When copper residue is formed on the dish due to formation of copper I oxide This phenomenon is called?

The acute toxicity of aluminium metal and aluminium-containing compounds is relatively low (Appendix A). The reported oral LD50 values of aluminium compounds from toxicological animal studies are between 162 and 980 mg/kg b.w. (IPCS, 1997). The acute toxicity is dependent upon factors such as the solubility and bioavailability of the aluminium compounds, the route of administration, and the physiological status (renal function) of treated animals. Because aluminium hydroxide and aluminium oxide are poorly absorbed after GI, respiratory, dermal or i.v. administration (Flarend et al., 1997; Hem, 2002; Priest, 2004; Priest et al., 1996; Schönholzer et al., 1997) (see also Toxicokinetics, Absorption), it is expected that these compounds also produce low acute toxicity when administered by these routes. The i.p. LD50 (mouse) for aluminium oxide is >3600 mg/kg body weight (Filov, 1988) which suggests that aluminium oxide produces low acute toxicity. Aluminium hydroxide toxicity is predominantly seen in uraemic animals after i.p. injection and is manifested by symptoms of lethargy, periorbital bleeding, anorexia, and subsequently death (Berlyne et al., 1972a). Increased aluminium plasma levels and excessive aluminium deposition in the brain, liver, heart and muscle have also been documented following aluminium hydroxide overload (Berlyne et al., 1972a; Thurston et al., 1972).

Intratracheal instillation of aluminium compounds in laboratory animals has been used as a simple and relatively inexpensive method for screening aluminium for fibrogenicity or other types of pulmonary toxicity, including carcinogenesis. Experimental studies to evaluate fibrogenic potential in rats i.e., the ability to induce pulmonary fibrosis of 4 different types of aluminium fibres including alpha (uncalcined form) and gamma alumina (calcined form) following single intratracheal injections, were performed by Dalbey & Pulkowski (2000). Six months after dosing, pulmonary function tests (functional residual capacity, deflation pressure-volume curves, maximal forced deflation, single breath carbon monoxide diffusion capacity, and pulmonary resistance) and histopathological evaluation were performed. Rales were noted during the first week of instillation in aluminium treated groups, but not in the groups given glass beads or quartz. Standard lung volume and maximal forced exhalation parameters were decreased at 6 months after instillation in aluminium treated groups as compared to animals injected with saline and glass beads (controls). Single-breath carbon monoxide diffusing capacity was significantly decreased in aluminium treated animals compared to both types of controls which indicated the presence of a physical barrier between the air in the alveoli and the blood. The weight of the postcaval lung lobe was significantly increased for all groups administered aluminas, and the most marked increase was seen in the quartz group. The histopathological changes were similar in all treated groups and consisted of areas of granulomatous inflammation with early collagenization (fibrosis). The presence of multinuclear giant cells and the infiltration of macrophages were suggestive of a foreign body type reaction. Interstitial fibrosis was also apparent and was characterized by a thickening of alveolar walls with collagen. Both groups treated with uncalcined aluminas tended to have a higher incidence and severity of granulomas with fibrosis. Although minor pulmonary changes were noted in the aluminium treated groups, these effects were significantly less pronounced than the changes induced by the instillation of the positive control (quartz). Results are consistent with previously published work (Ess et al., 1993; King et al., 1955; Stacy et al., 1959) and point to the variation in responses to material within the class of alumina compounds. In interpreting these results, it must be considered that large doses were instilled with the intent of overloading normal clearance mechanisms in the lung to exaggerate any reaction that might occur. The dose of 50 mg is equivalent to about 30 mg/g lung, well above the 1 mg/g generally associated with the onset of overloading during long-term studies (Oberdorster et al., 1992). Influx of alveolar macrophages (AM), accumulation of particles, inflammation, and fibrosis are changes which would be expected following the administration of a large dose of relatively insoluble particles producing low toxicity to rats. The main goal of these instillations was to rank several alumina samples for their general potential to induce pulmonary fibrosis.

Lindenschimdt et al. (1990) examined the effects of aluminium on the development of pulmonary fibrosis and histological changes/inflammatory responses in the lungs of rats instilled with 1 or 5 mg Al2O3/100 g body weight. A dose-dependent minimal and generally transient increase in inflammatory responses was measured in the bronchoalveolar lavage fluid (BALF) including; activity of lactate dehydrogenase (LDH) an index of cell membrane damage; beta-glucurnidase and N-acetylglucosaminidase, markers of macrophage/polymorphonuclear membrane damage; and levels of total protein, an index of potential fibrotic activity and/or vascular damage. Increase in total cells at this dose was primarily due to elevation in neutrophils and lymphocytes. At low dose, the only significant change was an increase of neutrophils on day 1 which returned to the control level by day 7. The changes observed at high doses returned slowly to normal values during the 2-month study period. Although intratracheal instillation is not the normal route of exposure, the minimal and generally transient changes induced by Al203 are consistent with the lack of significant lung toxicity found in both humans and animals. Significant pathologic response at high doses might be due to the overload phenomenon of aluminium oxide dust (~9.1 mg/g lung tissue). Morrow (1996) showed that deposition of large amounts of inert dust in the lungs (> 1-2 mg/g lung tissue) resulted in inhibition of phagocytic removal of dust, leading to a delayed clearance from the lung.

Tornling et al. (1993) administered intratracheal instillations of aluminium oxide (primary alumina), aluminium oxide with adsorbed fluorides (secondary alumina), and saline to three different groups of rats. The alumina dust (40 mg) was suspended in saline. BALF was obtained and histological examination of the lungs was performed 1, 4, and 12 months after exposure. No signs of fibrosis were found in any of the animals. No significant changes in alveolar cell concentrations were noted for the group treated with primary aluminium; however the secondary aluminium group exhibited increased concentrations of macrophages and neutrophils one month and one year after exposure. This suggests that fluoride plays an important role in early changes to alveolar cell populations. One year after exposure both the aluminium treated groups exhibited significantly raised concentrations of fibronectin, which indicates that alumina, not fluoride, is essential for this observed effect. The biochemical properties of fibronectin support the formation of an extracellular matrix network, and therefore fibronectin may be an early marker of fibrosis. Due to the administration of aluminium by intratracheal instillation, which is not a physiological route, the results observed in this study need to be confirmed by further investigations in which inhalation is used as a route of exposure. Instillation may have led to pulmonary overload which could have contributed to the development of the observed effects.

Pigott & Ishmael (1992) assessed the effects of a single intrapleural injection (0.2 mL suspension/20 mg suspended solids) of refractory alumina fibres (Saffil fibres) obtained immediately after manufacturing or, later, after extensive thermal ageing. The potential for these fibres, which had different diameters, to result in the development of mesotheliomas in groups of rats was examined. No mesothelioma was detected in any of the rats dosed with the Saffil fibres, or in the negative controls. Malignant mesothelioma was diagnosed in 7 rats in the asbestos group (positive control) and in 3 rats in one of the aluminosilicate groups. However, it must be considered that intra-cavity injections result in a high deposition of the test material directly on the target tissue. This does not reflect inhalation exposures in which the fibres must first be deposited in the alveolar region of the lung and penetrate lung tissue before it reaches the pleural space. The increased mesothelioma proliferation and malignant mesotheliomas detected in the aluminosilicate B group as compared to the aluminosilicate A group is likely a reflection of the size of the fibres. Coarse fibres were found to be more irritating than fine fibres. The results of this study suggest that Saffil alumina fibres are inert and are not associated with mesothelioma induction. This study supports the results from a previously conducted inhalation study (Pigott et al., 1981).

After a single intrapleural instillation of Al(OH)3 at a dose of 0.3 g/mL saline to rats there was an increase in chest wall elastic properties and viscoelastic pressure accompanied by pleural inflammation after 7 days (Albuquerque et al., 2002). The pleural adherence was associated with a marked increase in the type I/type III collagen ratio after 30 days. Histological examination demonstrated no significant differences in lung parenchyma in the aluminium hydroxide treated and control groups.

In vitro studies

Gusev et al. (1993) and Warshawsky et al. (1994) conducted in vitro studies to examine the effects of aluminium on lung cell related functions. Gusev et al. (1993) showed that phagocytosis of alumina dust by rabbit AM did not produce exogenous generation of superoxide radicals and hydrogen peroxide as measured by nitroblue tetrazolium reduction in resting and stimulated cells when compared to quartz dust. Alumina dust exerted no effect on hydrogen peroxide generation and substantially decreased the level of superoxide radical generation by human granulocytes. Warshawsky et al. (1994) also conducted a study to assess the role of AM after exposure to aluminium oxide. The cytotoxicity of aluminium oxide particles (median size was equal or less than 0.36 μm and surface area 198.4 m2/g) to hamster and rat AM in vitro was measured at 0.1-0.5 mg/L ×106 cells at 24 and 48 hr using trypan blue exclusion procedures. The viability of the hamster AM in the presence of aluminium oxide up to the highest concentration was similar to control. After 24 and 48 hr, the viability of the AM was approximately 80 and 70%, respectively. Results demonstrated that aluminium oxide showed no changes in AM viability under in vitro conditions.

As discussed in Toxicokinetics, Absorption, Animal Studies, Oral Administration, the oral bioavailability of silicon and aluminium from Zeolite A (30 mg/kg), sodium aluminosilicate (16 mg/kg), magnesium trisilicate (20 mg/kg), and aluminium hydroxide (675 mg) in dogs was examined by Cefali et al. (1995). Twelve female dogs received a single oral dose of each compound at one-week intervals. One of the 12 dogs receiving aluminium hydroxide displayed frothy emesis, and two dogs excreted soft stool.

Intracellular binding of aluminium was examined in the mucosa of the stomach, duodenum, jejunum and ileum of adult rats following a single oral administration (300 mg/kg) of aluminium hydroxide (More et al., 1992). A second group of rats received a daily oral administration of Al(OH)3 (300 mg/kg) for 5 days. No marked differences in body weight and no microscopic lesions in the GI tract (body and antrum of the stomach, duodenum, jejunum and ileum) were observed in either group of animals. Six hr after single Al(OH)3 administration, aluminium deposits were observed in the gastric lumen, in the duodenum, and in the lumen of both the jejunum and ileum. After repeated administration, the presence of aluminium-reactive deposits was noted only in the lumen of the stomach (at the bottom of the antral glands) and in the lumen of the intestine from day 3 to day 7. Other data (discussed in Toxicokinetics, Absorption, Animal Studies, Oral Administration, The Site and Mechanisms of Oral Aluminium Absorption) have demonstrated that aluminium absorption occurs in the small intestine by a paracellular pathway process via the tight junctions (Garbossa et al., 1998b; Provan & Yokel 1988a). The results also suggest that after repeated administration of large oral doses, aluminium accumulates in the antral mucosa of the stomach and is released slowly in the digestive tract.

Aluminium hydroxide is one of the adjuvants most commonly used in routine human vaccines against hepatitis B virus (HBV), hepatitis A virus, and tetanus toxoid (TT) and in veterinary vaccines (see also Effects on Humans, Effects from Non-Occupational Exposure, Irritation, Irritation after Injection of Aluminium-Adsorbed Proteins (Vaccines and Hyposensitization Regimens)). Although it has been investigated since 1926, the mechanisms of action of aluminium adjuvants are not yet fully understood. It is likely that aluminium adjuvants induce immune activation which includes interleukin (IL) -1 production by monocytes, induction of eosinophilia, compliment activation and increased specific and non-specific immunoglobulin (Ig) G1 and IgE antibody responses (Gupta & Siber, 1995; HogenEsch, 2002; Jensen & Koch, 1988; Larsen et al., 2002; Norimatsu et al., 1995; Shi et al., 2001). Limitations of aluminium adjuvants for human vaccination include local reactions, augmentation of IgE antibody responses, ineffectiveness against some antigens and inability to augment cell-mediated immune responses, especially cytotoxic T-cell responses (Gupta, 1998).

Gherardi et al. (2001) administered a single i.m. injection of an aluminium hydroxide-containing HBV vaccine (GenHevac, 250 μL) to rats in an attempt to reproduce lesions characteristic of MMF (also see Effects on Humans, Case Reports). The aluminium hydroxide-containing vaccine induced a large necrotic area containing damaged muscle fibres and neutrophils, surrounded by abundant lymphocytes and macrophages (days 7-15), that progressed to a mature lesion (21 and 28 days). The focal infiltration of densely packed PAS-positive macrophages, without giant cell formation or muscle fibre damage, was similar to the macrophage infiltrate seen in MMF. Crystalline inclusions similar to those of MMF were detected by electron microscopy. It was proposed that aluminium hydroxide forms a deposit which damages the injected tissue, subsequently eliciting a signal from stressed cells. This signal attracts inflammatory and antigen presenting cells and the aluminium hydroxide deposit is then subject to phagocytosis (Balouet et al., 1997; IPCS, 1997; Schijns, 2000). Phagocytized aluminium hydroxide increases survival of macrophages and enhances the effects of granulocyte/monocyte stimulating factor (Hamilton et al., 2000). A number of aluminium loaded macrophages accumulate locally, resulting in the characteristic granuloma formation, while others migrate to the regional lymph nodes (IPCS, 1997). A recent study in monkeys showed that macrophage accumulation persisted more that 1 year after injection (Verdier et al., 2005). A residence time longer than 6 months was observed in rats (Gherardi et al., 2001).

Verdier et al. (2005) evaluated the local reaction and aluminium concentration following i.m. injection of aluminium adjuvant vaccines in Cynomolgus monkeys. Two groups of 12 male monkeys received a single i.m. injection of either aluminium phosphate adjuvant diphtheria-tetanus vaccine or aluminium hydroxide adjuvant diphtheria-tetanus vaccine. Four monkeys from each of the two groups were sacrificed 85, 169, or 366 days after the single i.m. injection, and macroscopic examination of the injected site was performed to detect any sign of local intolerance. Macrophage aggregation was graded as moderate to marked and was accompanied by a lymphoid infiltration in all cases following the initial sacrifice. Analysis of the injection site revealed high aluminium content for both aluminium treated vaccine groups; however, the aluminium concentration of the reactive zones of animals treated with aluminium hydroxide was 4 times higher than in those treated with aluminium phosphate. The size of the inflammatory lesion was greater in the monkeys given the aluminium hydroxide adjuvant. Six months after the vaccine injection 3 out of 4 monkeys exhibited appreciable lesions composed primarily of macrophages. One of the lesions had an extensive cyst-like structure which contained degenerate macrophages. Two of 4 monkeys in the aluminium hydroxide group had persistent macrophages aggregations with associated minor lymphocytic infiltrations one year following the injection. The histological appearance and persistence of the lesion observed at the injection site is similar to the lesions observed in human cases of MMF. Therefore these results suggest that this type of lesion is a usual reaction following the injection of an aluminium adjuvant vaccine by the i.m. route, and can occur in normal healthy animals following the administration of both aluminium phosphate and aluminium hydroxide containing vaccines.

A field trial involving 45 pigs was conducted to validate the hypothesis of aluminium-induced granulomas (Valtulini et al., 2005). The animals were randomly allocated to receive the same aluminium hydroxide adjuvant vaccine which induced the formation of nodules in the muscles of pigs from one particular farm; the adjuvant alone, distilled water, or the adjuvant and distilled water. The pigs were injected twice i.m. and slaughtered at about 165 kg weight. Granulomas located within muscular tissue were observed for all the aluminium containing vaccine groups; granulomas were not detected in any of the pigs who received only water. Granulomas were characterized by aggregates of macrophage-derived epithelioid cells, with some containing oval nucleus, a pale pink cytoplasm, and indistinct cell borders. These cells were surrounded by an infiltrate of mixed inflammatory cells, including large multinucleated giant cells, macrophages, lymphocytes, plasma cells and eosinophilic elements. In most samples, multiple granulomas were joined by a unique fibrous shell. X-ray microanalysis and atomic absorption revealed the presence of considerable amounts of Al, both within and outside the cells. These results indicate that high amounts of aluminium hydroxide have the potential to produce granuloma formulation.

Administration of endotoxin and aluminium hydroxide adjuvant (0.85 mg) s.c. to Sprague-Dawley rats demonstrated that aluminium hydroxide was able to protect animals from the adverse effects of a 15 μg/kg dose of endotoxin. Shi et al. (2001) suggested that the detoxification of endotoxin by Al-containing adjuvants occurs due to the irreversible binding of endotoxin to the surface of Al. These results suggest that all of the surface aluminium in the aluminium hydroxide adjuvant was able to covalently bind to the phosphate groups of endotoxin, and absorption of endotoxin was subsequently inhibited due to phosphate binding. The pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 were not detected in the serum of animals receiving endotoxin with the aluminium hydroxide adjuvant (Shi et al., 2001).

The comparative irritancy of several aluminium salts was assessed by Lansdown (1973) in three different species. Groups of 5 mice, 3 rabbits and 2 pigs were treated daily for 5 consecutive days with applications of 10 % w/v aluminium chloride, aluminium nitrate, aluminium chlorhydrate, aluminium sulphate, aluminium hydroxide (the pH of the solution was highest at 7.2 among these chemical species of Al tested) or basic aluminium acetate. Twenty-four hr after the final treatment with aluminium hydroxide, signs of erythema, thickening, scaling hyperkeratosis, acanthosis, microabsecesses and the presence of aluminium in keratin were not observed. After single dermal application of aluminium hydroxide (10%) on mouse, rabbit and pig skin no signs of dermal irritation or inflammation were found (Lansdown, 1973).

Inhalation/intratrachael exposure

The fibrogenic potential of very fine metallic aluminium powder was investigated by Gross et al. (1973). Three different types of aluminium powder were tested. Pyro powder and flaked powder were composed of flake-like particles, and the atomized powder consisted of atomized spherical particles. Aluminium oxide dust was used as a negative control. Two chambers, containing 30 rats and 30 hamsters each, were held at dust concentrations of 100 mg/m3 of the pyro powder and the atomized metal powder respectively, two additional chambers were held 50 mg/m3 of the respective powders. Six chambers, each containing 30 rats and 15 guinea pigs, were maintained at dust concentrations of 15 and 30 mg/m3 respectively, for each of the three types of metallic aluminium powders. The animals were exposed for 6 hr daily, 5 days each week, for 6 months for the 50 and 100 mg/m3 groups, and for 12 months for all other animals. An additional group of 30 rats and 30 hamsters was exposed to aluminium oxide dust at an average concentration of 75 mg/m3 for 6 months, and 30 rats and 12 guinea pigs were exposed to aluminium oxide at a concentration of 30 mg/m3 for one year. Intratracheal injection of the aluminium powders at different dose levels was also conducted. Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats. All three species of animals developed alveolar proteinosis, the severity and extent of which were not consistently or clearly related either to the type of aluminium powder or to the severity of the dust exposure. The alveolar proteinosis resolved spontaneously and the accumulated dust deposits cleared rapidly from the lungs after cessation of exposure. Intratracheal injection of large doses of aluminium powders into rats produced focal pulmonary fibrosis; no fibrosis occurred in the lungs of hamsters following intratracheal injection. The results of this experiment indicate that inhalation of fine metallic aluminium powders does not produce fibrogenic effects, and that intratracheal injection of these powders is likely an artefact of the injection itself.

Christie et al. (1963) examined the pulmonary effects of aluminium in rats and hamsters (see also Effects on Laboratory Mammals and In Vitro Test Systems, Irritation, Inhalation Exposure). Inhalation exposure to 100 mg/hr aluminium, in the form of powder, or 92 mg Al/per 2 hr, as a fume, each day for 9-13 months showed a significant retention of aluminium in the lungs of both groups of animals. The aluminium retention in the lungs in rats and hamsters exposed to fume was much greater than when exposed to powder. Following exposure to fresh air, aluminium oxide was cleared rapidly from the lungs of the both powder and fume groups. Weight of wet lung, ash and aluminium oxide content of lungs in exposed animals increased. The initial pulmonary tissue response was proliferation of macrophages within alveolar spaces as well as lipoid pneumonia. The focal aggregates of macrophages were located around the small bronchioles and small pulmonary arterioles; lymphoid hyperplasia was observed. After chronic exposure to aluminium powder, rats showed focal deposits of hyaline in alveolar walls, and focal areas of lipoid pneumonia developed in hamsters.

The pulmonary reaction to inhalation exposure of refractory alumina fibre (Saffil fibres), either as manufactured or in a thermally aged form, was assessed in rats (Pigott et al., 1981). Animals were exposed to the fibres 5 days a week, for a 6 hr period, for a duration of 86 weeks. Pulmonary reaction to both forms of alumina fibre was minimal. Focal necrosis and regeneration of olfactory epithelium was seen in the nasal cavity in 2 Saffil fibre treated animals, and the appearance of aluminium fibres in the mediastinal lymph nodes indicated that fibres and particles may also have been transported via macrophages into the lymphatic system. Benign and malignant pulmonary tumours were confined to the rats in the positive control group which were dosed with asbestos. The results of this study indicate that inhalation of refractory alumina fibres is not associated with an increase in pulmonary or other tumours.

Ess et al. (1993) studied the fibrogenic effect of intratracheal instillation of 7 alumina samples in rats. Five of the samples were used for aluminium production, one sample was a chemical grade form of alumina characterized by small particle diameter and high chemical purity, and the last sample was a laboratory-produced alumina. Quartz was used as a positive control because of its well-known fibrogenic activity. The alumina samples were administered at a total dose of 50 mg by 5 injections given over a period of 2 weeks. Groups of 5 animals were sacrificed at 60, 90, 180, or 360 days after exposure. Histopathological examinations were carried out on all animals and bronchoalveolar lavage was performed to assess inflammatory reactions. Fibrogenic potential was not detected for any of the 5 aluminas used for primary aluminium production, while it was reported that the other 2 samples induced fibrotic lesions. A correlation between cytological and biochemical parameters studied in BALF and the fibrosis determined by histology was not noted for the alumina-treated animals. A persistent inflammatory alveolar reaction was seen in the animals instilled with the alumina samples, which was less severe than the reaction produced by the instillation of quartz. The route of administration needs to be considered in interpreting these results. Intratracheal instillation may have overloaded clearance mechanisms; however this cannot account for differences of intensity between samples which were administered at the same dose.

