          44-53          7.4-8.2   chloride       48           3.9 n            Biesinger &
    Daphnia                                                                                                                      Christensen
    magna                                                                                                                        (1972)
                               stat         12-15          240            7.2-7.8   ammonium       48           59.6             Khangarot
                                                                                    sulfate                     (45.8-73.3) ne   & Ray
                                                                                                                                 (1989)
                                                                                                                                              

    a    Stat = static conditions (water unchanged for duration of test)
    b    Hardness expressed as mg CaCO3/litre
    c    n = based on nominal concentrations;  m = based on measured concentrations
    d    Salinity (%)
    e    EC50 based on immobilization
    
    water to crustaceans. The subsequent addition of 20 mg/litre aluminium
    resulted in 100% mortality of  Daphnia within 20 h, whereas the
    addition of other metals (iron, nickel and zinc) did not restore the
    toxicity.

         Havas (1985) studied the effect of aluminium chloride (0.02, 0.32
    and 1.02 mg Al/litre), pH (6.5, 5.0 and 4.5) and calcium (2.5 and
    12.5 mg/litre) on the survival of  Daphnia magna during a 48-h
    exposure period. Maximum aluminium toxicity was observed at pH 6.5 and
    a calcium concentration of 2.5 mg/litre. A pH of 5.0 was toxic to
     D. magna in soft water, 50% of the daphnids being immobilized within
    24 h. Aluminium marginally increased the toxicity of water at pH 5.0.
    At pH 4.5, high concentrations of aluminium significantly reduced the
    hydrogen ion toxicity. However, this amelioration was short lived and
    all of the  Daphnia had died within 24 h. Havas & Likens (1985)
    exposed the crustaceans  Daphnia catawba and  Holopedium gibberum, 
    and the insect larvae  Chaoborus punctipennis and  Chironomus 
     anthrocinus to the same aluminium concentrations (0.02, 0.32 and
    1.02 mg Al/litre) at pH levels of 3.5, 4.0, 4.5, 5.0 and 6.5. The
    crustaceans were exposed for 72 h and the insect larvae for 168 h.
     D. catawba was the most acid-sensitive species, mortality being
    significantly increased at and below pH 5.0; high concentrations
    of aluminium significantly increased mortality only at pH 6.5.
     H. gibberum was less sensitive to both hydrogen ions and aluminium
    than  D. catawba. The highest aluminium concentration was moderately
    toxic at pH 6.5; however, as with  D. catawba, the effect of
    aluminium at lower pH was completely masked by hydrogen ion toxicity.
    Neither aluminium nor hydrogen ions affected the mortality of
     C. punctipennis or  C. anthrocinus.

         Lamb & Bailey (1981) studied the effects of aluminium sulfate on
    larvae of the midge  Tanytarsus dissimilis at pH 7.8. There was no
    apparent effect of aluminium on either second or third instar larvae
    at aluminium sulfate doses of between 80 and 960 mg/litre after 96 h.
    Owing to the polymeric, coagulant nature of aluminium sulfate, a white
    grey precipitate (up to 3-4 mm) formed in all solutions.

         Six common macro-invertebrates were exposed to 200 µg/litre
    aluminium sulfate at pH 4.5 and a calcium concentration of
    2.45 mg/litre. The order of acid sensitivity (mean 48-h survival is
    given in parentheses) for the species tested was:  Caenis sp. (2%)
    >  Hyalella azteca (12%) >  Enallagma sp. (20%) >  Gyraulus sp.
    (55%) > Chironomidae (94%) > Hydracarina (99%). Aluminium
    significantly reduced survival still further in  H. azteca, Gyraulus 
    sp. and Chironomidae. However, the addition of aluminium significantly
    increased survival for  Enallagma sp. and  Caenis sp. when compared
    with the acid-only group (Havens, 1993).

    b)    Long-term toxicity

         France & Stokes (1987) studied the effect of nominal aluminium
    concentrations of 0.05 to 0.70 mg/litre on the hydrogen ion toxicity
    to the amphipod  Hyalella azteca over an 8-day period. Aluminium
    concentrations of 0.25 and 0.40 mg/litre at pH 4.8 and 0.40 mg/litre
    at pH 4.3 significantly increased the mortality of  H. azteca 
    compared with that in reference aluminium concentrations of
    0.05 mg/litre. Mortality rates remained unchanged with the addition of
    0.25 mg Al/litre at pH 4.3 or 5.3 and with either 0.40 mg Al/litre or
    0.70 mg Al/litre at pH 4.0. The authors predicted from these results
    that mortality of this amphipod from springmelt pulses will be
    determined primarily by hydrogen ions and only secondarily by
    aluminium in the pH range 4.3 to 5.3. Berrill et al. (1985) found no
    effect of aluminium (up to 200 µEq/litre) on the accumulated 10-day
    mortality caused by hydrogen ions in the crayfish  Orconectes 
     rusticus, O. propinquus and  Cambarus robustus.

         Biesinger & Christensen (1972) exposed water fleas ( Daphnia 
     magna) to aluminium chloride for a period of three weeks in Lake
    Superior water (pH 7.4-8.2). An LC50 of 1.4 mg total aluminium/litre
    was calculated and the EC50, based on reproductive impairment, was
    found to be 0.68 mg/litre.

         Burton & Allan (1986) exposed three species of stream
    invertebrates ( Nemoura, Asellus and  Physella) to aluminium
    concentrations of 250 or 500 µg/litre at pH 4, 5 and 7 for 28 days in
    experimental streams. Survival of all species was significantly
    decreased at pH 4; the addition of aluminium at 15°C did not cause
    additional mortality. However, at 2°C or with low organic matter the
    addition of 500 µg/litre caused a significant additional mortality for
    both  Nemoura and  Asellus. Addition of citrate reduced the effect
    of aluminium in low-organic treatments.

         Petrich & Reish (1979) studied the effect of aluminium chloride
    (pH 7.6-8.0) on the polychaetes  Neanthes arenaceodenata, Capitella 
     capitata and  Ctenodrilus serratus. Neither  Capitella nor Neanthes
    were affected by a 7-day exposure to 2 mg/litre aluminium chloride
    (the maximum concentration that could be used without precipitation in
    seawater).  Ctenodrilus showed significant reproductive suppression
    during a 28-day exposure to aluminium chloride concentrations of
    0.5 mg/litre or more.

    c)    Physiological and biochemical effects

         Herrmann & Andersson (1986) exposed the nymphs of three mayfly
    species  Heptagenia fuscogrisea, H. sulphurea and  Ephemera danica 
    to total inorganic monomeric aluminium levels of 500 and 2000 µg/litre
    at pH 4.0 and 4.8 for 10 days. The oxygen consumption rate of nymphs

    was monitored. The rate showed a tendency to increase at 500 µg/litre
    for  H. sulphurea and  E. danica. At 2000 µg/litre there were
    significant increases in the oxygen consumption rate for all three
    species at both pH levels.  E. danica, which is restricted to less
    heavily acidified regions, was the most severely affected by the
    aluminium treatments. Exposure of  E. danica and  H. sulphurea to
    the same aluminium and pH regimes for 14 days caused significant
    aluminium-related decreases in sodium levels (Herrmann, 1987).

         Malley & Chang (1985) studied calcium-45 uptake by postmoult
    crayfish ( Orconectes virilis) exposed to aluminium chloride
    concentrations of 200, 500 and 1000 µg Al/litre for 2 to 3 h at pH 5.3
    to 7.2. An aluminium concentration of 200 µg/litre had no effect on
    calcium uptake at neutral pH. However, reducing the pH to 5.5 caused
    an inhibition of calcium uptake. Exposure of crayfish to 500 µg/litre,
    under acidic conditions, also caused a significant reduction in
    calcium uptake. However, exposure to acidic conditions alone revealed
    that most of the reduction was due to acidic conditions rather than
    aluminium. In fact, transferring the crayfish from 500 µg Al/litre to
    1000 µg Al/litre, under acidic conditions, had no significant effect.
    Witters et al. (1984) maintained the air-breathing water bugs
    ( Corixa punctata) at aluminium chloride concentrations of 0.15, 0.3
    (the natural level), 2.5, 5, 10 and 50 mg Al/litre at pH 3 and 4. A
    dose-related decrease in sodium-influx was observed and there was a
    significant 50% decrease when comparing the lowest concentration with
    10 mg/litre.

    d)    Population studies

         Havens (1991) studied the effect of aluminium on the survival
    of littoral zooplankton species collected from alkaline lakes.
    Toxicity tests were performed at pH 4.5 with or without aluminium
    (500 µg/litre) for 24 h. The four cladocerans  Simocephalus 
     serrulatus, Diaphanosoma birgii, Acantholeberis curvirostris and
     Chydorus sphaericus were unaffected by either the acidic conditions
    or aluminium. The cladoceran  Eurycercus lamellatus and the copepod
     Acanthocyclops vernalis suffered 100% mortality at pH 4.5 with or
    without aluminium. The cladocerans  Camptocercus rectirostris, Alona 
     costata and  Pleuroxus denticulatus and the copepod  Mesocyclops 
     edax showed decreased survival at pH 4.5 and a significantly greater
    decrease in survival under acid conditions and aluminium exposure.

         Havens & Heath (1989) carried out an  in situ mesocosm study of
    zooplankton responses to acidification and aluminium. Large plastic
    enclosures were acidified (pH 4.5) with or without the addition of
    aluminium, giving an inorganic monomeric aluminium concentration of
    180 µg/litre. The populations of acid-sensitive species declined more
    rapidly in the acid-plus-aluminium treatment than in the acid-alone

    treatment. Two cladocerans ( Bosmina longirostris and  Chydorus 
     sphaericus) were tolerant to acidity and aluminium. Havens & Decosta
    (1987) performed bioassays using  in situ enclosures to expose
    zooplankton to acidified waters (pH 4.7) with and without the addition
    of aluminium (300 µg/litre) for up to 49 days. Acidification did not
    affect abundance of zooplankton or succession because all species were
    acid-tolerant. However, addition of aluminium resulted in a reduction
    in zooplankton abundance.

    9.1.2.3  Fish

         The bioavailability and toxicity of aluminium varies with its
    chemical speciation. In the case of fish, higher polymers are less
    toxic than monomers and polymers of low relative molecular mass.
    Polymerization is a slow process, hence the biological activity of
    aluminium in water depends not only on aluminium concentration and
    conditions such as pH, temperature and the presence of complexing
    ions, but can also depend on the pre-history of the water. The various
    aluminium species differ in their effects on fish gills, either
    disturbing the ion balance or interfering with respiration. The
    toxicity diminishes if the aluminium is inactivated by complexation
    with organic ligands, fluoride or silicate, or by extensive
    polymerization to large molecules in the water (Rosseland & Staurnes,
    1994).

    a)    Acute toxicity

         The acute toxicity of aluminium to fish is summarized in Table
    25. The 96-h LC50 values range from 0.095 mg/litre (American
    flagfish) to 235 mg/litre (mosquito fish). However, care must be taken
    when interpreting these results because of the significant effects of
    pH on the availability of aluminium. The wide range of LC50 values
    probably reflects this variable availability. LT50 values for
    salmonids are also summarized in Table 25. Muramoto (1981) found that
    addition of the complexans NTA and EDTA reduced the acute (48-h)
    toxicity of aluminium to carp ( Cyprinus carpio).

         Rosseland & Skogheim (1984) exposed three salmonid species,
    Atlantic salmon ( Salmo salar), brown trout ( Salmo trutta) and
    brook trout ( Salvelinus fontinalis), to inorganic monomeric
    aluminium concentrations of 120, 225 and 415 µg/litre (as aluminium
    sulfate) under flow-through conditions. Owing to the acidity of the
    aluminium sulfate the pH decreased from 6.6 to 4.9. Pre-smolt salmon
    were the most sensitive, showing 100% mortality within 48 h at
    245 µg/litre. Brook trout were the least sensitive, mortalities only

        Table 25.  Toxicity of aluminium to fish (laboratory studies)
                                                                                                                                              

    Organism       Size/    Stat/flowa  Temperature  Hardnessb   Calcium       pH          Salt        LT50 (mg     96-h LC50c    Reference
                   age                  (°C)         (mg/litre)  concentration                         inorganic    (mg Al/litre)
                                                                 (mg/litre)                            monomeric
                                                                                                       (Al/litre)
                                                                                                                                              

    Atlantic       1 +      flow        5.2          5           2.0           4.95        sulfate        59        0.245 m      Rosseland &
    salmon         2 +                                                         4.95                       33        0.245 m      Skogheim
    (Salmo salar)  1 +      flow        5.2          5           2.0           4.94        sulfate        57        0.313 m      (1984)
                   2 +                                                         4.94        sulfate        22        0.313 m
                   1 +                                                         4.90                       27        0.463 m
                   2 +                                                         4.90                       15        0.463 m

    Brown trout    2 +      flow        5.2          5           2.0           4.94        sulfate        40        0.313 m
    (Salmo trutta) 1 +                                                         4.90                       57        0.463
                   2 +                                                         4.80                       30        0.463

    Atlantic       2 +      stat        3.7                      1.3           5.06        chloride      108        0.075        Skogheim &
    salmon         (38 g)                                        1.3           4.92                       38        0.137 m      Rosseland
    (Salmo salar)                                                1.3           4.90                       32        0.177 m      (1986)

    Mummichog      2.7 g    stat        20           6.6d                                  ammonium                 3.6 n        Dorfman
    (Fundulus                                                                              sulfate                               (1977)
    heteroclitus)  2.7 g    stat        20           17d                                   ammonium                 27.5 n
                                                                                           sulfate
                   2.7 g    stat        20           7.9d                                  chloride                 3.6 n        Dorfman
                   2.7 g    stat        20           18.8d                                 chloride                 31.5 n       (1977)

    Mosquito fish           stat        20-21                                  4.3-7.2     chloride                 133 n        Wallen et al.
    (Gambusia               stat        19-22                                  4.4-7.7     sulfate                  235 n        (1957)
    affinis)
                                                                                                                                              

    Table 25.  (Con't)
                                                                                                                                              

    Organism       Size/    Stat/flowa  Temperature  Hardnessb   Calcium       pH          Salt        LT50 (mg     96-h LC50c    Reference
                   age                  (°C)         (mg/litre)  concentration                         inorganic    (mg Al/litre)
                                                                 (mg/litre)                            monomeric
                                                                                                       (Al/litre)
                                                                                                                                              

    Fathead        0.45 g   stat        22           38                        7.4         nitratee                 4.25         Mayer &
    minnow                                                                                                          (3.3-5.5)    Ellersieck
    (Pimephales    0.45 g   stat        22           38                        7.4         sulfatef                 4.4          (1986)
    promelas)                                                                                                       (3.4-5.6)

    American       2-3      stat        25           6.0                       5.8                                  0.095 m      Hutchinson &
    flagfish       days                                                                                                          Sprague
    (Jordanella                                                                                                                  (1986)
    floridae)
                                                                                                                                              

    a    Stat = static conditions (water unchanged for duration of test)                 d    Salinity (%)
    b    Hardness expressed as mg CaCO3/litre                                            e    7.2% technical material
    c    n = based on nominal concentrations;  m = based on measured concentrations      f    8.1% technical material
        occurring at 463 µg/litre (less than 25% over the 64-h exposure). The
    authors reported that whenever aluminium sulfate was added excessive
    mucus was observed between the gill lamellae; or all species mucus
    clogging increased with an increased addition of aluminium. However,
    there was no excessive mucus on gills of fish that died in acid brook
    water with naturally occurring aluminium concentrations.

         Schofield & Trojnar (1980) exposed brook trout ( Salvelinus 
     fontinalis) fry to aluminium (0.1-0.5 mg/litre) at various pH levels
    (4.0-5.2). At pH 4.0 survival of fish was not related to aluminium
    concentration, the LT50 values ranging from 2.8 to 5.2 days. However,
    at pH levels of > 4.4, mortality increased with increasing
    aluminium concentration. At pH 4.9 and 5.2 neither acidity nor 0.1 mg
    Al/litre affected fish mortality; 0.5 mg Al/litre produced LT50
    values ranging from 1.6 to 3.3 days. Symptoms of stress were darkening
    of skin coloration and cessation of feeding. All fish at pH 4.0 and
    4.4 showed these symptoms, although they took longer to develop at pH
    4.4 with 0 or 0.1 mg/litre aluminium. No symptoms were observed at pH
    4.9 and 5.2 for aluminium concentrations of 0.1 mg/litre; however,
    stress symptoms were seen in all groups exposed to > 0.25 mg/litre
    aluminium at any pH level. Heavy accumulations of mucous and cellular
    debris on the gills were found in trout exposed to > 0.25 mg/litre
    aluminium at pH levels of > 4.4. Histopathological changes
    observed in sections of gills from fish exposed to aluminium levels
    > 0.5 mg/litre included cell proliferation at the distal ends of
    gill filaments, lamellar oedema and fusion, epithelial desquamation,
    filament collapse, and general loss of gill structure.

         Gundersen et al. (1994) exposed rainbow trout ( Oncorhynchus 
     mykiss) to aluminium at pH values ranging from 7.97 to 8.56 in 96-h
    tests. No significant mortality was observed at pH 8.33 or less and
    filterable aluminium concentrations of 0.52 mg/litre or less. However,
    100% mortality was found at pH 8.58 and a filterable aluminium
    concentration of 1 mg/litre. The 96-h LC50 values ranged from 0.36 to
    0.79 mg filterable aluminium/litre at weakly alkaline pH levels.

         Young brown trout ( Salmo trutta) exposed for 5 days to pH 5 in
    high calcium water at temperatures of 4 and 12°C showed no alterations
    in growth or in mucous cell concentration and volume. However,
    exposure to aluminium (230 µg/litre) under the same testing regime
    resulted in significant growth depression but no changes to mucous
    cell morphometrics (Segner et al., 1988).

         Freeman & Everhart (1971) found that the toxicity of aluminium
    hydroxide complexes (5.2 mg/litre) to rainbow trout ( Oncorhynchus 
     mykiss) increased with the amount of aluminium dissolved. At pH 6.8,

    8.0, 8.5 and 9.0 the amounts of aluminium dissolved were 1%, 10%, 31%
    and 97%, respectively, and the respective LT50 values were 38.90,
    31.96, 7.46 and 2.98 days. Surviving fish recovered rapidly in all
    groups, except those exposed at pH 8.0, with normal growth being
    resumed within 2 weeks (Freeman, 1973).

    b)    Long-term toxicity

         Hickie et al. (1993) exposed rainbow trout ( Oncorhynchus 
     mykiss) to aluminium for 23-26 days after hatching at pH 5.8 and
    4.9. The 144-h LC50 for total aluminium was found to be > 1050
    and 91 µg/litre at the two pH levels, respectively. An LC50 of
    1.17 µg/litre was calculated for fish exposed from 16 to 19 days after
    hatching at pH 4.9.

         Neville & Campbell (1988) exposed juvenile rainbow trout
    ( Oncorhynchus mykiss) to aluminium (2.8 µmol/litre nominal
    concentration) in a flow-through system over a pH range of 4.0 to 6.5
    for up to 11 days. The response of trout to aluminium was most severe
    at pH 4.5 (electrolyte loss) and 6.1 (asphyxia). At pH 4.0 there was
    competition between hydrogen ions and aluminium for binding at the
    gill surface which reduced toxicity. However, the toxic response at pH
    6.1 appeared to be more complex being either a bimodal response to two
    different aluminium species or a physical response to precipitation on
    the gill surface.

         Driscoll et al. (1980) studied the toxic effect of aluminium on
    brook trout ( Salvelinus fontinalis) fry. At pH values of 4.4 and 5.2
    there was no effect on survival during the 14-day exposure period. The
    addition of inorganic monomeric aluminium (0.42-0.48 mg/litre)
    produced an LT50 of 115 h at pH 5.2 and 256 h at pH 4.4. Treatment
    with excess fluoride or citrate reduced the toxicity of aluminium.
    Skogheim & Rosseland (1986) exposed Atlantic salmon ( Salmo salar) to
    aluminium at varying pH levels. No mortality occurred during a 20-day
    exposure to pH 5.07 alone. At pH 5.06 and 75 µg Al/litre the LT50 was
    108 h, at pH 4.92 and 137 µg Al/litre the LT50 was 38 h, and at pH
    4.9 and 177 µg Al/litre the LT50 was 32 h. Brown (1983) exposed brown
    trout ( Salmo trutta) to aluminium (0, 0.25 and 0.5 mg/litre) at pH
    values ranging from 4.5 to 5.4 and calcium concentrations ranging from
    0.5 to 2.0 mg/litre for 16 days. Survival was relatively unaffected by
    pH except at a calcium level of 0.25 mg/litre and a pH of 4.5. High
    mortality was observed at both aluminium exposure levels at calcium
    levels of 0.25 and 0.5 mg/litre. At calcium levels of 1.0 and
    2.0 mg/litre there was increased mortality at the highest aluminium
    concentration.

