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There were no studies available in which the toxicokinetic properties of Reaction mass of aluminium and magnesium oxide and spinel (Mg(AlO2)2) were investigated. Reaction mass of aluminium and magnesium oxide and spinel (Mg(AlO2)2) consist predominantly of Al and Mg. Mg is neglected because of its essential physiological role. Thus, read-across from supporting substances was performed following a structural analogue approach. Aluminium compounds were considered for this approach, since the pathways leading to toxic outcomes are dominated by the chemistry and biochemistry of the aluminium ion (Al3+) (Krewski et al., 2007; ATSDR, 2008).


Aluminium is poorly absorbed following either oral or inhalation exposure and is essentially not absorbed dermally (ATSDR, 2008). Both animal and human studies have shown that aluminium absorption is influenced by several factors including solubility, pH. Thus, less soluble species such as aluminium borate, glycinate, hydroxide and sucralfate are generally less well absorbed than more soluble compounds such as aluminium chloride, lactate, nitrate and citrate (Yokel and McNamara, 1988; Priest et al., 1996). At lower pH (e.g. in the stomach), absorption of some aluminium compounds is increased (Krewski et al., 2007). Aluminium hydroxide and sucralfate are less soluble at pH 3, 6 and 7 than aluminium lactate and chloride and were also less well absorbed, based on urinary aluminium excretion (Froment et al., 1989).

Occupational exposure to aluminium fumes, dusts and flakes can elevate serum, bone and urine aluminium. Pulmonary aluminium absorption appears to be more efficient than gastrointestinal absorption (Yokel and McNamara, 2001; Elinder et al., 1991). There are no reports on the percentage of aluminium absorbed following inhalation exposure from occupational toxicokinetic studies (ATSDR, 2008). However, a fractional absorption of 1.5 -2% was estimated based on the relationship between urinary aluminium excretion and the airborne soluble aluminium to which workers were exposed (Yokel and McNamara, 2001).

Aluminium in food and drinking water is poorly absorbed via the gastrointestinal tract. Small scale human studies have estimated aluminium absorption efficiencies of 0.07-0.4% after administration of a single dose of the radionuclide aluminium-26 (26Al) in drinking water (Hohl et al., 1994; Priest et al., 1998; Stauber et al., 1999; Steinhausen et al., 2004; Yokel and McNamara, 2001). Other studies also used 26Al for estimation of the aluminium bioavailability from drinking water. When aluminium levels in urine and bone were considered, absorption rates of 0.04-0.06% were estimated in rats (Drueke et al., 1997; Jouhanneau et al., 1993); when liver and brain aluminium levels were also considered, an absorption rate of 0.1% was estimated (Jouhanneau et al., 1997).

In a human study, the bioavailability of aluminium in diet was examined. An absorption efficiency of 0.28-0.76% was estimated in subjects ingesting 3 mg Al/day (0.04 mg Al/kg/day) or 4.6 mg Al/day (0.07 mg Al/kg/day) (Greger and Baier 1983; Stauber et al., 1999). Aluminium absorption decreased to 0.094% when 125 mg Al/day (1.8 mg Al/kg/day) as aluminium lactate in fruit juice was added to the diet, (Greger and Baier, 1983). Yokel and McNamara (2001) suggested that the bioavailability of aluminium from the diet is 0.1% based on daily urinary excretion levels of 4-12μg and average aluminium intakes by adults in theof 5-10 mg/day.

Aluminium bioavailability is strongly influenced by the aluminium compound and the presence of dietary constituents which can complex with aluminium andthereby enhance (e.g. carboxylic acid) or inhibit (e.g. phosphate or dissolved silicate) its absorption (ATDSR, 2008). Froment et al. 1989 and Johanneau et al. 1997 concluded that citrate must have an additional effect on aluminium absorption, either by facilitating transcellular absorption or by opening the tight junctions and enhancing the paracellular movement of aluminium, which is considered the main mechanism of absorption.