There are a number of limitations in these studies. First, most studies do not demonstrate a dose-response relationship. Few data are available concerning exposure conditions and the size of the ambient aerosol. Some studies were of relatively short duration compared with the life-span of the animals employed; consequently, although no adverse 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 and whether the time-span of the experiment may have been too short to demonstrate delayed effects.

Several repeated dose toxicity studies have been conducted in order to assess the effects of oral exposure to aluminium hydroxide on clinical signs, food and water consumption, growth, haematology and serum chemistries, tissue and plasma concentrations of aluminium, and histopathology.

In a study conducted by Hicks et al. (1987) there were no treatment-related effects in rats fed up to 288 mg Al/kg b.w./day as aluminium hydroxide in the diet for 28 days.

Berlyne et al. (1972a) investigated the effects of repeated oral, s.c., and i.p. aluminium hydroxide administration in normal and uraemic rats. Groups of nephrectomised rats were administered 1 or 2% AlCl3 or Al2(SO4)3 in the drinking-water or oral Al(OH)3 (150 mg of elemental aluminium/kg/day) by gavage. Groups of non-nephroctomised rats received the same treatments. The duration of the treatment was not indicated. Groups of nephrectomized and normal rats also received i.p. and s.c. injections of Al(OH)3. The clinical signs of intoxication in nephrectomized animals observed following i.p. administration (90 mg/kg b.w.) included periorbital bleeding, lethargy, anorexia and death. Plasma, liver, muscle, heart, brain, and bone levels of aluminium were markedly elevated in the i.p.-treated group. S.c. injection was apparently less toxic, resulting in no mortality, but periorbital bleeding occurred in nephrectomized animals. Aluminium levels were elevated in all tissues, the highest concentration being in the brain. Administration of high doses of aluminium chloride (180 mg/kg b.w.) and aluminium sulphate (300 mg/kg b.w.) in drinking water to nephroectomized rats produced periorbital bleeding and 100% death in treated animals. Periorbital bleeding was noted for the rats which received drinking water supplemented with Al(OH)3. In normal rats only aluminium sulphate produced periorbital bleeding in 3 of 5 rats, but no mortality.

Thurston et al. (1972) examined aluminium deposition in the tissues of rats following dietary aluminium hydroxide exposure in order to assess whether the toxicity of this compound was modified when hypophosphatemia was prevented. Weanling rats (6 per group) were assigned to either a whole meal diet; a whole meal diet with aluminium hydroxide (3.2 g/kg) added; or a whole meal diet with added aluminium hydroxide (3.2 g/kg) plus 10 g/kg disodium hydrogen phosphate. An additional group underwent partial nephrectomy and was assigned to the whole meal diet with added aluminium hydroxide.

The duration of the experiment was 4 weeks; after the treatment the animals were sacrificed, blood samples were taken and a complete post-mortem examination was conducted. Animals in the aluminium hydroxide group exhibited a significant impairment of growth, while animals receiving both aluminium hydroxide and the phosphate supplement showed a normal rate of growth. The adverse effects on growth were more severe in uraemic rats but the pattern was the same for aluminium hydroxide treated and untreated animals. Skeletal aluminium content was raised in the normal animals given aluminium hydroxide or aluminium hydroxide and phosphate; however, the uraemic animals showed the most marked increase in skeletal aluminium levels. These results suggested that some aluminium accumulation is seen following oral exposure but that adverse effects are not exhibited if hypophosphatemia is avoided.

The accumulation of aluminium in bone and various regions of the CNS in rats treated with aluminium hydroxide (100 mg/kg b.w./day) or aluminium citrate (100 mg/kg b.w./day) i.g. for either 4 or 9 weeks (6 times a week) was studied by Slanina et al. (1984). However, a decrease in weight gain was observed after 4 weeks of aluminium hydroxide treatment indicating the presence of subacute adverse effect.

Subchronic oral administration (18 days) of aluminium hydroxide (271.3 μg Al/g diet) resulted in significantly increased tibia weight compared to rats fed aluminium phosphate (272 μg/g), aluminium lactate (262 μg/g), or aluminium palmitate (268 μg/g) (Greger et al., 1985).

Body weight of weanling and adult rats was not affected after repeated oral exposure to high doses of aluminium hydroxide mixed with sucrose in the diet (2000 ppm for 67 days) (Sugawara et al., 1988). Rats were fed test diets that had been supplemented with aluminium hydroxide at levels of 989 and 1070 μg Al/g diet. An additional group of rats was fed a control diet containing 26 μg Al/g. No aluminium-induced anaemia or hypophosphatemia was observed in young or adult rats and serum aluminium did not exceed the normal level. Aluminium concentration in the intestinal tract mucosal membrane increased significantly but no effect on inflammatory infiltration or necrosis was noted in the intestine. Serum and hepatic triglyceride levels and adipose weight were decreased significantly in young rats, but neither serum cholesterol nor phospholipid levels was affected by aluminium ingestion. In the adult group, aluminium hydroxide produced a decrease in only hepatic glycogen content (Sugawara et al., 1988).

The body burden of aluminium in weanling rats fed one of 4 diets for 29 days was assessed by Greger & Powers (1992). Rats were assigned to receive a diet containing 40 μmol Al/g diet with or without citrate, a diet containing 100 μmol Al/g diet with citrate, or a control diet containing 0.39 μmol Al/g diet. Rats were injected with DFO or buffer 24 hr prior to sacrifice. Rats fed Al-supplemented diets accumulated significantly more metal in their tissues than rats fed the basal diet, the accumulation was greatest in the rats fed aluminium with citrate. Haematocrit levels following oral aluminium exposure were inversely correlated to tissue aluminium concentrations. It was expected that DFO might mobilize aluminium from tissues subsequently increasing serum and urinary aluminium levels proportionately to bone aluminium concentrations. However, the changes induced by DFO were small and the elevated serum and urine aluminium concentrations were not more correlated to the body load of Al, as indicated by tibia aluminium concentrations. It was estimated that approximately 0.01 to 0.04% dietary aluminium was absorbed. Aluminium hydroxide added to the diet (0.05%) of rats during the 30 days did not affect vitamin A bioavailability (Favaro et al., 1994). Hicks et al. (1987) found no treatment related effects in rats fed up to 302 mg Al/kg bw as aluminium hydroxide for 28 days.

Oral administration of high doses of aluminium hydroxide (1513, 2697 or 3617 mg/kg) in rats for 30 days did not produce any clinical signs or gross symptoms of intoxication, or any significant differences in body weight and food intake. However, in treated animals, behavioural changes (memory and learning ability disturbances) associated with elevated brain aluminium content were observed (Thorne et al., 1986).

Dlugaszek et al. (2000) examined the effects of long term exposure to aluminium in drinking water, including the distribution of the ingested aluminium and changes in the tissue levels of essential elements. Aluminium was administered in drinking water as aluminium chloride, dihydroxy aluminium sodium carbonate, or aluminium hydroxide. Animals in the Al(OH)3-treated group exhibited an increase in Mg concentration in bones, a decreased Fe concentration in the stomach, and a decline of copper in the kidneys and liver. The group which received AlCl3 exhibited the highest elevation of aluminium in the tissues following oral exposure.

Bilkei-Gorzo (1993) investigated neurotoxic effects following daily oral administration (90 days) of insoluble aluminium hydroxide (300 mg/kg Al(OH)3), water soluble AlCl3 (30 or 100 mg/kg) and chelated aluminium hydroxide (100 mg Al(OH)3/kg + 30 mg citric acid/kg) in rats. The ability to learn (determined by the number of runs necessary to learn the labyrinth) was affected in all aluminium treated groups; the learned performance was altered to a greater extent in the Al(OH)3 and AlCl3 treatment groups. The aluminium content of the brain was elevated in each treatment group; however, the elevation was highest in the groups treated with soluble aluminium compounds. Similarly, all treatments resulted in elevated acetylcholinesterase activity, with significant increases in the AlCl3 group, and in Al(OH)3 chelated to citric acid. No relevant differences in body weights, general conditions, or water and food intake were noted between control and treated groups. These results suggested that, although water-soluble aluminium compounds exhibit greater neurotoxicity, the highly insoluble aluminium hydroxide compound appeared to be absorbed subsequently producing some effect on nervous system functions.

Ecelbarger et al. (1994b) conducted a study to assess the impact of chronic exposure to dietary aluminium on aging rats. Male rats were fed diets containing 0.4 or 36.8 μmol Al/g diet in the form of aluminium hydroxide for 8 months until they reached 23 months of age. One day prior to sacrifice, one-half of the rats in both treatments were i.p. injected with DFO, and the remaining rats were injected with saline in order to investigate the usefulness of DFO for estimating body burden of Al. The rats exhibited little evidence of aluminium toxicity as body weight, feed intake, or changes in the relative size of tissues did not appear to be affected by the treatments.

The possible relation between aluminium intake, levels of aluminium in the brain, and dementia was investigated in rats and dogs following chronic oral aluminium hydroxide exposure (Arieff et al., 1979). Clinical signs of intoxication were not apparent in rats with normal renal function (n=10) or rats with chronic renal failure (n=14) exposed to an oral daily dose of 300 mg aluminium hydroxide, for 5 months. Brain Al3+ was significantly greater than normal for both groups of rats, the most marked increase being in the group with renal failure. The effects of aluminium were also investigated in two groups of mongrel dogs. One group of dogs received a diet which included 3 g of added aluminium hydroxide daily for 5 months, while the other group received the same diet without Al. In the aluminium loaded dogs the content of Al3+ in the cerebral cortex was significantly greater than in that of the controls. Electroencephalograms (EEG) were conducted in the exposed dogs and the results for the aluminium treated dogs were within the normal range. It must be considered that the number of animals in each treatment group was not clearly reported.

A significant increase in tubular phosphate reabsorption with an increase in the apparent velocity of maximal tubular transport was reported in rats following aluminium i.v. administration (Mahieu et al., 1998). Proximal tubule damage was reported in rats (Ebina et al., 1984) and rabbits (Bertholf et al., 1989) following i.v. administration of aluminium. Rats consuming a high aluminium diet (36.8 μmol Al/g diet) for 8 months excreted significantly more protein in urine which is indicative of renal damage (Ecelbarger et al., 1994b).

Studies on the effects of oral administration of aluminium on pregnant animals and their offspring are presented in Effects on Laboratory Mammals and In Vitro Test Systems, Reproductive and Developmental Toxicity.

Repeated s.c. injection of aluminium hydroxide for 5 or 10 months to rabbits and guinea-pigs did not induce any apparent symptoms or visceral alterations. Limited local lesions characterized by the presence of monocytes and macrophages were observed (Levatidi et al., 1968).

S.c. implants of aluminium foil induced subcutaneous tumours in 8 of 18 rats (O’Gara & Brown, 1967). Histologically, the tumours were fibrosarcomas, rhabdomyosarcomas, or combination of these types. One fibrosarcoma had metastasized to the lungs. The significance of aluminium in tumour induction is unknown as the smooth surface of the aluminium implant may be responsible for the induction of the observed lesions.

Mahieu et al. (2000) examined the effects of chronic i.p. administration of aluminium hydroxide on haematological parameters in rats. Male rats received 80 mg/kg body weight aluminium hydroxide three times a week for 6 months. Control rats were injected with saline solution for the same period. Animals in the aluminium treatment group developed a progressive microcyotosis which became more prominent with time. Significant decreases in mean corpuscular haemoglobin and mean corpuscular volume were noted throughout the duration of the experiment. The haematocrit levels were significantly reduced during months 1, 3, or 4 for the treated animals. The haemoglobin levels of aluminium-treated animals decreased in months 3 and 4 and then began to increase in months 5 and 6. These results suggest that chronic i.p. aluminium administration may interfere with different stages of red blood cell synthesis. Persistent exposure appears to trigger a compensating mechanism leading to restored haematocrit and haemoglobin concentrations, with persistence of microcytosis and depressed mean corpuscular haemoglobin levels.

Bazzoni et al. (2005) studied the effect of repeated i.p. injection of aluminium hydroxide on red blood cell parameters in rats. Male rats were injected with 80 mg/kg body weight of aluminium hydroxide 3 times a week, for a duration of 3 months. A control group of rats was injected with saline at the same frequency and volume. Significant decreases in haematocrit and haemoglobin concentrations were noted in the treated rats as compared to controls. The treated animals showed a high quantity of abnormally shaped (stomatocytes) erythrocytes which became more resistant to haemolysis, and the rigidity index was also substantially higher in the aluminium treated rats. It was reported that the observed effects may have been due to aluminium induced alterations in the mechanical properties of red blood cells resulting in disorganization of the erythrocyte membrane. These alterations likely result in a reduction of the viability of the circulating red blood cells which may lead to anaemia in aluminium intoxicated animals.

Effects of chronic parenteral aluminium administration on parameters of renal function, P and Ca movements at the tubular level, and the possible proximal cell mechanisms were studied by Mahieu et al. (1998). Rats were treated with an 80 mg/kg body weight i.p. dose of aluminium hydroxide (three times per week for 6 months). Control rats received saline for the same duration and frequency. Treated rats showed a significant decrease in asymptotic weight gain and in the initial efficiency of food conversion compared to the controls. Treated rats also exhibited a significant decrease in the haemoglobin level, haematocrit index, and serum Fe concentrations in the peripheral blood compared to control rats. The Ca balance in treated rats was significantly less than in the control group and was accompanied by a significant increase in Ca excreted in faeces, correlated with less intestinal absorption. Accumulation of aluminium on the surface of the trabecular bone and a reduction in the skeletal Ca mass (without any changes in the bone Ca resorption rate), were observed in all treated rats; however, there were no differences when expressed as per 100 g body weight. The reduction in bone turnover was accompanied by a lower recovery velocity from calcemia in the aluminium treated group. The fractional reabsorption of P and sodium was significantly lower in treated animals compared to controls. There did not appear to be any significant differences in the acid-base balance nor in the Ca and P concentrations in the plasma between treated and control animals. It was postulated that aluminium exposure interferes with P excretion by decreasing PTH or by diminishing the affinity for PTH receptors at the level of the renal tubule. These results are in agreement with other studies which demonstrated that aluminium is a potent inhibitor of PTH secretion (Morrisey et al., 1983; Morrissey & Slatopolsky, 1986). Smans et al. (2000) reported that aluminium inhibited PTH secretion in vivo, implying potential for lowered Ca release from the bone to blood.

Cointry et al. (2005) examined aluminium effects on the diaphyseal structure and biomechanics of rat bones. After subchronic i.p. injection of 27 mg Al(OH)3 in 20% glycerol/water solution for a duration of 26 weeks, blood aluminium levels were significantly higher in treated rats. A significant difference was observed between tibial aluminium concentrations in control vs. Al-treated rats. A significant delay in femur length growth was noted in treated animals. The volumetric bone mineral density and cortical bone material properties (elastic modules and the stress at the yield point) were significantly reduced in treated animals compared to controls. The bone geometric and structural properties were unaffected by treatment. The serum Ca and P levels were not affected by aluminium treatment. No changes were observed in urine volume (diuresis) and urinary excretion of Ca and Pi. No significant differences were noted in the body weights of treated and control groups at the end of the study (Cointry et al., 2005).

An aluminium-induced inhibition of bone mineralization (Cointry et al., 2005) is consistent with other studies showing similar aluminium effects on bone mineralization in vitro and in vivo (Ballanti et al., 1989; Bellows et al., 1995; Blumenthal & Posner, 1984; Chan et al., 1987; Mjoberg et al., 1997; Posner & Blumenthal, 1985). Potential mechanisms proposed include; changes in the biosynthesis of collagen, increased collagen cross-links, altered osteocalcin levels (Blahos et al., 1991; Chan et al., 1987; Mjoberg et al., 1997), and physicochemical dissolution of mineral crystals (Bushinsky et al., 1995). Different combinations of these effects were described as aplastic bone disease (Ballanti et al., 1989; Malluche, 2002) and osteomalacia (Galceran et al., 1987; Lieuallen & Weisbrode, 1991; Malluche, 2002; Mjoberg et al., 1997; Quarles et al., 1985). Chronic oral or parenteral aluminium hydroxide administration was found to produce aluminium accumulation in bone and on the bone surface accompanied by a decrease of P and Zn concentrations in tibias (Berlyne et al., 1972a; Ecelbarger et al., 1994b; Greger et al., 1985; Greger & Donnabauer, 1986; Greger & Powers, 1992; Mahieu et al., 1998; Thurston et al., 1972).

Fiejka et al. (1996) conducted a study to determine the compartmentalization of aluminium in mice following i.p. injection of aluminium hydroxide. One group of mice (n=30) received aluminium hydroxide containing 1 mg of elemental aluminium every two weeks; another group (n=30) received an injection of aluminium hydroxide which contained 0.1 mg elemental aluminium 5 days a week. Controls were treated with saline. Ten animals from each group were sacrificed 48 hr after a cumulative dose of 2, 4 or 6 mg of elemental Al. In the liver the development of aluminium containing granulomas represented by swollen macrophages and multinucleated giant cells were observed; the number of granulomas increased with the aluminium dose. These results suggest that the physiochemical nature of the Al(OH)3 is an important factor in the development of this type of foreign-body response (Fiejka et al., 1996).

Histochemical and immunochemical studies were carried out after repeated intracerebroventricular aluminium injections (5.4 or 0.68 μg/day for 5 days) in the adult rat brain in animals allowed to survive for a period of either 1 or 6 weeks. Platt et al. (2001) demonstrated that aluminium concentrated in the white matter of the medial striatum, corpus callosum, and singulate bundle. Inflammatory responses and damage in the singulate bundle was noted in Al-treated animals which led to a severe anterograde degeneration of cholinergic terminals in the cortex and hippocampus. These findings suggested that the enhancement of inflammation and interference with cholinergic signalling may be the modes of action through which aluminium results in learning and memory deficits in mammals (Platt et al., 2001).

The injection of 0.3 ml of a 1% suspension of aluminium (metallic) powder into the CSF (cisterna magna) of adult rabbits induced a slowly progressing encephalopathy characterized by alterations of posture, myoclonic jerks and muscle weakness (Bugiani & Ghetti, 1982). The presence of neurons with neurofibrillary degeneration (NFD) and proximal axon swelling was observed between 1 and 81 days after injection. In some animals, large axons with thin or no myelin sheath were also observed. In treated animals pathological changes in the peripheral nerves and muscles were also found. The neuropathological investigation confirmed that the vulnerability of the brain to aluminium is a time-related event. Within the observed time interval (1-81 days), NFD developed in every nuclear complex of the CNS other than the striatum and the amygdala. The factors regulating the time related degeneration of adult rabbit neurons resulting from exposure to aluminium were not clarified by this study. No relation was found between the chronology or the topography of the NFD and the size of the cell bodies, the site of the injection, and the distance from the subarachnoid space and the ventricles (Bugiani & Ghetti, 1982). These data are consistent with other studies which have demonstrated that aluminium salts induce an encephalopathy with NFD after subarachnoid injection in receptive animals (rabbits, cat, ferret) (Crapper et al., 1973; Klatzo et al., 1965; Wisniewski & Kozlowski, 1982). Although the mechanism by which aluminium induces the accumulation of neurofilaments is unknown, it has been demonstrated that these neurofilaments are morphologically identical to filaments that accumulate following the administration of tubulin-binding agents. These compounds bind to tubulin, induce a disruption of microtubules (Ghetti & Ohcs, 1978; Remillard et al., 1975) that is followed by the accumulation of filaments in the cell pericarion, in dendrites and proximal axonal segments.

Developmental toxicity

It is noteworthy that the reproductive consequences of aluminium occur only at excessively high non-environmentally amounts. The high amount of aluminium plays a key role in chemical-induced alterations in reproductive function and consequent mammalian development. Various investigators have demonstrated an adverse effect on reproductive capacity due to the chemical species of aluminium ingested (Domingo, 1995; Golub & Domingo, 1996). Embryotoxic and adverse developmental effects were found in rats and mice following administration of aluminium nitrate (Albina et al., 2000; Paternain et al., 1988), aluminium chloride (Colomina et al., 1999; Cranmer et al., 1986; Misawa & Shigeta, 1993) or aluminium lactate (Golub et al., 1987; Gonda et al., 1996; Poulos et al., 1996), although these effects may be directly related to aluminium exposure or the result of a secondary consequence (e.g., maternal toxicity, systemic toxicity). These forms of aluminium are water soluble, and are therefore absorbed to a greater extent than non-soluble aluminium forms, such as Al(OH)3 (Colomina et al., 1994; Domingo, 1995).

The embryotoxic and teratogenic potential of Al(OH)3 administered orally to pregnant mice was investigated by Domingo et al. (1989). Mated female mice were administered 0, 66.5, 133 or 266 mg/kg b.w. of Al(OH)3 daily from gestation days 6 through 15. No signs of maternal toxicity were observed in any group as evidenced by changes in maternal weight gain or gross signs of abnormalities. The number of implantations, number of resorptions, number of live and dead foetuses, and body weights of foetuses were not significantly affected by any dose of aluminium hydroxide administered. The foetuses of Al-treated dams did not exhibit any significant differences in the number and type of external malformations, internal soft-tissue defects or skeletal abnormalities as compared to controls. Domingo et al. (1989) proposed that the lack of any apparent demonstrated embryo/foetal toxicity of Al(OH)3 in mice was likely due to the low GI absorption of this compound as compared to other forms of aluminium. A similar study was also conducted by Gómez et al. (1990). Higher doses of Al(OH)3 were used in order to evaluate the potential of Al(OH)3 to induce adverse developmental effects in rats. Al(OH)3 was administered by gavage at dose levels of 0, 192, 384, and 768 mg/kg b.w./day to pregnant rats from day 6 through 15 of gestation. No significant maternal or developmental toxicity was observed at any Al(OH)3 dose level administered.