         Gundersen et al. (1994) studied the effects of aluminium on
    rainbow trout ( Oncorhynchus mykiss) in 16-day tests. Growth rates
    were higher at weakly alkaline pH (7.97-8.10) than at near-neutral pH
    (7.30-7.35). The authors concluded that polymeric and colloidal forms
    of aluminium are more potent than soluble forms in restricting growth.
    Trout exposed to aluminium at 0.53 to 2.56 mg/litre and humic acid at
    4.31 to 5.23 mg/litre had higher specific growth rates and lower
    mortality than those exposed to aluminium and no humic acid at all the
    pH values tested. When exposed to sub-lethal concentrations of
    aluminium (38 µg/litre nominal concentration) in a synthetic soft
    water of pH 5.2, rainbow trout became acclimated to aluminium and
    showed increased resistance when exposed to lethal levels of aluminium
    (162 µg/litre nominal concentration) in the same soft water.
    Acclimation was associated with reduced disturbances of ionoregulation
    and respiration (Wilson et al., 1994a). Acclimation to 38 µg/litre
    (nominal concentration) also caused a 4-fold increase in gill mucous
    density and a reduction in apparent lamellar surface area (Wilson et
    al., 1994b). Acclimation to sub-lethal levels of aluminium could
    explain the continued presence of fish populations in acidified lakes
    and rivers containing more than 100 µg Al/litre. Wicklund Glynn et al.
    (1992) exposed minnows ( Phoxinus phoxinus) to acidic water (pH 5.0)
    with and without aluminium (150 µg/litre) at various calcium (0, 0.07
    and 2 mmol/litre) and humus (5 and 25 Pt) concentrations for 15 days.
    Mortality among fish exposed to aluminium was higher than among
    unexposed fish but was less at the highest calcium level. At 0.07 mmol
    calcium/litre, the aluminium-induced mortality was reduced by the
    presence of humus. Gill morphology was altered after exposure to
    aluminium at pH 5.0, but was not affected by different concentrations
    of calcium or humus.

         Juvenile brook trout ( Salvelinus fontinalis) were
    intermittently or continuously exposed to aluminium (0.2 to
    1.2 mg/litre) at pH 4.4 or 4.9 for 24 days. There was 100% survival of
    fish at both pH levels in the absence of aluminium, regardless of
    exposure regime. Aluminium significantly reduced survival at
    0.2 mg/litre or more for all exposure regimes except the intermittent
    exposure at pH 4.4 where significant mortality was observed at
    0.4 mg/litre or more. When aluminium concentration was expressed as
    the 24-day mean, it was shown that intermittent exposure was more
    toxic than continuous exposure (Siddens et al., 1986). Ingersoll et
    al. (1990) exposed 1-year-old brook trout ( Salvelinus fontinalis) to
    combinations of aluminium, pH and calcium during a 28-day experiment.
    Survival was reduced at inorganic monomeric aluminium concentrations
    of 29 µg/litre at pH 5.2 and > 228 µg/litre at pH 4.4 or 4.8. Fish
    weight was reduced at an aluminium concentration of > 34 µg/litre
    and pH < 4.8. The gills sampled from low pH groups showed lifting of
    the outer epithelium and hypertrophy of chloride and epithelial cells.
    These effects were more pronounced at low pH with elevated aluminium
    concentrations. Effects such as vacuolation and degeneration of
    epithelial and chloride cells and the presence of dense cells were
    also observed at low pH and elevated aluminium concentration.

         No mortality of lake trout ( Salvelinus namaycush) embryos
    occurred during 5-day exposures to aluminium sulfate (0, 100 and
    200 µg Al/litre) at pH 5.0 or during 21- and 32-day recovery periods.
    None of the embryos or later alevins displayed erratic swimming
    behaviour or mucus accumulation around the mouth or gills. After
    21-day (late embryos) and 32-day (early embryos) recovery periods,
    fish at the highest aluminium concentrations were significantly
    smaller in length, had reduced whole body concentrations of calcium
    and potassium, and were significantly less successful as predators on
     Daphnia magna (Gunn & Noakes, 1987).

         Cleveland et al. (1991) exposed brook trout ( Salvelinus 
     fontinalis) to a nominal aluminium concentration of 200 µg/litre
    for 56 days under flow-through conditions at pH 5.3, 6.1 and 7.2.
    The weights of trout exposed to pH 5.3 and 6.1 did not differ
    significantly throughout the study. After day 3 fish exposed to pH 7.2
    weighed significantly more than those at pH 5.3 and 6.1. Mortality was
    significantly higher in brook trout exposed to pH 5.3 than in those
    exposed to pH 6.1 (except on day 56) or 7.2.

    c)    Lifestage effects

         Not only do species differences in response to a given pH and
    aluminium concentration exist but great differences in sensitivity
    also exist between strains of the same species as well as between
    different life-history stages (Rosseland et al., 1990; Rosseland &
    Staurnes, 1994).

         Fivelstad & Leivestad (1984) studied the toxicity of aluminium to
    different life-stages of Atlantic salmon ( Salmo salar) and brown
    trout ( Salmo trutta). To study the effect of acidity citrate was
    added. Only 1 of 200 swim-up salmon larvae died during a 108-h
    exposure at pH 4.9; no behavioural responses were observed. However,
    when exposed to aluminium concentrations ranging from 110 to
    300 µg/litre, salmon swim-up larvae were more sensitive than the
    postlarval stage. Toxicity was found to be most significantly
    correlated with inorganic monomeric aluminium concentration, survival
    time decreasing with increasing aluminium concentration. The LT50 at
    an inorganic monomeric aluminium concentration of 148 µg/litre was
    26 h for swim-up larvae. Exposure of salmon parr to natural aluminium
    variations (50-180 µg/litre) at pH 5.3 induced hyperventilatory
    responses together with increases in haematocrit and small decreases
    in chloride. The authors concluded that coughing, hyperventilation and
    excessive mucous clogging on the gill surface was due to an irritant
    effect of aluminium. Brown trout exposed at pH 5 to the same aluminium
    regime showed no sublethal stress symptoms.

         Rosseland & Skogheim (1984) demonstrated the increased
    sensitivity of Atlantic salmon undergoing smoltification compared to
    younger year classes. In a laboratory study at pH 4.9-5.0 and
    inorganic monomeric Al concentrations of 130-463 µg/litre, pre-smolt
    (age 2 years) were more sensitive than parr (age 1 year) in all
    combinations of pH and aluminium. For instance, at pH 4.95 and 245 µg
    Al/litre, the LT50 for pre-smolt was 35 h whereas the LT50 for parr
    was 60 h.

         Early life-stage (fertilized eggs, alevins and swim-up fry)
    golden trout ( Oncorhynchus aguabonita aguabonita) were exposed to
    low pH (4.5-6.5) and aluminium (50-300 µg Al/litre, nominal
    concentration) for 7 days. Significant mortality occurred at pH 4.5
    in the absence of aluminium, at pH 5.5 in the presence of 100 µg
    aluminium/litre for larvae and at pH 5.0 with 300 µg aluminium/litre
    for alevins. The duration of swimming and feeding activity was
    unaffected by treatment in golden trout exposed as eggs. Locomotory
    behaviour of alevins was severely inhibited at both pH 5.0 and 5.5
    irrespective of treatment and at pH 4.5 and 6.0 in aluminium-exposed
    fish. Feeding activity was reduced at pH 4.5, at pH 5.0 with 
    > 50 µg aluminium/litre and at pH 5.5 with 100 µg/litre. Swimming
    activity was not greatly affected among fish exposed as swim-up
    larvae. Feeding activity was greatly inhibited at all aluminium
    concentrations and at pH 4.5 (DeLonay et al., 1993).

         Farag et al. (1993) studied the effect of aluminium (50-300 µg
    Al/litre, nominal concentration) on eggs, eyed embryos, alevins and
    swim-up larvae of cutthroat trout ( Oncorhynchus clarki bouvieri) at
    pH values ranging from 4.5 to 6.5 for either 7 days or during
    continuous exposure until 40 days after hatching. Fish survival
    decreased when pH was lowered to 5.0 or 4.5 for 7 days during the egg
    stage. Alevin and swim-up larval stages were less sensitive to low
    pH and more sensitive to aluminium, with 100 µg/litre at pH 5.0
    significantly decreasing survival. The eyed embryo stage was the most
    resistant; there was > 90% survival in all groups except in the
    presence of > 100 µg/litre at both pH 5.0 and 5.5. During continuous
    exposure, survival decreased with time and individuals died earlier in
    each life-stage when exposed to combinations of pH and aluminium than
    did those exposed to pH alone. Swim-up larvae were the most sensitive
    group with regard to growth and all larvae exposed to 50 µg/litre
    showed significantly reduced growth.

         Buckler et al. (1987) exposed striped bass ( Morone saxatilis)
    of different ages to total aluminium (up to 400 µg/litre) at various
    pH levels (pH 5.0-7.2) in a flow-through diluter system for 7 days.
    Eleven-day-old fish showed significant mortality at pH 6.0
    irrespective of aluminium exposure; significant mortality was observed
    at 25 µg/litre for pH 6.5 and at 400 µg/litre for pH 7.2. Older fish
    (160 days) were less sensitive, showing significant mortality at 50 µg

    Al/litre for pH 6.0, 200 µg/litre for pH 6.5, and 400 µg/litre for pH
    7.2. In a similar test, 300 µg/litre was lethal to 100% of both 159-
    and 195-day-old bass at pH 5.5, but produced no observable adverse
    effects at pH 6.5 or 7.2. Mortality among 159-day-old fish held in
    water at pH 5.5 without aluminium was 22% after 7 days, there being no
    deaths among control fish. No mortality was observed among 195-day-old
    fish exposed to pH 5.5 alone.

         Eggs, larvae and post-larvae of white suckers ( Catostomus 
     commersoni) and brook trout ( Salvelinus fontinalis) were exposed
    to pH levels of 4.2 to 5.6 and inorganic monomeric aluminium
    concentrations ranging from 0 to 0.5 mg/litre. White sucker embryos
    were very sensitive to low pH levels, with none surviving to the eyed
    stage at pH levels of 5.0 or less. The addition of aluminium increased
    embryo survival through the eyed stage but did not increase hatching.
    At pH levels of 5.4 and 5.6 survival to eyed stage increased to 38% to
    69% and was 74% to 81% in controls. At pH levels above 5.2 the
    presence of aluminium resulted in embryo deformities. Survival of
    trout eggs through the eyed stage was unaffected at pH 4.6 or more
    irrespective of aluminium treatment. However, in the absence of
    aluminium at pH levels of 4.4 survival decreased and at pH 4.2 no
    embryos survived. The addition of aluminium to low pH groups
    significantly increased survival through the eyed stage to hatching.
    All white sucker larvae died within 146 h at pH levels below 5.0 with
    or without aluminium. In the absence of aluminium at pH levels greater
    than 5.0, more than 80% survived the 13-day experiment; however, the
    addition of aluminium further decreased the survival of larvae. At pH
    levels of 4.4 or more > 97% of trout larvae survived without
    aluminium. The addition of more than 0.1 mg Al/litre at all pH levels
    decreased the survival of larvae. White sucker post-larvae were
    sensitive to low pH levels, only 16 to 68% surviving at pH 4.6. The
    addition of aluminium to acidic solutions further decreased survival.
    In the presence of high levels of aluminium (0.3 or 0.5 mg/litre) at
    all pH levels, all post-larvae died within 75 h. At aluminium levels
    of 0.1 and 0.2 mg/litre at low pH levels all post-larvae died within
    145 h. Brook trout post-larvae were tolerant of low pH levels. All
    post-larvae survived at pH levels ranging from 6.99 to 4.22 without
    aluminium. At aluminium levels of 0.2 mg/litre or more survival was
    decreased at all pH levels (Baker & Schofield, 1982).

         Cleveland et al. (1986) carried out a partial life-cycle toxicity
    study on brook trout ( Salvelinus fontinalis) for 60 days in a flow-
    through proportional diluter. Eyed brook trout eggs and the resultant
    larvae were exposed in water containing 3 mg calcium/litre at
    nominal pH values of 7.2, 5.5 and 4.5 with and without aluminium
    (300 µg Al/litre, nominal concentration) until 30 days after hatching.
    Mortality of trout eggs was not influenced by aluminium but was
    significantly increased by low pH. Larval growth and mortality was
    unaffected by aluminium at pH 7.2 and 4.5, but mortality was

    significantly increased and growth decreased by aluminium at pH 5.5.
    DNA and RNA content was significantly reduced by aluminium at pH 5.5.
    In general swimming and feeding behaviour were unaffected by aluminium
    at pH 7.2 and significantly reduced by aluminium at pH 5.5. At pH 4.5
    behaviour was inhibited to such an extent that possible effects of
    aluminium were masked. In a second experiment 37-day-old trout were
    exposed to similar conditions. Mortality was significantly increased
    by aluminium at pH 5.5 and 4.5. Aluminium significantly reduced growth
    at pH 7.2 and 5.5. DNA and RNA content was significantly increased by
    aluminium at pH 5.5. Juvenile trout behaviour was less affected by
    acid conditions than in the case of larvae; there were significant
    decreases in behaviour in the presence of aluminium at pH 5.5 and 4.5.
    Hunn et al. (1987) utilizing a similar experimental set-up found that
    embryo mortality exceeded 80% at pH 4.5, averaged 15% to 18% at pH 5.5
    and was less than 2% at pH 7.5. Aluminium significantly increased
    mortality at pH 4.5 but did not affect mortality at pH 5.5 or 7.5.
    Hatching success was pH-dependent and was not influenced by aluminium
    exposure. Brook trout larvae suffered 100% mortality at pH 4.5, 20%
    mortality at pH 7.5 with or without aluminium, 69% mortality at pH 5.5
    without aluminium and 100% mortality within 15 days with aluminium.
    Cleveland et al. (1989) reported that 60-day no-observed-effect
    nominal concentrations for aluminium at pH 5.6 to 5.7 were 29 µg/litre
    for swimming capacity, 68 µg/litre for weight and 142 µg/litre for
    frequency of movement (2 min period), strike frequency (directed at
    prey), fry mortality and length. At pH 6.5 to 6.6 no-observed-effect
    concentration (NOEC) values were 88 µg/litre for length and weight,
    169 µg/litre for fry mortality and > 350 µg/litre for movement,
    strike frequency and swimming capacity.

    d)    Physiological and biochemical effects

         Physiological and biochemical effects have recently been reviewed
    by Rosseland & Staurnes (1994).

         Witters (1986) studied the effect of total aluminium
    (350 µg/litre), pH (4.1 and 6.1) and calcium concentration (38 and
    190 µEq/litre) on ion balance and haematology in rainbow trout
    ( Oncorhynchus mykiss) exposed for 3.5 h. None of the treatment
    combinations affected the number of erythrocytes or the haemoglobin
    content. However, exposure to aluminium under acidic conditions
    significantly reduced plasma osmolarity and increased plasma potassium
    levels. Plasma sodium and chloride levels were significantly reduced
    under acidic conditions with or without aluminium. The haematocrit
    value was significantly increased and plasma ammonium decreased by
    aluminium only under acidic conditions and at low calcium
    concentration.

         Muniz & Leivestad (1980) reported that brown trout ( Salmo 
     trutta) exposed to acidic conditions (pH 4.3 to 5.5) showed plasma
    losses of both chloride and sodium. These losses were enhanced by the
    addition of total aluminium at 900 µg/litre. Fish showing signs of
    stress exhibited hyperventilation, coughing and excessive mucus
    clogging of the gills. The authors reported that the changes in blood
    electrolytes indicate that aluminium toxicity is similar to that seen
    with hydrogen ion stress. However, aluminium can cause such effects at
    pH levels that are not physiologically harmful.

         Wood & McDonald (1987) studied the physiology of brook trout and
    rainbow trout exposed to inorganic monomeric aluminium concentrations
    ranging from 111 to 1000 µg/litre (as aluminium chloride) at pHs
    ranging from 4.4 to 6.5. Acid stress alone for 10 days was not lethal
    to adult brook trout, but there was a net loss of sodium and chloride
    ions. The addition of aluminium resulted in an increased loss of ions
    and severe mortality. At pH 4.8, low calcium level (25 µEq/litre) and
    an aluminium concentration of 333 µg/litre, the LT50 was found to be
    39 h. At a lower pH (4.4) the average survival time was twice as long.
    The cause of death was ionoregulatory failure. However, increasing the
    calcium levels (400 µEq/litre) still killed fish almost as quickly but
    the cause of death was respiratory disturbance. Rainbow trout were
    more sensitive to both acid and acid/aluminium than brook trout.
    Respiratory disturbances were found to be the cause of death in both
    high and low calcium groups exposed to acid/aluminium conditions. For
    both species there was a correlation between toxic effects and
    aluminium accumulation in gills.

         Dalziel et al. (1986) exposed brown trout to nominal aluminium
    concentrations of 8 µmol/litre at pH levels ranging from 7.0 to 4.0
    and calcium levels of 10 or 50 µmol/litre. Low pH had little effect on
    the influx of sodium, but the addition of aluminium significantly
    reduced influx at pH 4.5 and 4.0. Efflux of sodium tended to be
    increased by low pH, but no further effect was caused by aluminium.
    Aluminium at higher pH values appeared to have no effect on sodium
    fluxes. Dalziel et al. (1987) found that reduced pH levels had no
    effect on the sodium influx in brown trout ( Salmo trutta). However,
    the presence of aluminium at concentrations of 2 µmol/litre at pH 4.5
    and 4.0 significantly decreased sodium influx. At pH 5.4 there was no
    effect of aluminium on influx. Sodium efflux was significantly
    increased at low pH. Increasing the aluminium concentration at pH 5.4,
    and to a smaller extent at pH 4.5, tended to increase efflux. There
    was no effect of aluminium on sodium efflux at pH 4.0.

         Booth et al. (1988) studied the effects of total aluminium at
    concentrations of 333 and 1000 µg/litre and at low pH (5.2-4.4) on
    net ion fluxes and ion balance in the brook trout ( Salvelinus 
     fontinalis) over a period of 11 days. Low pH caused a pH-dependent
    net loss of sodium and chloride ions and the addition of aluminium
    increased this loss. The authors reported that any fish losing more

    than 4% of total sodium ions during the initial 24 h of aluminium
    exposure was 90% more likely to die. All fish exposed to aluminium
    accumulated it on gill surfaces; fish that died accumulated more
    aluminium than survivors.

         Leivestad et al. (1987) studied the effect of inorganic monomeric
    aluminium on Atlantic salmon ( Salmo salar) exposed for 28 weeks at
    pH levels of 4.8-6.5 and aluminium concentrations of 50-350 µg/litre.
    The authors found that failure in ionic regulation was the primary
    cause for mortality and that Na-K-ATPase activity was reduced at toxic
    aluminium levels. The symptoms were correlated with ion-exchangeable
    aluminium, precipitating aluminium hydroxide having low toxicity.
    Staurnes et al. (1993) maintained smolting Atlantic salmon in soft
    water at pH 5 both with and without 50 µg/litre total aluminium.
    Exposure to acid water resulted in osmoregulatory failure and high
    mortality, and aluminium greatly enhanced the toxicity. Sensitivity to
    acid and acid-aluminium increased when fish had developed to seawater-
    tolerant smolts. Gill carbonic anhydrase activity was reduced by
    aluminium exposure. Fish in both treatment groups had low seawater
    tolerance and this was related to a decline in Na+/K+-ATPase
    activity.

