Identity, Physical and Chemical Properties, Analytical Methods

A compendium is provided of aluminium compounds used in industrial settings, and as pharmaceuticals, food additives, cosmetics and as other household products. Most aluminium compounds are solids exhibiting high melting points. The solubility of aluminium salts is governed by pH, because the aluminium(III)-cation (Al3+) has a strong affinity for the hydroxide ion, which promotes precipitation. Like Mg2+ and Ca2+ ions, Al3+ in most situations seeks out complexing agents with oxygen-atom donor sites such as carboxylate and phosphate groups, including in biological systems. Aluminium oxides, hydroxides and oxyhydroxides occur in numerous crystallographic forms, which exhibit different surface properties. Few compounds of aluminium are classified in Annex 1 of the European Economic Union Council (EEC) Directive 67/1548, with aluminium powder and sodium aluminium fluoride (cryolite) as examples of exceptions, as well as compounds in which the anion renders them reactive such as aluminium phosphide. And finally, the more recent analytical methods available for the study of chemical speciation in solids and solution, and for quantitative analysis, have been applied to the determination of aluminium and the identification of its various forms.

Sources of Human Exposure

Aluminium and its compounds comprise about 8% of the Earth’s surface; aluminium occurs naturally in silicates, cryolite, and bauxite rock. Natural processes account for most of the redistribution of aluminium in the environment. Acidic precipitation mobilizes aluminium from natural sources, and direct anthropogenic releases of aluminium compounds associated with industrial processes occur mainly to air. Certain uses lead to the presence of aluminium in drinking water and foodstuffs.

Bauxite is the most important raw material used in the production of aluminium. Bauxite is refined to produce alumina from which aluminium metal is recovered by electrolytic reduction; aluminium is also recycled from scrap. Aluminium hydroxide is produced from bauxite. In 2004, primary aluminium was being produced in 41 countries, the largest producers being China, Russia, Canada and the United States. In that year, worldwide production of primary aluminium, alumina and aluminium hydroxide reached about 30, 63, and 5 million tonnes per annum, respectively. More than 7 million tonnes of aluminium is recovered annually from recycled old scrap.

The largest markets for aluminium metal and its alloys are in transportation, building and construction, packaging and in electrical equipment. Transportation uses are one of the fastest growing areas for aluminium use. Aluminium powders are used in pigments and paints, fuel additives, explosives and propellants. Aluminium oxides are used as food additives and in the manufacture of, for example, abrasives, refractories, ceramics, electrical insulators, catalysts, paper, spark plugs, light bulbs, artificial gems, alloys, glass and heat resistant fibres. Aluminium hydroxide is used widely in pharmaceutical and personal care products. Food related uses of aluminium compounds include preservatives, fillers, colouring agents, anti-caking agents, emulsifiers and baking powders; soy-based infant formula can contain aluminium. Natural aluminium minerals especially bentonite and zeolite are used in water purification, sugar refining, brewing and paper industries.

Aluminium has not been classified with respect to carcinogenicity; however, “aluminium production” has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) (for further explanation, please see Effects on Humans, Effects from Occupational Exposure, Cancer). Occupational limits exist in several countries for exposures to aluminium dust and aluminium oxide. For non-occupational environments, limits have been set for intake in foods and drinking water; the latter are based on aesthetic or practical, rather than health, considerations.

Environmental Levels and Human Exposure

Aluminium may be designated as crustal in origin, and thus surface soils at uncontaminated sites constitute a source of soluble aluminium species in surface water and aluminium-containing particulates in sediments and ambient-air aerosols. Not surprisingly, the latter are present extensively in air samples in agricultural communities and when road dust is extensive. Environmental acidification is known to mobilize aluminium from land to aquatic environments. Interestingly, aluminium levels and its various forms (species) are often similar in source water and after its treatment with potassium alum as a flocculent during drinking water purification.

Workers in the aluminium production and user industries, as well as aluminium welders, experience considerable exposures to the metal and/or its compounds. In absence of occupational exposures and chronic use of aluminium-containing antacids and buffered aspirin, food is the major intake source of aluminium, followed by drinking water. When considering bioavailability, namely the fraction that is actually taken up into the blood stream, food is again the primary uptake source for individuals not occupationally exposed. However, chronic use of antacids, buffered aspirins and other medical preparations would likely constitute the major uptake source, even when exposed at work.

Kinetics and Metabolism


The use of 26Al as a tracer and accelerator mass spectrometry has enabled safe studies of aluminium toxicokinetics with real exposure-relevant doses in humans. Aluminium bioavailability from occupational inhalation exposure is ~ 2% whereas oral aluminium bioavailability from water has been reported to be 0.1 to 0.4%. Oral aluminium bioavailability is increased by citrate, acidic pH, and uraemia and may be decreased by silicon-containing compounds. Oral aluminium bioavailability is also inversely related to iron status.