Although based on the studies by Domingo et al. (1989) and Gómez et al. (1990) Al(OH)3 alone did not produce adverse reproductive effects, other studies showed that concurrent ingestion of Al(OH)3 with other dietary constituents such as ascorbic acid results in an increase in the GI absorption of aluminium (Colomina et al., 1994; Domingo et al., 1991b) (see also Toxicokinetics, Absorption, Animal Studies, Oral Administration, Factors Influencing Oral Aluminium Absorption). Gómez et al. (1991) assessed in rats the influence of citric acid on the embryonic and/or teratogenic effects potentially induced by high doses of Al(OH)3. Three groups of pregnant rats were administered daily doses of Al(OH)3 (384 mg/kg b.w.), aluminium citrate (1064 mg/kg b.w.), or Al(OH)3 (384 mg/kg b.w.) concurrently with citric acid (62 mg/kg b.w.) on gestational days 6-15. A fourth group received distilled water and served as a control group (n=17). Maternal and foetal body weights were significantly reduced in the group treated with Al(OH)3 and citric acid. There were no significant treatment-related differences on pre- or post-implantation sites, number of live foetuses per litter, or gender ratio. Although no significant differences in the number of malformations were detected between any of the groups (data not shown), delayed sternabrae and occipital ossification was observed in the foetuses treated with Al(OH)3 and citric acid as compared to the control group (p < 0.05).

The potential influence of lactate on developmental toxicity attributed to high doses of Al(OH)3 was also evaluated in mice (Colomina et al., 1992). Oral daily doses of Al(OH)3 (166 mg/kg b.w.), aluminium lactate (627 mg/kg b), or Al(OH)3 (166 mg/kg b.w.) concurrent with lactic acid (570 mg/kg b.w.) were administered to pregnant mice from gestational day 6 to15. An additional group of mice received lactic acid alone (570 mg/kg b.w.). A control group received distilled water during the same period. Concurrent administration of Al(OH)3 with lactic acid resulted in significant reductions in maternal weight compared to the control group of mice who received distilled water without the addition of aluminium lactate or lactic acid. In the group given lactate only, a quantitative rise in the concentration of aluminium was detected in whole foetuses; however this was not statistically different from the mean levels found in the control group. Aluminium lactate administration resulted in significant decreases in foetal body weight accompanied by increases in the incidence of cleft palate and delayed ossification. Although not statistically significant, the incidence of skeletal variations was higher in the concurrent Al(OH)3 and lactic acid group compared to the control group. No other signs of developmental toxicity were detected in this group.

In a similar experiment, Colomina et al. (1994) assessed the concurrent ingestion of high doses of Al(OH)3 and ascorbic acid on maternal and developmental toxicity in mice. Three groups of pregnant mice were given daily doses of Al(OH)3 (300 mg/kg b.w.), ascorbic acid (85 mg/kg b.w.), or Al(OH)3 concurrent with ascorbic acid (85 mg/kg b.w.) from gestational day 6 to 15. A fourth group of animals received distilled water and served as the control group. No embryotoxic or foetotoxic effects were detected in any group. Gross, internal, or skeletal malformations did not vary according to treatment group. The number of resorptions, dead and live foetuses, percent implantation loss, and foetal body weight did not differ between among the control and treated groups (Colomina et al., 1994). Placenta and kidney concentrations of aluminium were significantly higher in mice receiving Al(OH)3 and Al(OH)3 plus ascorbic acid compared to controls. In contrast, Gómez et al. (1990) found no significant differences in placental concentrations of aluminium in rats administered higher doses of Al(OH)3 alone.

Competition between aluminium and other essential trace elements was proposed as one of the possible mechanisms to explain adverse reproductive outcomes related to aluminium toxicity including delayed ossification, foetal malformations and reduced weight gain (Bellés et al., 2001). Bellés et al. (2001) examined in rats the effect of oral Al(OH)3 on the accumulation and urinary excretion of Ca, Mg, Mn, Cu, Zn and Fe. Three groups of rats were given either 0, 200 or 400mg/kg b.w./day Al(OH)3 from gestational day 1 to 20. Three groups of non-pregnant female rats also received the same doses of Al(OH)3 for 20 consecutive days. Urinary concentrations, as well as samples of liver, bone, spleen, kidney and brain removed post-sacrifice, were analyzed for Al concentrations, as well as levels of Ca, Mg, Zn, Cu, and Fe. Treatment with oral doses of Al(OH)3 did not produce any overt signs of toxicity in pregnant or non-pregnant rats; however, there were differences in the pattern of metal tissue distribution. In pregnant rats, the highest aluminium concentration was found in kidneys while, in non-pregnant animals, the brain had the highest level of aluminium. In the non-pregnant control group, the highest tissue accumulation of aluminium was also in brain. The hepatic and renal concentrations of several essential elements, as well as the levels of calcium in bone and copper in brain, were significantly higher (p < 0.05) in the treatment groups as compared to the control group for the pregnant rats. In contrast, fewer differences between hepatic, renal and bone concentrations of the elements examined were found between the treatment and control groups of the non-pregnant animals. These results suggest that pregnancy may be a period of enhanced susceptibility for aluminium accumulation and subsequent toxic outcome.

Donald et al. (1989) and Golub et al. (1991) evaluated developmental neurobehavioural toxicity. Donald et al. (1989) conducted a study which demonstrated that elevated dietary exposure of mouse dams to aluminium during gestation and lactation resulted in persistent neurological defects during the post weaning period in offspring. Pregnant mice were assigned to receive a diet containing 25, 500, or 1000 μg aluminium lactate/g diet. The experimental diet commenced on day 0 of gestation and continued throughout pregnancy and lactation. Four pups from each litter were selected for further neurobehavioural assessment after weaning. These pups were fed a control diet containing 25 μg aluminium lactate/g. Neither maternal nor reproductive toxicity was detected. Neurobehavioural maturation of the pups was tested on days 8 through 18 with the Wahlsten test battery which included: forelimb and hindlimb grasps, fore- and hindpaw placement on sticks of two widths, vibrissae placing, visual placing, auditory and air puff startle, eye opening, screen grasp, screen cling, and screen climb. The only difference among the aluminium groups in terms of pup toxicity prior to weaning was poor performance in a climbing test in the 1000 μg Al/g diet group. Several significant differences in neurological signs were exhibited between weanlings whose dams were fed control or high aluminium diets; some of these manifestations persisted after a 2 week recovery period from the diet. Foot splay, forelimb and hindlimb grip strengths, and thermal sensitivity (tail removal latency) were associated with higher maternal dietary aluminium levels. These results suggested that maternal dietary exposure to excess aluminium during gestation and lactation resulted in neurobehavioural toxicity in weanling mice even in the absence of maternal toxicity.

In a similar experiment, Golub et al. (1991) fed pregnant mice a diet of either 25 (control) or 1000 (high) μg aluminium lactate/g from conception through lactation. Litters were fostered either within or between groups at birth to create the following 4 groups related to the aluminium concentration of the maternal diet: (1) control during gestation and lactation, (2) high aluminium during gestation, control during lactation, (3) control during gestation, high aluminium during lactation, (4) high aluminium during both gestation and lactation. Forelimb grasp strength was influenced by high aluminium exposure during gestation, negative geotaxis was influenced by exposure during lactation, and hindlimb grasp and temperature sensitivity were affected by exposure during both gestation and lactation. Although aluminium exposure during gestation or lactation did not influence brain and liver aluminium concentrations, exposure during lactation resulted in significantly lower manganese and iron concentrations in the liver, and significantly less manganese concentrations in the brain of the pups at weaning. These results demonstrated that high maternal dietary aluminium intake, during both gestation and lactation, might result in neurodevelopmental adverse effects and altered essential trace element metabolism in offspring.

It has been suggested that maternal stress during pregnancy could enhance aluminium-induced developmental toxicity in mouse and rat offspring (Colomina et al., 1998; 1999; 2005; Roig et al., 2006). Colomina et al. (1998) administered i.p. injections of AlCl3 at 37.5 and 75 mg/kg/day to two groups of pregnant mice on days 6-15 of gestation who were also subjected to restraint for 2 hours/day. AlCl3 was also administered at the same frequency and doses to two groups of mice who were not restrained. Foetal weight was significantly lower (p < 0.05) in the groups whose dams were concurrently exposed to aluminium (37.5mg/kg and 75mg/kg) plus restraint, and in the group exposed to 75 mg/kg without restraint, as compared to those in the group subjected to restraint only. A significant increase (p < 0.05) in the number of litters with skeletal anomalies, as well as the total number of litters with internal and skeletal defects, was observed in the group exposed to 75 mg AlCl3/kg/day plus maternal restraint as compared to any of the other groups.

In a more recent study, Colomina et al. (2005) did not detect a significant influence of maternal restraint on the postnatal developmental and behavioural effects in the offspring of rats exposed parentally to aluminium nitrate nonahydrate in drinking water. In this study, female rats were exposed to 0 (control group), 50, or 100 mg/kg/day of aluminium (as aluminium nitrate nonahydrate) in drinking water with citric acid (355 or 710 mg/kg/day) for a duration of 15 days. The female rats were then mated with untreated males and aluminium exposure was maintained throughout the gestational, lactational, and post-weaning periods. Half of the animals in each group were restrained for 2 hours/day on days 6-20 of gestation. No significant differences were noted in the activity of the offspring (postnatal day 30) measured in an open field test between animals with prenatal aluminium exposure, alone or plus restraint, as compared to the control group. Rats exposed to 100 mg/kg/day all through their life following prenatal restraint stress showed improved performance in a passive avoidance task. A significantly improved performance in a water maze test was also noted for rats exposed to 50mg/kg/day of aluminium as compared to the non-aluminium exposed groups. Maternal restraint did not appear to affect the water maze performance for rats also exposed to aluminium.

Roig et al. (2006) investigated the long-lasting neurobehavioural effects of prenatal restraint stress and oral aluminium exposure in rats. Pregnant females were orally exposed to 0, 50, and 100 mg/kg/day of Al. Each Al exposed group was divided into two subgroups, one of these groups was subjected to restraint stress for 2 hours/day on gestation days 6-20. The offspring of the treated females received the same Al treatment until the time of sacrifice at 1 or 2 years of age. An open field test and a water maze test were conducted to assess behavioural performance of the offspring one or two years after birth. Prenatal restraint did not appear to modify behavioural performance in the rats. In addition, brain aluminium accumulation was significantly higher (p < 0.05) in rats exposed to 100mg/kg/day aluminium, without prenatal restraint, in all brain structures analyzed (cortex: 31.7 ug/g, olfactory bulb: 28.1 ug/g, cerebellum: 36.3 ug/g, striatum: 51.1 ug/g, hippocampus: 79.7 ug/g, and brain stem: 26.7 ug/g), as compared to rats who experienced prenatal restraint and were exposed to the same dose of aluminium (cortex: 0.8 ug/g, olfactory bulb: 9.1 ug/g, cerebellum: 2.6 ug/g, striatum: 7.1 ug/g, hippocampus: 4.2 ug/g, and brain stem: 3.1 ug/g). Therefore, prenatal restraint stress appeared to prevent aluminium accumulation.

Until the actual delivered dose to the foetus, the suckling pup, and to the target organs is well characterized, any determination of a vulnerable window of effect or comparison of animal to human data will remain limited.

Reproductive toxicity

To our knowledge no studies have been conducted to assess the reproductive toxicity of Al(OH)3 or Al2O3 in male mice; however, adverse reproductive effects were documented following i.p. injections of aluminium nitrate to male mice. Llobet et al. (1995) administered i.p. aluminium nitrate injections to adult male mice at doses of 0, 50, 100 or 200 mg/kg b.w./day for 4 weeks before mating with untreated females. The pregnancy rate was significantly reduced for the 100 and 200 mg/kg b.w./day dose groups compared to controls. Testicular and epididymal sperm counts were significantly decreased in the group administered 200 mg/kg b.w./day aluminium nitrate and the count of spermatids was significantly reduced at 100 mg/kg b.w./day. In the 100 and 200 mg/kg b.w./day groups histological changes, including necrosis of spermatocytes/spermatids, were noted in 5 and 6 mice, respectively. Histological lesions were not detected in the control mice or in the group that received 50 mg/kg b.w./day aluminium nitrate.

In another study, focal necrosis of the testes and destruction of spermatozoa was observed following a single intratesticular injection on 4.3 mg Al/kg (as aluminium sulphate) to rats (Kamboj & Kar, 1964). A proliferation of interstitial cells and a reduction in the number and motility of spermatozoa was observed following chronic exposure (6 months) of an oral dose of 2.5 mg/kg (as aluminium chloride) in rats (Krasovskii et al., 1979).

Albina et al. (2000) conducted a study to determine if a chelating agent, deferiprone, could protect against aluminium-induced maternal and developmental toxicity in mice. Pregnant mice were randomly divided into 5 groups. One group was administered 1,327 mg/kg b.w. of aluminium nitrate nonahydrate by gavage on gestation day 12, a second group was given 24 mg/kg b.w./day of deferiprone on days 12-15 of gestation, and a third group was given 1,327 mg/kg b.w. of aluminium nitrate nonahydrate on gestation day 12 followed by deferiprone (24 mg/kg b.w. at 2, 24, 48 and 72 hr following aluminium exposure. The controls received sodium nitrate or deionised water. Administration of deferiprone alone did not produce any apparent signs of developmental toxicity. Aluminium-induced maternal toxicity included significant reductions in body weight gain, absolute liver weight and food consumption compared to controls. Administration of deferiprone did not offer protection against these aluminium induced maternal effects. In contrast, deferiprone administration following aluminium exposure resulted in a more pronounced decrease in maternal weight gain and corrected body weight change. Developmental toxicity was manifested by delayed ossification of a number of bones in the aluminium treated groups compared to controls. The group treated with aluminium nitrate and deferiprone exhibited a higher number of litters with foetuses showing skeletal deficiencies. These results suggested that deferiprone is not an effective agent to protect against aluminium-induced developmental toxicity and might increase the severity of aluminium-induced maternal and developmental adverse effects in mice.

Silicon-containing compounds were shown to limit absorption of ingested aluminium (Edwardson et al., 1993). Therefore, it was proposed as exerting a protective effect against aluminium-induced toxicity (see also Toxicokinetics, Absorption, Animal Studies, Oral Administration, Factors Influencing Oral Aluminium Absorption, Silicon-Containing Compounds). Bellés et al. (1999) conducted a study to test this hypothesis. Aluminium nitrate monohydrate was administered to three groups of pregnant mice by gavage (398 mg/kg b.w./day) on gestation days 6-15. These animals received silicon in drinking water at concentrations of 0, 118 or 236 g/L on days 7-18 of gestation. Three additional groups of pregnant mice received 270.6 mg/kg of sodium nitrate and the same concentrations of silicon in drinking water as the aluminium-treated groups. The percentage of aluminium-induced deaths, abortions and early deliveries was significantly reduced in the group administered 236 mg/L silicon. However, no significant differences were noted at 118 or 236 mg/L silicon on aluminium induced foetotoxicity.

The scientific literature is replete with reports linking (or dissociating) various chemical forms of aluminium with neurotoxicity and neurodegeneration. Interested readers can gain a grasp of the literature and the differing views as to the potential mechanisms of aluminium toxicity, through a number of existing reviews and hypotheses papers (Atchison, 2003; Becaria et al., 2002; Campbell, 2002; 2004; Campbell & Bondy, 2000; Domingo, 1996; Elmore et al., 2003; Emmett, 2004; Exley, 1999; 2005; Flaten, 2001; Gupta et al., 2005; Kagan et al., 2002; Kumar, 1999; Oteiza et al., 2004; Priest, 2004; Rao et al., 1998; Reinke et al., 2003; Rob et al., 2001; Shin et al., 1995; Savory et al., 2003; Sim & Benke, 2003; Solfrizzi et al., 2003; Soni et al., 2001; Szutowicz, 2001; Tanaka, 2004; Van Landegham et al., 1998; Yokel, 2000). Here, we will focus on some of the literature from the last 10 years that addresses the potential for aluminium to cause neurotoxicity and/or provides insight into the mechanisms of toxicity.

In examining the literature on in vivo studies, it is useful to consider several factors in determining whether a given study may provide significant insight. For studies in animals, the over-riding considerations are dose, mode of administration, speciation of the metal, and measures of outcome. Human Exposure, Total Human Uptake from All Environmental Pathways (Combined Exposure) summarizes the most common sources of human exposure to aluminium. For the majority of individuals, these various sources of exposure result serum concentrations of 1-2 μg of aluminium per Litre of plasma. It is notable that daily doses can be much higher in individuals who use aluminium-based antacids (Lione, 1983). Typically, toxicological studies in rodents utilize doses that are 10-20 times the anticipated human dose. This calculation is based on increased metabolic rates for rodents and is meant to account for differences in the metabolism of the toxin. Therefore, one potential approach to relate experimental studies in rodents, which are most commonly used, to humans is to assume that studies in rodents that achieve serum levels of >10-20 μg/L would mimic normal environmental exposure levels of humans. Studies that achieve higher concentrations of aluminium in serum could be viewed as challenging the animal to determine the toxic potential of the metal.

Investigators have used a variety of routes of exposure, including oral, i.v. injection, and i.p. injection. A variety of aluminium salts have been used in these studies. As discussed in Toxicokinetics, soluble aluminium salts that are introduced into the body are subject to re-speciation with most aluminium in serum being bound to Tf, a minority found as aluminium citrate, and smaller amounts bound to other molecules. Aluminium citrate is usually excreted by the kidney rather quickly, and thus one could expect that Tf would be the major carrier of aluminium into the brain. In CSF, which has higher concentrations of citrate, aluminium dissociates from Tf with the majority bound to citrate. In studies where soluble aluminium salts have been given orally or by injection (i.p. or i.v.), the most likely species of aluminium in brain would be bound to Tf and citrate. In studies where aluminium has been injected directly into the brain there would be also be re-speciation but there would be opportunity for exposure to novel aluminium salts. For the purposes of review, studies involving oral and i.p, or i.v., injection methods of exposure are probably most informative regarding potential effects in humans. Studies in which aluminium salts have been injected directly into the brain have a greater probability of producing non-physiologic effects.

Studies in both cell culture models and in vivo have clearly established the potential for aluminium to cause significant neurotoxicity. Likewise, well documented cases of encephalopathy associated with long-term dialysis establish a connection between aluminium and neurotoxicity in humans. One of the first proposed consequences of aluminium exposure in humans was an elevated risk of developing AD. AD is defined by both clinical and pathologic symptoms. Clinically, the symptoms include loss of cognitive ability, psychiatric symptoms, and emotional changes, progressing to profound motor dysfunction and death. Pathologically, AD is defined by the presence of senile plaques, composed of fibrillar extracellular deposits of amyloid β peptide, and NFTs, composed of fibrillar intracellular accumulations of hyperphosphorylated tau protein. Several disorders can produce clinical symptoms that overlap with, or duplicate, the clinical symptoms of AD, including frontotemporal dementia and vascular dementia.

The scientific literature contains numerous reviews that discuss the extant literature regarding AD and aluminium exposure. The initial lines of evidence linking AD to aluminium exposure were numerous reports of elevated levels of aluminium in the brains of AD patients and an association of aluminium with disease-specific lesions (amyloid senile plaques and NFTs). However, subsequent studies utilizing more sophisticated technology demonstrated that aluminium levels are not particularly elevated in the brains of AD patients, and aluminium is not disproportionately distributed to senile plaques or NFT (Lovell et al. 1993; Xu et al., 1992c) (see Tables 19-​21). A well controlled study by Makjanic et al. (1998), demonstrated that the detection of aluminium in tissues from AD patients may partially result from methods of tissue preparation as measures of aluminium in frozen-untreated tissue preparations failed to detect aluminium (<20 ppm) (Makjanic et al., 1998). Studies of a very limited number of autopsied brains suggested that aluminium may preferentially accumulate in lipofuscin granules (Tokutake et al., 1995), which are a common pathology in the aged, and thought to represent remnants of lysosomes that contain undigestable-material.

In regard to animal studies designed to directly test the potential role of aluminium in the development of AD-related pathologies, Pratico et al. (2002) utilized a transgenic mouse model of Alzheimer amyloid pathology. Animals were fed diets enriched in aluminium (dose and chemical form not clarified in the publication) to determine whether aluminium induced changes in the rate or severity of amyloid deposition in this model. The authors reported significant increases (~ 2-fold) in brain loads of soluble and insoluble amyloid peptide and in the levels of isoprostane 8,12-iso-iPF2α-VI, which was examined as a marker of lipid peroxidation. Huang et al. (1997) also reported increases in the expression of the precursor to amyloid peptide, termed amyloid precursor protein (APP), in cervical spinal cords of rabbits given intracisternal injections of aluminium maltolate (2.5 mmole). Intracellular accumulations of APP immunostaining in neurons of the medulla have also been reported by Zhang et al. (2004), who described increased numbers of neurons immunoreactive for APP in the cortex and hippocampus of rats given aluminium chloride in drinking water (3 mg/mL) for 90 days (Zhang et al., 2003). Together, these data suggest that aluminium may modulate the expression and, or, processing of APP. If a life-time of constant exposure results in sustained elevations in APP expression or production of amyloid peptide, then increases in amyloid peptide could accelerate the rate of senile plaque formation and hasten the onset of AD (Jankowsky et al., 2004).

In a study in which rats were given large doses of aluminium sulphate by oral gavage, El-Rahman (2003) reported histological changes that resemble those found in AD patients. Animals were given daily doses of aluminium ranging from 4.59 to 17 mg/100 g b.w./day for 35 days. The brains of animals receiving the highest doses were reported to have developed both classic amyloid deposits and NFTs in the cortex. The report, however, did not quantify the prevalence of either pathology and relied on histological stains, rather than antibody immunostaining, to define pathology. The highest dose in this study would equate to a daily exposure for humans of 170 mg/kg b.w./day. Unfortunately, serum levels of aluminium were not reported, making if more difficult to assess exposure to tissue. Although this dose is far and above normal exposure levels, humans who take aluminium-containing antacids may be exposed to between 15 and 50 mg/kg b.w./day (Lione, 1983). Therefore the dose used in this study was within the 10 to 20-fold excess that is routinely used in rodent toxicological studies. If replicated, and examined with more precise methods, this study could be construed as evidence that very high exposure to aluminium could lead to AD-related pathologic changes in the brain.