         Hutchinson et al. (1987) studied the effects of total aluminium
    (0-1000 µg/litre) at pH levels ranging from 3.8 to 6.0 on the early
    lifestages of lake trout ( Salvelinus namaycush), brook trout
    ( Salvelinus fontinalis) and pumpkin seed sunfish ( Lepomis 
     gibbosus). Three different responses were observed: a) aluminium
    toxicity at pH < 5.0 represented joint action with hydrogen ions
    producing ionoregulatory failure; b) at pH 5.0-6.0 aluminium toxicity
    required concentrations of inorganic forms that greatly exceeded
    theoretical gibbsite solubility; c) at acutely lethal levels of pH and
    ionic strength, aluminium increased the resistance time of eggs, fry
    and adults.

         Ogilvie & Stechey (1983) studied the respiratory responses of
    rainbow trout ( Oncorhynchus mykiss) to aluminium exposure (50 to
    500 µg/litre) at a pH of 6.0 and an exposure period of 26 h. Mean
    opercular rate was significantly increased at 500 µg aluminium/litre
    and mean cough rate was significantly increased at both 200 and
    500 µg/litre. Spontaneous locomotion and mean activity levels were
    variable in all groups.

         Neurotoxic effects on the olfactory organ of rainbow trout were
    demonstrated by Klaprat et al. (1988), who exposed the fish to pH 7.7
    and pH 4.7 both with (5.0, 9.5 and 20.0 µmol total Al/litre) and
    without aluminium. At pH 4.7 alone, increased mucous was observed over
    parts of the olfactory epithelium. After Al additions, however, loss
    of receptor cell cilia, irregular shaped olfactory knobs, changed
    microvilli and swellings of microridge cells were observed. Electrical
    response from the olfactory nerve to L-serin was not changed by pH

    alone, but was depressed by aluminium additives. Since sensory organs
    play a very important role in the behavioural ecology of fish
    populations (feeding, alarm signals, pheromones, imprinting, spawning,
    etc), neurotoxic effects on the olfactory organ can have great adverse
    effects in nature (Rosseland & Staurnes, 1994).

    e)    Pathological effects

         Hunter et al. (1980) noted that rainbow trout ( Oncorhynchus 
     mykiss) which survived exposure to 50 mg/litre aluminium at pH 8.0
    to 9.0 showed several pathological signs of toxicity. These included
    proliferative changes in the gills and congestion of the secondary
    lamellae, slight demyelination of the brain, extensive necrosis of the
    liver, severe inflammatory glomerular necrosis of the kidney and some
    evidence of skin hyperplasia. Karlsson-Norrgren et al. (1986b) exposed
    brown trout ( Salmo trutta) to aluminium sulfate (50, 200 and 500 µg
    total aluminium/litre) at pH 5.5 and 7.0 for up to 6 weeks. Advanced
    gill lesions (enlargement of secondary lamellae due to the increased
    number of chloride cells in the epithelia) were observed in fish
    exposed to aluminium at pH 5.5 and a temperature of 2.5°C. The lesions
    contained cytoplasmic aluminium precipitates. The addition of humus or
    increasing the pH to 7.0 reduced or inhibited the effects of
    aluminium. A water temperature of 15°C reduced the gill lesions
    observed at 2.5°C. However, prolonged exposure to higher water
    temperatures produced gill alterations even in controls. Eggs and the
    resulting fry of Atlantic salmon ( Salmo salar) exposed to aluminium
    (38-300 µg/litre) at pH 5.5 were investigated. Scanning electron
    microscopy revealed gill abnormalities, which included poorly
    developed or absent secondary lamellae, fused primary lamellae,
    proliferation of epithelial cells and increased numbers of surface
    pits. These effects were not noted when fish were raised in aluminium-
    free water at pH values ranging from 4.5 to 7.2 (Jagoe et al., 1987).

    9.1.2.4  Amphibians

         Clark & LaZerte (1985) exposed eggs and tadpoles of the American
    toad ( Bufo americanus) and the wood frog ( Rana sylvatica) to total
    aluminium concentrations of 10, 20, 50, 100 and 200 µg/litre at pH
    ranging from 4.14 to 5.75. A nominal pH of 4.14 significantly reduced
    hatching in the absence of aluminium. Aluminium had no effect on
    hatching at pH 4.75 or pH 5.75. However, at pH 4.14 there was a
    significant reduction in hatching for eggs exposed to any aluminium
    concentration compared with eggs without aluminium at the same pH
    level. Tadpoles that hatched out were not affected by any aluminium
    concentration or pH level.

         Clark & Hall (1985) studied the effects of total aluminium
    (7-210 µg/litre), pH (pH 4.41-6.29) and dissolved organic content
    (2.2-9.9 mg/litre) at calcium concentrations of 2 mg/litre on
     B. americanus, R. sylvatica and the spotted salamander ( Ambystoma 
     maculatum). High aluminium, low pH and high dissolved organic
    content (DOC) significantly reduced hatching success of  B.
     americanus. For  R. sylvatica neither aluminium nor pH correlated
    significantly with hatching success over the range of pH tested.
    Hatching success for  A. maculatum ranged from 41% at pH 4.4 to 68%
    at pH 6.1. Although pH was not significantly correlated with hatching
    success, a greater number of eggs hatched above pH 5.0 than below, the
    difference being significant. Decreased hatching success was
    correlated with high aluminium and high DOC. In a second experiment
    the authors studied the effects of aluminium (total aluminium
    54-75 µg/litre) and pH (pH 4.23-5.8) at calcium concentrations of
    2 mg/litre. Hatching success of  B. americanus and  R. sylvatica was
    unaffected at pH 4.8 and 5.8 with total aluminium concentrations of 54
    to 63 µg/litre. However, there were significant reductions in hatching
    at a pH of 4.3 and total aluminium concentration of 75 µg/litre.
    Hatching success of  A. maculatum was not correlated significantly
    with pH. However, hatching success was only 57% at the highest pH
    value and lowest aluminium concentration.

         Gascon et al. (1987) studied the affects of total dissolved
    aluminium (7.4 µmol/litre), pH (4.5 and 6.2) and calcium (25 and
    500 µEq/litre) on the eggs and tadpoles of  Rana sylvatica. There was
    no egg mortality in any group. Hatching was significantly delayed in
    groups exposed to aluminium under acidic conditions. Tadpoles exposed
    to aluminium at pH 4.5 and calcium at 25 µEq/litre suffered 100%
    mortality. In a similar group where the pH was allowed to drift up to
    5.3, mortality was not significant. Metamorphosis in surviving
    tadpoles was significantly delayed by acidic conditions and aluminium
    exposure. Growth, as measured by dry weight, was significantly
    depressed in the group suffering 100% mortality. In the groups exposed
    to aluminium with either pH rising to 5.3 or calcium at 500 µEq/litre,
    growth was significantly increased over controls.

         Freda & McDonald (1990) exposed embryos (4 to 5 days) and
    tadpoles (96 h) of the leopard frog ( Rana pipiens) to a range of
    total aluminium concentrations (250-1000 µg/litre) and pHs (4.2-6.5).
    The pH and the aluminium concentration had a significant effect on the
    survival of embryos. All control embryos hatched whereas 94% of
    embryos at pH 4.2 failed to hatch. At pH 4.2 and 4.4 the addition
    of aluminium ameliorated the effects of low pH, increasing
    hatchability to 78-99%. At pH 4.6 and 4.8 aluminium was found to be
    toxic. The LC50 values for aluminium at pH 4.6 and 4.8 were 811 and
    403 µg/litre, respectively. Tadpoles (pre-stage 25) were less
    sensitive to low pH than embryos, showing 20% mortality at pH 4.2.
    However, they were much more sensitive to aluminium, all the tadpoles

    dying at aluminium concentrations > 500 µg/litre and pH 4.4 or 4.6,
    and at > 250 µg/litre and pH 4.8. Three-week-old tadpoles were less
    sensitive to lowered pH and elevated aluminium than embryos or newly
    hatched tadpoles. Low pH (4.2) had no effect on the survival of
    tadpoles, and aluminium was only toxic at pH 4.8 with 40% mortality at
    1000 µg/litre.

         Common frog ( Rana temporaria) tadpoles were raised to
    metamorphosis at total aluminium concentrations of 800 and
    1600 µg/litre and at pH 4.4. Decreasing pH reduced maximum body size
    and delayed metamorphosis. Growth was depressed and metamorphosis
    delayed at 800 µg Al/litre; at 1600 µg/litre small tadpoles had
    arrested growth and development and subsequently died, whereas large
    tadpoles metamorphosed at a very small size (Cummins, 1986).

    9.1.3  Terrestrial organisms

    9.1.3.1  Plants

         Numerous studies exist of plants exposed to aluminium in nutrient
    solution or sand culture. They show that exposure causes diminished
    root growth and development, reduced uptake of plant nutrients
    (notably phosphorus, calcium and magnesium) and stunted plant growth
    (Bartlett & Riego, 1972a,b; Göransson & Eldhuset, 1987; Boxman et al.,
    1991; Keltjens & Tan (1993). The effect of aluminium on plants is
    complex. It can act directly on plant cell processes (Taylor, 1991) or
    indirectly by interfering with plant nutrition (Roy et al., 1988;
    Taylor, 1991).

         Plant species vary in their response to aluminium (Roy et al.,
    1988; Taylor, 1995). Even within species (e.g., wheat,  Triticum 
     aestivum), aluminium sensitive and tolerant varieties exist (Taylor
    & Foy, 1985; Kinraide et al., 1992; Huang et al., 1992a; Wheeler et
    al., 1993). There are reports that aluminium can benefit plants
    (Hackett, 1962, 1964, 1967). Various proposed mechanisms are listed in
    the review by Roy et al. (1988). However, it seems that exposure to
    excessive concentrations of aluminium is detrimental to plants, but
    the level that is excessive is highly variable.

    9.1.3.2  Invertebrates

         No data have been reported on the effects of aluminium on
    terrestrial invertebrates.

    9.1.3.3  Birds

         Hussein et al. (1988) fed Japanese quail ( Coturnix coturnix 
     japonica) on diets containing 0.05, 0.1, 0.15 and 0.3% aluminium (as
    aluminium sulfate) for 4 weeks. Egg production was significantly
    decreased at 0.1% and body weight gain at 0.15%. Feed intake was
    significantly depressed temporarily at 0.1 and 0.15% and permanently
    at 0.3%. Eggshell breaking strength was temporarily reduced (after 1
    week only) at 0.1, 0.15 and 0.3%.

         Hussein et al. (1989a) fed white leghorn laying hens on a diet
    containing 0.05, 0.1 or 0.15% aluminium (as aluminium sulfate) for 28
    days. Feed intake, body weight, tibia breaking strength and plasma
    inorganic phosphorus were significantly reduced at 0.15%. Egg
    production was only significantly depressed after 21 days at 0.15%.
    Eggshell breaking strength was unaffected by the treatment. In a
    second experiment hens were exposed to diets containing up to 0.3%
    aluminium for 42 days. Feeding 0.3% aluminium significantly decreased
    plasma inorganic phosphorus in samples collected immediately following
    oviposition (10 to 42 days). Plasma calcium, tibia weight and tibia
    breaking strength were unaffected. Egg production and feed intake were
    significantly reduced during days 1 to 21 but not during days 22 to
    42. The effects of 0.3% aluminium on the egg production and shell
    quality of laying hens are similar to those obtained with conventional
    force-moulting procedures using feed restriction (Hussein et al.,
    1989b). White leghorn laying hens were maintained on a diet containing
    0, 0.15 or 0.3% aluminium for 17 weeks. Hatchability of eggs was
    unaffected while fertility and body weight of chicks were
    significantly depressed at both aluminium treatments. Total egg
    production and feed consumption both were significantly reduced at the
    highest aluminium dose (Wisser et al., 1990).

         Carričre et al. (1986) fed ring doves ( Streptopelia risoria)
    on a diet containing 0.1% aluminium sulfate with reduced calcium
    and phosphorus levels (0.9% Ca; 0.5% P) for a period of 4 months.
    There were no significant effects on egg production, fertility,
    hatchability, growth or final weight of chicks. Egg permeability was
    initially decreased but subsequently recovered to normal levels. The
    diet had no effect on plasma calcium, phosphorus or magnesium. There
    was no effect on weight or growth rate in juvenile doves fed diets
    containing 500, 1000 or 1500 mg/kg aluminium sulfate from day 21 to
    day 63.

    9.2  Field observations

    9.2.1  Microorganisms

         No data have been reported regarding effects in the field of
    aluminium on microorganisms.

    9.2.2  Aquatic organisms

    9.2.2.1  Plants

         Hörnström et al. (1984) studied the effects of pH and different
    levels of aluminium on lake phytoplankton from the Swedish west coast
    area. They concluded that the absence of several phytoplankton species
    in acid lakes was not caused by the low pH but rather a raised
    aluminium supply from the surrounding land, which produced
    oligotrophic waters through precipitation of phosphorus. Comparing
    phytoplankton communities in strongly acid lakes with low and high
    levels of aluminium revealed that aluminium toxicity alone contributed
    significantly to the reduced numbers of phytoplankton species.

    9.2.2.2  Invertebrates

         Aston et al. (1987) found that for streams in Wales and the Peak
    district, United Kingdom, the population density and biomass of
    freshwater invertebrates were generally lowest in streams with low pH
    and high aluminium content. Hörnström et al. (1984) reported that most
    zooplankton species found in acidic lakes of the Swedish west coast
    were relatively resistant to acidity but were more susceptible to the
    oligotrophication process caused by the precipitation of phosphorus by
    aluminium. There was also an inverse correlation between the number of
    invertebrates and the aluminium concentration.

         Hall et al. (1985) added aluminium chloride (0.28-3.8 mg total
    Al/litre) to a stream to simulate episodic release during acidic
    snowmelt. Significant decreases in pH and dissolved oxygen content
    accompanied increases in aluminium. There was an increased drift of
    invertebrates with increasing aluminium concentration. The gradually
    increasing drift rate of benthic macro-invertebrates appeared to be a
    stress response to the aluminium/hydrogen ion concentrations. Drift of
    terrestrial insects feeding at the water surface appeared to be due to
    the reduction in surface tension of the aluminium-treated portion of
    the stream. Hall et al. (1987) found that during second-order stream
    experiments, overall more aquatic invertebrates drifted at pH 5.0
    during aluminium chloride addition (> 0.28 mg total Al/litre) than at
    pH 5.0 during hydrochloric acid addition (0.012 mg total Al/litre).
    McCahon et al. (1987) subdivided a stream into sections of low pH
    (4.3) and low aluminium concentration (0.052 mg total Al/litre) by

    adding sulfuric acid and high aluminium concentration (0.35 mg total
    Al/litre; pH 5.0) by adding aluminium sulfate. In the acid zone,
    mayfly mortalities of 20% and 5.3% after 24 h were observed for
     Baetis rhodani and  Ecdyonurus venosus, respectively. Mortality
    rose to 52.6% after 48 h for  E. venosus. Mayflies killed during the
    exposure did not stain for aluminium or mucus. Similar mortalities
    were observed for both species in the acid/aluminium zone. However,
    both species gave an aluminium-positive reaction for all parts of the
    body examined, aluminium being concentrated in the gut, within and
    surrounding the gill plates, and on the outer surface of the abdomen.

         Ormerod et al. (1987a) created simultaneous episodes of low pH
    (4.28), and low pH (5.02) with increased aluminium content (347 µg
    Al/litre) in a soft-water stream in upland Wales . In situ toxicity
    tests were performed, and  Chironomus riparius, Hydropsyche 
     angustipennis and  Dinocras cephalotes were found to have suffered
    no mortality.  Ecdyonurus venosus, Baetis rhodani and  Gammarus 
     pulex showed up to 25% mortality in both treatment zones. Drift
    densities increased, especially in the aluminium-treated zone,
     Baetis rhodani showing an increase of 8 times.  Baetis rhodani was
    the only invertebrate to show a significant decline in benthic density
    (in the aluminium zone), which was due mostly to drift. Weatherley et
    al. (1988) created 24-h experimental episodes by adding acid,
    aluminium and citric acid to different treatment zones of an upland
    stream. Drift density was only observed for the ephemerophteran  Baetis
     rhodani, and was found to be unaffected by flow at pH 7 or
    organically-bound aluminium. Both acidity (pH 4.9) and labile
    aluminium (0.11 mg/litre) increased drift density. Benthic density was
    significantly decreased by both labile and organically bound
    aluminium.

    9.2.2.3  Vertebrates

         Grahn (1980) reported two fish kills in lakes Ransjön and Ämten,
    two pristine acid lakes in Sweden, during 1978 and 1979. In 1978 the
    main part of the ciscoe ( Coregonus albula) population was wiped out.
    One week later the pH was found to be 5.4 at the surface and 4.9 at
    the bottom, with maximum aluminium levels of 0.91 mg/litre in
    groundwater and 0.31 mg/litre in stream water. One year later a
    similar incident occurred when the pH was 6.0 in surface water and 5.4
    in bottom water. Total aluminium concentrations ranged from 0.36 to
    0.52 mg/litre. Analysis of fish gills revealed that aluminium
    concentrations were at least 6 to 7 times higher than those found in
    fish gills from reference lakes in the area. The authors conclude that
    weather patterns caused an increase in phytoplankton, which in turn
    increased pH levels near the surface. Aluminium hydroxide was
    precipitated out in the epilimnion water. Ciscoes migrate to the
    surface to feed where the flocculated aluminium hydroxide caused fish
    gills to clog and fish to die of suffocation.

         Hunter et al. (1980) investigated Black Cart water, a tributary
    of the River Clyde, Scotland, following sporadic occurrences of fish
    kills (brown trout  Salmo trutta) during 1974 and 1975. Aluminium
    levels were 475 mg/kg (dry weight) in the lateral muscle of dead fish
    and 358 mg/kg in live fish. Effluent waters from an anodizing factory
    (pH 6.3-7.3; total aluminium 12-530 µg/litre and soluble aluminium
    20-360 µg/litre) were mixed with waters of pH 8.35-8.70 and total and
    soluble aluminium concentrations of 190-220 µg/litre and < 20
    µg/litre, respectively. Downstream of the confluent, which was the
    area of fish kills, the waters varied in pH between 8.1 and 8.5, and
    in total (200-1300 µg/litre) and soluble (20-33 µg/litre) aluminium.
    The authors suggested that when a high pH river receives high loadings
    of aluminium from water-treatment works soluble aluminium
    concentrations lethal to fish can occur.

         Schofield & Trojnar (1980) reported that lakes in the Adirondack
    mountains, USA, in which stocked brook trout ( Salvelinus fontinalis)
    were not recovered in netting surveys during 1975, were those with
    significantly lower mean pH (4.79 versus 5.25), calcium level (1.62
    versus 1.87 mg/litre) and magnesium level (0.30 versus 0.39 mg/litre),
    and higher mean aluminium concentrations (0.29 versus 0.11 mg/litre).
    The covariance analysis of water quality suggested that aluminium
    intoxication may have been a primary factor in determining the success
    or failure of fish stocking, whereas both pH and calcium level showed
    a lack of significance.

         Henriksen et al. (1984) showed the acid-aluminium-rich (pH 5.1;
    inorganic monomeric aluminium 30 µg/litre) waters of the river
    Vikedal, in southwestern Norway, during a period of increased water
    flow, to be toxic to pre-smolt Atlantic salmon ( Salmo salar).
    Skogheim et al. (1984) reported massive deaths of adult Atlantic
    salmon in the River Ogna in south-west Norway in 1982. Newly run
    migrating spawners were killed when acid tributary water (pH 4.7;
    inorganic monomeric Al 340-360 µg/litre) was mixed into the falling
    main stream flow of better water quality (pH 5.96-6.18; inorganic
    monomeric Al 12-13 µg/litre). A near total mortality of salmon
    occurred for several km downstream of the confluent (pH 4.76-5.41;
    inorganic monomeric Al 110-307 µg/litre). Blood samples from highly
    stressed fish (plasma chloride 103-113 mEq/litre) demonstrated
    osmoregulative failure (normal values 120-135 mEq/litre), and gill
    aluminium accumulation (70-341 µg Al/g fresh weight) was around 10
    times higher than normal values.

         Harriman et al. (1987) studied the long-term fish population
    changes in streams and lochs of south-west Scotland during 1978, 1979
    and 1984. Trout were not caught in areas known to have contained them
    in the past. Fish-less lochs and streams contained the levels of
    acidity (pH 4-5) and aluminium (up to 300 µg labile monoesic Al/litre)
    known to be toxic to fish. The authors concluded that acidic
    deposition was probably the major cause of the change in the fish
    population in this area.

