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Gupta et al. (1986) reported about kinetic analyses of aluminium in the rat following intravenous and oral doses of aluminium chloride. The authors stated, that aluminium did not significantly penetrate the cellular components of blood. Plasma protein binding was determined to be about 98%. Sixty per cent of the intravenous dose was excreted in the urine and the remaining 40% was excreted in the faeces.

A study was conducted to determine the bioavailability of ingested Al-26 labeled aluminium and aluminium compounds in Sprague Dawley rats (ToxTest, 2010). The animals were orally (gavage) treated with formulations of aluminum citrate, sulfate, nitrate, chloride and hydroxide, each delivering 30 mg/kg bw Al3 +, daily for 7 days or 14 days. Blood and organs were collected and analyzed for aluminum, manganese, iron and copper concentrations. All animals survived until their scheduled necropsies. No abnormal clinical observations were made, and food/water consumption, body weights and growth patterns were not influenced by treatment. The results produced in the rat showed a similar GIT bioavailability of the above-mentioned salts. Apart from bone (males, day 7) and kidney (day 7 males and day 14 females), there were no significant differences in aluminum concentration between treated and control animals for any tissue. The results suggest that aluminium citrate is a little more soluble than aluminium chloride and nitrate, but this result was not unexpected since citrate will chelate aluminium ions, holding them in solution and increasing their chances of uptake through the gut wall.

The recent study of Priest (2010) investigated the bioavailability of several Aluminium salts (Aluminium sulphate, Aluminium citrate, Aluminium hydroxide) as well as Aluminium chloride. The results performed showed that the measured mean bioavailability in rat for some of soluble Aluminium salts of interest in this dossier decreased in the order: Aluminium sulphate (0.21%), Aluminium citrate (0.079%), Aluminium chloride (0.054%), Aluminium hydroxide (0.025%). Although the result for Aluminium sulphate was unexpectedly higher than for other mineral acid salts tested, it corresponds closely with the uptake levels measured in two human volunteers that swallowed drinking water that contained26Al introduced as Aluminium sulphate (0.20%). Due to the use of the same experimental methods for the different substances, the results from the human study can be quantitatively compared to the data from the animal study as both test substances were administered without co-exposures to ligands that may influence the bioavailability. The human result for Aluminium hydroxide (0.01%) was similar to that obtained using the rat model. Additionally, the measured bioavailability of the Aluminium citrate in the rat was well within the range of measured/estimated values of 0.047% to 1% in man for citrate (and orange juice).

General discussion of aluminium kinetics:

The information below is taken from the following sources:

U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry (ATSDR): Toxicological Profile for Aluminum, 2008

Health Council of the Netherlands: Aluminium and aluminium compounds - Health-based recommended occupational exposure limit, 2010

World Health Organization, Joint FAO/WHO Expert Committee on Food Additives (JECFA): Safety evaluation of certain food additives and contaminants, WHO food additives series: 65, 2012

European Commission, Scientific Committee on Consumer Safety (SCCS): Opinion on the safety of aluminium in cosmetic products.

The absorption of aluminium via the gastrointestinal tract is generally considered to be low, ca. 0.1 -1%, depending on the type of aluminium compound ingested and the composition of the diet (ATSDR, 2008; Health Council of the Netherlands, 2009).

Evidence for absorption of aluminium after inhalation exposure in humans is available from several occupational studies. Occupational exposure to aluminium fumes, dusts, and flakes has resulted in increases in aluminium levels in serum, tissue, and urine. The percentage of aluminium absorbed following inhalation exposure was not reported in the occupational toxicokinetic studies.Mechanisms of inhalation absorption of aluminium are not well characterised, although it seems likely that relatively large aluminium-containing particles retained in the respiratory tract are cleared to the gastrointestinal tract by ciliary action.

The database regarding aluminium absorption after dermal exposure to aluminium or its compounds is poor. Aluminium compounds are common additives in deodorants or antiperspirants and are soluble at very low pH in the formulation, however once aplied on the skin they form chemically intert polymeric complexes with basic components of sweat and skin. This limits the bioaccessibility of aluminium on living skin.

Aluminium binds to various ligands in the blood and distributes to every organ, with highest concentrations found in bone and lung tissues. Aluminium can form complexes with many molecules in the body (organic acids, amino acids, nucleotides, phosphates, carbohydrates, macromolecules). Free aluminium ions (e.g., Al(H2O)63+) occur in very low concentrations. In the blood, aluminium is mostly bound to transferrin in the serum (89%) (Health Council of the Netherlands, 2009). Cellular uptake of aluminium by organs and tissues is believed to be relatively slow and most likely occurs from the aluminium bound to transferrin (Ganrot, Environ Health Perspect 65:363 -441, 1986). It is likely that the density of transferring receptors in different organs influences the distribution of aluminium to organs.

Urinary excretion is the primary route of elimination of absorbed aluminium. Unabsorbed aluminium is excreted primarily in the feces.