Another potential mechanistic connection between aluminium and AD comes from work of Silva et al. (2002) who examined cholesterol levels in the brains of rats fed high doses of aluminium (1 g per day for 10 days or 0.03 g per day for 4 months). Under both conditions, there were significant and robust changes in the ratio of cholesterol to total phospholipids. There were also robust diminutions in membrane fluidity, attributed to the loss of cholesterol. Recent studies from a number of laboratories (Refolo et al., 2000; Smith et al., 2001) demonstrated that the proteolytic generation of amyloid peptide (the principal component of senile plaques in AD patients) is elevated by hypercholesterolemia. The findings by Silva noted above would suggest that aluminium exposure might indirectly reduce amyloid production. However, such beneficial effects could be offset by the reported ability of aluminium to increase the rate at which amyloid peptides (Kawahara et al., 1994; 2001; Mantyh et al., 1993), and other pathogenic proteins such as α-synuclein (Uversky et al., 2001), to assemble into more stable and pathologic fibrillar structures. Additionally, regardless of whether there is a direct action of aluminium on CNS membranes or an indirect metabolic consequence of aluminium exposure, changes in membrane fluidity and cholesterol content could account for the numerous reports of deleterious effects of aluminium on neurotransmitter systems and synaptic function (Csoti et al., 2001; Dave et al., 2002; El-Rahman, 2003; Nayak & Chatterjee, 2001; Wang et al., 2002; Zatta, 1997; Zhang et al., 2004).

The most convincing data to dissociate AD from aluminium exposure are detailed histological analyses of patients who have undergone long-term haemodialysis and succumbed to encephalopathy. To control serum phosphorus levels, patients take high doses of hydroxyl-aluminium gel over long periods, leading to elevated levels of aluminium in many tissues at autopsy. The brains of these patients have characteristic accumulations of aluminium in sub-cellular compartments of both neurons and glia (Reusche et al., 2001a). Morphologically, these structures are most commonly ovid in nature, intracellular, and appear to be lysosome-derived. In rare cases, where pathologic changes that meet criteria for diagnosis of AD in patients with dialysis-encephalopathy (one case out of 127 analyzed), the pathology associated with each disorder remains morphologically distinct (Reusche, 1997). Importantly, in the study by Reusche et al. (2001a), there was no association between AD-like pathology and long-term ingestion of aluminium. The most informative group of patients included 10 who received high doses of aluminium (> 500 g total intake over at least 5 years), for whom the frequency of AD-related pathology was no greater than controls. Moreover, in patients over 60 years of age the degree of AD-related pathology (subclinical levels) in dialysis patients was similar to that in controls. Collectively, these studies in humans support the view that exposure to aluminium poses no direct risk for development of AD. However, caution in over-stating the importance of the data from DAE patients is warranted given the rather small number of highly definitive cases. The animal studies cited above suggest that a life-time of exposure to low doses of aluminium, or exposure to a single-high-dose, might pose a risk for developing AD or contribute to the aetiology of a subset of cases.

It has been known since 1965 that the rabbit is uniquely vulnerable to aluminium toxicity and produces both clinical and pathologic features of motor neuron disease (Klatzo et al., 1965). Intracisternal (directly into CSF) injection of aluminium salts (chloride, phosphate, maltolate) can be used to cause both acute and chronic neurotoxicity. Single high doses of aluminium (1 mg) cause rapidly progressing motor neuron dysfunction with hindlimb paralysis, whereas repeated low dose injections (100 μg) can induce a chronic motor dysfunction (for review see Savory et al., 2001). Detailed neuropathological studies of the chronic rabbit model have defined the similarities and differences between aluminium intoxication in the rabbit and human disease. First and foremost, aluminium intoxication in the rabbit is reversible. Symptoms and pathology associated with chronic low dose aluminium intoxication can be ameliorated if aluminium exposure is reduced at the first signs of symptoms. In humans, motor neuron disease is progressive and almost uniformly fatal. Pathologically, the major resemblance between aluminium intoxication in the rabbit and human disease is the appearance of intracellular inclusions in motor neurons of the spine and brain stem. These inclusions are formed by filamentous aggregations of neurofilament protein (He & Strong, 2000a; Wakayama et al., 1996). Absent from the rabbit model are significant numbers of inclusions that are immunoreactive with cystatin C, ubiquitin, and tau (Wakayama et al., 1996). Also conspicuously absent is evidence of astrocytic gliosis and activation of microglia, both of which are hallmarks of human ALS (He & Strong, 2000a; 2000b; Wakayama et al., 1996). In a chronic aluminium intoxication model, Ghribi et al. (2002) found evidence of caspase-3 activation, an important step in programmed cell death; however, others failed to detect the definitive marker of apoptosis, DNA fragmentation (He & Strong, 2000a), despite ~50% losses in the numbers of lumbar spinal motor neurons. Relevant to AD, Muma & Singer (1996) reported alterations in tau protein phosphorylation and accumulation, the principal component of NFT pathology of AD, in the spinal motor neurons of rabbits chronically given moderate intracisternal doses of aluminium (~ 200 μg of elemental aluminium). Notably, DAE patients do not show increased levels of neurofibrillary pathology (see below).

Neuropathology

The pathology of DAE patients provides insight into potential mechanisms of aluminium neurotoxicity and its transport into the nervous system. As discussed above, Reusche et al. (1997) noted an abundance of intracellular argentophyllic (silver binding) granules in the brains of DAE patients, which are most commonly ovid, intracellular, and lysosomal in appearance. LAMMA revealed high concentrations of aluminium in the cytoplasm of cells exhibiting these structures. One of the major carriers of aluminium in the serum and interstitial fluids is Tf (see Toxicokinetics, Distribution (Including Compartmentalization), Human Studies, Transport in Blood). At physiological pH, aluminium in serum is bound to transferrrin, although less tightly than Fe would be bound. In CSF, higher concentrations of citrate result in significant re-speciation to aluminium citrate (Yokel, 2001). Uptake of Tf by neural cells involves receptor-mediated endocytosis via the Tf receptor. Indeed, in the CNS, Tf-mediated uptake has recently been used as a molecular means of introducing novel compounds or proteins into the brain. Importantly, receptor-mediated endocytosis would be expected to deliver material to the endosomal and then lysosomal compartments. Hence, in DAE patient, the subcellular distribution of aluminium in neural cells (neurons and cells of the choroid plexus) is consistent with a mode of exposure that involves Tf-mediated delivery to the nervous system. The extent to which aluminium citrate is taken up by neural cells is unclear.

Rodent models of aluminium toxicity by direct injection

To bypass limitations of absorption, some investigators have directly i.p. injected aluminium-salts. Esparza et al. (2003) injected rats with aluminium lactate at concentrations of 5 mg/kg/day and 10 mg/kg/day for 8 weeks (5 injections per week) and then assessed markers of oxidative stress and cognitive function (see below). The estimated exposure would be >1000 times normal. Levels of aluminium in cortex, hippocampus, cerebellum and liver were measured, with only cerebellum and liver showing significant accumulations of aluminium. Levels of aluminium in serum were not reported. Significant reductions in the levels of manganese and copper were found in brain, with no change in Fe in any organ. In this model, the hippocampus showed the largest number of changes indicative of oxidative stress, including increased GSH, increased measures of lipid peroxidation (thiobarbituric acid reactive substances (TBARS)), increased levels of oxidized glutathione (GSSG), and increased SOD levels. In the liver, the levels of GSH were similarly increased, however, paradoxically, the levels of lipid peroxidation were lower than control. Importantly, the magnitude of the changes in these markers never approached the level of 2-fold and most were less then 50%.

A follow up study by these investigators (Gómez et al., 2005) utilized a similar paradigm of 7 mg/kg/day i.p. injections of aluminium lactate into rats for 11 weeks (5 injections per week), focusing on oxidative markers in the hippocampus. The most robust evidence of general toxicity included 30% reductions in body weight. The levels of aluminium in hippocampus increased ~5-fold, to 22 μg/g. While this study reported a similar elevation in TBARS (~ 2-fold), increases in GSSG were not detected. Slight elevations (~50%) in mitochondrial superoxide dismutase (SOD) mRNA, an important antioxidant enzyme that is induced by oxidative stress, were noted.

Platt et al. (2001) examined the impact of aluminium on CNS integrity by direct intracerebroventricular injection, via cannula, of 5.4 μg of aluminium chloride for 5 consecutive days; followed by either 7 days or 6 weeks of no treatment before sacrifice. Interpretation of the study is somewhat confounded by damage to the brain resulting from instillation of the cannula and from disruption of the BBB, however several findings were revealing. Aluminium was found to distribute readily along white matter tracts and resulted in activation of both astrocytes and microglia at sites distal to the injection site. Although not a mimic of chronic exposure from drinking water or food sources, these data suggest that acute exposure of neural tissues to aluminium salts elicits responses indicative of neurotoxicity. Overall, however, the reported increases in markers of oxidative stress were of a relatively low magnitude.

In another example of acute toxicity, Sreekumaran et al. (2003) examined several parameters of neuronal morphology following a one-time injection of 8 mg/kg aluminium chloride into CSF, via the cisterna magna of rats. Following a 30 day survival, animals were sacrificed and tissues were prepared for Golgi impregnation to reveal dendritic and axonal structure. Significant reductions (averaging 30 to 40%) in axonal length and dendritic branching were noted in the treated group.

Yang et al. (2004) reported evidence of apoptotic cell death in the CNS of rats given a single injection of aluminium maltolate (100 μl of 500 μM solution). In a small number of animals (n = 4), 5 days after injection, TUNEL positive cells were detected in hippocampus along with biochemical evidence of DNA fragmentation. Biochemical evidence of caspase activation (caspase 3 and 12) was also reported. The study did not identify which type of cell(s) in the hippocampus were affected.

Dramatic evidence of aluminium toxicity in retina of rats was reported by Lu et al. (2002). Chronic i.p. injection of 12 mg of aluminium chloride for 16 weeks resulted in severe atrophy of the retina with losses of photoreceptors. Interestingly, in this model, the location of accumulated aluminium mimicked that seen in DAE patients. Aluminium was concentrated in cytoplasmic granules that resemble lysosomes. There was no report of neurofibrillary pathology or discussion of mechanisms of cell death.

Miu et al. (2003) studied rats given i.p. injections of aluminium gluconate 85 ug/100 g body weight 3 times a week for 6 months. At sacrifice, the authors showed evidence of reductions in neuronal density in the hippocampus, intracellular accumulations of aluminium in dense granules, and thickening of meningeal blood vessels. Serum levels of aluminium were measured at 3 intervals, recording levels of 86.8, 38.9, and 69.7 μg/100 mL of serum (mean values for n=12). These levels were roughly 5 to 40-fold higher than controls. The average level of aluminium in human serum ranges from 1-2 μg/L. Hence the levels in these rats were about 3 to 8-fold the normal human level.

In a parallel study, using the same method of dosing and concentration of aluminium gluconate for 12 weeks, Miu et al. (2004) reported finding similar lesions in addition to changes in myelin structure and evidence of mitochondrial swelling in hippocampal neurons. None of these pathologies was quantified however.

A key issue in the foregoing studies, however, relates to the speciation of aluminium and mechanisms of uptake by neural cells. The pathologic distribution of aluminium in DAE patients, and in some of the animal studies described above, are consistent with Tf-receptor-mediated endocytosis. Free-flow endocytosis of aluminium citrate could produce a similar pattern. Indeed, the pattern of aluminium accumulation in patients suffering from DAE, membrane delineated lysosomal-like structures, is consistent with an endocytic mechanism of uptake. It is unclear as to whether acute exposure to high levels of aluminium salts by direct injection into CNS reasonably simulates the exposures which result from long-term low level intakes via the oral route. In some of the acute exposure studies, aspects of human neurogenerative disease are produced. However, as described above, pathologic analyses of DAE patients do not reveal the pathologies found in AD and other neurodegenerative diseases, including neurofibrillary pathology, symptoms of motor neuron disease (as occurs in rabbits), or senile plaques. Overall, the connection between aluminium exposure and neuropathologic features of human disease is not particularly strong, though some resports of positive associations continue to foster debate.

Rodent models of aluminium toxicity by oral exposure

Aluminium has been implicated in the aetiology of ALS in Kii peninsula of Japan and the islands of Guam. In these environments, the levels of aluminium and manganese in drinking water are high while the levels of calcium and magnesium are low (for review see Garruto, 1991). Kihira et al. (2002) reported that mice feed diets high in aluminium (1.56 g/100 g) and low in Ca/Mg (50% reduction from control diet) developed pathologic features of human disease (Kihira et al., 2002), including neuronal accumulation of tau immunoreactivity in a pattern resembling pre-tangles of AD. Reductions in the density of cortical neurons were also noted in mice on low calcium/magnesium diets and in mice on the aluminium + low Ca/Mg diet. Mice given high doses of aluminium alone showed no evidence of neuronal loss. No symptoms of motor neuron disease were noted and animals exhibited near normal lifespans. Lowering Ca and Mg in diet induced a greater number of abnormalities in general health and appearance than Al laced diets (with or without manipulation of calcium/magnesium levels). Intracellular accumulations of aluminium were noted. Although it is possible that the levels of other minerals in the diet could influence the toxicity of aluminium, the most informative outcome of this study was that chronically high doses of aluminium did not result in obvious neurodegeneration, profound neuropathology, or clinical symptoms relevant to motor neuron disease. The average 25g mouse consumes about 5 g of food per day (formulated to contain 15.60 mg/g of aluminium). Therefore, the estimated consumption of aluminium by these animals would be about 3 g/kg/day, a dose nearly unattainable in humans. Despite this extremely high dose for a prolonged period, these animals developed relatively few phenotypes related to human neurological disease.

In a study of chronic exposure to aluminium in diet (rats fed 32 mg aluminium sulphate per day for 5 weeks), no evidence of apoptotic cells (TUNEL positive) was noted in cerebral cortex (Rodella et al., 2001). Similarly, the relative density of neurons in cortex was not obviously diminished. The authors did report that the density of NADPH-diaphorase positive neurons in cortex was diminished by 50%, but a better validation of such a reduction could be made by unbiased stereological assessments of these neurons (Gundersen et al., 1988).

Swegert et al. (1999) examined the effects of aluminium exposure on oxidative metabolism in rats given diets supplemented with aluminium chloride at an estimated dose of 20 mg/kg/day, which is approximately 20 times higher than the maximum amount normally consumed by humans from food. Animals were treated for 90-120 days at which time tissues were harvested and mitochondria were isolated for further study. Thirty to forty percent reductions in mitochondrial respiration rates were noted in brain mitochondria, with a paradoxical increase (~2-fold) in respiration rates in heart.

Flora et al. (2003) reported similar changes in oxidative markers in rats given aluminium nitrate in water at a concentration of 0.2% (2 g/l) for 8 months. Levels of aluminium in blood increased from ~3 μg/dL to >20 μg/dL. In brain, the levels increased from ~8 μg/dL to ~16 μg/dL. Indices of lipid peroxidation (TBARS) and the levels of GSSG were increased in brain. Again, however, the magnitude of changes in these measures was less than 2-fold with only very modest increases in the levels of GSSG.

Golub et al. (2000) fed mice defined diets containing 1000 μg/g of aluminium lactate from conception to sacrifice at 24 months of age (~ dose 100 mg/kg/day). Several parameters were analyzed (see below for discussion of cognitive behaviour), but relevant to this section was an absence of evidence for oxidative stress (no increase in TBARS). Surprisingly, however, despite the high dose of aluminium in the diet, the levels of accumulated aluminium in the brain were not significantly greater than that of controls.

Collectively, these studies establish that dietary aluminium intake can lead to accumulation of aluminium (speciation uncertain) in the brain of rats and mice. Modest increases in measures of oxidative stress have been noted, but evidence of significant neuropathology related to aluminium intake was not consistently noted. The level of sustained oxidative injury that is required to produce neuropsychological abnormalities is unknown, few of the oxidative markers measured in the foregoing studies increased as much as 2-fold.

Before reviewing the literature concerning the cognitive behaviour of laboratory animals exposed to aluminium, it is worth noting that there are detailed longitudinal studies of humans exposed to elevated levels of aluminium in the workplace. Buchta et al. (2003) examined a battery of neuropsychological and motor skills in a large cohort of auto manufacturing workers. They recorded average urine levels of aluminium of 70 μg/L, which compares with 1-2 μg/L in most individuals (Buchta et al., 2003). Individuals who had experienced at least 6 years of exposure were selected for analysis and their results were compared with those of co-workers of similar age, gender, and education who worked in other areas of manufacturing. The only measure by which the workers exposed to aluminium could be distinguished was a small reduction in reaction time (speed to respond to a question or perform a motor task). In all other cognitive measures including intelligence quotient (IQ), verbal intelligence, and the European Neurobehavioral Evaluation System, workers exposed to aluminium were no different from control populations (Buchta et al., 2003). Thus in humans, exposure to significant levels of aluminium does not lead to robust changes in cognitive function. However, the above study did not assess the levels of aluminium in blood, which would indicate absorption. Though there are clearly too few human studies, much of the data from studies in adult animals also suggests aluminium exposure does not lead to significant reductions in cognitive function.

As mentioned above, a lifelong exposure of Swiss Webster and C57BL/6J mice to high doses of aluminium (~100 mg/kg/day in feed) was utilized as a paradigm by Golub et al. (2000). With the caveat that brain levels of aluminium were not elevated in the treated mice, suggesting poor absorption, there were little or no deleterious effects of the aluminium-laced diet on several behavioural measures, including grip strength (slight reduction ~10%), temperature sensitivity (slight increase), and spatial reference memory. In the latter task, data from the C57Bl/6J mice are most informative where no adverse impact on acquisition or retention of memory was noted. A prior study by Golub et al. (1995) fed Swiss Webster mice food supplemented with either 500 μg or 1000 μg/g aluminium lactate (calculated dose 200 mg/kg/day) from conception to sacrifice at 150-170 days of age. In several measures of cognitive function, mice fed the aluminium laced diet performed as well as controls. However, 10 to 15% reductions in fore and hindlimb grip strength were noted.

Similarly, although Esparza et al. (2003) reported increased levels of several oxidative markers in the brains of rats given high doses of aluminium (5 and 10 mg/kg/day by i.p. injection), no changes in performance in a passive avoidance task were noted in animals treated with either dose. The classic passive avoidance task involves an electric shock deterrent in which rats are required to remember that the more preferred location (a dark enclosure next to the lighted open space) is associated with shock. Retention of the memory is usually tested 24 hr after conditioning. Hence the task is a measure of memory function.

In contrast to the results of the study by Esparza et al. (2003), Zhang et al. (2003) reported dramatic reductions in performance in passive avoidance in rats exposed to aluminium through drinking water. In the latter paradigm, aluminium chloride was provided through drinking water at a concentration of 3 mg/mL for 90 days. Serum levels of aluminium were not reported. Interestingly, in this study, an extract of Dispsacus asper (a herbal medicine) and vitamin E were shown to alleviate the memory deficits. The authors suggested that the anti-inflammatory and/or anti-oxidant properties of these drugs contributed to the improvements.

Domingo et al. (1996) examined passive avoidance in rats provided drinking water containing aluminium nitrate at concentrations that would equate to doses predicted to be 50 and 100 mg/kg/day for 6.5 months. No effects of the high aluminium exposure on measures of spontaneous motor activity or learning in passive avoidance tasks were noted.

Struys-Ponsor et al. (1997) studied rats given i.p. injections of 667 μg of aluminium gluconate 3 times per week for 60 days prior to assessment of spatial memory in a radial water maze task. Although a slowing of reaction time was noted, there were no statistically significant deficits in the ability of the aluminium-injected animals to perform the task.

Two studies by Miu et al. (2003; 2004), the pathological findings of which are described above, also assessed neuropsychiatric parameters. The 2003 work reported slight reductions in performance in a passive-avoidance memory task and in a spatial reference memory task. The latter work (2004) reported changes in behaviour in open fields which were interpreted as reductions in spontaneous activity and emotional responses.

Overall, the data on neuropsychological measures in rodents given high doses of aluminium by oral routes are not suggestive of profound toxicity. However, none of these animal studies is able to reproduce life-time exposures that could occur over the life-span of humans. It is clear that humans with compromised renal function develop neuropsychological symptoms upon exposure to elevated levels of aluminium. However, from the study of individuals exposed occupationally to aluminium fumes, humans with normal kidney function seem to tolerate high levels of exposure relatively well (see above). The degree to which the chemical form of aluminium, the route of exposure, and the age/health of the individual could modulate the neurotoxicity of aluminium is uncertain and has not been extensively modeled in animals.

The bone constitutes a primary site for the deposition of aluminium (Mahieu et al., 2004) (see also Toxicokinetics, Distribution (Including Compartmentalization), Animal Studies, Bone). Elevated aluminium levels in humans, primarily in individuals with impaired renal function, have been associated with several bone disorders including osteomalacia (excess unmineralized osteoid) and aplastic bone disease which is characterized by normal or decreased osteoid (Firling et al., 1999). The mechanism by which aluminium exerts its effects on bone tissue has not been fully elucidated (Cointry et al., 2005). Experimental evidence in a number of different animal models has led to a variety of proposed ways in which aluminium might influence new bone development. It has been suggested that aluminium may directly interfere with osteoblast activity thereby influencing the production or mineralization of osteoid (Firling et al., 1999). Bone formation may be impaired due to aluminium induced reductions in the total number of osteoblasts (Sedman et al., 1987). Direct physiochemical inhibition of mineralization sites has also been proposed as a potential mechanism (Firling et al., 1999). Aluminium-induced alterations in the PTH-calcium axis have also been extensively investigated with respect to aluminium-induced bone toxicity (Mahieu et al., 2004). One of the functions of the PTH is to stimulate bone resorption by increasing osteoblast activity (Quarles, 1990). It has been proposed that aluminium impairs the secretion of this hormone from parathyroid glands (Morrisey et al., 1983). Numerous studies, using a variety of animal models, have been conducted to investigate the effects of aluminium on bone. In interpreting the results of these studies, it is important to consider the difference in bone remodelling physiology between species. It is thought that larger animals such as the dog and pig approximate the bone physiology of humans more closely than rats and mice (Quarles, 1990). The route of aluminium administration and the duration of the study period may also have had significant impacts on the overall results of these studies. It should also be noted that the use of large doses of aluminium in some of these experimental studies may have resulted in a generalized toxicity to the animals, which could complicate the interpretation of aluminium-induced bone toxicity endpoints (Quarles et al., 1988). Some of the in vitro and animal studies investigating the effects of aluminium and bone have been reviewed and are summarized below.