         Eaton et al. (1992) compared laboratory exposure of four embryo-
    larval fish species to aluminium (< 6.0-70 µg/litre) and pH levels of
    4.5 to 7.0 with field observations. Laboratory results showed that
    monomeric aluminium concentrations of approximately 50 µg/litre, which
    were comparable to aluminium concentrations in the acidified half of a
    lake, increased low pH toxicity. However, the laboratory tests
    for largemouth bass ( Micropterus salmoides) and rock bass
    ( Ambloplites rupestris) underestimated field toxicity, those for
    black crappie ( Pomoxis nigromaculatus) overestimated field toxicity
    and those for yellow perch ( Perca flavescens) were similar to those
    observed in the field.

         Karlsson-Norrgren et al. (1986a) collected and examined brown
    trout ( Salmo trutta) from two fish farms within acid-susceptible
    areas in Sweden. The total aluminium concentrations in the water were
    200 to 300 µg/litre. Trout from a third non-acidified location
    (aluminium levels in water 35 µg/litre) were also examined. Light and
    electron microscopic examination of fish from the acid-susceptible
    areas revealed two major types of gill lesion characterized by
    chloride cell hyperplasia, and enlargement of the intercellular
    spaces, in the secondary lamellar epithelium. The gills from the
    control area appeared normal, exhibiting features characteristic of
    salmonids.

         Norrgren & Degerman (1993) transferred eyed eggs of Atlantic
    salmon ( Salmo salar) and brown trout ( Salmo trutta) in plastic
    boxes to various locations on the Morrum river, Sweden. The pH levels
    ranged from 5.1 to 6.7 and total mean aluminium levels ranged from 933
    to 569 µg/litre (mean reactive aluminium concentrations ranged from
    8 to 203 µg/litre). No significant effects were observed on hatching
    (13 days) or fry survival (77 days) at pH > 5.7 and reactive
    aluminium concentrations of up to 49 µg/litre. At pH 5.1 and a total
    aluminium concentration of 569 µg/litre (reactive aluminium =
    203 µg/litre), there was a significant reduction in the salmon hatch
    but not the trout hatch; total fry mortality after 77 days was 100%
    for salmon and 94% for trout. Histochemical studies revealed aluminium
    precipitates in the gills of dead fish; precipitates were associated
    with the apical plasma membrane.

         Stoner et al. (1984) carried out 17-day survival studies of caged
    brown trout ( Salmo trutta) in streams of the river Tywi catchment,
    Wales. All streams where fish died had concurrent mean total aluminium
    concentrations exceeding 21 µEq/litre and mean pH levels of less than
    6. There was a high positive correlation between fish mortality
    (expressed as the inverse of LT50) and mean filterable aluminium
    concentration. Differences in LT50 values reflected differences in
    aluminium at similar pH levels. There were considerable differences in
    gill aluminium concentrations between "control" fish (61 µg/g) and
    those that died most rapidly (3505 µg/g). There was also a positive

    correlation between mortality rate and gill aluminium concentration.
    Weatherley et al. (1990) studied the survival of eggs, alevins and
    parr of brown trout ( Salmo trutta) in streams of different acidity
    (pH 4.7-6.9). Egg survival from fertilization to hatching was
    independent of the mean total monomeric aluminium concentration, which
    ranged from 3 to 397 µg/litre. However, the survival of alevins was
    strongly related to both aluminium and pH; LC50 values for 28- and
    42-day exposures were approximately 19 and 15 µg total monomeric
    aluminium/litre, respectively (equivalent to 79 and 72 µg/litre of
    0.45 µm filterable aluminium). The 21-day LC50 for parr (3 months)
    was between 84 and 105 µg/litre filterable aluminium.

         Ormerod et al. (1987a) created an acidic episode in a softwater
    stream in upland Wales. Three stretches were identified: (a) upper
    reach with natural waters of pH 7.0 (40 µg total Al/litre), (b)
    addition of sulfuric acid to pH 4.2-4.5 (52 µg total Al/litre), and
    (c) pH 5.2 (347 µg total Al/litre). Caged salmon ( Salmo salar) and
    brown trout ( Salmo trutta) showed 7-10% mortality in the acid zone
    (b) and 50-87% in the aluminium zone (c). Salmon (14.7 h) had a
    significantly shorter LT50 than trout (23.5 h) in the aluminium zone
    (c). Ormerod et al. (1987b) reported that brown trout ( Salmo trutta)
    exposed to similar episodes showed reduced plasma sodium at low pH
    (4.2), which appeared to be decreased by the addition of aluminium;
    however, at pH 4.8 to 5.1 aluminium increased the effect. At pH
    4.8-5.1 with the addition of aluminium, fish showed an increased
    frequency of ventilation. At lower pH effects on ventilation were less
    consistent.

         McCahon et al. (1987) reported that trout and salmon exposed to
    acid conditions (pH 4.3) alone and low aluminium concentration
    (0.052 mg/litre) did not stain for aluminium, although increased mucus
    production was demonstrated in the gills. Fish exposed to aluminium
    (0.35 mg/litre) at low pH (5.0) exhibited extensive aluminium and
    mucus coating of the secondary gill lamellae. Fish that died in the
    acid/aluminium zone showed large significant increases in gill
    aluminium content compared with controls or with fish from the acid-
    only zone. Mean aluminium concentrations in fish gills from the
    acid/aluminium zone were 2950 and 3050 µg/g (dry weight) for trout and
    salmon, respectively.

         Rosseland et al. (1992) exposed  in situ caged smolts of
    Atlantic salmon ( Salmo salar) and sea trout ( Salmo trutta) to
    waters in an acid tributary (pH 4.8; inorganic monomeric aluminium
    236 µg/litre) and the mixing zone with the limed river Audna (Norway)
    (pH 7.0; inorganic monomeric aluminium 17 µg/litre). In the acid
    tributary LT50 values were 22 h and 40 h for the two species,
    respectively. However, in the mixing zone, between 1 and 3 min after
    mixing (pH 5.8-5.9; inorganic monomeric  Al 78-111 µg/litre), both

    species gave an LT50 of 7 h. Fish showed osmoregulatory failure (loss
    of plasma ions and reduced gill Na/K-ATPase) and gill lesions. No
    mortality occurred 5 min after mixing or in the limed water. The
    authors concluded that the increased toxicity in the mixing zone was
    due to the transformation of aluminium from a low to a high molecular
    weight precipitating species. The ecological importance of these
    mixing zones was pointed out (especially being related to seasonal
    changes) as low temperatures (longer polymerization period) and high
    flows both would increase the river stretch being affected by these
    processes.

         Poléo et al. (1994) used the same water sources to a channel
    experiment with control mixing of the waters. Caged Atlantic salmon
    were exposed to acid stream water (pH 4.89; inorganic monomeric
    Al 139 µg/litre), limed stream water (pH 6.41; inorganic monomeric
    Al 14 µg/litre) and the mixture of the two (pH 5.64; inorganic
    monomeric Al 70 µg/litre). No mortality occurred in the limed water,
    but there was a 27% mortality in the acid stream water after 72 h
    exposure. In the mixed water, mortality of up to 90% (mean of 75%)
    occurred in the first two metres and up to 1 min after mixing, the
    LT50 being 60 h. Within the next 3 min of reaction a total mortality
    of 16% was found. Fish in the most toxic zone lost plasma ions at a
    slower rate than in the acid, less toxic zone, apparently
    demonstrating a different mechanism of toxicity. Although no mortality
    occurred towards the end of the channel (4-7 min after mixing), loss
    of plasma ions and increased haematocrit were found, indicating
    suboptimal conditions.

         Lydersen et al. (1994) exposed caged one-year-old parr of brown
    trout to mixing zone conditions in a channel, using as input water
    from an acid lake (pH 5.3; total Al 379 µg/litre and inorganic
    monomeric Al 350 µg/litre) and a neutral lake of pH 7.0, total Al
    38 µg/litre. After mixing, a constant pH of 6.1-6.2 was achieved all
    along the channel. Total mortality in the lake water was 15% after
    24 h. Downstream of the confluent (9 seconds of mixing) mortality
    started after 5 h, reaching 100% after 17 h. The LT50 values after 9,
    18, 45, 136, 180 and 225 seconds of mixing were 7.5, 9, 12, 17, 23 and
    26 h, respectively. Through the use of improved  in situ aluminium-
    separation techniques, the authors could for the first time
    demonstrate the increase in high molecular Al forms (polymerization)
    at stations along the channel and relate this directly to toxicity.

         Freda & McDonald (1993) transplanted embryos and tadpoles of the
    wood frog ( Rana sylvatica), the American toad ( Bufo americanus)
    and the spotted salamander ( Ambystoma maculatum) to acidified ponds.
    Statistical analysis revealed that pH was the only significant
    parameter in determining mortality; the concentrations of total and
    labile aluminium were not correlated with the survival of any of these
    species.

    9.2.3  Terrestrial organisms

    9.2.3.1  Plants

         Aluminium toxicity to plants is well known in agriculture and
    forestry (Wild, 1988). Direct and indirect effects of enhanced
    aluminium availability in soil due to soil acidification may be a
    cause of current problems in some European forests (Abrahamsen et al.,
    1994).

         Reich et al. (1994) monitored the light-saturated net
    photosynthesis, dark respiration and foliar nutrient content of Scots
    pine ( Pinus sylvestris) growing in polluted and non-polluted sites.
    At the polluted site soil pH and calcium and magnesium contents were
    10 times lower and aluminium content 10 times higher than at the
    control site. The rate of photosynthesis was lower and that of dark
    respiration was higher at the polluted site. Photosynthesis was found
    to be negatively correlated to the aluminium:calcium ratio across both
    sites. Dark respiration rate increased with nitrogen and aluminium
    contents. Based on the data, the authors concluded that at the
    polluted site there were excessive soil aluminium levels and deficient
    levels of magnesium. Low needle magnesium level and high aluminium
    concentrations and aluminium:calcium ratios resulted in reduced
    photosynthetic capacity and increased respiration.

         Cronan et al. (1987) reported that observed field total
    monomeric aluminium concentrations and aluminium ion activities were
    considerably lower than laboratory-based toxic thresholds for several
    tree species. However, analysis suggests that calcium/aluminium ratios
    for fine roots were near to critical levels. Aluminium toxicity could
    possibly have been acting as a stress factor either directly or
    indirectly by nutritional interference.

         Joslin et al. (1988) sampled roots and foliage of spruce trees
    from five sites in North America and Europe. Aluminium concentrations
    in fine roots from B horizons were highly correlated with soil
    solution monomeric aluminium. Sites with higher levels of plant-
    available aluminium had spruce trees with lower foliage levels of
    calcium and magnesium. The authors concluded that this may be evidence
    of aluminium interference in calcium and magnesium uptake and
    transport. There was no obvious interference of aluminium in the
    uptake and translocation of phosphorus.

         Godbold et al. (1988b) studied the effects of aluminium on
    nutrient fluxes in  Picea abies. The authors reported that, using
    X-ray microanalysis, the distribution of aluminium, magnesium, calcium
    and potassium was found to be similar in roots to those collected from
    declining spruce stands in Solling, Germany.

         Cuenca & Herrera (1987) reported that trees analysed from a
    tropical cloud forest growing in acid/aluminium-rich soil were found
    to have two distinct strategies for survival: accumulator plants, with
    aluminium levels of > 1000 mg/kg, and non-accumulators. Both types
    contained large amounts of aluminium in the roots, but in accumulators
    the plasmalemma in endodermic cells was permeable to aluminium. The
    authors found that both groups were able to accumulate aluminium in
    cell walls, alkalinize the surrounding rhizosphere and produce
    chelating agents, but all at a high ecological cost and with low
    growth rates as a result.

         Most cultivated plants are non-accumulators and efficiently
    exclude aluminium from the harvested parts. A notable exception is tea
    ( Camellia sinensis) where aluminium concentration in mature leaves
    can reach 1.7% Al/dry weight (Chenery, 1955; Coriat & Gillard, 1986).

         Clarkson (1967) studied the aluminium tolerance of four species
    of  Agrostris from different sites in the United Kingdom. The most
    sensitive species was  A. stolanifera from a site with no detectable
    soil aluminium (as exchangeable ions) and the most tolerant was
     A. setacea from a site with soil levels of 3.6 mEq Al/kg. Growing
    the species in soils from each of the different sites revealed that
    peak growth was achieved in soil from the site where the plant was
    collected.

    9.2.3.2  Invertebrates

         No information has been reported regarding the field effects of
    aluminium on terrestrial invertebrates.

    9.2.3.3  Vertebrates

         Nyholm (1981) found aluminium in the bone marrow tissue of the
    humeri of pied flycatchers ( Ficedula hypoleuca) with impaired
    breeding from the shores of Lake Tjulträsk, Sweden. The impairments
    included production of small clutches, defective eggshell formation
    and intrauterine bleeding. The authors stated that these impairments
    compare with the symptoms of aluminium intoxication in mammals.
    However, the effects may be indirect, the result of phosphate binding
    in the intestinal tract rather than direct toxicity of aluminium.

         Ormerod et al. (1986) reported that sites without breeding
    dippers ( Cinclus cinclus) had significantly higher mean
    concentrations of filterable aluminium, lower mean pH, fewer
    trichopteran larvae and ephemeropteran nymphs, and were on rivers with
    more conifer afforestation on their catchments than sites where
    dippers were present. Ormerod et al. (1988) found no evidence that
    aluminium (0.47-2.13 mg/g; dry weight) in the invertebrate prey of
    dippers ( Cinclus cinclus) collected from streams of different pH
    from Wales and Scotland adversely affected shell thickness or mass of
    eggs.

    10.  EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT

    10.1  Health effects

         The overall assessment of the risks of aluminium exposure to
    healthy, non-occupationally exposed humans is rendered uncertain by
    several deficiencies in the database, namely:

    i)   the questionable relevance to humans of animal experiments
         designed for hazard identification, in which massive doses were
         administered by parenteral routes, and the lack of data based on
         oral dosing at relevant exposure levels;

    ii)  the dubious relevance to humans of the many biochemical findings
         from cell culture experiments and other  in vitro models;

    iii) the uncertainty in the analytical and estimated cumulative
         exposure data in epidemiological studies of the relationship of
         aluminium in drinking-water to Alzheimer's disease (AD), and the
         less than robust dose-response data obtained from such studies;

    iv)  the complete lack of epidemiological studies relating to total
         aluminium exposure, when it is considered that aluminium derived
         from drinking-water is responsible for only a small fraction of
         such exposure.

         It should be noted, however, that animal models employing oral
    aluminium administration provide some limited support for cognitive
    and motor impairment in the absence of neuropathological changes.

         Adverse health effects from aluminium exposure have been
    definitely established in one special group, i.e. patients with
    severely impaired renal function. These patients are at risk from
    severe neurological dysfunction and are also at risk of vitamin-D-
    resistant osteomalacia and microcytic anaemia from iatrogenic exposure
    to aluminium-containing preparations. The toxicity of oral aluminium-
    containing preparations is exacerbated by concurrent use of oral
    citrate-containing preparations under these circumstances.

         An increased tissue loading of aluminium, especially in bone, has
    been shown in premature infants without azotaemia. Current paediatric
    practice is to warn about the potential risk that may be associated
    with increased tissue levels of aluminium following parenteral
    administration or oral intake of products with elevated aluminium
    content.

    10.1.1  Exposure assessment

         Human exposure to aluminium can vary greatly depending on diet,
    use of specific medications, sources of drinking-water and exposure to
    other ambient and occupational sources of aluminium. In many countries
    non-occupationally exposed adults are exposed to between 2.5 and 13 mg
    aluminium/day from air, water and food (0.08-0.18 mg/kg body weight
    per day for a 60-kg individual). However, large variations in daily
    intake can occur as a consequence of differing intakes of foods
    containing commonly encountered food additives. Infants consuming
    formulae based on cow's milk have very low aluminium intakes
    (0.1-0.8 mg/litre), whereas those fed soya-based formulae have much
    greater aluminium intakes (3.1-4.3 mg/litre). Moreover, use of
    aluminium containing antacids and/or buffered analgesics can increase
    daily intake between 10 and 1000 times. Actual exposures will vary
    from country to country, but the above figures can be used as a first
    approximation for assessing human health risks from aluminium
    exposure.

         Occupationally exposed populations have background exposure
    levels similar to those of non-occupationally exposed populations, but
    their work can lead to significantly increased exposure. Actual levels
    of exposure depends on the specific work tasks performed, the type and
    form of aluminium compound encountered, and the adequacy of workplace
    hygiene practices. Inhalation is the most important route of
    occupational exposure, but the extent of pulmonary uptake and
    retention has not been determined in most occupational settings. Based
    on limited data, daily occupational aluminium exposure can range from
    <1 mg to 40 mg per 8-h shift.

    10.1.2  Evaluation of animal data

         Information from toxicokinetic studies in animals is consistent
    with and complementary to that obtained in humans. Available studies
    indicate that oral bioavailability is low (< 1%) and they provide
    valuable information on dose-related concentrations and effects in
    target tissues.

         In general, the animal studies evaluated were not designed for
    risk assessment purposes. However, these studies provide information
    relevant to hazard identification and some data on dose-response.

         The target tissues in animals are similar to those in humans and
    include the bone and nervous system.

         In developmental studies in rodents, reduced intrauterine
    weight gains were noted in the female offspring of dams gavaged with
    aluminium nitrate at doses as low as 13 mg Al/kg body weight per

    day, whereas male offspring were not affected at this dose level.
    Neurobehavioural and motor development were affected at 100 and
    200 mg Al/kg body weight per day when aluminium lactate was
    administered to mice in the feed.

         There is no indication that aluminium is carcinogenic.

    10.1.3  Evaluation of human data

         There is no indication that aluminium is acutely toxic after oral
    intake. A causal relationship between short-term exposure to high
    levels of aluminium in drinking-water and adverse health effects is
    not supported by available data.

         The information available is insufficient to classify the
    carcinogenic risk to humans from exposure to aluminium and aluminium
    compounds.

         No information is available associating aluminium exposures with
    adverse reproductive effects.

         Although human exposure to aluminium is widespread, only a few
    reports of hypersensitivity exist. In all cases the hypersensitivity
    followed dermal or parenteral administration.

         In the healthy general population the major health concern
    relates to the purported association between the intake of aluminium
    and the development and/or acceleration of the onset of AD and other
    neurotoxic effects. After an in-depth analysis of the available
    epidemiological data (section 8.1.3 - Table 22), considering study
    design, exposure measurements and relative risks reported, it was
    concluded that:

    *    On the whole, the positive relationship between aluminium in
         drinking-water and AD, which was demonstrated in several
         epidemiological studies, cannot be totally dismissed. However,
         strong reservations about inferring a causal relationship are
         warranted in view of the failure of these studies to account for
         demonstrated confounding factors and for total aluminium intake
         from all sources.

    *    Taken together, the relative risks for AD from exposure to
         aluminium in drinking-water above 100 µg/litre, as determined in
         these studies, are low (less than 2.0). But, because the risk
         estimates are imprecise for a variety of methodological reasons,
         a population-attributable risk cannot be calculated with
         precision. Such imprecise predictions may, however, be useful in
         making decisions about the need to control exposures to aluminium
         in the general population.

    *    In light of the above studies, which consider water-borne
         aluminium as the sole risk factor, and the recent findings that
         water accounts for less than 5% of daily intake of aluminium, it
         is difficult to reconcile this with the presumed impact on
         cognition. Several lines of investigation should be pursued to
         further elucidate the nature of the relationship found in these
         studies.

         Data from many clinical studies have firmly established the
    causal relationship between aluminium exposure in patients with
    chronic renal failure (including premature infants with kidney
    failure) and the development of encephalopathy (dementia), vitamin-D-
    resistant osteomalacia, and microcytic anaemia. The major sources of
    aluminium exposure have been indicated as the level of aluminium in
    the water used to prepare the dialysis fluids and treatment with
    aluminium-containing phosphate binders. Dialysis encephalopathy was
    found to be rare when the aluminium level in the dialysis fluid was
    maintained below 50 µg/litre. The use of aluminium-free phosphate-
    binding agents will also decrease the risk of developing
    encephalopathy in patients treated for kidney failure.

         In many occupational settings workers are exposed not simply to
    aluminium fumes and dust, but rather to a complex mixture of chemicals
    and dusts, of which only some contain aluminium. Therefore, it is
    essential that urinary aluminium levels be determined as a measure of
    exposure (dose), in addition to workplace levels of particulates, if a
    causal association between aluminium and effects on the respiratory
    and nervous systems is to be developed with any degree of certainty.
    Only a few of the published surveys contain such information.