Oral aluminium bioavailability is greater from water than from aluminium hydroxide or sucralfate. Oral aluminium bioavailability from aluminium hydroxide is ≤ 0.1%, and is less with higher doses. Increased oral aluminium absorption has been suggested in Alzheimer’s disease (AD) and Down’s subjects. Oral aluminium bioavailability from the diet has been estimated to be ~ 0.1 to 0.3%, based on daily aluminium intake and urinary elimination. Results of a few studies with a controlled diet and tea are consistent with this estimate.

Steady state serum to whole blood aluminium concentrations are ~ equal. Slightly > 90% of plasma aluminium is associated with transferrin (Tf), ~ 7 to 8% with citrate, and < 1% with phosphate and hydroxide. Normal plasma aluminium concentration is believed to be 1 to 2 μg/L. Normal tissue aluminium concentrations are greater in lung (due to entrapment of particles from the environment) than bone than soft tissues. Approximately 60, 25, 10, 3 and 1% of the aluminium body burden is in the bone, lung, muscle, liver and brain, respectively. Higher concentrations are seen in uraemia and higher still in dialysis encephalopathy.

Tissue aluminium concentration increases with age. Some studies have reported that the aluminium concentration in the bulk brain samples, neurofibrillary tangles (NFT) and plaques was higher in AD subjects than controls. Other studies have found no difference. Hair aluminium concentration has been described but its value as an indicator of aluminium body burden has not been demonstrated.

Greater than 95% of aluminium is eliminated by the kidney; ~ 2% in bile. Occupational aluminium exposure increases urinary more than plasma aluminium concentration above their normal levels. Depending on the type and route of exposure, aluminium clearance has been characterized as having multiple half-times and are estimated in hours, days, and years. Most of the Al was eliminated within the first week; the terminal half-life probably represents < 1% of the injected aluminium.

Biological monitoring of human aluminium exposure has been conducted with urine, which is thought to indicate recent exposure, and plasma, which is thought to better reflect the aluminium body burden and long-term exposure. However, neither is a very good predictor of the aluminium body burden, which is better estimated by bone aluminium, the desferrioxamine challenge test, or combined measurement of serum iPTH (parathyroid hormone) and the desferrioxamine test.

Serum aluminium > 30 μg/L in dialysis patients has been associated with osteomalacia and related disorders and > 80 μg/L associated with encephalopathy. Up to 5 mg/kg of desferrioxamine once or twice weekly has been shown to be safe and effective for long-term treatment of aluminium overload.


In studies of animals, pulmonary deposition of fly ash was 2 to 12% and was inversely related to particle size. Oral aluminium bioavailability from water appears to be ~ 0.3%. The very limited data available suggest oral aluminium bioavailability from food is less than from water.

Oral aluminium bioavailability is increased by citrate, and to a lesser extent, other carboxylic acids, increased solubility of the aluminium species, acidic pH, uraemia, increased dose of soluble aluminium species, and perhaps fluoride. Oral aluminium bioavailability is decreased by silicon-containing compounds. Oral aluminium bioavailability is also inversely related to iron, calcium and sodium status.

Absorption of aluminium from the gastrointestinal tract (GI) appears to be primarily in the distal intestine. There is evidence supporting several mechanisms of intestinal aluminium absorption, including sodium transport processes, an interaction with calcium uptake, and paracellular diffusion. Aluminium penetration of the skin is very shallow. Aluminium may be able to enter the brain from the nasal cavity by a direct route, bypassing systemic circulation, but convincing evidence is lacking. Absorption of aluminium from intramuscularly (i.m.) injected aluminium hydroxide and aluminiun phosphate adjuvants is significant, and may eventually be complete. Tissue aluminium concentration increases with age.

The volume of distribution (Vd) of aluminium is initially consistent with the blood volume, and then increases with time. Steady state serum to whole blood aluminium concentrations are ~ equal. Greater than 90% of serum aluminium is bound to Tf. Although aluminium has been reported in many intracellular compartments, concentrations were often greater in the nucleus. Ferritin can incorporate aluminium.

Following i.v. injection, ~ 0.001 to 0.01% of the aluminium dose enters each gram of brain and ~ 100-fold more each gram of bone. Brain aluminium uptake across the blood-brain barrier (BBB) may be mediated by Tf-receptor mediated endocytosis (TfR-ME) and a Tf-independent mechanism that may transport aluminium citrate. There appears to be a transporter that effluxes aluminium from the brain into blood. Aluminium distributes into the placenta, foetus, milk, hair, and can be quantified in all tissues and fluids. Greater than 95% of aluminium is eliminated by the kidney, probably by glomerular filtration. Less than 2% appears in bile.

Aluminium clearance is characterized by multiple half-lives (t½), suggesting multiple compartments. The terminal t½ from the lung is ~ 100 days and from the brain and other soft tissues > 100 days. Prolonged aluminium residence in the bone may account for the prolonged t½ observed in most organs, including the brain.

There are no published reports of physiologically based pharmacokinetic (PBPK) modelling of aluminium. A few models have been developed that incorporate the reported results of toxicokinetic studies with aluminium.

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