PTH is considered to enhance osteoblast-directed osteoclast activity, and it has been proposed that aluminium may inhibit the production or secretion of this hormone (Jeffery et al., 1996). Morrissey et al. (1983) used dispersed bovine parathyroid cells to determine if aluminium directly affects PTH secretion. Digested bovine parathyroid glands were placed in media containing varying concentrations of aluminium, ranging from 0.5 to 2.0 mM. The incubations were terminated after 2 hr and the amount of hormone secreted into the medium was determined by radioimmunoassay. The secretion of PTH decreased with increasing amounts of aluminium. Hormone secretion decreased by an average of 68% in cells incubated with 2.0 mM aluminium compared to the cells incubated in the absence of aluminium. To examine if there was an irreversible toxic effect of aluminium with respect to PTH secretion, the cells were incubated for 1 or 6 hr with 2.0 mM aluminium, washed with low calcium buffer, and re-incubated in media without aluminium. Hormone secretion appeared to be restored and was comparable to that of cells which had not been incubated with aluminium. Cells were also incubated with radio-labelled leucine to examine the effect of aluminium on the biosynthesis of proparathyroid hormone, PTH, and parathyroid secretory protein. Examination of the incorporation of this radio-labelled amino acid into these proteins revealed that the biosynthesis of these compounds was not affected by aluminium incubation. Therefore, the results of this study suggest that aluminium directly affects the secretion of protein from parathyroid cells.

Ellis et al. (1979) investigated the effects of aluminium on bone toxicity in a group of 20 rats given daily i.p. injections of aluminium chloride for periods of up to three months. Sixteen rats received daily i.p. injections of 0.27 mg Al/day (as aluminium chloride), increasing gradually to a dose of up to 2.7 mg Al/day. The periods for the injections ranged from 48 to 85 days and, in 5 animals, no further injections were given after 63 or 84 days of treatment until sacrifice, 27 or 49 days later. The total dose of aluminium ranged from 38 mg to 109 mg. Four controls were i.p. injected with saline. The whole femur bone aluminium content was higher in the 16 rats given aluminium chloride (176 ± 8.2 ppm/ash compared with the controls (15.4 ± 4.7 appm). A mineralization defect of bone was detected in the rats after 53 days of aluminium treatment, and this increased in severity as the injections were continued. This was marked by an excess of osteoid on the surface of normally mineralized cartilage at the usual site of endochondral ossification. The excess osteoid was typical of osteomalacia with abnormally wide seams and no calcification front. Endochondral ossification was restored to normal, but osteomalacia persisted for up to 49 days after the cessation of treatment.

Chan et al. (1983) investigated the effects of i.p. aluminium chloride (1.5 mg/kg/day) for a duration of 9 weeks in normal (n=16) and uraemic (n=23) rats. Eight rats in the nonuraemic group and 10 rats in the uraemic group received the aluminium treatment, while no injections were given to the remaining control animals. At the end of the treatment period, the rats were euthanized and tissue aluminium, serum vitamin D metabolites, and quantitative bone histology were measured. Bone aluminium concentrations were higher in uraemic rats (121 ± 27 mg/kg) than in normal rats (47 ± 4 mg/kg), and liver aluminium values were higher in the normal group (175 ± 47 mg/kg) than in the uraemic rats (100 ± 36 mg/kg). Aluminium did not appear to have an effect on the levels of any vitamin D metabolites; however, serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were reduced as a direct result of uraemia. The nonuraemic aluminium treated animals did not exhibit any significant skeletal changes as compared to the controls. Marrow fibrosis and osteomalacia developed in some of the uraemic, non-aluminium treated animals. However, osteomalacia as defined by (1) an increase in osteoid area (29 ± 13% uraemia + aluminium vs. 3 ± 6% uraemia, no aluminium), (2) an increase in osteoid surface (42 ± 16% vs. 7 ± 11%), and (3) an abnormal pattern of tetracycline uptake at the calcification front, was more severe in uraemic animals treated with aluminium than in untreated uraemic animals.

Robertson et al. (1983) conducted a study to investigate the effects of aluminium on bone histology and PTH levels, and to determine if chronic renal failure accentuates aluminium toxicity. Male Wistar rats were divided into 5 groups. The first group (n=5) received a low dose of aluminium (i.p. injection 0.1 mg aluminium as aluminium chloride 5days/week), the second group (n=5) received a high dose of aluminium (i.p. injection of 1.0 mg aluminium as aluminium chloride 5 days/week); the control group (n=4) was administered an i.p injection of an equal volume of diluent over the same injection schedule. One group (n=6) of rats underwent partial nephrectomy and received an i.p injection of diluent, and another group (n=5) underwent partial nephrectomy and received an i.p. injection of 1.0 mg aluminium as aluminium chloride 5 days/week. The treatment lasted for 120 days for the control and low dose aluminium group, but for a shorter period (between 90-100 days) for the other three groups due to the need for early sacrifice as a result of high attrition in these groups. The trabecular bone of the ischium and the iliac wing was obtained from each animal and examined histologically; the bone mineralization process was evaluated by double tetracycline labelling. There were no differences in bone parameters between the low dose aluminium group and the controls. In the other three groups, the relative osteoid volume (p < 0.02) and the osteoid seam width (p < 0.001) were significantly increased as compared to the controls. These parameters are indicators of osteomalacia. The number of osteoclasts/mm2 increased in nephrectomized rats not exposed to aluminium (p < 0.02) and decreased (p < 0.05) in rats with normal renal function exposed to high doses of aluminium. The number of osteoclasts/mm2 was not significantly different from that of the control level for the aluminium treated nephrectomized rats. Animals with normal renal function given the high dose were the only group to exhibit a decrease in PTH level, which may explain the reduced osteoclast numbers in this group. However, the increase in osteoclasts/mm2, as compared to controls (8.13 ± 2.92 vs. 3.93 ± 100 osteoclasts/mm2), in the non-exposed renal failure group, compared to the reduction of osteoclasts in the exposed renal failure group (2.34 ± 1.38 osteoclasts/mm2 vs. 3.93 ± 100 osteoclasts/mm2), indicates that aluminium may have a direct toxic effect on osteoclastic activity.

Cortical bone growth was measured in rats given aluminium to study the early effects of aluminium on bone (Goodman, 1984). Thirty weanling male rats were assigned to one of three groups: control (n=10), experimental (n=10), or basal (n=10). Rats in the experimental group were given i.p. injections of aluminium chloride (2 mg aluminium, 5 days per week); animals in the control group received an injection of saline vehicle at the same frequency, and the basal animals did not receive any treatment. The treatment period lasted for 44 days. Bone growth was assessed over two consecutive periods of 28 and 16 days in the control and experimental rats, using tetracycline labelling of bone. Rats in the basal group were sacrificed on the first day of the experimental period. Histological measurements in sections of bone obtained from the basal group were interpreted to represent the status of the bone at the beginning of the bone-labelling period in rats from the control and experimental groups. Bone (0.017 ± 0.004 mm3/day) and matrix formation (0.017 ± 0.004mm3/day) in the experimental group remained at control levels (bone formation: 0.020 ± 0.004, matrix formation 0.02 ± 0.004 mm3/day) during the first period of assessment (28 days after treatment initiation); however, both these measurements were significantly lower (p <0.01) than control values at the end of the entire 44 day study (bone formation: 0.014 ± 0.003 mm3/day vs. 0.022 ± 0.003mm3/day, matrix formation:0.014 ± 0.003mm3/day vs. 0.022 ± 0.003mm3/day). Bone and matrix apposition at the periosteum in aluminium treated animals was significantly reduced (p < 0.0001) from control levels at the end of the 44 day treatment period, but was not significantly different at the assessment following 28 days of treatment. Aluminium treatment did not induce a state of osteomalacia as no significant effect on the osteoid width or the mineralization front width was apparent. The results of this study indicate that aluminium reduces bone and matrix formation early in the course of aluminium exposure, prior to the development of histologically apparent osteomalacia. Aluminium may affect matrix synthesis by reducing the total number of active osteoblasts or diminishing the cellular activity of individual osteoblasts.

Goodman et al. (1984a) examined the effect of short-term (4 week exposure) aluminium administration on bone growth and histology, and evaluated the role of renal insufficiency in mediating the skeletal effects of aluminium. Thirty rats underwent partial nephrectomy and were assigned to one of three groups: control, aluminium-treated, or basal control. Thirty additional rats with intact renal function were divided into the same treatment assignments. Aluminium treated rats received i.p. injections of aluminium chloride (AlCl3) in saline 5 days/wk for 4 weeks; the aluminium dose was 2 mg/day. Control rats received injections of saline only, according to the same treatment schedule. Bone growth, bone formation, mineralization, and resorption were measured using double tetracycline labelling of bone. Total bone and matrix formation and periosteal bone and matrix formation were reduced in both nephrectomized and normal renal function rats treated with aluminium as compared to the respective controls. Periosteal bone and matrix formation were similarly reduced in both groups. There was no difference in bone parameters between the control rats of the nephrectomized group as compared to the normal renal function control rats; however, total bone, total matrix, periosteal bone, and periosteal matrix formations were all less in the nephrectomized aluminium treated rats as compared to the non-nephrectomized aluminium treated rats. Resorption surface was greater in both aluminium- (1.70 ± 0.41mm vs. 1.33 ± 0.34 mm) and nephrectomized-aluminium-treated (1.87 ± 0.6 mm vs. 165 ± 0.43 mm) rats compared to the respective controls, and resorptive activity at the endosteum was greater (p < 0.05) in the nephrectomized aluminium treated group (12.2 ± 6.3 μm/d) than in the controls (7.9 ± 4.9 μm/d). Serum calcium and phosphorus concentrations were similar in aluminium-treated and control animals, suggesting that PTH secretion was not substantially affected by aluminium administration. Osteomalacia was not detected, but it should be considered that the duration of this study may not have been of sufficient length for this condition to develop. The results of this study suggest that aluminium exerts is toxic effects on bone by acting directly to reduce new bone and matrix synthesis. In addition, it appears that aluminium may act to increase bone resorption. The enhanced effect of aluminium in nephrectomized rats may be a result of increased aluminium accumulation due to an impaired ability to excrete the metal; however, aluminium in bone was not quantified in this study.

In order to investigate the effects of aluminium on the vitamin D-dependent mineralization process, aluminium chloride (1 mg/kg) was administered i.v. 3 times per week for 3 weeks to normal (n=5) and vitamin D-deficient (n=5) beagle puppies (Quarles et al., 1985). Vitamin deficiency was induced in the 5 dogs by providing a diet deficient in vitamin D and calcium for a period of 15 weeks before treatment initiation. Bone biopsies and plasma were obtained before and after the 3 week treatment period in each group. In the next phase of this study, aluminium chloride administration was continued at a lower dose (1 mg/kg twice a week) and both groups received the diet fortified with calcium and vitamin D. This phase of the study lasted for 11 weeks. The vitamin D deficient dogs displayed biochemical and bone biopsy evidence of osteomalacia before administration of aluminium. Plasma phosphorus, PTH, and 25-hydroxyvitamin D concentrations did not appear to be affected by the 3 weeks of aluminium administration in either group. However, bone aluminium content increased to a greater extent in the vitamin D-deficient dogs (390 ± 24.3 μg/g) than in the normal dogs (73.6 ± 10.6 μg/g). After 3 weeks of aluminium treatment, the bone histology in both groups revealed changes consistent only with aging. Provision of a calcium/vitamin D replete diet to the deficient dogs, and reduction of aluminium dosage for 11 weeks resulted normalization of their plasma biochemistry and healing of the osteomalacia. The bone aluminium content of the non-vitamin D deficient dogs increased during the additional 11 weeks of aluminium exposure to 151.0 ± 11.3 μg/g as compared to a bone aluminium content of 73.6 ± 10.6 μg/g after 3weeks of exposure. In contrast, the bone aluminium content in the vitamin D deficient dogs decreased from 390 ± 24.3 μg/g to 173.5 ± 5.6 μg/g at the end of the additional 11 weeks of exposure. Histochemical staining for bone aluminium revealed no apparent aluminium in the normal group and, in the vitamin-D deficient group, there was identifiable aluminium at the mineralization fronts after the 3 weeks of treatment. At the end of the 11 weeks of additional exposure staining for aluminium was detectable only in the cement lines, indicating that mineralization occurred over the previous sites of aluminium deposition. The results of this investigation indicate that aluminium accumulates preferentially in pre-existent osteomalacic bone and localizes at the calcification front (osteoid-bone interface). The presence of aluminium at the calcification front did not impair vitamin D-dependent mineralization as remineralization occurred in the bones of the osteomalacic pups following vitamin-D repletion. Osteomalacia did not occur in the normal pups; however, this does not eliminate the possibility that aluminium administration at higher doses or for prolonged periods might cause bone toxicity in these animals. Therefore, although aluminium may have the potential to cause osteomalacia, its presence at mineralization fronts does not appear to be the mechanism through which this occurs.

Alfrey et al. (1985) studied aluminium compartmentalization in rats with an induced state of uraemia or hypoparathyroidism. Seventy four male rats were divided into two main study groups. The first group consisted of 10 animals that underwent selective PTX, 10 animals were rendered uraemic by uninephrectomy, 11 animals underwent both nephroctomy and PTX, and 8 animals served as controls. 1,25(OH)2D3 was administered to normalize serum calcium levels. All animals received 1.5 mg/kg aluminium (as AlCl3) by i.p. injection 5 days/wk for 79 days. There was a significantly greater (p < 0.001) trabecular bone osteoid area (percent total bone area) in the PTX uraemic group than in the uraemic group (45 ± 9.7% compared to 13.4 ± 10.6%). Plasma calcium levels were significantly higher in the uraemic PTX group (10.7 ± 0.9 mg/dL) and lower in the control PTX group (9.0 ± 0.5 mg/L) than in their respective controls (9.9 ± 0.6 g/L: uraemic group; 9.8 ± 0.3 mg/L: control group), and phosphorus levels were significantly higher in both the PTX uraemic group (9.3 ± 1.5 mg/L) and PTX control group (8.1 ± 0.6mg/L) as compared to the controls (5.9 ± 0.3mg/L). The second study group was comprised of 35 uraemic rats; 8 of these rats had previously undergone selective PTX and were given 1,25(OH)2D3. The uraemic PTX animals and 8 of the uaremic animals received 1.5 mg AlCl3/kg by i.p. injection 5 days/week for 35 days, and were killed at the end of this treatment period. Aluminium injections were discontinued in the remaining animals, and nine underwent selective PTX at this time. These animals were followed for an additional 30 days. Bone aluminium levels in the animals killed after 35 days were lower (p < 0.05) in the PTX uraemic group than in the uraemic control group (37 ± 7.6 and 47 ± 7.6 mg/kg, respectively). The bone aluminium levels in the uraemic group that underwent PTX after aluminium loading (53 ± 8 mg/kg) and in the uraemic group (48 ± 5.7 mg/kg) 30 days after aluminium discontinuation were not significantly different. The results of this study suggest that PTX affects the compartmentalization of aluminium in bone, especially in animals in a uraemic state. It also appears that PTX may intensify aluminium-induced osteomalacia as the PTX group had significantly greater bone osteoid area than the uraemic group of rats.

Galceran et al. (1987) conducted a study to further characterize the mechanism of aluminium induced osteomalacia. One group of dogs (n=7) was treated i.v. with 0.75 mg aluminium, 5 days a week for 3 months; 7 additional dogs served as controls. At the end of the treatment period, the dogs were killed, and the tibiae were obtained and perfused in vitro. PTH and methylxanthine (an inhibitor of phosphodiesterase) were added to the perfusate. The serum aluminium level was 20.4 ± 2.3 μg/L before treatment, and rose significantly to 206.2 ± 28.3 (p < 0.01) after aluminium administration. No significant difference in PTH levels was detected before and after aluminium treatment. Because PTH acts to stimulate cAMP release from bone, cAMP levels were measured in both groups before and after PTH administration to examine the effect of aluminium on this process. Although the basal cAMP secretion was the same in both groups of dogs, cAMP increased to a peak of 188.2 ± 30.6 pmol/min in the normal dogs vs. 113 ± 8.15 pmol/min in the aluminium treated dogs after PTH was added to the perfusate (p < 0.05). Examination of bone biopsies taken before and after aluminium administration revealed that the number of osteoblasts had decreased 8-fold (p < 0.01) following aluminium treatment. Aluminium treatment led to an increase in the percent total osteoid surface (44.3 ± 4.7% vs. 22.1 ± 4.1%), decreased mineral apposition rate (0.5 ± 0.4 μm/day vs. 1.3 ± 0.2 μm/day), and aluminium deposition at the mineralization front. Despite the decrease in osteoblast number, the histological features of the post aluminium treatment biopsies indicated that aluminium stimulated osteoblastic activity at some point during its administration. This was apparent from the presentation of new woven bone formation in two dogs, and a layer of newly deposited lamellar bone covering all trabecular surfaces in another. Aluminium also appeared to stimulate the activity of fibroblasts as indicated by the presence of extensive marrow fibrosis in five of the treated dogs. These data support the possibility that aluminium is capable of both stimulating and suppressing matrix synthesis at different times throughout the exposure period. Although the levels of PTH were similar in the aluminium exposed and control animals, the decreased generation of cAMP following the addition of PTH to the perfused bones of the aluminium treated group suggests that aluminium may cause bones to be resistant to the effects of PTH.

Sedman et al. (1987) examined the effects of i.v. aluminium injections for a duration of 8 weeks on various bone parameters in growing piglets. Four piglets were administered 1.5 mg AlCl3/kg/day parenterally, and 4 control piglets received daily injections of deionised water for the same period. Quantitative bone histology and measurements of bone formation were assessed at three skeletal sites (two in the proximal tibia and one in the distal femur) in both the experimental and control groups. Bone aluminium was significantly higher (p < 0.001) in experimental animals (241 ± 40 mg/kg) as compared to the controls (1.6 ± 0.9 mg/kg). Osteomalacia, as defined by histological criteria, was documented in all aluminium-treated animals. The rate of mineralized bone formation was also lower in the aluminium-treated group compared to that in the controls at all three sites. However, it was found that, at sites of continued osteoblastic activity, total osteoid production did not differ between the two groups. These results suggest that bone mineralization is inhibited by aluminium via a decrease in the number of active osteoblasts rather than by an inhibition of the calcification of osteoid.

Ott et al. (1987) conducted a study to investigate the development and reversibility of aluminium-induced bone toxicity in weanling and adult rats. Four groups of weanling rats and one group of adult rats were used in this study. Each group consisted of 18 rats. Half the rats in each group received daily i.p. injections 10mg Al/kg as aluminium chloride. The other half of the group was given normal saline solution. Weanling rats were sacrificed after 3, 6, or 9 weeks of treatment. The remaining group of weanling rats received injections for 9 weeks, and was allowed to recover for 3 weeks. The adult group received aluminium treatment for 9 weeks. The effects of aluminium on blood serum levels of various compounds, and on aluminium bone content, and rate of bone formation were assessed after intervals of 3, 6, and 9 weeks. The calcium, phosphate, creatinine, and PTH levels were similar in aluminium-treated rats and controls. Aluminium was detectable by histochemical stain after 6 weeks in the aluminium treated animals; however, other bone parameters did not differ significantly at this time between the treated animals and the controls. A decrease in bone formation (measured by tetracycline labelling) on trabecular and endosteal surfaces was apparent by 9 weeks in the aluminium exposed groups. The weanling rats had a bone formation rate of (0.15 ± 0.2 mm2/100 days vs. 0.46 ± 0.14 mm2/100 days) which was significantly lower (p < 0.02) than the rate in the controls, while the adult rats had a rate of (0.04 ± 0.06 mm2/100 days) vs. (0.23 ± 0.12 mm2/100 days) in the controls. One group of rats was allowed to recover for 3 weeks without any aluminium administration. The bone formation rate in the younger group was similar to that of the controls after 3 weeks of recovery. Adult rats showed signs of early osteomalacia as evidenced by an increase in the length (4.75 ± 2.3 vs. 2.15 ± 1.5% surface) and width (18.4 ± 9.7 vs. 4.8 ± 1.3 μm) of the trabecular osteoid as compared to the controls. In this study it appeared that aluminium administration led to decreased rates of bone formation in rats despite normal calcium and parathyroid levels, and normal renal function. It is possible that aluminium induced decreased bone formation by inhibiting osteoblast formation or activity.

Quarles et al. (1988) conducted a study to define the primary effects of aluminium on bone in the mammalian species, and to examine the dose/time-dependent actions of aluminium on bone. Two year-old beagles were assigned to one of three treatment regimens. The first group (n=6) received 0.75 mg Al/kg as aluminium chloride i.v. three times per week, the second group (n=6) received 1.20 mg Al/kg at the same dosing schedule, and the third group (n=6) received sodium chloride i.v. and served as controls. The treatment period lasted for 16 weeks. Transcortical bone biopsies were taken from each group after 8 weeks and 16 weeks. In both the low and high dose aluminium groups, serum aluminium levels were significantly elevated compared with those of controls, but calcium, or PTH levels were not altered by treatment. Bone biopsies taken at 8 weeks in the low dose group displayed characteristics of a low turnover state, as marked by a reduction of bone resorption (2.6 ± 0.63% vs. 4.5 ± 0.39%) and osteoblast–covered bone surfaces (2.02 ± 0.51% vs. 7.64 ± 1.86%) as compared to the controls. The mineralized bone formation rate was also found to be significantly decreased. Biopsies taken at week 16 of aluminium administration in the low dose group displayed evidence of de novo bone formation, as well as an increase of bone volume (38.9% ± 1.35 vs. 25.2% ± 2.56) and trabecular number (3.56/mm ± 0.23 vs. 2.88 ± 0.11) compared to the controls. The 16 week biopsies displayed a persistence of inactive osteoid marked by a diminished mineralization front in the low dose group compared to the controls (46.0 ± 4.2% vs. 71.9 ± 2.92%). The bone biopsies obtained from the high dose aluminium group at 8 weeks displayed changes similar to those exhibited after 16 weeks of the low dose treatment. De novo bone formation was evidenced by an increase in trabecular number as compared to the controls (3.41 ± 0.18/mm vs. 2.88 ± 0.11/mm) and increased bone volume (36.5 ± 2.38% vs. 25.2 ± 2.56%). Poorly mineralized woven bone accounted for a large proportion of the newly synthesized tissue, comprising 11.5 ± 4.6% of the bone volume. High dose treatment for 16 weeks further enhanced bone volume (50.4 ± 4.61%) and trabecular number (3.90 ± 0.5/mm). The woven osteoid volume at 16 weeks decreased to 2.43 ± 0.96% of the total bone volume, indicating that heterogeneous calcification of this tissue was more complete. The observation of histological changes similar to those observed in disorders characterized by low bone turnover in the low-dose aluminium group after 8 weeks, combined with the observation of new bone formation and stimulation of cellular activity after longer treatment, suggests that aluminium may exert both inhibitory and stimulatory effects on osteoblasts.