         In the past, exposure to stamped pyrotechnic aluminium powder,
    usually coated with mineral oil lubricants, has caused pulmonary
    fibrosis. However, exposure to other forms of aluminium has not proved
    to be a cause of pulmonary fibrosis.

         There is no evidence of specific toxicity of any immunological
    reaction to the element aluminium as a cause of occupational asthma.
    This disorder is considered to be irritant-induced following exposure
    during the production of compounds such as aluminium sulfate,
    aluminium fluoride and potassium aluminium tetrafluoride, or in
    production areas of primary aluminium smelting. Exposure to dust and
    particulate in workers fabricating (welding) aluminium have been
    associated with an increased level of chronic bronchitis or decreased
    lung function. A causative role of non-aluminium fume or dusts, e.g.,
    fluorides, cannot be ruled out. It was reported that the chronic
    bronchitis noted in aluminium welders was similar to that in welders
    working with stainless steel or iron.

         There is some evidence that aluminium exposure in welders, miners
    and foundry workers can lead to an impairment of cognitive and motor
    functions. However, owing to the small cohorts used in some studies,
    methodological deficiencies in most studies, and conflicting results
    from different studies, there is considerable uncertainty in ascribing
    a causative role for aluminium in the neurological effects reported.
    In one large study of miners exposed to aluminium powder, the
    difficulties in adequately controlling for confounding factors also
    lead to much uncertainty in accepting the positive effects observed on
    cognition. There is a need for additional studies to clarify the
    uncertainties in these data.

    10.2  Evaluation of effects on the environment

    10.2.1  Exposure

         Aluminium is among the least mobile of the major elements of the
    geological sedimentary cycle. In air it is present mainly as wind-
    blown soil particles. Aluminium-bearing solid phases are relatively
    insoluble, particularly in the circumneutral pH range, and so most
    natural waters contain low concentrations of dissolved aluminium.
    However, the solubility of aluminium is highly dependent on pH,
    increasing at both low and high pH values, which reflects the
    amphoteric nature of the element. This fact, coupled with the large
    reservoir of aluminium in soils and sediments, means that aluminium
    concentrations can be substantially enhanced in acidic or poorly
    buffered environments subjected to sustained or periodic exposure to
    strong acidifying inputs. Under such conditions aluminium can be
    transported from soil to surface waters. Afforestation, the cessation
    of liming, and sulfide oxidation all contribute to acidification and
    thus to the release of previously bound aluminium. However, a major
    cause of acidification is acidifying deposition from the atmosphere.

    10.2.2  Effects

         Laboratory and field studies have revealed that the inorganic
    mononuclear aluminium complexes are more toxic to both aquatic
    organisms and terrestrial plant species than the organically complexed
    forms. Aluminium has been shown to affect adversely both aquatic
    organisms and terrestrial plants at concentrations found in acidic or
    poorly buffered environments. However, there exist large species,
    strain and life-history stage differences in sensitivity. Elevated
    concentrations of inorganic monomeric aluminium have detrimental
    biological effects that are mitigated in the presence of organic
    acids, fluoride, silicate, and high concentrations of calcium and
    magnesium. There is a substantial reduction in species richness
    associated with the mobilization of the more toxic forms of aluminium
    in acid-stressed waters; this loss of species diversity is reflected
    at all trophic levels. In waters with non-steady-state aluminium
    chemistry (ongoing polymerization), toxicity can become extreme in pH
    ranges not normally associated with toxicity.

    11.  CONCLUSIONS AND RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH
         AND THE ENVIRONMENT

         In reaching the following conclusions with regards to the risks
    from aluminium exposure the Task Group felt it was appropriate to
    consider separately the human populations at risk as well as the
    environment. The conclusions are, therefore, grouped as to the risk to
    the healthy general population, healthy workers and individuals with
    impaired kidney function. This is followed by conclusions regarding
    the risk to the environment from aluminium.

    11.1  Conclusions

    11.1.1  Healthy general population

         Hazards posed by aluminium to intrauterine and neurological
    development and brain function have been identified through animal
    studies. However, aluminium has not been shown to pose a health risk
    to healthy, non-occupationally exposed humans.

         There is no evidence to support a primary causative role of
    aluminium in Alzheimer's disease (AD). Aluminium does not induce AD
    pathology  in vivo in any species, including humans.

         The hypothesis that exposure of the elderly population in some
    regions to high levels of aluminium in drinking-water may exacerbate
    or accelerate AD is not supported by available data.

         It has also been hypothesized that particular exposures, either
    occupational or via drinking-water, may be associated with non-
    specific impaired cognitive function. The data in support of this
    hypothesis are currently inadequate.

         There is insufficient health-related evidence to justify
    revisions to existing WHO Guidelines for aluminium exposure in
    healthy, non-occupationally exposed humans. As an example, there is an
    inadequate scientific basis for setting a health-based standard for
    aluminium in drinking-water.

    11.1.2  Subpopulations at special risk

         In people of all ages with impaired renal function, aluminium
    accumulation has been shown to cause the clinical syndrome of
    encephalopathy, vitamin-D-resistant osteomalacia and microcytic
    anaemia. The sources of aluminium are haemodialysis fluid and
    aluminium-containing pharmaceutical agents (e.g., phosphate binders).
    Intestinal absorption can be exacerbated by the use of citrate-
    containing products. Patients with renal failure are thus at risk of
    neurotoxicity from aluminium.

         Iatrogenic aluminium exposure poses a hazard to patients with
    chronic renal failure and to premature infants. Every effort should be
    made to limit such exposure in these groups.

    11.1.3  Occupationally exposed populations

         Workers having long-term, high-level exposure to fine aluminium
    particulates may be at increased risk of adverse health effects.
    However, there are insufficient data from which to develop, with any
    degree of certainty, occupational exposure limits with regards to the
    adverse effects of aluminium.

         Exposure to stamped pyrotechnic aluminium powder, usually
    coated with mineral oil lubricants, has caused pulmonary fibrosis
    (aluminosis), whereas exposure to other forms of aluminium has not
    been proved to cause pulmonary fibrosis. Most reported cases involved
    exposure to other potentially fibrogenic agents.

         Irritant-induced asthma has been shown to be associated with
    inhalation of aluminium sulfate, aluminium fluoride and potassium
    aluminium tetrafluoride, and found to occur within the complex
    environment of primary aluminium production, especially in potrooms.

    11.1.4  Environmental risk

         Aluminium-bearing solid phases in the environment are relatively
    insoluble, particularly at circumneutral pH values, resulting in low
    concentrations of dissolved aluminium in most natural waters.

         In acidic or poorly buffered environments subjected to strong
    acidifying inputs, concentrations of aluminium can increase to levels
    resulting in adverse effects on both aquatic organisms and terrestrial
    plants. However, there exist large species, strain and life-history
    stage differences in sensitivity to this metal.

         The detrimental biological effects from elevated concentrations
    of inorganic monomeric aluminium can be mitigated in the presence of
    organic acids, fluorides, silicate and high levels of calcium and
    magnesium.

         A substantial reduction in species richness is associated with
    the mobilization of the more toxic forms of aluminium in acid-stressed
    waters. This loss of species diversity is reflected at all trophic
    levels.

    11.2  Recommendations

    11.2.1  Public health protection

    a)   Strategies should be developed to limit exposure for patients
         with severly impaired renal function who are exposed to aluminium
         from pharmaceutical products.

    b)   For patients with end-stage renal failure treated by dialysis,
         exposure to aluminium should be limited by treatment of the water
         and elimination of aluminium contamination of the chemicals used
         to prepare dialysis fluid. It is suggested that dialysis fluids
         should contain less than 15 µg aluminium/litre.

    11.2.2  Recommendations for protection of the environment

    a)   Soil and water acidification can mobilize aluminium and have
         detrimental effects on aquatic and terrestrial lifeforms. Actions
         that cause enhanced acidification, e.g., emissions of SO2, NOx
         and NH3, should continue to be restricted.

    b)   When waters are limed to mitigate aluminium toxicity to fish, it
         should be done in such a manner that sufficient time is available
         for establishment of equilibrium between the aluminium species
         before the water reaches the most biologically sensitive or
         valuable parts of the system.

    12.  FURTHER RESEARCH

         In order to improve the scientific database on aluminium for the
    assessment of the risks to human health, thus decreasing the present
    level of uncertainty, the Task Group considered that additional
    research in several areas was essential.

    12.1  Bioavailability and kinetics

    (a)  Future studies should address the issue of whether aluminium in
         drinking-water is more bioavailable than that from other sources
         such as food, consumer products and food additives paying
         particular attention to the study of factors that can modify
         aluminium uptake by the body. This question is best answered by
         studies in humans using 26Al although appropriately designed
         animal experiments would provide useful data.

    (b)  Once aluminium has gained access to the brain, at what rate is it
         mobilized or excreted? Is the brain a "one-way sink for
         aluminium"? These questions can only be addressed successfully in
         an animal model where serial cortical biopsies can be performed.

    (c)  In view of the importance of achieving international concordance
         of accurate chemical analysis for aluminium in environmental and
         biological samples, it is recommended that the development of
         expert reference laboratories and systems of quality control
         should be facilitated and supported.

    12.2  Toxicological data

    (a)  It is thought unlikely that further studies of parenteral
         aluminium exposure to normal animals will improve the database
         significantly. There is, however, a need for well-designed animal
         studies focusing on neurotoxicity and reproductive and
         developmental end-points using protocols developed for the
         assessment of dose-response relationships for exposures by either
         the oral or inhalation routes.

    (b)  Research in experimental animals on the factors related to the
         development of Alzheimer's disease (AD) is hampered by the lack
         of a suitable model. However, aged primates or transgenic mice
         bearing the human APP gene with familial AD point mutation could
         potentially be used for this purpose (with some reservations).
         The advantage of these models is that total aluminium intake can
         be controlled during the relevant portion of the animal's life
         span (about 3-10 years and 1-2 years for primates and mice,
         respectively).

    (c)  There is a requirement for further studies to determine the
         effects of diminished renal function on aluminium toxicokinetics.
         Such studies should be designed to assess the impact of early-
         stage renal disease (varying degrees) and age-related decreases
         in renal function on aluminium retention and toxicity.

    12.3  Research on the relationship between aluminium exposure and
          Alzheimer's disease

    (a)  Further studies of aluminium levels in bulk tissues from brains
         of patients with AD are unlikely to be of value in resolving the
         current controversy or enable the distinction to be made between
         a pathogenic factor and an epiphenomenon.

    (b)  The knowledge base is unlikely to be advanced significantly by
         further ecological retrospective studies of exposure to aluminium
         in drinking-water and AD. Rather, prospective studies of matched
         cohorts of elderly people from stable populations living in areas
         with high and low levels of aluminium in drinking-water are
         required, with special attention to known confounding factors.
         Exposure should preferably be assessed through monitoring of
         aluminium in the tap water of all cohort members. Although as an
         outcome measure it is preferable to compare the pathological
         configuration of AD to reference populations, this may be
         impractical, and standardized clinical assessments have to be
         relied on using carefully considered criteria for the diagnosis
         of Alzheimer-type dementia.

    (c)  As Alzheimer-type neuropathology is almost universal in older
         Down's syndrome subjects, and as decline in cognitive function,
         as assessed by decline in activities of daily living skills, is
         relatively common (25-35), a point study of rates of cognitive
         impairment in Down's syndrome patients over 40 years of age from
         high and low water aluminium areas might be performed relatively
         quickly and with small numbers of subjects. Unbiased subject
         recruitment would, however, present problems.

    (d)  If the hypothesis that higher drinking-water aluminium levels are
         an accelerating or exacerbating factor for AD is correct, a
         neuropathological assessment of elderly subjects dying of an
         unrelated cause requiring routine postmortem examination (e.g.,
         passengers in road traffic accident) ought to reveal a greater
         burden of Alzheimer's pathology in those from areas with high
         aluminium levels in drinking-water than those from areas with low
         aluminium levels.

    12.4  Occupational exposure

         The possible adverse effects of occupational aluminium exposure
    on the health of workers should be a specific priority for future
    research.

    13.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

         At the Thirty-third Meeting of the Joint FAO/WHO Expert Committee
    on Food Additives and Food Contaminants, a provisional tolerable
    weekly intake (PTWI) of 7.0 mg/kg body weight was recommended. This
    value included the intake of aluminium from its use as a food additive
    (FAO/WHO, 1989).

         On the basis of non-health-related criteria, a WHO Drinking-Water
    Guideline of 0.2 mg/litre has been proposed (WHO, 1993). No health-
    based guideline was recommended.

         The carcinogenic risk from aluminium and its compounds has not
    been evaluated by the International Agency for Research on Cancer
    (IARC). However, that there is sufficient evidence that certain
    exposures occurring during aluminium production cause cancer in
    humans. Most epidemiological studies suggest pitch volatiles to be
    the causative agent (IARC, 1987).

         Regulatory standards for aluminium and some aluminium compounds
    established by national bodies in several countries and the European
    Union are summarized in the legal file of the International Register
    of Potentially Toxic Chemicals (IRPTC, 1993).

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    RESUME ET CONCLUSIONS

    1.  Identité, propriétés chimiques et physiques

         L'aluminium est un métal ductile et malléable de couleur blanc
    argenté. Il appartient au groupe IIIA de la classification périodique
    et se trouve généralement au degré d'oxydation III dans ses dérivés
    usuels. Il constitue environ 8% de l'écorce terrestre et c'est l'un
    des métaux usuels les plus réactifs. En présence d'eau, d'oxygčne et
    d'autres oxydants, il se recouvre d'une couche superficielle d'oxyde
    qui lui confčre une grande résistance ŕ la corrosion. L'oxyde
    d'aluminium est soluble dans les acides minéraux ainsi que dans les
    bases fortes, mais il est insoluble dans l'eau. Par contre, le
    chlorure, le nitrate et le sulfate sont solubles dans l'eau. Les
    halogénures, l'hydrure et les premiers termes de la série des
    alkylaluminiums réagissent violemment avec l'eau.

         L'aluminium a une forte conductivité thermique et électrique,
    sa densité est faible et sa résistance ŕ la corrosion élevée. On
    l'utilise souvent en alliage avec d'autres métaux. Ces alliages sont
    légers, résistants et faciles ŕ usiner.

    2.  Méthodes d'analyse

         On a mis au point diverses méthodes d'analyse pour la recherche
    et le dosage de l'aluminium dans les milieux biologiques et les
    échantillons prélevés dans l'environnement. Les plus fréquemment
    utilisées sont la spectrométrie d'absorption atomique avec four ŕ
    électrode de graphite (GF-AAS) et la spectrométrie d'émission atomique
    avec plasma ŕ couplage inductif (ICP-AES). La principale source
    d'erreur est la contamination des échantillons, lors du prélčvement
    et de la préparation de la prise d'essai, par l'aluminium présent
    dans l'air, les récipients et les réactifs. Selon les traitements
    préliminaires subis par l'échantillon et les techniques de séparation
    et de concentration utilisées, les limites de détection vont de 1,9 ŕ
    4 µg/litre dans les liquides biologiques et de 0, 005 ŕ 0,5 µg/g de
    poids sec dans les tissus quand on procčde par GF-AAS, et de 5 µg/m3
    d'air ou de 3 µg/litre d'eau quand on procčde par ICP-AES.

    3.  Sources d'exposition humaine et environnementale

         De l'aluminium est libéré dans l'environnement tant ŕ la faveur
    de processus naturels que d'activités humaines. Il est présent sous
    une forme trčs concentrée dans les poussičres que produisent les
    exploitations miničres et agricoles ainsi que dans les particules
    produites par la combustion du charbon. Les silicates d'aluminium
    (argiles), qui sont des constituants majeurs des sols, contribuent
    pour une large part ŕ la teneur des poussičres en silicates. L'appport
    d'aluminium ŕ l'environnement trouve beaucoup plus son origine dans
    des processus naturels que dans l'activité humaine. La mobilisation de

    l'aluminium du fait d'activités humaine est, pour une large part,
    indirecte et provient de l'émission de substances acidifiantes. D'une
    façon générale, une diminution du pH entraîne une augmentation de
    la mobilité et de la biodisponibilité des formes monomčres de
    l'aluminium. La matičre premičre la plus importante pour la production
    de l'aluminium est la bauxite, qui contient jusqu'ŕ 55% d'alumine
    (oxyde d'aluminium). La production mondiale de bauxite a été de 106
    millions de tonnes en 1992. Le métal a des usages trčs variés, dans
    les industries du bâtiment, de l'automobile et de l'aéronautique, et
    peut également ętre utilisé sous la forme d'alliages. Les dérivés de
    l'aluminium ont également des usages trčs divers, notamment dans
    l'industrie du verre, de la céramique et du caoutchouc ainsi que pour
    la confection de produits destinés ŕ la protection du bois, de
    produits pharmaceutiques et de tissus imperméables. Les minéraux
    naturels contenant de l'aluminium, en particulier la bentonite et la
    zéolite, sont utilisés pour la purification de l'eau, ainsi que dans
    les sucreries, les brasseries et l'industrie papetičre.

    4.  Transport, distribution et transformation dans l'environnement

         L'aluminium est omniprésent dans l'environnement sous forme de
    silicates, d'oxydes et d'hydroxydes, combiné ŕ d'autres éléments comme
    le sodium et le fluor ou encore sous forme de complexes organiques. On
    ne le rencontre pas ŕ l'état natif du fait de sa réactivité. Dans la
    nature, il n'existe qu'au degré d'oxydation (+3) ; son transport et sa
    distribution ne dépendent donc que de sa chimie de coordination et des
    caractéristiques physico-chimiques de l'environnement local. Aux
    valeurs du pH supérieures ŕ 5,5, les dérivés de l'aluminium d'origine
    naturelle existent principalement sous forme non dissoute, par exemple
    sous forme de gibbsite (Al(OH)3) ou d'aluminosilicates, sauf en
    présence de grandes quantités de matičres organiques en solution qui
    se lient ŕ l'aluminium et peuvent conduire ŕ une augmentation de la
    teneur en aluminium dissous, dans les cours d'eau et les lacs, par
    exemple. Plusieurs facteurs influent sur la mobilité de l'aluminium
    et, par voie de conséquence, sur son transport dans l'environnement.
    Il s'agit en particulier de la nature des espčces chimiques en cause,
    des trajectoires d'écoulement, des interactions entre le sol et l'eau
    et de la composition des matériaux géologiques sous-jacents. La
    solubilité de l'aluminium en équilibre avec Al (OH)3 en phase solide
    dépend fortement du pH et de la présence d'agents complexants comme
    les fluorures, les silicates, les phosphates et les matičres
    organiques. On peut considérer que la chimie de l'aluminium
    inorganique dans les sols acides et les cours d'eau fait intervenir
    les processus suivants: solubilité des espčces minérales, échange
    d'ions et miscibilité ŕ l'eau. Lorsqu'il y a acidification du sol,
    l'aluminium peut passer en solution et ętre ainsi transporté dans les
    cours d'eau. La mobilisation de l'aluminium par précipitation en
    milieu acide permet aux plantes de fixer une plus grande quantité de
    cet élément.

    5.  Concentrations dans l'environnement et exposition humaine

         L'aluminium est présent en proportion importante dans un certain
    nombre de constituants de l'atmosphčre, en particulier des poussičres
    arrachées au sol (qu'elles soient d'origine naturelle ou qu'elles
    résultent de l'activité humaine) et des particules issues de la
    combustion du charbon. En milieu urbain, la concentration de
    l'aluminium dans la poussičre des rues varie de 3,7 ŕ 11,6 µg/kg. La
    teneur de l'air en aluminium va de 0,5 ng/m3 au-dessus de
    l'Antarctique ŕ plus de 1000 ng/m3 dans les zones industrialisées.