Human data on the dermal absorption of aluminium is limited. Applying 26Al labelled aluminium chlorohydrate (a common additive in underarm antiperspirants) to the underarm of two subjects, it was estimated that 0.012% of the applied aluminium had been absorbed through the skin (Flarend et al., 2001). In animal study, increased levels of aluminium were found in the urine of mice exposed to 0.1 or 0.4μg/day aluminium chloride (0.01-0.04μg Al/day) applied to a 4 cm2 shaved area daily for 130 days (Anane et al., 1995). However, the results of this study should be interpreted with caution because of the lack of control measures to prevent the animals from licking their fur and thus ingesting aluminium.


Aluminium distribution depends on the species used, route of administration and aluminium compound. In general, the highest aluminium concentrations were found in the liver (Myers and Mull 1928), spleen, bone and kidney. Since aluminium tissue uptake is slow, probably due to high protein binding at high aluminium plasma levels, short lengths of observation will bias the results towards lower values (Wilhelm et al. 1990). The aluminium levels of plasma, liver, spleen, and kidneys were significantly higher in treated pregnant rats than non-pregnant female rats. The aluminium content of the 20-day old foetuses did not significantly differ between the treated and control groups (Muller et al. 1993).

Aluminium distributes unequally to all tissues throughout normal and aluminium-intoxicated human beings and aluminium-treated experimental animals. Growing, mature and ageing rats differed in regard to the initial distribution of aluminium in their tissues after a large oral dose (Greger and Radzanowski 1995). Within blood, aluminium is approximately equally distributed between plasma and cells. The higher concentration in lung of normal humans may reflect entrapment of airborne aluminium particles, whereas the higher concentrations in bone, liver and spleen may reflect aluminium sequestration. The skeletal system and lung have ~50 and 25% of the 30-50 mg aluminium body burden of the normal human; brain has ~1%. Considering the aluminium species in plasma, it is likely that aluminium transferrin and aluminium citrate account for the majority of the aluminium that distributes to tissues from the vascular compartment.

The brain has lower aluminium concentrations than many other tissues. Increased brain aluminium is seen in aluminium-associated neurotoxicity in humans. Aluminium can enter the brain from blood. Dietary aluminium in guinea pigs led to elevated aluminium concentrations in brain regions, highest in spinal cord, brainstem, and cerebellum, and decreased during late gestation and lactation (Golub et al. 1996). There is evidence that transferrin can mediate aluminium transport across the blood-brain barrier by transferrin-receptor mediated endocytosis of aluminium-transferrin, the predominant aluminium species in plasma. A second mechanism transporting aluminium citrate across the blood-brain barrier into the brain is suggested that is independent of transferrin (too fast to be receptor-mediated). There appears to be a mechanism to transport aluminium out of the brain. It is likely that aluminium citrate is the aluminium species transported out of the brain.

Bone aluminium concentration in normal human beings is a few times greater than brain aluminium. In humans, the largest long-term deposition of aluminium occurs in the bones (Steinhausen et al 2004). Several animal studies showed ~100 times higher bone than brain 26Al concentrations after a single 26Al dose, suggesting greater aluminium entry into bone than brain. Aluminium concentrates at the mineralization front of bone (Yokel and McNamara 2001). About 50% of absorbed aluminium is rapidly (<2 hours) and permanently accumulated in the skeleton of young rats (Johanneau et al. 1997). In rats, a single gavage treatment with 26Al, showed that the fraction absorbed retained in the skeleton (0.025 -0.030%) was of the same order of magnitude as the fraction excreted in the 48 hour urine (0.035 -0.037%). Furthermore, it was shown that 26Al administered to pregnant rats and/or lactating rats is transferred to their offspring through transplacental passage and/or maternal milk (Yumoto et al. 2000).

Skin exposure to aluminium chloride produced a significant increase of aluminium accumulation in the brain, especially in the hippocampal area. This finding was confirmed by microanalysis on slices of hippocampus showing accumulation of aluminium silicates (Anane et al. 1995). Cutaneous aluminium uptake in mice also led to an increase of aluminium in maternal and foetus samples (serum, amniotic fluid and organs) as compared to controls (Anane et al. 1997). However, as mentioned above, oral exposure through grooming cannot be excluded.