To further examine the influence of osteoblast function on aluminium-induced of de novo bone formation, Quarles et al. (1989) compared the effects of aluminium in TPTX beagles (n=4) with beagles which underwent thyroidectomy but had intact parathyroid glands (n=4). The animals underwent TPTX as a means to reduce osteoblast number and activity. The treatment procedure began 2 months after surgery, when sufficient time had elapsed to achieve a new steady state of bone remodelling activity. 1.25 mg AlCl3/kg was administered to both groups of animals by i.v. three times per week for 8 weeks. The TPTX animals received supplements of calcium carbonate and calcitrol in order to maintain normal plasma 1,25-dihydroxyvitamin D levels as well as normocalcemia. Both groups were administered thyroxine to sustain normal free thyroxine concentrations. Although both groups of animals received the same aluminium treatment, TPTX beagles exhibited a significantly higher (p < 0.05) serum aluminium level (2386.1 μg/L) as compared to the controls (1087.0 μg/L). Aluminium administration did not alter the plasma calcium, creatinine, or PTH from baseline levels in either group of animals. Bone biopsies taken from the control animals after 8 weeks of treatment displayed evidence of de novo bone formation as compared to baseline bone parameters. This was evidenced by an increased bone volume (47.0 ± 1.0 vs. 30.4 ± 09%) and trabucular number (4.1 ± 0.2 vs. 3.2 ± 0.2/mm). Deposition of poorly mineralized woven bone accounted for much of the enhanced bone volume (9.9 ± 2.7%). TPTX animals demonstrated significantly less evidence of bone formation. Bone volume (35.5 ± 1.7% vs. 27.7 ± 1.9% at baseline) and woven tissue volume (1.4 ± 0.8% vs. 9.85 ± 2.66%), as well trabecular number (3.3 ± 0.1/mm vs. 4.2 ± 0.2/mm) were significantly less than those of the aluminium treated non-TPTX controls. It appears that the diminished functional osteoblast pool in the TPTX beagles limited the ability of aluminium to stimulate neo-osteogenesis.

Bellows et al. (1999) examined the effects of aluminium on osteoprogenitor proliferation and differentiation, cell survival, and bone formation in long-term rat calvaria cell cultures. The cells obtained from foetal rats were incubated in medium with or without aluminium added. The aluminium treated cells were incubated at various concentrations ranging from 1 uM to 1 mM of aluminium for up to 19 days. The numbers of mineralized and unmineralized bone or osteoid nodules in each culture dish were quantified by in situ staining. Alkaline phosphatase activity, cell viability, and cytotoxicity were also determined. Nodule formation was significantly increased (p < 0.001) by 30-1000 μM aluminium incubation, in a dose dependent manner, at 11 days but not at 17 days. Control and aluminium-treated cultures appeared similar with respect to nodules and cell layers at day 13 of culture. However, at day 17 of culture, aluminium concentrations of 30 μM and above resulted in reduced cellularity and an increased fibrilar appearance of the matrix that had formed outside of, or adjacent to, nodules. Aluminium also increased alkaline phosphatase activity at all time points in a dose-dependent manner. Significantly fewer viable cells were present in the 300 μM aluminium-containing cultures after 13 and 17 days. The results of this experiment indicate that aluminium has a stimulatory effect upon existing osteoprogenitor cells leading to an accelerated rate of osteoblastic differentiation and nodule formation, while inhibiting nodule mineralization. The concentration of aluminium at which this effect occurred resulted in decreased cell viability and enhanced cytotoxicity.

The effect of aluminium administration on bone, in a model of osteopoenia induced by chronic acid overload in rats with normal renal function, was examined by Gomez-Alonso et al. (1999). Thirteen male rats with induced osteopoenia were divided into two groups. The first group (n=8) received 10 mg/kg of AlCl3 i.p. 5 times per week for 4 months, the second group (n=5) did not receive any aluminium treatment. At the end of the experiment, both tibias from each animal were extracted for the determination of aluminium content, in vitro bone densitometry, and histological analysis. Bone mineral density, measured at the proximal end of the tibia, was found to be significantly higher (<0.05) in the aluminium-treated group (0.292 ± 0.01 g/cm2) as compared to the controls (0.267 ± 0.02 g/cm2). Histomorphometric analysis showed a significant increase (p < 0.01) in bone volume (18.59 ± 5.66% vs. 7.69 ± 3.08%), cortical thickness (0.52 ± 0.06 mm vs. 0.36 ± 0.07 mm), osteoid thickness (14.05 ± 4.72 μm vs. 5.25 ± 090 μm), and osteoclast number (2.44 ± 0.52 N Oc/mm2 vs. 1.30 ± 0.01 N Oc/mm2) in the aluminium-treated group as compared to the controls. No significant differences in serum calcium, phosphorus, creatinine, hydroxyproline, or PTH were apparent between the aluminium-treated and control animals. There was no evidence of osteomalacia in the aluminium-treated rats. These findings indicate that aluminium is able to induce bone formation in rats with normal renal function even when osteopoenia is present.

Firling et al. (1999) examined the influence of aluminium citrate administration on tibia formation and calcification in the developing chick embryo. Tibia formation and mineralization were assessed by radiology, total bone calcium content, calcium incorporation rate, collagen synthesis rate, bone alkaline phosphatase activity, and serum levels of osteocalcin, procollagen carboxy-terminal propeptide, and PTH. The chick embryos derived from White Leghorn strain eggs were divided into three treatment groups (aluminium citrate, sodium citrate, sodium chloride), and were treated acutely or chronically. Acutely treated embryos received 100 μL of 60 mM aluminium citrate, 60 mM sodium citrate or 0.7% sodium chloride via injections into the air sac of the egg on day 8 of incubation. Chronically treated embryos received a daily 25 μL dose of the solutions beginning on day 8. The embryos were incubated for an additional 2 to 8 days following treatment. Radiographic analysis of the tibias and femurs of the embryos revealed that the mineralization of the aluminium treated animals was less dense and restricted to a shorter length of the mid-diaphysis as compared to the other two groups. The bone calcium content of embryos acutely or chronically administered aluminium and incubated for 10 to 12 days was significantly lower (p < 0.05) compared to that of the other treatment groups. The calcium content of tibias from embryos chronically treated with aluminium remained lower than the controls for 12 day and 16 day embryos while, by day 14, there were no significant differences in the total calcium content from acutely treated embryos compared to the controls. Significantly higher (p < 0.05) levels of alkaline phosphatase activity were found in the tibias collected from embryos chronically treated with aluminium incubated from 12 (2.16 units/tibia/hr vs. 1.32 units/tibia/hr) to 16 days (10.38 units/tibia/hr vs. 6.78 units/tibia/hr) as compared to the sodium chloride control group. Aluminium did not have a significant effect on the rate of tibia collagen, non-collagenous protein synthesis or serum levels of procollagen carboxy terminal propeptide, osteoclacin or PTH. The lack of change in these parameters suggests that embryonic osteoblast number and activity is not markedly diminished by aluminium exposure at these doses. The authors suggested that the observed under-mineralization of the tibias in the aluminium treated embryos may be a manifestation of the production of defective osteoid, an inhibited terminal maturation of osteoblasts, or physiochemical inhibition of mineralization nucleation sites.

Zafar et al. (2004) investigated the effect of chronic exposure to dietary aluminium on calcium absorption and calbindin concentrations in male weanling rats fed various levels of calcium and aluminium for 3 and 6 week periods. One group of rats (n=40) was fed a calcium adequate diet, three other groups of 40 animals each were fed a calcium-deficient diet with 0, 0.05 or 0.1% aluminium, as aluminium chloride. After 3 weeks, 20 rats per group were fasted overnight and 10 rats per group were given an oral dose of 25 mg calcium labelled with 6 μCi 45Ca by gavage. The other 10 rats in each group were given 6 μCi 45Ca as an interperitoneal injection. Rats were anaesthetized the following day, blood was collected and the femurs were obtained. The remaining animals (20 per group) were switched to a calcium adequate diet containing the same level of aluminium they had been fed previously, and were maintained on these new diets for another 3 weeks. No difference in 45Ca absorption was observed among the 4 groups at either 3 or 6 weeks. Aluminium supplementation at 0.05 and 0.1% of the diet reduced calbindin concentrations (compared to the group receiving a calcium deficient diet without aluminium). Total bone calcium decreased with aluminium supplementation. The bone calcium content was significantly different (p < 0.05) in the calcium deficient-no aluminium group, and in the calcium deficient groups supplemented with 0.05 and 0.1% aluminium, as compared to the calcium adequate group at both 3 and 6 weeks of treatment. In addition, the bone calcium content was significantly lower (p < 0.05) in the calcium deficient, 0.1% aluminium group as compared to all the other groups. Aluminium treatment reduced the breaking strength parameters of the bones from rats on the calcium-deficient diets. When the animals were switched to a calcium adequate diet for 3 weeks, there were no differences in the resistance to breaking due to aluminium intake. The results of this study suggest that dietary aluminium has detrimental effects on bone quality when calcium is deficient.

Cointry et al. (2005) analyzed the effects of aluminium accumulation on whole-bone behaviour in rats. Rats (n=14) received i.p. doses of 27mgAl/day, as aluminium hydroxide (Al(OH)3), for a period of 26 weeks. Fourteen control rats received a 20% glycerol/water solution at the same dosing schedule. At the end of the experimental period, the left tibiae was obtained from each animal for bone ash determination. Both femurs from each animal were also dissected and examined for the volumetric mineral density of the cortical bone region and for cross-sectional properties of the cortical bone region. Mechanical testing of the femurs was also conducted. The Young’s modulus of elasticity (a measure of stiffness) was calculated, as well as the stress of the cortical tissue at the yield point, which is an indicator of the tissue’s ability to support loads before any crack initiation. Aluminium concentration was significantly higher (p < 0.001) in the tibias of treated animals (103 ±18 μg/g) as compared to those of control animals (6 ±1 μg/g). The volumetric bone mineral density was significantly reduced in the treated animals with respect to the controls. Up to the yield point, the structural stiffness and strength of the bones did not differ between groups; however, an aluminium-induced impairment of the ability to resist loads beyond the yield point was observed. Treatment had a negative impact on the bending stiffness (Young’s elastic modulus) and the yield stress of cortical bone. These parameters were decreased by 18 and 13% respectively in treated animals as compared to those of controls (p< 0.05). The cortical second moment of inertia, which is a measure of the architectural efficiency of the cortical bone, was significantly improved in aluminium-treated rats (+10% change, p <0.01) as compared to that of the control group. This suggests that an adaptive response to aluminium treatment may have caused an improvement of the spatial distribution of the available cortical tissue resulting in an enhanced ability of the bone to resist anterior-posterior bending. The results of this study suggest that the apparent adaptive response of the bone to aluminium may have maintained normal stiffness and strength, but aluminium may have reduced the ability of the bone to resist loads beyond the yield point, or the ultimate strength of the bone.

The effects of aluminium on metabolic parameters in humans are not well understood. There have been relatively few studies of the effects of occupational exposure to aluminium on mineral metabolism. Ulfvarson & Wold (1977) examined the levels of trace metals in the blood of welders of aluminium and stainless steel. Although the authors did not report the levels of aluminium in blood, which would have been useful in gauging exposure, other studies of aluminium welders have noted relatively high levels of exposure (Buchta et al., 2003). In the study by Ulfvarson & Wold (1977), the levels of lead, strontium, rubidium, bromine, gallium, zinc, copper, cobalt, iron, manganese, chromium, calcium, potassium, sulphur, phosphorus, silicon, and magnesium in the blood of aluminium welders were not statistically different from the levels of controls. However, significant variability in the data was noted. Little is known regarding the effects of aluminium on other metabolic parameters in humans.

Most of the data on the effects of aluminium on trace metal, and general, metabolism originates from studies on animals given aluminium by various routes. There is clear evidence that aluminium can influence iron metabolism in the context of haematopoiesis (see Effects on Laboratory Mammals and In Vitro Test Systems, Effects on Haematopoieses). However, as described below, alterations in iron levels in solid organs have also been noted, but with inconsistent outcomes. Studies of the metabolism of trace metals have yielded similarly conflicting outcomes. There have also been reports of alterations in a variety of metabolic pathways in response to aluminium exposure.

Golub et al. (1995) reported that mice fed diets containing as much as 1 mg Al/g for 150 days had small, but statistically significant, reductions in the levels of iron in spinal cord and liver. The calculated dose of aluminium exposure in this experiment was 200 mg/kg b.w./day, which is about 100-fold greater than dietary exposure in humans. Animals exposed to these levels of aluminium had no significant differences in body weight.

Ward et al. (2001) injected rats (i.p.) with aluminium gluconate (2 mg/kg b.w.) 3 times a week for 8 weeks and then examined iron levels in liver, kidney, heart, spleen, and brain. Two to three-fold increases in tissue iron levels were noted in liver, spleen, and brain. Blood levels of aluminium were not reported, but the levels of aluminium in liver and spleen were recorded as 100 ng/mg protein and 150 ng/mg protein, respectively, indicating substantial exposure.

Han et al. (2000) examined non-haem iron levels in kidney, liver, and intestine of chicks fed diets containing 0.15 and 0.3% (by weight) aluminium for 3 weeks. Chicks receiving the higher dose of aluminium were reported to have gained 28% less weight. Levels of iron in liver were reduced by 40%, with 30% reductions in iron levels in intestine.

Esparza et al. (2003) examined the levels of manganese, iron, and copper in the brain and liver of rats given i.p. injections of aluminium lactate (5 mg/kg b.w.) 5 days per week for 8 weeks. Rats exposed to this level of aluminium showed 5-fold increases in aluminium levels in liver (8.45 μg/g compared to 48.35 μg/g) with a 2-fold increase in cerebellum (5.49 μg/g compared to 12.51 μg/g). The cortex and hippocampus of brain showed trends towards increased aluminium accumulation, but were not statistically different from those of controls. In liver, manganese levels were reduced by 40% with no alterations in iron or copper levels. In cerebellum, there were no statistically significant changes in the levels of any of these metals while, in cortex and hippocampus, the levels of copper were reduced 25 to 40%. Cortex also showed 25% reductions in manganese. Animals injected with aluminium lactate gained 25% less weight than control animals injected with vehicle.

The levels of copper, zinc, and manganese have been measured in the serum of rabbits exposed to aluminium by s.c. injection of aluminium sulphate (600 μmol aluminium/kg b.w./day) five times per week for 3 weeks (Liu et al., 2005). The total aluminium exposure per rabbit for the entire study was 243 mg/kg b.w. Aluminium levels in serum increased from 0.25 μg/mL to 1.3 μg/mL after 21 days of treatment before levelling to 1.2 μg/mL by day 42 of treatment. There were no statistically significant changes in the levels of zinc, copper, or manganese in serum after either 21 days or 42 days of treatment. The authors reported weight loss in the aluminium-treated group but did not specify the degree of loss.

Fattoretti et al. (2004) examined the levels of copper, zinc, and manganese in the brains of rats exposed to aluminium through drinking water (2 g AlCl3 /L) for 6 months beginning at the age of 22 months. Serum levels of aluminium were not reported, making it difficult to assess the level of exposure. The authors sampled 3 domains of the brain; fore- and mid-brain together, pons and medulla together, and cerebellum. In cerebellum, there was no significant change in the levels of any metal. The authors reported accumulations of aluminium in fore- and mid-brain (94% increase) with increases in copper, zinc, and manganese (32, 41, and 50%, respectively). Pons and medulla showed 53% increases in aluminium accumulation with 46, 46, and 41% increases in copper, zinc, and manganese, respectively.

Sanchez et al. (1997) described an analysis of calcium, magnesium, manganese, zinc, copper, and iron levels in rats of 3 age groups exposed to aluminium in drinking water. The doses used were 50 and 100 mg/kg b.w./day of aluminium nitrate with added citrate at 355 and 710 mg/kg/day, respectively, to increase absorption of the metal. The ages at which studies were initiated were at 21 days, 8 months, and 16 months. Studies were terminated after 6.5 months of exposure and the levels of each trace element were measured in liver, bone, testes, spleen, kidney, and brain. The authors did not report the levels of aluminium in serum or bone, so it is difficult to assess the relative exposures of the animals. The amounts of aluminium in the water were roughly 10,000 times the average exposure level of humans and the addition of citrate would likely have increased absorption. Under these conditions, for each trace element, there were statistically significant effects of aluminium for multiple tissues; however, there were not always dose-dependent responses and the response of young vs. older animals sometimes differed. Among the most striking changes were the 25 to 50% reductions in calcium levels in kidney and brain of the mid and old age groups given the highest dose of aluminium. In young animals given the highest dose, however, the levels of calcium in these organs were ~2-fold higher than in those of controls. The testes of older animals also showed 2 to 3-fold increases in calcium levels. The data on copper levels showed significant fluctuations among age and treatment groups. The most robust finding was that, in young animals exposed to both doses of aluminium, the level of copper was reduced 30 to 50% in both kidney and brain. However, in older animals there were no changes in these organs. Magnesium, manganese, iron, and zinc levels fluctuated less among age and treatment groups in the various tissues, and there was less definitive evidence that aluminium caused consistent changes the amount of these elements in the tissues examined. There was evidence of a robust and consistent effect on levels of manganese in spleen, where, in all age groups, the highest dose of aluminium correlated with the highest tissue levels of manganese. There was also evidence of an effect on iron levels in spleen of young animals given the highest dose (30% increase in iron) and in kidney of older animals (25% reduction).

The authors also examined urinary excretion of trace metals at 2 time points within the treatment (at 3 and 6.5 months). The most robust and consistent changes in excretion were noted for zinc with a 3-fold reduction in excreted zinc at both doses in middle-aged group. In all other groups and for all other elements, the changes were either far less robust or inconsistent across age and treatment groups.

Yasui & Ota (1998) examined the levels of magnesium and calcium in serum, spinal cord, and bone in rats fed diets low in calcium (3 mg/100g diet) and high in aluminium (194 mg/100g diet) as aluminium lactate. Control diets contained 1250 mg/100g diet calcium and 10 mg/100g diet aluminium. After 60 days of exposure, the levels of aluminium in serum increased from 0.25 μg/dL to 1.25 μg/dL. Control diet low in calcium had no effect on aluminium levels and only slightly lowered serum levels of calcium. By contrast, there was a 2-fold reduction in serum calcium levels in animals exposed to both low calcium and high aluminium. None of the diets affected serum levels of magnesium. In spinal cord, the combined low calcium/high aluminium diet led to very modest reductions in the levels of magnesium (~10% reduction). However, in lumbar vertebra, magnesium levels were reduced by 25% on the combined diet. Diets low in calcium had no effect in either tissue. The authors did not comment on whether these diets affected weight gain.

In a study of much shorter duration (18 days) in which lower doses of aluminium were used (~270 μg/g of food), Greger et al. (1985) examined the levels of phosphorus, calcium, magnesium, iron, manganese, zinc, and copper in bone, kidney, and liver of rats exposed to aluminium in diet. Two food formulations provided trace metals at levels that were at the minimum requirement and at 2-3 times the minimum requirement. The chemical form of aluminium was varied, using aluminium palmitate, aluminium lactate, aluminium phosphate, and aluminium hydroxide. No significant differences in levels of aluminium accumulation in bone were noted among the different chemical forms of exposure (control 1.9 μg/g; treated 13-15 μg/g). The authors found no significant changes in the levels of any of the studied minerals in the tissues examined in animals exposed to aluminium by any of the methods.

Boudey et al. (1997) examined the effects of low doses of aluminium on growth rates and calcium metabolism of young weanling rats; an additional variable in the study included reductions in calcium levels. Animals were given control diets (8.4 mg Al/kg b.w. or supplemented diet (10.6 mg Al /kg b.w.), with or without altering calcium levels (7.6 g Ca /kg b.w. vs. 0.4 g Ca/kg b.w). Animals exposed to the higher dose of aluminium in calcium deficient diets weighed 40% less at the end of the 90 day study. Aluminium levels in brain, liver, and bone were approximately 3-fold higher than those of animals given diets containing normal levels of calcium and the lower dose of aluminium. The authors also noted that, in the presence of normal levels of calcium, the higher dose of aluminium caused 25 to 40% reductions in the levels of calcium in bone, liver, and brain. One conclusion of the study was that young animals may be more sensitive to the effects of aluminium if diets are deficient in calcium.

In comparison to these outcomes, Julka & Gill (1996) reported that young (100-150 g) rats exposed to very high doses of aluminium by i.p. injection (10 mg/kg b.w. per day) for 4 weeks had elevated levels of calcium (2 to 3-fold) in cortex and hippocampus of brain. Other physiological consequences related to calcium included decreased (~40%) calcium influx in isolated synaptic preparations from the aluminium-treated animals and reduced ability of calmodulin to stimulate cAMP phosphodiesterase (~25% reduction in activity).