         Dans les eaux douces superficielles ou souterraines, la
    concentration de l'aluminium peut varier dans des proportions
    importantes, en fonction de facteurs physico-chimiques et géologiques.
    L'aluminium peut se trouver en suspension ou en solution. Il peut ętre
    lié ŕ des coordinats organiques ou inorganiques ou exister ŕ l'état
    d'ion libre. En milieu aqueux naturel, les espčces chimiques dans
    lesquelles l'aluminium est engagé existent ŕ l'état de monomčres
    ou de polymčres. La nature de ces espčces dépend du pH et de la
    concentration en carbone organique dissous, fluorures, sulfates,
    phosphates et particules en suspension. Au voisinage de la neutralité,
    la concentration de l'aluminium dissous est généralement assez faible,
    de l'ordre de 1,0 ŕ 50 µg/litre. Lorsque l'acidité de l'eau augmente,
    elle peut monter jusqu'ŕ 500-1000 µg/litre. Dans les eaux rendues
    extręmement acides par les liquides de drainage de mines, on a mesuré
    des concentrations d'aluminium en solution qui atteignaient
    90 mg/litre.

         L'exposition humaine non professionnelle ŕ l'aluminium présent
    dans l'environnement se produit principalement lors de l'ingestion
    d'eau ou de nourriture, la nourriture étant essentiellement en cause.
    L'apport journalier d'aluminium par les aliments et la boisson se
    situe, chez l'adulte, entre 2,5 et 13 mg, ce qui représente 90 ŕ 95%
    de l'apport total. Compte tenu de la valeur-guide internationale
    actuellement en vigueur, l'apport par l'eau de boisson pourrait
    se situer aux environs de 0,4 mg par jour, mais il est plus
    probablement de l'ordre de 0,2 mg. La contribution de la voie
    d'exposition respiratoire peut atteindre 0,04 mg/jour. Dans certaines
    circonstances, par exemple en cas d'exposition professionnelle ou lors
    de l'utlisation d'antiacides, l'exposition pourra ętre beaucoup plus
    intense. Par exemple, deux comprimés d'antiacide moyennement dosés
    peuvent apporter plus de 500 mg d'aluminium. Les études effectuées
    avec de l'aluminium-26 indiquent que le citrate constitue la forme
    la plus disponible biologiquement et que sous cette forme,
    l'aluminium pourrait ętre absorbé ŕ hauteur de 1%. L'absorption par
    l'intermédiaire de l'eau de boisson ne représenterait en revanche que
    3% de l'apport quotidien total, cette source étant relativement
    mineure par rapport ŕ l'apport alimentaire. Il n'est pas trčs facile
    de déterminer quelle est la quantité effectivement fixée ŕ la suite
    d'une telle exposition en raison des problčmes d'analyse et
    d'échantillonnage que cela pose.

    6.  Cinétique et métabolisme

    6.1  Chez l'homme

         L'aluminium et ses dérivés sont mal absorbés par l'organisme
    humain, encore que la vitesse et le taux d'absorption n'aient pas été
    suffisamment étudiés. Un moyen facile d'évaluer la résorption de
    l'aluminium consiste ŕ en mesurer la concentration dans l'urine et le
    sang; on a d'ailleurs constaté une augmentation de la concentration
    urinaire chez des soudeurs ŕ l'aluminium et des ouvriers travaillant ŕ
    la production de poudre d'aluminium.

         Le mécanisme de résorption de l'aluminium au niveau
    gastrointestinal n'est pas encore parfaitement élucidé. Les variations
    observées résultent des propriétés chimiques de cet élément et de la
    formation de diverses espčces chimiques, sous l'influence du pH, de la
    force ionique, de la compétition avec d'autres éléments (silicium) ou
    agents complexants présents dans les voies digestives (des citrates,
    par ex.).

         On a étudié le comportement biologique de l'aluminium et son
    absorption dans les voies digestives humaines au moyen de l'isotope
    radioactif Al-26. Des différences interindividuelles importantes ont
    été mises en évidence. La littérature donne ainsi des taux de
    résorption de 5 × 10-3 pour le citrate, de 1,04 × 10-4 pour
    l'hydroxyde et de 1,3 × 10-3 pour l'hydroxyde ingéré avec du citrate.
    Une étude de la résorption fractionnée de l'aluminium présent dans
    l'eau de boisson a donné une valeur de 2,35 × 10-3. On en a conclu
    que les membres de la population générale qui boivent quotidiennement
    1,5 litre d'eau contenant 100 µg/litre d'aluminium, absorberaient de
    la sorte 3% de leur apport total d'aluminium, selon les concentrations
    présentes dans leur nourriture et leur utilisation éventuelle
    d'antiacides.

         La proportion d'Al3+ normalement lié aux protéines chez
    l'Homme peut atteindre 70-90% chez les malades hémodialysés, avec une
    augmentation modérée de l'aluminium plasmatique. C'est dans les
    poumons que l'on peut trouver les taux les plus élevés d'aluminium,
    parfois présent sous formes de particules inhalées insolubles.

         C'est l'urine qui constitue la voie d'excrétion la plus
    importante de l'aluminium. Aprčs administration par voie orale d'une
    dose unique d'aluminium, 83% ont été excrétés dans l'urine en l'espace
    de 13 jours, contre 1,8% dans les matičres fécales. La demi-vie de
    l'aluminium urinaire chez des soudeurs exposés pendant plus de 10 ans
    s'est révélée ętre d'au moins 6 mois. Chez des ouvriers ŕ la retraite
    qui avaient été exposés ŕ de la poudre d'aluminium, le calcul de la
    demi-vie a donné une valeur comprise entre 0,7 et 8 ans.

    6.2  Chez l'animal

         La résorption dans les voies digestives est en général inférieure
    ŕ 1%. Elle dépend principalement de l'espčce chimique en cause et de
    sa solubilité ainsi que du pH. Les agents complexants organiques comme
    les citrates, augmentent la résorption. Il peut également y avoir
    interaction avec le calcium et le systčme de transport du fer.
    L'absorption par la voie respiratoire et la voie percutanée n'a pas
    été étudiée en détail. L'aluminium se répartit dans la plupart des
    organes en s'accumulant principalement dans les os, du moins
    lorsque les doses sont fortes. Dans une proportion limitée encore
    qu'indéterminée, il franchit la barričre hémato-encéphalique et peut
    parvenir jusqu'au foetus. Il est efficacement éliminé par la voie
    urinaire. Sa demi-vie plasmatique est d'environ 1 h chez les rongeurs.

    7.  Effets sur les mammifčres de laboratoire et les systčmes d'épreuve
        in vitro

         L'aluminium et ses composés n'ont qu'une faible toxicité aiguë,
    les valeurs publiées de la DL50 par voie orale étant de l'ordre de
    quelques centaines de mg ŕ 1000 mg d'aluminium par kg de poids
    corporel et par jour. On n'a pas connaissance de la valeur de la Cl50
    par inhalation.

         Lors des études toxicologiques ŕ court terme qui ont été
    effectuées sur des rats, des souris ou des chiens avec un eventail
    suffisant de points d'aboutissement et divers composés de l'aluminium
    (phosphate sodique, hydroxyde et nitrate) incorporés ŕ la nourriture
    ou ŕ l'eau de boisson,on n'a constaté que des effets minimes
    (réduction du gain de poids généralement associée ŕ une moindre
    consommation de nourriture ou effets histopathologiques modérés aux
    doses les plus élevées, c'est-ŕ-dire 70 ŕ 300 mg d'aluminium par kg de
    poids corporel et par jour). Parmi les effets généraux observés aprčs
    administration parentérale, on peut citer une insuffisance rénale.

         On n'a pas eu connaissance de l'existence d'études d'inhalation
    satisfaisantes. Aprčs administration intratrachéenne d'oxyde
    d'aluminium, on a observé une fibrose induite par les particules
    d'oxyde qui était analogue ŕ celle que les études sur la poussičre de
    silice et de charbon ont mise en évidence.

         Aprčs avoir gavé des rats avec des rations quotidiennes contenant
    respectivement 13, 26 ou 52 mg d'aluminium (sous forme de nitrate)
    par kg de poids corporel, on n'a constaté aucune foetotoxicité
    manifeste ni effet délétčre sur l'ensemble des paramčtres génésiques.
    Toutefois, on a noté un retard de croissance lié ŕ la dose dans la
    descendance de ces animaux, retard qui s'observait ŕ la dose de
    13 mg/kg chez les femelles et ŕ la dose de 26 mg/kg chez les mâles.
    La dose la plus faible produisant un effet délétčre observable

    (LOAEL) sur le développement, ŕ savoir, une mauvaise ossification,
    une augmentation de la fréquence des malformations vertébrales
    et sternébrales, ou encore une réduction du poids des foetus,
    s'établissait ŕ 13 mg/kg (nitrate d'aluminium). Ces effets n'ont pas
    été observés aprčs administration d'hydroxyde d'aluminium, ŕ des doses
    pourtant beaucoup plus fortes. A la dose de 13 mg/kg de nitrate
    d'aluminium, on a observé une réduction de la croissance postnatale
    mais on n'a pas cherché ŕ relever la présence éventuelle d'effets
    toxiques chez les mčres. Les études portant sur le développement
    cérébral ont mis en évidence une diminution de la force d'agrippement
    dans la descendance de rattes qui avaient reçu 100 mg d'aluminium
    par kg de poids corporel sous forme de lactate incorporé ŕ leur
    nourriture, sans présenter elles-męmes d'effets toxiques.

         Rien n'indique que l'aluminium soit cancérogčne. Il peut former
    des complexes avec l'ADN et provoquer la réticulation des protéines et
    de l'ADN chromosomiques, mais il ne se montre pas mutagčne pour les
    bactéries et n'induit pas de mutations ou de transformations dans des
    cultures de cellules mammaliennes  in vitro. Toutefois, des
    aberrations chromosomiques ont été observées dans les cellules de la
    moelle osseuse, chez des souris et des rats exposés.

         Une somme trčs importante de faits expérimentaux incite ŕ penser
    que l'aluminium est neurotoxique chez l'animal d'expérience, encore
    qu'il y ait des différences considérables entre les espčces. Chez
    celles qui sont sensibles, les effets toxiques consécutifs ŕ
    l'administration parentérale d'aluminium se caractérisent par des
    altérations neurologiques progressives qui conduisent ŕ la mort dans
    un état de mal épileptique (DL50 = 6 µg d'aluminium/g de tissu
    cérébral sec). Sur le plan morphologique, l'encéphalopathie
    progressive est associée, au niveau de la moelle épiničre, du tronc
    cérébral et de certaines parties de l'hippocampe, ŕ une atteinte des
    neurofibrilles dans les neurones de grande taille et de taille
    moyenne. Ces lésions de dégénérescence neurofibrillaire sont
    morphologiquement et biochimiquement distinctes de celles que l'on
    observe dans la maladie d'Alzheimer. Des troubles comportementaux ont
    été observés, en l'absence d'encéphalopathie ou de lésions du tissu
    cérébral, chez des animaux ayant reçu des sels solubles d'aluminium
    (chlorure, lactate, par ex.) dans leur alimentation ou leur eau de
    boisson ŕ des doses quotidiennes égales ou supérieures ŕ 50 mg
    d'aluminium par kg de poids corporel.

         L'ostéomalacie, sous la forme oů elle se manifeste chez l'homme,
    s'observe réguličrement chez les gros animaux (par exemple, le chien
    ou le porc) exposés ŕ l'aluminium; une pathologie du męme genre
    s'observe chez les rongeurs. A ce qu'il paraît, ces effets se
    produisent chez toutes les espčces, y compris l'Homme, ŕ des
    concentrations d'aluminium de 100 ŕ 200 µg/g de cendres d'os.

    8.  Effets sur l'Homme

         On n'a pas décrit d'effets pathogčnes aigus consécutifs ŕ une
    exposition de la population générale ŕ l'aluminium.

         En Angleterre, une population d'environ 20 000 personnes a été
    exposée pendant au moins 5 jours ŕ des concentrations excessives de
    sulfate d'aluminium qui avait été déposé accidentellement dans une
    installation fournissant de l'eau potable. On a fait état ŕ cette
    occasion de cas de nausée, de vomissements, de diarrhée, d'ulcérations
    buccales et cutanées, d'éruptions et d'arthralgies. A l'examen, ces
    symptômes se sont révélés pour la plupart bénins et de brčve durée.
    Aucun effet pathologique durable n'a pu ętre attribué ŕ des cas précis
    d'exposition ŕ l'aluminium présent dans l'eau de boisson.

         On a émis l'hypothčse que la présence d'aluminium dans l'eau de
    boisson serait responsable de la survenue ou de l'évolution plus
    rapide de la maladie d'Alzheimer ou encore de la détérioration des
    fonctions intellectuelles chez les personnes âgées. On a également
    avancé que les fumées dégagées lors de la compression de l'aluminium
    pulvérulent pouvaient également avoir une responsabilité dans la
    détérioration des fonctions intellectuelles et les pneumopathies
    observées chez certaines professions.

         Une vingtaine d'études épidémiologiques ont été effectuées pour
    vérifier si la présence d'aluminium dans l'eau de boisson était
    effectivement un facteur de risque de la maladie d'Alzheimer et deux
    d'entre elles ont consisté ŕ évaluer l'association entre ce facteur et
    la détérioration des fonctions intellectuelles. Ces études allaient
    des enquętes écologiques aux études cas-témoins. Huit études
    effectuées sur des populations de Norvčge, du Canada, de France, de
    Suisse et d'Angleterre ont été jugées d'une qualité suffisante pour
    satisfaire aux critčres retenus pour l'évaluation de la relation
    exposition-effet avec correction pour tenir compte d'au moins quelques
    facteurs de confusion. Sur les six études consacrées ŕ l'existence
    éventuelle d'une relation entre l'aluminium de l'eau de boisson et la
    démence sénile ou la maladie d'Alzheimer, trois seulement ont conclu
    par l'affirmative. Il est toutefois ŕ noter que chacune de ces études
    présentait des défauts de conception (par exemple, dans l'évaluation
    de l'exposition environnementale, pas de prise en compte de
    l'exposition ŕ l'aluminium de toutes origines, ni de correction pour
    tenir compte des importants facteurs de confusion que sont le niveau
    d'instruction, la situation socio-économique et les antécédents
    familiaux, le recours ŕ des critčres de jugement différents pour la
    maladie d'Alzheimer et le biais de sélection). En général le calcul a
    donné une valeur de 2 pour le risque relatif, avec un large intervalle
    de confiance, lorsque la concentration totale de l'aluminium dans
    l'eau de boisson était égale ou supérieure ŕ 100 µg/litre. Compte

    tenu des connaissances actuelles sur la maladie d'Alzheimer et de
    l'ensemble des résultats fournis par ces études épidémiologiques, on a
    conclu que les données épidémiologiques ne militent pas en faveur de
    l'existence d'une relation causale entre la maladie d'Alzheimer et la
    présence d'aluminium dans l'eau de boisson.

         Outre les études épidémiologiques précitées qui ont porté sur la
    relation entre la maladie d'Alzheimer et la présence d'aluminium dans
    l'eau de boisson, deux autres études ont été consacrées ŕ ce męme type
    de relation chez les populations âgées. Lŕ encore, on a obtenu des
    résultats contradictoires. La premičre étude, qui a porté sur 800
    octogénaires du sexe masculin qui consommaient une eau contenant
    jusqu'ŕ 98 µg d'aluminium par litre, n'a pas mis en évidence de
    relation de cause ŕ effet. La seconde étude, pour laquelle le critčre
    de jugement retenu était "tout signe de détérioration des fonctions
    mentales", a évalué ŕ 1,72 le risque relatif pour des teneurs en
    aluminium supérieures ŕ 85 µg/litre chez 250 sujets du sexe masculin.
    Ces données ne permettent pas de conclure que l'aluminium est ŕ
    l'origine d'une détérioration des fonctions intellectuelles chez les
    personnes âgées.

         Comme on vient de le voir, les conclusions des travaux relatifs
    aux effets de l'aluminium sur les fonctions intellectuelles sont
    contradictoires. La plupart des études ont été effectuées sur des
    populations de faible effectif et la méthodologie utilisée est
    discutable, eu égard ŕ l'ampleur de l'effet constaté, ŕ l'appréciation
    de l'exposition efective et aux facteurs de confusion. Lors d'une
    étude au cours de laquelle on a comparé la détérioration des fonctions
    intellectuelles chez des mineurs exposés ŕ une poudre contenant 85%
    d'aluminium finement pulvérisé et 15% d'oxyde d'aluminium (ŕ titre de
    prophylaxie contre la silice) ŕ un groupe témoin constitué de mineurs
    non exposés, les résultats aux tests et le nombre de sujets présentant
    un déficit dans au moins un test ont mis en évidence un désavantage
    chez les mineurs exposés. On a constaté l'existence d'une tendance ŕ
    l'accroissement du risque qui était liée ŕ la dose.

         Dans toutes les études relatives ŕ l'exposition professionnelle
    qui ont été publiées, l'ampleur des effets constatés, la présence de
    facteurs de confusion, les problčmes posés par l'appréciation de
    l'exposition effective et le fait qu'on ne peut exclure l'exposition ŕ
    plusieurs substances, ne permettent gučre de conclure que l'aluminium
    provoque une détérioration des fonctions intellectuelles chez les
    personnes exposées de par leur profession.

         Lors d'études limitées sur des travailleurs exposés ŕ des vapeurs
    d'aluminium, des syndromes neurologiques et en particulier une
    détérioration des fonction intellectuelles, des troubles moteurs et
    des neuropathies périphériques ont été constatés. En comparant un
    petit groupe de soudeurs d'aluminium ŕ un groupe de soudeurs de fer,

    on a constaté chez les premiers un léger déficit de l'activité motrice
    lors de tâches répétitives. Dans une autre étude, une enquęte par
    questionnaire a permis de mettre en évidence une augmentation des
    symptômes neuropsychiatriques.

         Les insuffisants rénaux chroniques qui sont exposés ŕ l'aluminium
    présent dans les liquides de dialyse et reçoivent des médicaments qui
    en contiennent, peuvent souffrir de troubles iatrogčnes tels
    qu'encéphalopathies, ostéomalacies résistantes ŕ la vitamine D et
    anémies microcytaires. Ces syndromes cliniques peuvent ętre évités en
    réduisant l'exposition ŕ l'aluminium.

         Chez les prématurés, męme ceux dont l'insuffisance rénale n'est
    pas suffisamment grave pour provoquer une augmentation du taux sanguin
    de créatinine, il peut y avoir accumulation tissulaire d'aluminium,
    notamment au niveau des os, en cas d'exposition iatrogčne ŕ
    l'aluminium. A partir d'un certain degré d'insuffsance rénale, on peut
    craindre des convulsions et une encéphalopathie.

         L'exposition humaine ŕ l'aluminium est trčs courante, mais seuls
    quelques cas d'hypersensibilité ont été signalés ŕ la suite de
    l'application sur la peau ou de l'administration parentérale de
    certains composés de l'aluminium.

         Des cas de fibrose pulmonaire ont été rapportés chez quelques
    ouvriers employés ŕ la fabrication d'explosifs et de feux d'artifice
    et exposés ŕ de trčs fines poudres d'aluminium comprimées. Dans
    presque tous les cas, il y avait eu exposition ŕ des particules
    d'aluminium enrobées d'huile minérale. Ce procédé n'est plus utilisé.
    D'autres cas de fibrose pulmonaire ont pu ętre également attribués ŕ
    la présence d'autres minéraux comme la silice et l'amiante;
    l'aluminium n'était donc pas seul en cause.

         On a pu attribuer l'apparition d'un asthme d'irritation ŕ
    l'inhalation de composés tels que le sulfate et le fluorure
    d'aluminium, le tétrafluoraluminate de potassium ainsi qu'au séjour
    dans l'environnement complexe des ateliers de production de
    l'aluminium.

         On ne dispose pas de données suffisantes pour déterminer dans
    quelle catégorie de risque cancérogčne pour l'Homme se situent
    l'aluminium et ses dérivés. Quoi qu'il en soit, les études menées sur
    l'animal n'attribuent aucun pouvoir cancérogčne ŕ l'aluminium ou ŕ ses
    composés.