It is believed, that aluminium exists in four different forms in living organisms: free ions, low-molecular-weight complexes, physically bound macromolecular complexes, and covalently bound macromolecular complexes (Ganrot 1986). The free ion, Al3+, easily binds to many substances and structures; thus, its fate is determined by its affinity to each of these ligands and their relative amounts and metabolism. Low-molecular-weight complexes may also be formed with aluminium and organic acids, amino acids, nucleotides, phosphates, and carbohydrates. Such low-molecular-weight complexes are often chelates which may be very stable. These complexes, particularly the nonpolar ones, are metabolically active. Due to it very high affinity for proteins, polynucleotides, and glycosaminoglycans, much of the aluminium in the organism may exist as physically bound macromolecular complexes with these substances. These macromolecular complexes would be expected to be metabolically much less active than the smaller, low-molecular-weight complexes. In addition, aluminium may also form complexes with macromolecules, which are so stable that they are practically irreversible. Thus, there is evidence suggesting that the nucleus and chromatin are often sites of aluminium binding in cells (Crapper McLachlan 1989; Dyrssen et al. 1987; Ganrot 1986; Karlik et al. 1980).


In general, it is accepted that aluminium is mainly excreted in urine, while unabsorbed aluminium is excreted primarily in the faeces. In humans, 0.09 and 96% of the aluminium intake per day was cleared through the urine and faeces, respectively, during exposure to 1.71 mg Al/kg/day as aluminium lactate in addition to 0.07 mg Al/kg/day in basal diet for 20 days (Greger and Baier 1983). After years, all 26Al taken up by humans is excreted via the urine (Steinhausen et al. 2004; Priest et al. 1995). In rats, about 50% of absorbed aluminium is excreted in urine, with 90% of this excretion occurring during the first 48 hours after ingestion. Nevertheless, there is evidence that aluminium can also be eliminated via the bile. Biliary aluminium excretion accounted for only 0.1% of the total aluminium load, whereas 37% was renally excreted. Similar results were obtained in rats. It seems that under certain pathophysiological conditions biliary aluminium excretion is altered (Wilhelm et al. 1990).

Elimination half-lives in the range of years were seen after termination of occupational aluminium exposure, based on urinary aluminium excretion. This kinetic behaviour might result from retention of aluminium in a depot from which it is slowly eliminated. This depot is probably bone which stores ~50% of the human aluminium body burden (Elinder et al. 1991). Brain, serum and bone aluminium have been reported to increase with age. Aluminium clearance from bone is more rapid than from the brain, which is reasonable considering bone turnover and lack of neurone turnover. Urine accounts for >95% of excreted aluminium. Reduced renal function increases the risk of aluminium accumulation and toxicity in the very young, elderly and renally diseased human being. In rats, the half-life of aluminium in tissues was also affected by age. Ageing rats retained aluminium much longer in tibias than mature and growing rats. Also ageing and mature rats retained aluminium longer in kidneys than growing rats (Greger and Radzanowski 1995). Chelators and citrate can increase aluminium clearance into urine, bile and dialysate (Yokel and McNamara 2001).

References not in IUCLID

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

Crapper McLachlan, D.R. (1989). Aluminum neurotoxicity: Criteria for assigning a role in Alzheimer's disease. In: Lewis TE, ed.

Environmental chemistry and toxicology of aluminum.,: Lewis Publishers, Inc., 299-315.

Dyrssen, D. et al. (1987). Complexation of aluminum with DNA. J Inorg Biochem 29(1):67-75.

Ganrot, P.O. (1986). Metabolism and possible health effects of aluminum. Environ Health Perspect 65:363-441.

Hohl, C. et al. (1994).Medical application of 26Al. Nucl Instr Meth Phys Res B 92:478-482.

Karlik, S.J. et al.(1980). Molecular interactions of aluminum with DNA. Neurotoxicology 1:83-88.

Krewski, et al. (2007).Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide, A Report

Submitted to theEnvironmental Protection Agency. J Toxicol Environ Health B Crit Rev. 10 Suppl 1:1-269.

Priest, et al. (1998). Uptake by man of aluminum in a public water supply. Hum Exp Toxicol 17(6):296-301.

Stauber, J.L. et al. (1999).Bioavailability of Al in alum-treated drinking water. J Am Water Works Assoc 91(11):84-93.

Jouhanneau, P. et al. (1993). Gastrointestinal absorption of aluminum in rats using 26Al and accelerator mass spectrometry. Clin Nephrol 40(4):244-248.

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