Mahieu & Calvo (1998) examined renal function in rats exposed to aluminium by i.p. injection of aluminium hydroxide (80 mg/kg b.w., 3 times per week, for 6 months). After 6 months of exposure, aluminium levels in serum reached 800 μg/L as compared to controls (10 μg/L). These exposure levels are 400 to 800-fold higher than typically found in human serum (see Effects on Laboratory Mammals and In Vitro Test Systems, Neurotoxicity). Deposition of aluminium in trabecular bone was also observed, indicating significant exposure levels. Similar to results of other studies, the authors reported that treated animals showed reductions in weight (25%) and reduced efficiency of nutrient utilization. No obvious loss of renal function was noted; there were significant reductions in the excretion of phosphorus (40% less) with significant increases in calcium excretion. The suggested mechanism for the effects on renal function involved loss of PTH response, either by lower release of the hormone or reduced receptor sensitivity.

In another study of renal function, Braunlich et al. (1986) reported that aluminium exposure (i.p. injection of 0.5 mg/kg b.w., 5 times weekly for 12 weeks) led to increased urine output (45%) and increased sodium excretion (57%). Notably, the dose used in these studies was more in line with what would be used to achieve 10-fold increases in aluminium loads in rodents.

Mahieu et al. (2004) examined the intestinal absorption of phosphorus and its subsequent deposition in bone in rats exposed to aluminium. Animals were injected i.p. with aluminium lactate (5.75 mg/kg b.w.) 3 times per week for 3 months. By the end of the study, serum levels of aluminium were reported to be 600 μg/dL as compared to 10 μg/dL in controls. Slight reductions in body weight (10%) at 3 weeks of treatment were noted. In serum, there were no differences in calcium or phosphorus levels between control and treated groups at any age tested. At 1, 2, and 3 months of exposure, 25 to 30% reductions in the level of phosphorus excreted in urine were noted. Small, but statistically significant, reductions in the levels of phosphorus absorbed by the intestine were also noted. Similar reductions, small but statistically significant, in calcium absorption were also reported. Slight increases in calcium urinary excretion were detected along with 10% reductions in calcium levels in bone. A significant increase in the bone accretion of phosphorous (32P deposited/32P absorbed) was also noted in treated animals as compared to controls (27% increase). Bone calcium was significantly (p < 0.03) reduced in treated rats (10% decrease). These findings indicate that phosphorous metabolism may be modified by aluminium through direct action on the intestine, kidney, and bone.

There are several reports that provide evidence that aluminium may have effects on multiple metabolic pathways. There have been two studies on the effects of aluminium on metabolic enzymes. Rats exposed to 100 μM aluminium chloride in drinking water (2.6 μg Al/mL) for 12 months showed 2-fold elevations in aluminium in brain with reductions in the activities of hexokinase and glucose-6-phosphate dehydrogenase (G6PDH) (73 and 80% of normal) (Cho & Joshi, 1989). Reductions in erythrocyte activities of G6PDH and glutathione reductase (82% of normal for each) were reported in rats injected i.v. with 5 mg AlCl3/kg for 3 consecutive days and then harvested at 4 weeks post treatment (Zaman et al., 1993).

Another study examined nutritional effects of aluminium in drinking water (administered as aluminium nitrate at doses of 360, 720, 3600 mg/kg b.w./day) for 100 days (Domingo et al., 1987). Young female rats exposed to the highest dose gained 50% less weight than animals on lower doses or the controls. The largest difference in weight gain occurred in the first weeks of the study. Animals on the highest dose drank less water, consumed less food, and showed less urine and faecal output. No changes in blood uric acid, cholesterol, glucose, creatine, or urea levels were detected in any treatment group.

Gonzalez et al. (2004) reported that rats given aluminium hydroxide by i.p. injection (27 mg/kg b.w.) 3 times per week for 3 months show 25% reductions in bile flow, 39% reductions in bile salt output, 43% reductions in bile cholesterol output, and 38% reductions in total bile protein output. These effects were correlated with 40% reductions in the expression of multidrug-resistance-associated protein 2, which is the main multi-specific organic anion transporter of the bile duct. Plasma concentration of aluminium in these animals reached 750 μg /L (controls 9 μg/L), indicating very significant exposure. No change in weight was detected in the treated animals.

One of the most common abnormalities associated with renal failure and haemodialysis is anaemia. Many patients with this disease receive high doses of hydroxyl aluminium gel over long periods to control serum phosphorus levels. As described above in Effects on Laboratory Mammals and In Vitro Test Systems, Neurotoxicity, the majority of aluminium found in serum is bound to Tf, which is responsible for the transport of iron. As described below, Tf and iron are crucial regulators of erythropoiesis; thus an immediate suggestion of a mechanism behind anaemia in patients afflicted with renal failure is evident that implicates aluminium.

However, in the majority of these patients, treatment with erythropoietin, a hormonal stimulator of haematopoiesis, is effective in restoring haematocrits (percentage of cells in whole blood that are red blood cells), at least partially (Eschbach et al., 2002; Sakiewicz & Paganini, 1998). In most patients, one physiological basis of anaemia stems from compromised production of erythropoietin by diseased kidneys, leading to chronic anaemia. The condition is often exacerbated by iron deficiency, which can arise from decreased red blood cell t½, chronic loss of blood, decreased uptake, and other nutritional deficiencies (Drüeke, 2001; Sakiewicz & Paganini, 1998; Winearls, 1998). In the majority of haemodialysis patients, treatments with erythropoietin and iron supplements are sufficient to raise haematocrits to levels >30% of normal, a level that alleviates most symptoms of anaemia. Although some patients are hyporesponsive to erythropoietin, the levels of iron-saturated Tf and aluminium do not provide a correlative explanation (Eschbach et al., 2002); unresponsive patients do not have higher serum levels of aluminium or lower levels of iron saturated Tf. Thus, in patients who are exposed to high levels of aluminium, the physiological basis for anaemia is complex and involves, at least in part, a loss of hormonal stimulation. However, as outlined below, there are both cell culture and animal model data to indicate that aluminium has the capacity of perturb haematopoiesis and thus effects on this system should be considered in assessing aluminium toxicity.

The effects of aluminium on haematopoiesis have been investigated in various animal models. In these studies, aluminium exposure has been accomplished by both oral and injection routes. Data from selected studies involving direct injection of aluminium salts will be summarized first. As a point of reference, the average human exposure to aluminium in drinking water, is ~ 2.3 μg/kg b.w./day, with steady-state serum levels of aluminium averaging ~2 μg/L in most individuals (see Effects on Laboratory Mammals and In Vitro Test Systems, Neurotoxicity).

Chmielnicka et al. (1996) exposed rats to high doses of aluminium chloride (4 mg/kg b.w./day) for 21 days by i.p. injection. Although the levels of aluminium in serum were not reported, this exposure level equates to 800 μg/kg b.w./day of elemental aluminium. At 3, 7, 14, and 21 days of exposure, the authors measured platelet counts, red blood cell counts, serum levels of iron, total haemoglobin levels, and haematocrits. No significant changes in platelet or red blood cell counts were noted at any age. By 21 days of exposure, small, but statistically significant, decreases in total haemoglobin and haematocrit were reported. The most robust effect identified was a 25 to 30% reduction in the level of iron in serum.

Farina et al. (2002) exposed rats to aluminium sulphate (50 μmol/kg b.w. = 2.6 mg of aluminium/kg b.w.) through i.p. injections 5 times a week for 3 months. The levels of aluminium in serum were not reported. At the end of the exposure period, the authors reported finding several indications of toxicity to the haematopoietic system, including 32% reductions in total haemoglobin levels, 24% reductions in haematocrit, and 30% reductions in serum levels of iron. However, total iron-binding capacity of serum from exposed animals was not statistically different from controls.

I.p. injections of aluminium hydroxide (80 mg/kg b.w. – 3 times per week) have also been used as an experimental model of chronic exposure to aluminium. Mahieu et al. (2000) studied animals exposed for up to 28 weeks, while Bazzoni et al. (2005) examined animals treated for 12 weeks. Serum levels of aluminium were not reported in these studies and thus the sustained body burden is not known. The elemental aluminium content of this exposure was calculated to be ~27 mg/kg b.w. at each injection. Several haematological factors were measured in each study. Mahieu et al. (2000) noted progressive decreases in mean corpuscular volume (microcytosis) to a maximum of 28% reductions. However, minimal reductions in red blood cell counts and haematocrit were reported. Modest reductions in total haemoglobin (20% reduction) and small increases in red blood cell fragility were reported. Bazzoni et al. (2005) reported 20% reductions in total haemoglobin with 7% reductions in haematocrit. This latter study reported significant increases in red blood cells with deformed morphology (not quantified) with slight increases in fragility. Bazzoni et al. (2005) also reported that red blood cells in the treated animals were 3 times more rigid and less prone to aggregate.

Farina et al. (2005) conducted a second study of rats exposed to aluminium citrate (30 mM aluminium sulphate with 35 mM sodium citrate) in water for a total of 18 months. The daily exposure to aluminium was estimated to be 54.7 mg/kg b.w. Citrate would be expected to increase absorbance; however serum levels of aluminium were not reported. The authors reported that chronic exposure at this level led to reductions of 20% in red blood cell counts, 13% in haematocrit, 15% in total serum haemoglobin, and 40% in total levels of iron in serum. However there was no change in total iron binding capacity and no increase in red blood cell fragility. Turgut et al. (2004) exposed mice to aluminium for 3 months through drinking water containing aluminium sulphate. The estimated dose was 877 μmol/kg b.w./day = 47 mg of aluminium/kg b.w./day. Serum levels of aluminium were not reported. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. The levels of iron in serum were elevated by 59% with a small increase in the levels of Tf.

Garbossa et al. (1998a) have reported evidence that aluminium exposure may have direct effects on erythroid differentiation, which may account for the reductions in red blood cell counts and haematocrit in animals exposed to aluminium. Garbossa et al. (1998b) conducted a study in which rats were exposed to aluminium citrate at two levels by two routes for 15 weeks; 1 μmol/g b.w./day by oral gavage 5 days/week and by drinking water containing a 100 mM solution (estimated exposure 14-17 μmol/g b.w. day). Serum levels of aluminium were measured in this study with the dose given by oral gavage leading to serum aluminium levels of 2.9 μmol/L (78 μg/L), as compared to controls with 0.8 μmol/L (21.5 μg/L). The serum levels of aluminium in animals exposed through drinking water were 3.6 μmol/L (97 μg/L). The authors reported that animals given aluminium in drinking water had reductions in haematocrit (11%), increased osmotic fragility of red blood cells (20% more fragile), and 24% reductions in red blood cell t½. At both the lower and higher dose, there were reductions in the ability of isolated bone marrow stem cells to differentiate into erythrocytes after exposure to erythropoietin (colony-forming units – erythroid). In a later study by the same group, Vittori et al. (1999) exposed rats to aluminium via drinking water containing 80 mM aluminium citrate for 8 months. At the end of the study, the serum level of aluminium in the treated rats was 205 μg/L (range 120-790 μg/L) whereas the level in control animals was 15 μg/L (range 5 to 90 μg/L). These levels are between 10 (control) and 200 (treated) times the average level of aluminium in human serum (1-2 μg/L - see Effects on Laboratory Mammals and In Vitro Test Systems, Neurotoxicity). At this high exposure level, very significant reductions in erythrogenesis were found ~60% reduction in erythroid colony forming units (CFU-E) and decreased uptake of iron (~30% reduction). The authors also reported significant increases in abnormal red blood cell morphology.

Studies of the effects of aluminium on erythroid cell differentiation have suggested potential mechanisms by which aluminium could impact haematopoiesis. In a study by Vittori et al. (1999), direct evidence that aluminium inhibits erythroid differentiation was reported. Erythroid progenitor cells were concentrated from human blood and exposed to 100 μmol aluminium citrate (8 mg/L elemental aluminium) for 10 days and induced to differentiate with erythropoietin. The authors reported 30% reductions in CFU-E activity. However, in a similar study, Mladenovic (1988) reported that aluminium at levels of 1,035 ng/mL (1.035 mg/L) in medium did not significantly diminish CFU-E. However, if Tf was added to the medium along with aluminium, then CFU-E was diminished by 90%. If Tf was first saturated with iron, aluminium had no effect. The negative effects of Tf-aluminium were not overcome by adding excess levels of erythropoietin. One conclusion that could be drawn from this study was that a primary effect of aluminium on erythroid differentiation was mediated by competition for the Tf receptor. If excess Tf saturated with aluminium is present, then erythroid differentiation is inhibited by the binding of aluminium-metallated-Tf (aluminoxamine) to its receptor. However, the affinity of Tf for iron is 5 orders of magnitude greater than its affinity for aluminium. Hence excess aluminium alone cannot displace the iron from Tf-iron complexes that pre-exist in culture medium. Adding demetallated Tf to the medium allows aluminium to bind and thus creates the opportunity for Tf-aluminium-complexes to compete for binding to the Tf receptor. The extent to which a similar scenario may occur in vivo depends upon the levels of free Tf in serum at the time of aluminium exposure and on the level of iron in the serum. If sufficient iron is present, then aluminium binding to Tf would be less favoured. Individuals with iron deficiency could therefore be at greater risk for developing haematopoietic abnormalities upon exposure to aluminium.

Direct effects of aluminium salts on the morphology of red blood cells have been reported (Suwalsky et al., 2004; Vittori et al., 2002; Zatta et al., 1997). However, as outlined above in Effects on Laboratory Mammals and In Vitro Test Systems, Neurotoxicity, most studies of aluminium metabolism indicate that most of the aluminium, absorbed from drinking water or food, present in plasma would be bound to Tf. Thus, the amount of soluble aluminium salts that red blood cells would be exposed to is limited. However, Tf-mediated delivery of aluminium to erythroid progenitors does provide a means to expose these cells directly to the metal. Vittori et al. (2002) noted that red blood cells exposed to aluminium citrate in vitro acquired abnormal morphology and showed increased degradation of a protein involved in maintenance of cell shape (band 3 protein). Suwalsky et al. (2004) similarly reported that red blood cells exposed to aluminium fluoride in vitro developed abnormal morphology.

Oral exposure

There are reports of animal studies in which aluminium was given in large amounts orally for a considerable period of time that do not mention GI irritation, corrosion or sensitivity. These GI effects were not specifically examined in many of these studies and it is not known whether such effects were considered at all in these studies. Generally, the only adverse effect observed in most of the studies was a decrease in body weight gain. Some examples follow. Gross necropsy of male Sprague-Dawley rats fed diets containing 7000 to 30,000 mg/kg basic SALP, which is used as emulsifying agent, equivalent to 67 to 288 mg Al/kg b.w./day, for 28 days, showed no evidence of GI irritation (Hicks et al., 1987). Beagle dogs fed 80 mg Al/kg b.w./day as basic SALP for 26 weeks demonstrated histopathological changes in the liver and kidney that were attributed to reduced food intake, but no adverse effects on the stomach were noted (Pettersen et al., 1990). Male and female beagle dogs fed acidic SALP, a leavening agent, in a diet containing 0.3, 1.0 or 3.0% SALP for 6 months, showed no evidence of GI irritation on gross autopsy and histopathological examination (Katz et al., 1984). These SALPs are not very soluble, except in dilute HCl, which might be achieved in the stomach. Male Weizman Institute strain rats given 1% aluminium chloride or sulphate in their drinking water demonstrated periorbital bleeding after an unspecified period of exposure, but were not noted to demonstrate GI irritation. However, histology may not have been conducted on the GI tract (Berlyne et al., 1972b). Female Sprague-Dawley rats were given drinking water containing aluminium nitrate (375, 750 or 1500 mg/kg b.w./day, equivalent to 27, 54 and 108 mg Al/kg b.w./day, respectively) for 28 days; mild histological changes occurred in the liver and spleen but no histological changes in the presence of elevated aluminium were seen in the stomach or small or large intestine (Gómez et al., 1986).

In contrast to the above reports that were negative for aluminium-induced GI irritation, male albino rats given a single daily gavage dose of aluminium sulphate (17 to 172 mg/kg b.w./day) or potassium aluminium sulphate (29 or 43 mg Al/kg b.w./day) for 21 days demonstrated gastric mucosal layer thickening, hyperplasia and ulceration after exposure to 86 and 172 mg/kg b.w./day aluminium sulphate, but not to lower doses (Roy et al., 1991). It therefore appears that aluminium has the potential to produce irritation in rats after oral administration when high concentrations of soluble aluminium salts are administered (see Effects on Laboratory Mammals and In Vitro Test Systems, Single/Acute Exposure and Effects on Laboratory Mammals and In Vitro Test Systems, Repeated Exposure for more information on the effects of oral exposure to aluminium in mammals).

Inhalation exposure

The pulmonary response to various species of aluminium has been studied in animals after inhalation exposure and after intratracheal instillation (see Effects on Laboratory Mammals and In Vitro Test Systems, Irritation, Intratrachael Exposure). Many of these studies were conducted to better understand the adverse effects observed in humans exposed to very high levels of air-borne aluminium, and other materials, in industrial settings during the Second World War, and the postulated protective effect of inhaled aluminium against quartz dust-induced pulmonary fibrosis; this practice started in the mid-1940’s and continued for at least 10 years (see Effects on Humans, Effects from Occupational Exposure, Irritation, Inhalation Exposure). Various species of aluminium caused responses described as typical of foreign body reaction, alveolar proteinosis and wall thickening, some nodule formation, but not the extent of fibrosis caused by quartz dust.

Rabbits exposed to aluminium dust 1 to 2 hr daily for 20 to 40 days showed increased connective tissue in their lungs (Goralewski, 1939). In studies by Jötten & Eickhoff (1942), inhalation of finely powdered aluminium dust by rabbits caused few lung changes and no fibrosis. However, addition of a pneumococcal infection resulted in a diffuse sclerosis, collagen formation and rapid death, suggesting that aluminium somehow enhanced the toxicity of the infectious agent.

Exposure of rabbits to aluminium dusts resulted in three phases of pulmonary change, an initial exudation of leukocytes for a few hr or days, several months of an intermediate monocytic phase, and a final foreign body granulomatous phase that developed after several months of exposure (De Marchi, 1947). These are changes associated with a foreign body reaction (Chen et al., 1978; De Vuyst et al., 1987). Rats and guinea pigs were exposed to arc-produced fumes of pure aluminium oxide (alumina), silica, or “stack dust” (a mixture of alumina, silica and other oxides) for 18.3 hr daily for 6 months. Six months after completion of exposure, their lungs contained 1 to 11% of fume material. The alumina-exposed animals exhibited nodule-like collections of endothelial cells, fibroblasts and mononuclear leucocytes, similar to silicotic nodules (MacFarland & Hornstein, 1949). Inhalation of aluminium hydrate by guinea pigs led to hypertrophic reticular pneumonia and a histiolymphoid reaction as a general response to this insult and formation of nodules in the alveoli, demonstrating the harmfulness of this aluminium species (Jullien et al., 1952).

To assess the role of paraffin, which was used to coat aluminium dust during its production, in the toxicity associated with aluminium production, rabbits were exposed to paraffin-coated aluminium dust. They developed an interstitial fibrosis that began to appear about 75 days later, which was less frequent and severe than seen in rabbits exposed to uncoated dust (Van Marwyck & Eickhoff, 1950). These results did not support the hypothesis of Perry (1947) (see Effects on Humans, Effects from Occupational Exposure, Irritation, Inhalation Exposure) that paraffin substances coating the aluminium are the cause of aluminium-induced fibrosis, but are consistent with the hypothesis of Corrin (1963a) (see below).

Inhalation of 40 to 120 mg/m3 of boehmite, a gelatinous aluminium oxide, or 21 to 33 mg/m3 aluminium oxide, considered to be gibbsite, by guinea pigs 8 hr daily, 6 days weekly for 14 months apparently did not produce adverse pulmonary alterations (Gardner et al., 1944). The authors did note that this inhalation unfavourably influenced the resistance to tuberculosis, consistent with the response to concurrent exposure to finely powdered aluminium dust and pneumococci (see above).

Aluminium oxide exists in many chemical species (see Identity, Physical and Chemical Properties, Analytical Methods, Physical and Chemical Properties, Properties of Aluminium Compounds). The γ transitional form was believed to be the most biologically active (Klosterkotter, 1960). Mice and rats were exposed to a relatively well-defined γ transitional form of aluminium oxide having an average particle size of 0.005 to 0.04 μm and a surface area of 95 m2/g, although these particles aggregated during the experiment. Exposure was to 33 g/m3 by inhalation 5 hr daily for 285 days or by intratracheal instillation of a single dose of 35 mg of γ-Al2O3 suspended in 1 mL of tap-water. It was noted by the experimenters that this very high level inhalational exposure could not be tolerated and would be avoided by industrial workers. Inhalation exposure resulted in some deaths, some connective tissue thickening in the alveolar walls and bronchioles with mild collagenous fibrosis, but not the collagenous nodules seen in silicosis. These effects have been interpreted as alveolar proteinosis, a non-specific response to pulmonary dust exposure (Dinman, 1988).

Wistar rats and hamsters inhaled a powder composed of 20% aluminium and 80% aluminium oxide, 0.05 to 7 μm particle width, which was introduced hourly during an 8 hr day for 3 to 19 months (Christie et al., 1963). Increased exposure duration produced enlarged lungs covered by slightly thickened pleura with sub-pleural plaques. This progressed to consolidated areas surrounding the small bronchioles. Cystic spaces, usually sub-pleural, were seen after 9 months. They were surrounded by firm, fibrous plural walls and filled with pulpy material. Microscopic examination revealed diffuse alveolar catarrh, large macrophages, eosinophilic foamy vacuolated cytoplasm, some thickening of the alveolar walls which were lined by proliferation macrophages, foreign body giant cells, granulomas formed by histiocytes (tissue macrophages), and foreign body giant cells with large lipoid clefts. This constellation of effects was considered to be a lipid pneumonia. Acute inhalation of aluminium oxide particles, produced by a Wright dust constant feed generator, with a mean count size of 0.2 μm, and maximum size of 1 μm, as 0.38 or 0.58 mg/L (380 or 580 mg/m3), for 30 minutes by guinea pigs caused a constriction of pulmonary air flow (Robillard & Alarie, 1963a). In contrast, inhalation of aluminium oxide at a concentration of 0.38 mg/L (380 mg/m3) by rats for 3, 7 or 15 minutes produced a time-dependent lung dilatory effect, the opposite to that seen in the human, guinea pig, dog and cat (Robillard & Alarie, 1963b).