    9.  Effets sur les autres ętres vivants au laboratoire ou dans leur
        milieu naturel

         Chez les algues unicellulaires, on observe un effet toxique plus
    important aux faibles valeurs du pH, lorsque la biodisponibilité de
    l'aluminium augmente. Elles sont plus sensibles que les autres

    microorganismes, la plupart des 19 espčces lacustres testées
    présentant une inhibition totale de la croissance ŕ la concentration
    de 200 µg/litre d'aluminium total (pH 5,5). Il peut y avoir sélection
    des souches tolérantes ŕ l'aluminium. Ainsi, on a isolé des algues
    capables de se développer en présence d'une concentration d'aluminium
    de 48 µg/litre et d'un pH de 4,6. Dans le cas des invertébrés
    aquatiques, on a obtenu des valeurs de la Cl50 qui vont de
    0,48 mg/litre (polychčtes) ŕ 59,6 mg/litre (daphnies). En ce qui
    concerne les poissons, les valeurs vont de 0,095 mg/litre
    ( Jordanella floridae) ŕ 235 mg/litre (gambusies). il faut
    cependant interpréter ces résultats avec prudence du fait que la
    biodisponibililté de l'aluminium dépend fortement du pH. La grande
    dispersion des valeurs de la Cl50 traduit probablement les variations
    de la biodisponibilité. L'adjonction d'agents chélatants, comme le NTA
    ou l'EDTA, réduit la toxicité de l'aluminium pour les poissons.

         Les macroinvertébrés réagissent de maničre variable ŕ la présence
    d'aluminium. Lorsque le pH se situe dans les limites normales, la
    toxicité de l'aluminium augmente ŕ mesure que le pH diminue;
    toutefois, dans les eaux trčs acides, l'aluminium peut atténuer
    l'effet de l'acidité. Certains invertébrés sont trčs résistants ŕ
    l'acidité et peuvent abonder dans les eaux acides. On a constaté une
    augmentation de la dérive des invertébrés dans les cours d'eau oů ils
    sont soumis ŕ un stress dű au pH ou ŕ la présence d'aluminium. Il
    s'agit lŕ d'une réaction commune ŕ divers facteurs de stress. Lors
    d'un test, des invertébrés lacustres ont en général survécu ŕ une
    exposition ŕ l'aluminium mais ont souffert de la diminution des
    phosphates dans des conditions rendues oligotrophiques par la
    précipitation de l'aluminium. Les études toxicologiques ŕ court et ŕ
    long terme effectuées sur les poissons se sont déroulées dans des
    conditions trčs diverses et, ce qui est beaucoup plus important, dans
    des milieux de pH varié. Il ressort des données disponibles que des
    effets non négligeables ont été observés ŕ des concentrations en
    aluminium inorganique sous forme de composés monomčres ne dépassant
    pas 25 µg/litre. Toutefois, les relations complexes qui existent entre
    l'acidité et la biodisponibilité de l'aluminium rendent difficile
    l'interprétation des données toxicologiques. Lorsque le pH est trčs
    bas, c'est-ŕ-dire dans des conditions qui ne sont normalement pas
    celles qui rčgnent dans les eaux naturelles, c'est la concentration en
    ions hydrogčne qui constitue le facteur toxique, l'addition
    d'aluminium ayant tendance ŕ réduire la toxicité. C'est pour un pH
    compris entre 4,5 et 6,0 que l'aluminium en équililbre exerce son
    effet toxique maximal. On a également montré que la toxicité augmente
    avec le pH lorsque celui-ci est alcalin. On explique la toxicité de
    l'aluminium pour les poissons par le fait qu'ils ne peuvent plus
    assurer leur osmorégulation ainsi que par des problčmes respiratoires
    dus ŕ la précipitation de l'aluminium sur le mucus branchial. Le
    premier de ces effets est associé ŕ des valeurs basses du pH. Ces
    résultats de laboratoire ont été confirmés par des observation en
    milieu naturel, notamment dans des conditions d'acidité excessive.

         Les oeufs et les larves d'amphibiens souffrent de l'acidité et de
    la présence d'aluminium, ces deux facteurs étant en interaction. On a
    fait état d'effets tels que réduction de l'éclosion, éclosion
    retardée, métamorphose retardée ou ŕ petite taille, et mortalité pour
    des teneurs en aluminium inférieures ŕ 1 mg/litre.

         L'exposition des racines des plantes terrestres ŕ l'aluminium
    peut réduire la croissance de ces racines, diminuer la fixation des
    nutriments et provoquer un rabougrissement du végétal. On a cependant
    montré au laboratoire comme sur le terrain que les végétaux pouvaient
    manifester une tolérance ŕ l'aluminium.

    10.  Conclusions

    10.1  Population générale

         Des études sur l'animal ont permis de définir les risques que
    l'exposition ŕ l'aluminium présente pour le développement neurologique
    et les fonctions cérébrales. Toutefois, il n'apparaît pas que
    l'aluminium menace la santé des personnes en bonne santé qui ne sont
    pas soumises ŕ une exposition professionnelle.

         Rien n'indique que l'aluminium puisse jouer un rôle important
    dans l'étiologie de la maladie d'Alzheimer et en tout état de cause,
    il ne provoque chez aucune espčce animale ou chez l'Homme des
    pathologies de type Alzheimer.

         On ne dispose pas de données suffisantes pour donner corps ŕ
    l'hypothčse selon laquelle l'exposition ŕ l'aluminium des personnes
    vivant dans des régions oů l'eau a une forte teneur en cet élément
    pourrait exacerber la maladie d'Alzheimer ou en accélérer l'évolution.

         On ne dispose pas d'éléments d'appréciation suffisants, sur le
    plan sanitaire, pour entreprendre une révision des valeurs-guides de
    l'OMS concernant l'exposition ŕ l'aluminium des personnes en bonne
    santé non exposées professionnellement. Par exemple, il n'existe pas
    de base scientifique suffisante pour que l'on puisse établir une norme
    de concentration de l'aluminium dans l'eau de boisson.

    10.2  Sous-groupes de population exposés ŕ un risque particulier

         On a montré que chez des sujets de tous âges atteints
    d'insuffisance rénale, l'accumulation d'aluminium provoquait un
    syndrome clinique d'encéphalopathie, une ostéomalacie résistante ŕ la
    vitamine D et une anémie microcytaire. Cet aluminium peut provenir
    du liquide d'hémodialyse ou de produits pharmaceutiques qui en
    contiennent (par exemple les capteurs d'ions phosphate). La prise de
    produits contenant des citrates peut provoquer une exacerbation de
    l'absorption intestinale. Les insuffisants rénaux sont donc exposés au
    risque de neurotoxicité aluminique.

         L'exposition iatrogčne ŕ l'aluminium constitue une menace pour
    les insuffisants rénaux chroniques. Chez les prématurés, la charge de
    l'organisme en aluminium est plus élevée que chez les autres
    nourrissons. On s'efforcera donc de limiter ce genre d'exposition chez
    tous ces groupes vulnérables.

    10.3  Populations professionnellement exposées

         Le risque est plus important pour les travailleurs exposés
    pendant de longues périodes ŕ de fines particules d'aluminium.
    Cependant, on ne dispose pas de données suffisantes pour fixer avec
    quelque certitude des limites d'exposition qui protčgent contre les
    effets indésirables de l'aluminium.

         On connaît des cas de fibrose pulmonaire dus ŕ une exposition ŕ
    de la poudre d'aluminium ŕ usage pyrotechnique, trčs souvent enrobée
    d'huile minérale .En revanche, il n'est pas prouvé que l'exposition ŕ
    l'aluminium sous d'autres formes puisse également provoquer ce type de
    fibrose. Dans la plupart des cas de fibrose observés, il y avait eu
    exposition simultanée ŕ d'autres agents fibrogčnes.

         On a attribué un certain nombre de cas d'asthme d'irritation ŕ
    l'inhalation de sulfate, de fluorure d'aluminium ou de
    tétrafluoraluminate de potassium ou encore ŕ un séjour dans
    l'environnement complexe des ateliers de production de l'aluminium.

    10.4  Effets sur l'environnement

         L'aluminium présent dans l'environnement en phase solide est
    relativement insoluble, en particulier lorsque le pH est voisin de la
    neutralité, d'oů les trčs faibles concentrations d'aluminium en
    solution dans la plupart des eaux naturelles.

         Dans les milieux acides ou peu tamponnés oů l'apport d'acide est
    important, la concentration de l'aluminium peut atteindre des valeurs
    nocives pour les organismes aquatiques et les plantes terrestres.
    Toutefois, la sensibilité ŕ ce métal varie largement selon les
    espčces, les souches et les stades de développement.

         Les effets biologiques délétčres de fortes teneurs en aluminium
    inorganique sous forme monomčre peuvent ętre atténués par la présence
    d'acides organiques, de fluorures, de silicates et de concentrations
    élevées de calcium et de magnésium.

         Dans les eaux excessivement acides, il y a une réduction sensible
    de la diversité biologique due ŕ la mobilisation de l'aluminium sous
    des formes plus toxiques. Cette réduction de la diversité biologique
    s'observe ŕ tous les niveaux trophiques.

    RESUMEN Y CONCLUSIONES

    1.  Identidad, propiedades físicas y químicas

         El aluminio es un metal blanco plateado, dúctil y maleable.
    Pertenece al grupo IIIA de la Tabla Periódica, y en los compuestos
    suele encontrarse como AlIII. Forma cerca del 8% de la corteza
    terrestre y es uno de los metales comunes más reactivos. La exposición
    al agua, al oxígeno o a otros oxidantes conduce a la formación de una
    capa superficial de óxido de aluminio que confiere al metal una gran
    resistencia a la corrosión. El óxido de aluminio es soluble en ácidos
    minerales y álcalis fuertes, pero insoluble en agua, mientras que el
    cloruro, el nitrato y el sulfato de aluminio son solubles en agua. Los
    halogenuros, los hidruros y los alquilos más cortos de aluminio
    reaccionan violentamente con el agua.

         El aluminio posee una elevada conductividad térmica y eléctrica,
    baja densidad y gran resistencia a la corrosión. A menudo se alea con
    otros metales. Las aleaciones de aluminio son fuertes, ligeras y
    fácilmente susceptibles de conformación a máquina.

    2.  Métodos analíticos

         Se han desarrollado diversos métodos analíticos para determinar
    la presencia de aluminio en muestras biológicas y ambientales. Los dos
    métodos más utilizados son la espectrometría de absorción atómica en
    horno de grafito (GF-AAS) y la espectrometría de emisión atómico-
    plasmática inductivamente acoplada (ICP-AES). La contaminación de las
    muestras por el aluminio del aire, de los recipientes o de los
    reactivos durante el muestreo y preparación constituye la principal
    fuente de error analítico. En función del tratamiento previo de la
    muestra y de los procedimientos de concentración y separación, los
    límites de detección son de 1,9-4 µg/litro en los líquidos biológicos
    y 0,005-0,5 µg/g de peso seco en los tejidos al usar la GF-AAS, y de
    5 µg/m3 en el aire y 3 µg/litro en el agua cuando se emplea la
    ICP-AES.

    3.  Fuentes de exposición humana y ambiental

         El aluminio se libera en el medio ambiente tanto a través de
    procesos naturales como de fuentes antropogénicas. Está muy
    concentrado en el polvo de suelos dedicados a actividades tales como
    la minería y la agricultura, y en las partículas generadas por la
    combustión del carbón. Los silicatos de aluminio (arcillas), un
    importante componente de los suelos, contribuyen a los niveles de
    aluminio hallados en el polvo. Los procesos naturales superan con
    mucho la contribución antropogénica directa al medio ambiente. El
    aluminio movilizado por el hombre se forma en su mayoría de forma
    indirecta como resultado de la emisión de sustancias acidificantes.

    En general, un descenso del pH ocasiona un aumento de la movilidad y
    biodisponibilidad de las formas monoméricas de aluminio. La principal
    materia prima utilizada para producir aluminio es la bauxita, que
    contiene hasta un 55% de alúmina (óxido de aluminio). La producción
    mundial de bauxita fue de 106 millones de toneladas en 1992. El
    metal de aluminio tiene una gran variedad de usos, entre ellos la
    fabricación de materiales estructurales para los sectores de la
    construcción, el automóvil y la aviación, y la producción de
    aleaciones metálicas. Los compuestos y materiales de aluminio tienen
    también una amplia gama de usos, que incluyen la producción de vidrio,
    cerámica, caucho, conservantes de la madera, preparaciones
    farmacéuticas y tejidos impermeabilizantes. Los minerales de aluminio
    naturales, especialmente la bentonita y la zeolita, se emplean para
    depurar el agua, para refinar el azúcar, y en las industrias papeleras
    y de la fermentación.

    4.  Transporte, distribución y transformación en el medio ambiente

         El aluminio es un metal ubicuo en el medio ambiente, donde se
    encuentra en forma de silicatos, óxidos e hidróxidos, combinado con
    otros elementos como el sodio y el flúor, y formando complejos con
    materia orgánica. No se halla como metal libre debido a su
    reactividad. Sólo tiene un estado de oxidación (+3) en la naturaleza,
    por lo que su transporte y distribución en el medio ambiente dependen
    tan sólo de su química de coordinación y de las características
    físico-químicas del sistema ambiental concreto. A valores de pH
    superiores a 5,5 los compuestos naturales de aluminio aparecen
    predominantemente en forma no disuelta como gibbsita (Al(OH)3) o como
    aluminosilicatos, excepto en presencia de grandes cantidades de
    material orgánico disuelto, que se une al aluminio y puede dar lugar a
    un aumento de la concentración del aluminio disuelto en lagos y cursos
    de agua. La movilidad del aluminio y su ulterior transporte en el
    medio ambiente dependen de varios factores, entre los que cabe
    mencionar el tipo de especies químicas, los cursos hidrológicos, las
    interacciones suelo-agua y la composición del sustrato geológico. La
    solubilidad del aluminio en equilibrio con la fase sólida Al(OH)3
    depende en gran medida del pH y de agentes complejantes tales como
    fluoruros, silicatos, fosfatos y materia orgánica. La química del
    aluminio inorgánico en los suelos y los cursos de agua ácidos depende
    de la solubilidad de los minerales y de los procesos de intercambio y
    de mezcla de las aguas.

         La acidificación del suelo libera aluminio disolviéndolo, y el
    metal llega así a las corrientes de agua. La movilización del aluminio
    por precipitación ácida permite que haya más aluminio disponible para
    captación por las plantas.

    5.  Niveles ambientales y exposición humana

         El aluminio es uno de los principales constituyentes de varios
    componentes de la atmósfera, en particular del polvo procedente de
    suelos (tanto de fuentes naturales como de origen humano) y de
    partículas generadas por la combustión del carbón. En las zonas
    urbanas los niveles de aluminio en el polvo de la calle van de 3,7 a
    11,6 µg/kg. Los niveles de aluminio en el aire varían desde 0,5 ng/m3
    sobre la Antártida hasta más de 1000 ng/m3 en las zonas
    industrializadas.

         Las concentraciones de aluminio en las aguas superficiales y
    subterráneas son muy variables, dependiendo de factores geológicos y
    físico-químicos. El aluminio puede estar en suspensión o disuelto.
    Puede estar en forma de ligandos orgánicos o inorgánicos o de ion
    aluminio libre. En las aguas naturales el aluminio existe tanto en
    forma monomérica como polimérica. Las especies de aluminio dependen
    del pH y de las concentraciones de carbono orgánico disuelto (DOC)
    fluoruros, sulfatos, fosfatos y partículas en suspensión. Las
    concentraciones de aluminio disuelto en las aguas de pH
    aproximadamente neutro suelen ser bastante bajas, entre 1,0 y
    50 µg/litro. En aguas más ácidas se alcanzan valores de hasta
    500-1000 µg/litro. En condiciones de acidez extrema provocadas por el
    avenamiento ácido de minas se han medido concentraciones de aluminio
    disuelto de hasta 90 mg/litro.

         La exposición humana no ocupacional al aluminio en el medio
    ambiente se produce principalmente a través de la ingestión de agua y
    alimentos, sobre todo de estos últimos. La ingesta diaria de aluminio
    con los alimentos y bebidas es en los adultos de entre 2,5 y 13 mg.
    Esto representa un 90%-95% de la ingesta total. El agua de bebida
    puede contribuir con unos 0,4 mg diariamente, según los valores de las
    actuales directrices internacionales, pero más probablemente se sitúa
    en torno a los 0,2 mg/día. La exposición pulmonar puede contribuir
    hasta con 0,04 mg/día. En algunas circunstancias, como la exposición
    ocupacional y el uso de antiácidos, los niveles de exposición pueden
    ser mucho mayores. Con dos tabletas antiácido de tamańo medio, por
    ejemplo, se puede consumir más de 500 mg de aluminio. La evaluación de
    la captación consecutiva a ese tipo de exposiciones plantea algunos
    problemas debido a dificultades analíticas y de muestreo. Las
    investigaciones isotópicas realizadas con Al26 indican que una de las
    formas más biodisponibles del aluminio es el citrato, y que cuando el
    aluminio está en dicha forma podría darse hasta un 1% de absorción. No
    obstante, los seres humanos absorben al parecer sólo el 3% de la
    cantidad total de aluminio ingerida diariamente con el agua de bebida,
    una fuente relativamente secundaria en comparación con los alimentos.

    6.  Cinética y metabolismo

    6.1  Ser humano

         El aluminio y sus compuestos parecen ser mal absorbidos por los
    seres humanos, pero no hay estudios adecuados sobre la velocidad y el
    grado de absorción. Las concentraciones de aluminio en la sangre y la
    orina se han empleado como una medida fácilmente obtenible de la
    captación de aluminio, habiéndose observado niveles elevados en la
    orina de soldadores de aluminio y de productores de polvo de escamas
    de aluminio.

         El mecanismo de absorción gastrointestinal del aluminio todavía
    no ha sido totalmente dilucidado. La variabilidad se debe a las
    propiedades químicas del elemento y a las diversas especies químicas
    formadas en función del pH, la fuerza iónica, la presencia de
    elementos competitivos (silicio) y la presencia de agentes
    complejantes en el interior del tracto digestivo (p.ej., citrato).

         Se ha empleado el isótopo radiactivo Al26 para estudiar el
    destino biológico y la absorción gastrointestinal del aluminio en el
    hombre tras la ingestión de compuestos de aluminio. Se ha detectado
    una variabilidad significativa entre los individuos. Se han notificado
    fracciones de captación de 5 × 10-3 para el aluminio como citrato,
    1,04 × 10-4 para el hidróxido de aluminio y 1,36 × 10-3 para el
    hidróxido administrado con citrato. Un estudio sobre la captación del
    aluminio del agua de bebida reveló una fracción de captación de
    2,35 × 10-3, llegándose a la conclusión de que en la población
    general los individuos que consumen 1,5 litros/día de agua de bebida
    con un contenido de 100 µg aluminio/litro, absorben un 3% del aluminio
    total ingerido diariamente a partir de esa fuente, dependiendo de los
    niveles presentes en los alimentos y de la frecuencia del uso de
    antiácidos.

         La proporción de Al3+ plasmático normalmente unido a proteínas
    en el ser humano puede ser hasta del 70%-90% en los pacientes
    sometidos a hemodiálisis con niveles moderadamente altos de aluminio
    en el plasma. Los niveles más elevados de aluminio suelen encontrarse
    en los pulmones, donde puede hallarse en forma de partículas inhaladas
    insolubles.

         La orina es la vía más importante de excreción del aluminio. Tras
    la administración por vía oral de una dosis única de aluminio, pasados
    13 días se había excretado un 83% por la orina y un 1,8% por las
    heces. La semivida de las concentraciones urinarias en soldadores
    expuestos durante más de 10 ańos fue de 6 meses o superior. Entre
    trabajadores jubilados expuestos al polvo de escamas de aluminio, las
    semividas calculadas se situaban entre 0,7 y 8 ańos.

    6.2  Animales

         La absorción por vía gastrointestinal es normalmente menor
    del 1%. Los principales factores que influyen en la absorción son
    la solubilidad, el pH y las especies químicas. Los compuestos
    complejantes orgánicos, sobre todo el citrato, aumentan la absorción.
    La absorción del aluminio puede interferir en los sistemas de
    transporte del calcio y el hierro. La absorción cutánea y por
    inhalación no han sido estudiadas con detalle. El aluminio se
    distribuye en la mayoría de los órganos del cuerpo, y cuando las dosis
    son altas se acumula principalmente en los huesos. De forma limitada
    pero aún no determinada con precisión, atraviesa la barrera
    hematoencefálica, y llega también al feto. El aluminio se elimina
    eficazmente por la orina. El periodo de semieliminación plasmática es
    de aproximadamente 1 h en los roedores.

    7.  Efectos en mamíferos de laboratorio y en sistemas de pruebas
        in vitro

         La toxicidad aguda del aluminio metálico y de los compuestos de
    aluminio es baja; los valores notificados de la DL50 oral están
    comprendidas entre varios cientos y 1000 mg aluminio/kg de peso
    corporal. Los valores de la CL50 por inhalación no han sido
    establecidos.

         En estudios a corto plazo en los que se examinó una gama adecuada
    de variables de evaluación después de exponer ratas, ratones o perros
    a diversos compuestos de aluminio (fosfato sódico de aluminio,
    hidróxido de aluminio, nitrato de aluminio) a través de los alimentos
    o del agua, sólo se observaron efectos muy discretos (disminuciones
    del aumento de peso corporal, asociadas generalmente a un descenso del
    consumo de comida, o efectos histopatológicos leves) a las dosis más
    altas (70 a 300 mg aluminio/kg de peso corporal al día). Los efectos
    sistémicos que siguieron a la administración parenteral incluyeron
    también disfunción renal.

         No se han hallado estudios de inhalación adecuados. Después de la
    administración intratraqueal de óxido de aluminio se observó fibrosis
    asociada a partículas, parecida a la hallada en otros estudios sobre
    el sílice y el polvo de carbón.

         No se observaron signos manifiestos de fetotoxicidad, ni
    alteraciones de los parámetros reproductivos generales después del
    tratamiento de ratas con 13, 26 ó 52 mg aluminio/kg de peso corporal
    al día (en forma de nitrato de aluminio) mediante alimentación
    forzada. Sin embargo, se observó un retraso dosis-dependiente del
    crecimiento en la descendencia, a dosis de 13 mg/kg en el caso de las
    hembras y de 26 mg/kg en el caso de los machos. El nivel mínimo con
    efectos adversos observados (LOAEL) en el desarrollo (disminución de
    la osificación, aumento de la incidencia de defectos congénitos en las
    vértebras y el esternón y peso fetal reducido) fue de 13 mg/kg

    (nitrato de aluminio). Estos efectos no se observaron a dosis mucho
    más altas de hidróxido de aluminio. Se detectó una reducción del
    crecimiento posnatal al emplear 13 mg/kg (nitrato de aluminio), aunque
    no se analizó la toxicidad materna. En estudios sobre el desarrollo
    cerebral se detectó una disminución de la fuerza de aprehensión en la
    descendencia de hembras a las que se administraron con los alimentos
    100 mg aluminio/kg de peso corporal en forma de lactato de aluminio,
    no observándose signos de toxicidad materna.

         No existen indicios de que el aluminio sea carcinógeno. Puede
    formar complejos con el ADN, así como enlaces entre las proteínas
    cromosómicas y el ADN, pero no se ha demostrado que sea mutágeno en
    bacterias o que induzca mutaciones o transformaciones en células de
    mamífero  in vitro. Se han observado aberraciones cromosómicas en
    células de la medula ósea de ratas y ratones expuestos.

         Hay indicios fundados de que el aluminio es neurotóxico en
    animales de experimentación, aunque se da una considerable
    variabilidad entre especies. En especies susceptibles, la toxicidad
    que sigue a la administración parenteral se caracteriza por un
    deterioro neurológico progresivo, conducente a un estado epiléptico
    que acarrea la muerte (DL50 = 6 µg Al/g de peso seco del cerebro).
    Morfológicamente, la encefalopatía progresiva se asocia a una
    patología neurofibrilar de las neuronas grandes y medianas, sobre todo
    en la médula espinal, el tallo encefálico y determinadas zonas del
    hipocampo. Estos ovillos neurofibrilares son morfológica y
    bioquímicamente diferentes de los que caracterizan la enfermedad de
    Alzheimer. En animales de experimentación expuestos a sales solubles
    de aluminio (p.ej., lactato y cloruro) a través de los alimentos o el
    agua, a dosis de 50 mg aluminio/kg de peso al día o mayores, se ha
    observado un deterioro de la conducta sin signos concomitantes de
    encefalopatía o cambios neurohistopatológicos manifiestos.

         La osteomalacia que afecta al hombre se observa también
    sistemáticamente en las especies de cierto tamańo (p.ej., el perro
    o el cerdo) expuestas al aluminio; en los roedores se observan
    manifestaciones parecidas. Estos efectos parecen darse en todas las
    especies, incluido el hombre, a niveles de aluminio de 100 a 200 µg/g
    de cenizas óseas.

    8.  Efectos en el hombre

         No se han descrito efectos patógenos agudos en la población
    general como consecuencia de la exposición al aluminio.

         En Inglaterra una población de aproximadamente 20 000 individuos
    se vio expuesta durante por lo menos 5 días a niveles elevados de
    sulfato de aluminio, debido a la contaminación accidental de unas
    instalaciones de agua de bebida. Se informó de casos de náuseas,
    vómitos, diarrea, úlceras bucales, úlceras y erupciones cutáneas y

    dolores artríticos. Se comprobó que los síntomas eran en su mayoría
    leves y de corta duración. No se pudieron atribuir efectos duraderos
    sobre la salud a las exposiciones conocidas al aluminio del agua de
    bebida.

         Se ha propuesto la hipótesis de que el aluminio presente en
    el agua potable es un factor de riesgo por lo que se refiere al
    desarrollo o la aceleración de la enfermedad de Alzheimer y al
    deterioro senil de la función cognitiva. Se ha sugerido también que el
    polvo y los vapores de aluminio fino apisonado son quizá factores de
    riesgo que propician el deterioro de las funciones cognitivas y la
    aparición de enfermedades pulmonares en determinados trabajos.

         Se han llevado a cabo unos 20 estudios epidemiológicos para
    comprobar la hipótesis de que el aluminio del agua de bebida es un
    factor de riesgo de la enfermedad de Alzheimer, y dos estudios han
    evaluado la asociación entre el aluminio del agua de bebida y el
    deterioro de las funciones cognitivas. El diseńo de estos estudios
    abarcaba desde el control ecológico hasta el control de los casos. Se
    consideró que 8 estudios realizados en poblaciones de Noruega, el
    Canadá, Francia, Suiza e Inglaterra tenían la calidad necesaria para
    satisfacer los criterios generales establecidos a fin de evaluar la
    exposición y los resultados y de poder efectuar ajustes por lo menos
    en algunas variables de confusión. De los seis estudios que analizaron
    la relación entre el aluminio del agua de bebida y la demencia o la
    enfermedad de Alzheimer, tres hallaron una relación positiva, pero no
    así los otros tres. Sin embargo, todos los estudios presentaban
    algunos fallos de diseńo (relacionados por ejemplo con la evaluación
    de la exposición ecológica, la no consideración de todas las fuentes
    de exposición al aluminio y de factores de confusión importantes como
    la educación, la situación socioeconómica y los antecedentes
    familiares, el uso de medidas indirectas de la evolución de la
    enfermedad de Alzheimer, o unos métodos sesgados de selección). En
    general, los riesgos relativos determinados eran inferiores a 2, con
    grandes intervalos de confianza, a concentraciones totales de aluminio
    de 100 µg/litro o superiores en el agua de bebida. Sobre la base de
    los conocimientos disponibles acerca de la patogénesis de la
    enfermedad de Alzheimer y de todas las pruebas aportadas por estos
    estudios epidemiológicos, se llegó a la conclusión de que los datos
    epidemiológicos actuales no respaldan la hipótesis de una relación
    causal entre la enfermedad de Alzheimer y el aluminio del agua de
    bebida.

         Además de los estudios epidemiológicos realizados para analizar
    la relación entre la enfermedad de Alzheimer y el aluminio del agua
    de bebida en otros dos estudios se examinó la relación entre los casos
    de disfunción cognitiva y de enfermedad de Alzheimer en poblaciones
    de ancianos y los niveles de aluminio en el agua de bebida. Los
    resultados fueron una vez más contradictorios. En un estudio realizado
    en 800 octogenarios varones que consumían agua de bebida con

    concentraciones de aluminio de hasta 98 µg/litro no se halló relación
    alguna. El segundo estudio utilizó "cualquier indicio de deterioro
    mental" como criterio de seguimiento, calculando así un riesgo
    relativo de 1,72 para concentraciones de aluminio superiores a
    85 µg/litro en 250 varones. Tales datos son insuficientes para
    demostrar que el aluminio sea una causa de deterioro cognitivo en los
    ancianos.

         Los datos sobre el deterioro de la función cognitiva en relación
    con la exposición al aluminio son contradictorios. La mayoría de los
    estudios se han hecho en poblaciones reducidas, y la metodología
    utilizada es cuestionable en lo que respecta a la magnitud del efecto
    estudiado, la evaluación de la exposición y los factores de confusión.
    En un estudio comparativo del deterioro cognitivo entre mineros no
    expuestos y mineros expuestos a un polvo que contenía un 85% de
    aluminio molido muy fino y un 15% de óxido de aluminio (como
    profilaxis contra el sílice), los resultados de las pruebas cognitivas
    y la proporción de personas con dificultades en al menos una de las
    pruebas fueron peores entre los mineros expuestos. Se detectó una
    tendencia al aumento del riesgo relacionada con la exposición.

         En todos los estudios ocupacionales de los que se tiene noticia,
    la magnitud de los efectos observados, la presencia de factores de
    confusión, los problemas relacionados con la evaluación de la
    exposición y la probabilidad de exposiciones mixtas hacen que, en
    conjunto, los datos sean insuficientes como para extraer la conclusión
    de que el aluminio es una causa de deterioro cognitivo en los
    trabajadores expuestos al aluminio en su trabajo.

         En estudios limitados con trabajadores expuestos a vapores de
    aluminio se ha informado de síndromes neurológicos que incluyen el
    deterioro de la función cognitiva, disfunciones motoras y neuropatía
    periférica. Se ha informado de una pequeńa población de soldadores de
    aluminio que, comparados con soldadores de hierro, presentaron un
    ligero deterioro de la función motora repetitiva. En otros estudios
    realizado con cuestionarios se detectó un aumento de los síntomas
    neuropsiquiátricos.

         En los pacientes con insuficiencia renal crónica, la exposición
    iatrogénica a líquidos de diálisis o productos farmacéuticos con
    aluminio puede producir encefalopatía, osteomalacia resistente a la
    vitamina D y anemia microcítica. Estos síndromes clínicos pueden
    prevenirse reduciendo la exposición al aluminio.

         En los nińos prematuros expuestos a fuentes iatrogénicas de
    aluminio puede producirse un incremento del contenido de aluminio
    de los tejidos, particularmente en los huesos, incluso cuando la
    disfunción renal no es lo suficientemente grave como para provocar
    un aumento de los niveles de creatinina en sangre. En caso de
    insuficiencia renal pueden aparecer convulsiones y encefalopatía.

         Aunque la exposición humana al aluminio está muy extendida,
    sólo se ha informado de unos cuantos casos de hipersensibilidad
    consecutivos a la aplicación cutánea o la administración parenteral
    de algunos compuestos de aluminio.

         Se ha informado de casos de fibrosis pulmonar en algunos
    trabajadores expuestos a polvo muy fino de aluminio apisonado
    utilizado en la fabricación de explosivos y material pirotécnico. Casi
    todos los casos estaban relacionados con la exposición a partículas de
    aluminio cubiertas de aceite mineral. Dicho procedimiento ya no se
    utiliza. Otros casos de fibrosis pulmonar se han relacionado con
    exposiciones a otros agentes minerales como el sílice y el asbesto y
    no pueden atribuirse exclusivamente al aluminio.

         Algunos casos de asma inducida por sustancias irritantes se han
    asociado a la inhalación de sulfato de aluminio, fluoruro de aluminio
    o tetrafluoruro potásico de aluminio, así como al ambiente cargado de
    los cuartos de calderas utilizados en la producción de aluminio.

         La información disponible es insuficiente para poder clasificar
    el riesgo de cáncer asociado a las distintas formas de exposición
    humana al aluminio y sus compuestos. Los estudios en animales no
    indican que el aluminio o los compuestos del aluminio sean
    carcinógenos.

    9.  Efectos en otros organismos en el laboratorio y en el campo

         En las algas acuáticas unicelulares se ha detectado una mayor
    toxicidad a pH bajo, circunstancia que aumenta la biodisponibilidad
    del aluminio. Estas algas son más sensibles que otros microorganismos,
    y de 19 especies lacustres la mayor parte presentaron una inhibición
    completa del crecimiento a una concentración total de aluminio de
    200 µg/litro (pH 5,5). Es posible seleccionar cepas tolerantes al
    aluminio; se han aislado algas verdes capaces de crecer en presencia
    de 48 mg/litro a pH 4,6.

         En los invertebrados acuáticos la CL50 está comprendida entre
    0,48 mg/litro (poliquetos) y 59,6 mg/litro (dáfnidos). En los peces,
    la CL50 a las 96 horas va desde 0,095 mg/litro (pez estandarte
    americano) hasta 235 mg/litro (gambusia común). Sin embargo, estos
    resultados deben interpretarse con cautela dados los importantes
    efectos del pH en la disponibilidad del aluminio. El amplio margen de
    valores de la CL50 se debe probablemente a la distinta
    disponibilidad. La adición de agentes quelantes, como el NTA y el
    EDTA, reduce la toxicidad aguda del aluminio para los peces.

         Los macroinvertebrados responden de diversa forma al aluminio. En
    el margen normal de pH la toxicidad del aluminio aumenta al disminuir
    el pH, sin embargo en aguas muy ácidas el aluminio puede reducir los
    efectos del estrés ácido. Algunos invertebrados son muy resistentes al

    estrés ácido y pueden llegar a ser muy abundantes en aguas ácidas. Se
    ha informado de un aumento de la tasa de deriva de los invertebrados
    en cursos de agua en condiciones de estrés por pH o por pH/aluminio;
    esa es una respuesta común a diversos agentes estresantes.
    Invertebrados lacustres sobrevivieron en general a la exposición al
    aluminio en la naturaleza, pero sufrieron en condiciones oligotróficas
    debido a la disminución del fosfato inducida por la precipitación con
    el aluminio.

         Se han llevado a cabo pruebas de toxicidad en peces a corto y
    largo plazo en muy diversas condiciones y, lo que es más importante,
    a distintos valores de pH. Los datos muestran efectos significativos a
    niveles de aluminio inorgánico monomérico de tan sólo 25 µg/litro. No
    obstante, la compleja relación entre la acidez y la biodisponibilidad
    del aluminio dificulta la interpretación de los datos de toxicidad. A
    niveles de pH muy bajos (inhabituales en aguas naturales) la
    concentración de hidrogeniones parece ser el factor tóxico, y la
    adición de aluminio tiende a reducir la toxicidad. En el margen de pH
    4,5 a 6,0 el aluminio en equilibrio ejerce su máximo efecto tóxico. Se
    ha visto que la toxicidad también aumenta a niveles crecientes de pH
    en la región de pH alcalino. El mecanismo propuesto para explicar la
    toxicidad del aluminio en los peces es la incapacidad de los animales
    a mantener el equilibrio osmorregulador, y los problemas respiratorios
    asociados a la precipitación del aluminio en el moco de las branquias.
    El primero de estos efectos se asocia a niveles bajos de pH. Estos
    datos de laboratorio han sido confirmados por estudios realizados en
    la naturaleza, especialmente en zonas sometidas a estrés ácido.

         Los huevos y las larvas de los anfibios se ven afectados por
    la acidez y el aluminio, y se da una interacción entre estos dos
    factores. Se ha informado de fenómenos de disminución de la
    incubación, retraso de la eclosión, retraso de la metamorfosis,
    metamorfosis con tamańo reducido y aumento de la mortalidad en
    diversas especies a concentraciones de aluminio inferiores a
    1 mg/litro.

         La exposición de las raíces de plantas terrestres al aluminio
    puede frenar el crecimiento radicular, la captación de nutrientes y el
    desarrollo de la planta. Se ha demostrado la tolerancia al aluminio
    tanto en el laboratorio como en la naturaleza.

    10.  Conclusiones

    10.1  Población general

         Los estudios realizados en animales acerca de la exposición al
    aluminio han revelado riesgos para el desarrollo neurológico y las
    funciones cerebrales. Sin embargo, no se ha demostrado que el aluminio
    entrańe riesgos para la salud de las personas sanas y no expuestas en
    el trabajo.

         No existen pruebas de que el aluminio tenga un papel causal
    primordial en la enfermedad de Alzheimer, patología que el metal no
    induce  in vivo en ninguna especie, incluido el hombre.

         La hipótesis de que la exposición de la población anciana de
    algunas regiones a niveles elevados de aluminio en el agua de bebida
    puede exacerbar o acelerar la enfermedad de Alzheimer no está avalada
    por datos válidos.

         Tampoco hay datos válidos que corroboren la hipótesis de que
    determinadas exposiciones, ya sean ocupacionales o a través del agua
    de bebida, pueden asociarse a un deterioro inespecífico de la función
    cognitiva.

         No existen datos suficientes relacionados con la salud que
    justifiquen la revisión de las actuales directrices de la OMS respecto
    a la exposición al aluminio de individuos sanos no expuestos
    ocupacionalmente. Así, por ejemplo, no hay una base científica sólida
    para establecer una norma basada en criterios de salud sobre el
    aluminio en el agua de bebida.

    10.2  Subpoblaciones con un riesgo especial

         En pacientes con trastornos de la función renal, cualquiera que
    sea su edad, la acumulación de aluminio provoca un síndrome clínico
    caracterizado por encefalopatía, osteomalacia resistente a la vitamina
    D y anemia microcítica. Las fuentes de aluminio son los líquidos
    de hemodiálisis y las preparaciones famarcéuticas que contienen
    aluminio (p.ej., aglutinantes de fosfato). Los productos que contienen
    citrato pueden aumentar la absorción intestinal. Los pacientes con
    insuficiencia renal corren por tanto el riesgo de sufrir
    neurotoxicidad por aluminio.

         La exposición iatrogénica al aluminio entrańa riesgos para los
    pacientes con insuficiencia renal crónica. Los lactantes prematuros
    tienen en su organismo una mayor carga de aluminio que los otros
    lactantes. Deben tomarse toda clase de precauciones para limitar la
    exposición de esos grupos.

    10.3  Poblaciones expuestas ocupacionalmente

         Los trabajadores que han estado expuestos durante largo tiempo a
    niveles altos de partículas finas de aluminio corren quizá un mayor
    riesgo de sufrir efectos nocivos para su salud. Sin embargo, no hay
    datos suficientes para fijar con cierto grado de fiabilidad unos
    límites de exposición ocupacional en relación con los efectos adversos
    del aluminio.

         La exposición al polvo de aluminio pirotécnico apisonado,
    recubierto casi siempre de aceites lubricantes minerales, ha provocado
    fibrosis pulmonar (aluminosis), pero no se ha demostrado que la
    exposición a otras formas de aluminio produzca fibrosis pulmonar. En
    la mayor parte de los casos notificados había habido también
    exposición a otros agentes potencialmente fibrogénicos.

         Algunos casos de asma inducida por sustancias irritantes se han
    asociado a la inhalación de sulfato de aluminio, fluoruro de aluminio
    o tetrafluoruro potásico de aluminio, así como al ambiente cargado del
    interior de los cuartos de calderas utilizados en la producción de
    aluminio.

    10.4  Efectos ambientales en el medio ambiente

         Las fases sólidas que contienen aluminio en el medio ambiente son
    relativamente insolubles, en particular a un pH aproximadamente
    neutro, de ahí las bajas concentraciones de aluminio disuelto que
    tienen la mayoría de las aguas naturales.

         En los entornos ácidos o escasamente tamponados que reciben
    aportes muy acidificantes, las concentraciones de aluminio pueden
    aumentar hasta niveles perjudiciales tanto para los organismos
    acuáticos como para las plantas terrestres. No obstante, existen
    grandes diferencias en la sensibilidad a este metal según la especie,
    la cepa y la etapa de la vida.

         Los efectos biológicos adversos de las concentraciones elevadas
    de aluminio monomérico inorgánico son menores en presencia de ácidos
    orgánicos, fluoruros, silicatos y niveles altos de calcio y magnesio.

         En las aguas sometidas a estrés ácido se produce una reducción
    sustancial de la diversidad de especies, asociada a una movilización
    de las formas más tóxicas de aluminio. Dicha pérdida de diversidad se
    observa en todos los niveles tróficos.
    


    See Also:
       Toxicological Abbreviations
       Aluminium (WHO Food Additives Series 12)
       Aluminium (WHO Food Additives Series 24)
       ALUMINIUM (JECFA Evaluation)