Three metallic aluminium powders were introduced at dust concentrations of 15, 30, 50 or 100 mg/m3 into chambers containing rats, guinea pigs or hamsters 6 hr daily, 5 days weekly for 6 months. The powders were; pyro coated, flake-like particles (4% < 1 μm, 87% 1 to 4 μm and 8.5 % > 4 μm; mean 2.5 μm diameter), flake-like particles (19% 1 to 4 μm and 71 % > 4 μm; mean 4.8 μm diameter), and atomized spherical particles (1.5% < 1-4 μm, 96% 1 to 4 μm and 3 % > 4 μm; mean 2.2 μm diameter) (Gross et al., 1973). The response among all 3 animal species was alveolar proteinosis, characterized by generalized alveolar epithelial reactions, the appearance of pneumocytes, and occasional macrophages, but no fibrosis.

Male Syrian golden hamsters were exposed by inhalation to a propylene glycol complex of aluminium chloride hydroxide, which was used in some antiperspirants. Exposure was to 164 mg/m3 of the complex, for 6 hr on the first day and for 4 hr on the second and third days. The animals demonstrated acute bronchopneumonia and moderate thickening of the alveolar walls. Rabbits exposed to 212 mg/m3 of the complex for 5 days showed similar effects. Exposure of hamsters to 52 mg/m3 of the complex 6 hr daily 5 days weekly for 30 exposures demonstrated persistent numerous foci of macrophages and heterophils, especially at the bronchioalveolar junction (Drew et al., 1974). Fisher 344 rats and Hartley strain guinea pigs received inhalation exposure to large (2.45 to 3.09 μm mean mass equivalent aerodynamic diameter) aluminium chlorhydrate particles, 0.25, 2.5 or 25 mg/m3 6 hr daily, 5 days weekly for 6 months. This resulted in multi-focal granulomatous pneumonia characterized by proliferation and infiltration of mononuclear inflammatory cells and foci of giant macrophages in the alveoli, often containing vacuoles of fibrillar basophilic material, and granulomatous lesions in peribronchial lymph nodes, evidence of active phagocytosis and necrosis (Steinhagen et al., 1978; Stone et al., 1979). Rats exposed to aluminium chloride and aluminium fluoride dusts by inhalation, 1.3 to 1.8 mg/m3 for over 5 months, showed that aluminium affected AM integrity and increased lysozyme, alkaline phosphatase, and initial protein levels in lung lavage fluid, suggesting effects on Type II alveolar cells. This was considered to be an adaptive response to the dusts (Finelli et al., 1981). Inhalation exposure of male Fischer 344 rats for 4 hr to aluminium flakes, at aluminium concentrations of 10, 50, 100, 200 or 1000 mg /m3, demonstrated an influx of polymorphonuclear neutrophils into bronchopulmonary lavage fluid that persisted for 6 months post-exposure, an indication of a continued irritant response. Multifocal microgranulomas in lungs and hilar lymph nodes were also seen (Thomson et al., 1986).

Clinical observations of uncontrolled studies suggested inhalation of aluminium dust was beneficial in the treatment of silicosis and did not produce apparent adverse effects (see Effects on Humans, Effects from Occupational Exposure, Irritation, Inhalation Exposure). This treatment was based on the theory that silica exerted its toxicity following its dissolution to silicic acid. Aluminium was found to coat the silica particles with a thin film of hydrated gelatinous aluminium oxide, reducing particle solubility (Crombie et al., 1944). Denny et al. (1937;1939) found that exposure to 1% metallic aluminium powder and quartz dust for 6 months protected against quartz-induced silicosis in the rabbit. They then exposed rabbits to freshly ground, fine particulate metallic aluminium dust particles, (the majority with diameter < 3 μm), at an average airborne particle concentration of 7 × 109 /m3 for 12 hr daily for 14 months. This resulted in a dried lung aluminium concentration of 2,700 to 12,000 mg/kg. The authors observed no harmful effects other than occasional thickening of the alveolar walls that consisted of alveolar epithelial proliferation. Concurrent exposure to admixtures of quartz and 0.5 to 3% aluminium dusts resulted in fibrosis in some animals that had < 1% aluminium in their lungs, but no fibrosis was seen in rabbits whose lungs had hydrated aluminium oxide. Aluminium was visualized by aurine. Similarly, exposure of rabbits for 40 minutes to aluminium dust containing 7 × 109 particles/m3 before or after being exposed to quartz dust (20 × 109 particles/m3) for 12 hr daily protected against quartz-dust induced fibrosis. Exposure of guinea pigs to 2 types of hydrated aluminium oxide (aluminium hydroxide) for ≥ 1 year produced no adverse effects on the lungs, but did have a protective effect against silicosis (Gardner et al., 1944). Dworski (1955) described a series of studies, begun by Gardner and continued by others, on the effects of colloidal aluminium hydroxide, powdered aluminium hydrate and metallic aluminium powder on normal animals, on the prevention of quartz dust-induced-silicotic reaction and on the treatment of pre-established silicotic lesions. A beneficial effect was attributed to aluminium when given before, or with, quartz, irrespective of the route of quartz or aluminium administration, when the quartz and aluminium distributed to the same location. Some retardation of not-yet-mature silicotic lesions was observed, but aluminium did not affect fibrotic lesions. Metallic aluminium powder produced less effect and lower tissue aluminium concentrations. One observation related by the author of unintended aluminium exposure producing less than expected toxicity from quartz exposure during the course of their studies undermines confidence in the experimental control of these studies. Addition of 2% metallic aluminium powder, as used by Denny et al. (1937;1939), to quartz dust delayed the development of nodular retilulinosis and collagenous silicosis, which occurred by ~ the 200th and 300th days in the absence of aluminium, and by ~ the 300th and 400th days in the presence of aluminium, respectively (King & Wright, 1950). Addition of aluminium at a concentration of 4 mg/m3 as McIntyre powder to an inhaled dust mixture of 75% finely ground lean coal and 25% Dörentrup quartz powder, ~ 45 mg/m3 with a particle count of ~ 2. 5 × 109/m3, did not reduce the development of fibrosis or have any other beneficial effects (Weller et al., 1966). When the aluminium dust was inhaled after the coal-quartz dusting, further cellular granulomas reactions were seen. The authors concluded from studies of inhalation of the aluminium dust alone that it cannot be considered totally inert. Aluminium salts were shown to be beneficial in rats exposed to pure quartz or coal-quartz. The aluminium aerosols showed no toxicity (Le Bouffant et al., 1975). Aluminium lactate alone produced no significant effects. Treating quartz with aluminium lactate reduced the inflammatory response and attenuated oxidation and proteolysis of fibronectin (Brown et al., 1989). Exposure of sheep with silica-induced silicosis to 100 mg aluminium lactate aerosol in saline monthly for the first year, and weekly for the next 2 years, starting 1 year after radiographic evidence of silicosis, produced no benefit (Bégin et al., 1995).

Many, but not all, of the studies aimed at assessing the potential protective effect of aluminium against fibrosis induced by quartz dust reported beneficial effects, as reviewed above. It was often noted that the aluminium alone had little toxicity.

Zeolite (hydrated alkali aluminium silicate) inhalation produced respiratory disease in rats (Gloxhuber et al., 1983).

Inhalation of power plant fly ash, which had a MMAD of ~ 2 μm, at concentrations of up to 4.2 mg/m3, 8 hr/day for 180 consecutive days, produced no significant adverse effects in rats (Raabe et al., 1982). However, the increased number of macrophages found in the lung was interpreted as a natural response to inhaled particles.

Aluminium starch octenylsuccinate is used in cosmetic formulations as an anti-caking and viscosity-increasing agent. Rats exposed to 200 g/m3 for 1 hr showed no gross changes from 1 hr to 14 days later (Nair & Yamarik, 2002).

Intratracheal exposure

Implantation of a fine, pure aluminium wire in the lungs of Swiss mice produced interstitial infiltration of lymphocytes, macrophages, and diffusely spreading fibrosis (Greenberg, 1977). The author thought the effects were more extensive than those produced by powdered aluminium and suggested that metallic aluminium might act as an antigen in a hypersensitivity reaction and that aluminium-induced pulmonary fibrosis may be an expression of tissue immunity.

Intratracheal administration, rather than inhalation, of aluminium has been employed in many studies. Intratracheal injection of a rather coarse form of metallic aluminium powder produced an extensive foreign-body granuloma in rats (Belt & King, 1943). Intratracheal injection of stack fume dust, a causative agent in Shaver’s disease, to guinea pigs produced a rather abruptly developing fibrosis 8 to 12 months later (Pratt, 1950).

Intratracheal instillation of 100 mg of the same gelatinous, hydrated aluminium oxide (laths of 200 to 400 Å length and 50 to 100 Å width, or aggregates, 300 m2/g surface area) studied by Gardner et al. (1944) resulted in extensive confluent nodular and diffuse confluent grade 5 fibrosis after 270 days (King et al., 1955). Similar intratracheal application of fumes, comprising largely amorphous spherical particles of 0.02 to 0.5 μm with a surface area of 10 m2/g, from a corundum furnace produced mild, grade 2 to 3 fibrosis. Introduction of 50 mg of aluminium phosphate, in the form of thin tablets of 0.5 to 5 μm diameter and having a surface area of 1 m2/g, produced moderate, grade 3, fibrosis after 390 days (King et al., 1955). Further studies were conducted by this group in hooded rats given intratracheal instillation of various aluminium forms. Fourteen mg of aluminium hydroxide resulted in the development of firm, discrete, rarely confluent lung lesions and collagenous fibrosis. Fifty mg of aluminium oxide, aluminium phosphate or the equivalent dose as aluminium hydroxide were similarly injected. The aluminium oxide studied was the same as used by others (Gardner et al., 1944). Intratracheal instillation produced numerous white patches, often confluent, as early as 60 days after exposure. After 180 days there were firm fibrotic areas and, at day 210, almost the entire lung was a dense mass of fibrous tissue that progressed to a mass of confluent collagenous tissue. Aluminium hydroxide produced firm, confluent, fibrotic patches in the lungs after 150 or more days. Aluminium phosphate produced similar effects, although less severe than seen with aluminium oxide, whereas catalytically inert α-aluminium oxide did not produce adverse lung effects (Stacy et al., 1959). Similar experiments with powdered metallic aluminium (amorphous, 0.05 to 1 μm diameter) resulted in nodular fibrosis in hooded rats, similar to changes produced by quartz dust (King et al., 1958). The intratracheal administration of 35 mg of aluminium oxide produced slight (grade 1 to 2) fibrosis 150 days later, and grade 2 to 3 fibrosis 180 days later (Klosterkotter, 1960).

An intratracheal injection of 100 mg of stamped, thin, flake-like, aluminium particles (50% < 1 μm, 47% 1 to 5 μm and 3% > 5 μm) in 1 mL saline to Wistar rats produced nodules, enlarged hilar lymph nodes, macrophage infiltration, the development of collagen fibres and fibrosis over months. In contrast, instillation of granular aluminium (11% 1 to 5 μm, 17% 5 to 10 μm and 72% > 10 μm) resulted in a small number of macrophages and occasional collagen fibres after many months, but very little fibrosis (Corrin, 1963a).

Intratracheal installation of 2 to 100 mg of coated, flake-like particles or atomized spherical particles or 2 to 24 mg of the flaked powder to rats and hamsters resulted in dose-dependent collagenous fibrosis which was not seen below a dose of 24 mg (Gross et al., 1973).

Rats were given a single intratracheal instillation of a saline suspension of potroom dust from an aluminium reduction plant. Seven days after instillation of 0.5 mg dust, changes were seen at the pulmonary surface. After a 5 mg dose, marked changes were seen at the pulmonary surface and in lung tissue. There was a 16 to 20-fold increase in the number of polymorphonuclear leukocytes in the lung. By contrast, 5 mg virginal (primary) aluminium oxide caused an 8-fold increase which was interpreted by the authors as a standard response to a nuisance dust. Twenty-two weeks after a single intratracheal instillation of 5 mg of potroom dust or virginal aluminium oxide, all parameters measured had returned to control levels. The acute irritation and inflammation produced in rat lung suggested that this type of dust may have produced similar effects in human lung, thus contributing to the acute respiratory symptoms experienced by some potroom workers (White et al., 1987).

Dinman (1988) reviewed the experimental studies of the toxicity of aluminium oxide in the lung and concluded that the catalytically-active low temperature forms of aluminium oxide and the forms that are not catalytically-active and defined as γ can produce irreversible fibronodular changes, but only after intratracheal instillation. He termed this “alumina-related pulmonary disease”. He noted a positive correlation between the surface area of the aluminium oxide particles and the fibronodular response.

The ability of 7 aluminium oxide samples to produce lung cytotoxicity, measured by LDH and polymorphonuclear neutrophils in BALF, was tested in rats by comparing the intratracheal instillation of a total of 50 mg of aluminium oxide, with that of 25 mg of quartz, each given in 5 instillations over 2 weeks (Ess et al., 1993). The samples were smelter grade aluminas obtained from industries involved in aluminium production and a chemical grade and a laboratory produced aluminium oxide. They had median particle diameters of 1.3 to 12 μm except for the chemical grade that had a median diameter of 0.008 μm. Increased lung cytotoxicity was seen as surface area increased and α-content decreased. I.p. injection of 5 mg of the smelter grade aluminas in mice produced nodules, but no fibrosis. The BALF of rats given a single intratracheal instillation of 40 mg of potroom aluminium oxide was studied 1, 4 and 12 months later (Tornling et al., 1993). Compared to controls, there was a significant decrease of lymphocytes at 1 month, a significant decrease of albumin at 4 months and a significant increase of fibronectin at 12 months. The authors suggested that the increase of fibronectin might contribute to the inflammatory reaction and build up of an extrcellular matrix network. Rats were given a single intratracheal instillation of 20 mg of either condensed aerosols/dusts collected from a foundry or pure chemical grade α-alumina. They were suspended in 0.5 mL of saline. Before installation, samples were passed through a 36 μm diameter strainer (Halatek et al., 2005). Multiple endpoints were determined in the BALF 3, 6 and 9 months later. Clara cell protein 16 (CC16) was significantly lower in rats that received α-alumina 3 months after instillation and in rats that received foundry aluminium 6 months after instillation, compared to controls. Hyaluronic acid was significantly increased only in the rats terminated 6 months after α-alumina instillation. Nine months after treatment, neutrophils increased ~ 3-fold in rats given foundry aluminium and ~ 5-fold in those given α-alumina. Lung weights increased in the α-alumina-treated rats but not those that received foundry aluminium. Three months after α-alumina instillation macrophage accumulation was seen; after 6 and 9 months granuloma-like structures were observed. Six months after foundry aluminium instillation, young forms of lymphocytes, macrophages and fibroblasts were seen; after 9 months interstitial fibrosis was observed. The authors concluded that foundry aluminium can cause irritation and inflammation in the rat lung and that a lowering of CC16 was the most sensitive biomarker for this damage.

Some of the studies of the potential for aluminium to protect against quartz dust-induced pulmonary fibrosis employed intratracheal aluminium administration. Intratracheal insufflation in rats of 150 mg of quartz dust mixed with 3 mg of powdered aluminium in 1.5 mL milk-saline as a vehicle resulted in silicotic nodules in the presence of 1% aluminium in the lung in nearly all subjects, showing that aluminium failed to prevent experimentally-induced silicosis (Dworski, 1955). Similarly, aluminium alone (20 to 50 mg) produced an extensive foreign body reaction seen at ~ 16 months (Belt & King, 1943). Administration of 400 mg of a mixture of 98% quartz and 2% of the aluminium dust used by Denny et al. (1937; 1939) in 4 mL saline into the lungs of rabbits reduced lesions and collagen formation up to 1 year later and to a greater extent than when only quartz was administered (Belt & King, 1943; King et al., 1945). King et al. (1958) conducted further studies in hooded rats given intratracheal instillation of various aluminium forms. Powdered metallic aluminium given intratracheally in large amounts relative to quartz, which was given similarly, did not reduce quartz-induced fibrosis (King et al., 1958). Intratracheal administration in sheep of 100 mg quartz produced sustained increases in bronchoalveolar lavage cells, an alveolitis at 60 days, and early nodular silicotic lesions at 10 months. This was attenuated by treating the quartz with 11 or 100 mg aluminium lactate, which was believed to mask some of the active sites on the silica (Bégin et al., 1986; 1987; Dubois et al., 1988). Monthly inhalation of 100 mg aluminium lactate after intratracheal instillation of 100 mg quartz or instillation of 100 mg aluminium lactate-treated quartz enhanced pulmonary quartz clearance compared to when only quartz was inhaled (Dufresne et al., 1994).

I.v. and i.p. administration of an aluminium dextran complex, Mr = 150,000, protected against the development of silicotic nodules in the liver of mice injected i.v. with silica dust (James et al., 1960).

Aluminium species used in pharmaceuticals and cosmetics have been tested for pulmonary irritation and toxicity. Intratracheal installation of kaolin (hydrated aluminium silicate) in rats produced pulmonary toxicity manifested as fibrosis (Martin et al., 1975). Bentonite (hydrated colloidal aluminium silicate) given intratracheally to rats produced an increase in polymorphonuclear lymphocytes in the lung (Sykes et al., 1982), inflammation, and bronchopneumonia progressing to necrosis and storage-focal tissue reaction (Tatrai et al., 1983), elevated macrophages and acid phosphatase activity (Tatrai et al., 1985) and increased phospholipid (Adamis et al., 1986). Intratracheal montmorillonite (an aluminium magnesium silicate clay) produced dose-dependent interstitial fibrosis (Schreider et al., 1985). Intratracheal zeolite administration produced pneumoconiosis in rats (Kruglikov et al., 1990) and a storage type reaction that progressed to mild pulmonary fibrosis (Tatrai et al., 1991).

Single intratracheal administration of attapulgite (hydrated magnesium aluminium silicate) or Fiberfrax (an aluminium silicate) in rats produced granulomas accompanied by multinucleated giant macrophages and enhanced IL-1-like activity. Additionally, early fibrosis was seen after Fiberfrax exposure, and irreversible fibrosis 8 months following attapulgite administration (Lemaire, 1991; Lemaire et al., 1989).

Rats that inhaled refractory aluminium oxide fibre as manufactured, or after thermal aging for 86 weeks, showed minimal pulmonary reaction (Pigott et al., 1981). When 20 mg of these refractory aluminium oxide fibres were given by an intrapleural injection, they did not produce the malignant mesothelioma produced by aluminosillicate and asbestos fibres (Pigott & Ishmael, 1992).

Aluminium was applied in 0.5 mL solution as 2.5, 5, 10 and 25% aluminium chloride, or 10 or 25% aluminium chlorhydrate to 2 cm2 of shaved skin on the back of TF1 strain mice for 5 consecutive days. Aluminium was similarly applied for 5 days to mice, New Zealand rabbits and white strain pigs (1 mL of solution to 4 cm2) as 10% aluminium chloride, nitrate, chlorhydrate, sulphate, hydroxide (in suspension) and basic acetate (in suspension), and as 25% aluminium chlorhydrate. The 10% solutions of aluminium chloride and nitrate produced epidermal changes that included slight to severe hyperplasia with focal ulceration, epidermal damage, dermal inflammatory cell infiltration, hyperkeratosis, acanthosis, microabscesses, aluminium deposition and abnormal keratin (Lansdown, 1973). The other 4 aluminium forms did not produce these changes. The author suggested that the aluminium ion interacted with keratin to denature it, making the stratum corneum more permeable, thereby allowing aluminium penetration through the stratum corneum to cause toxicity to the epidermal cells. Magnesium aluminium silicate was a weak primary skin irritant in rabbits (CFTA, 1970). Therefore, aluminium can produce dermal irritation that is aluminium species-dependent.

The i.p. injection of ground aluminium phosphate in rats produced extensive fibrosis in the peritoneal cavity (Evans & Zeit, 1949). Zeolite injection produced a peritoneal fibrosis (Suzuki & Kohyama, 1984). Sub-plantar injection of bentonite produced granulomas in rats (Marek & Blaha, 1985).

Aluminium is used as an adjuvant in vaccines and hyposensitization treatments for allergies. Precipitation of toxins and toxoids by alum was found to enhance their antigenic properties and reduce the rate of absorption and elimination of the antigen (Glenny et al., 1926; 1931). However, an in vitro study demonstrated that proteins present in interstitial fluid that have a larger adsorption coefficient can displace aluminium-adsorbed proteins with a smaller coefficient, with > 50% protein displacement within 15 minutes. It has been suggested that this result does not support the proposed mechanism of aluminium-enhanced antigenicity by producing a persistent depot of antigen (Heimlich et al., 1999). In addition to delaying release, aluminium strengthens the immunological properties of weak antigens to improve antibody response, as shown by addition of aluminium hydroxide to triple vaccine, 2.5 mg in the 0.5 mL injection. This reduced toxicity and increased potency in laboratory tests, and reduced reactions in children. However it produced s.c. nodules (Butler et al., 1969) (see also Effects on Humans, Effects from Non-Occupational Exposure, Irritation, Irritation after Injection of Aluminium-Adsorbed Proteins (Vaccines and Hyposensitization Regimens)). Aluminium adjuvants may also increase antigenicity by increasing the production of a local granuloma which contains antibody-producing plasma cells (White et al., 1955); by increasing the immunogenicity of the aluminium-antigen complex; by increasing antigen specific as well as total IgE antibodies (Gupta, 1998); and by stimulating the body’s immune competent cells through activation of complement, induction of eosinophilia, and activation of macrophages, lymphocytes and lymph nodes (Gupta, 1998; Hunter, 2002). Aluminium hydroxide-stimulated macrophages contain aluminium and differentiate into mature, specialized antigen-producing cells that express surface molecules similar to those seen in cultured dendritic cells, including HLA-DRhigh, CD-86high, CD14-, and CD83 (Rimaniol et al., 2004). These effects seem to be aluminium-dependent, because aluminium, phosphate-adsorbed TT produced a prolonged synthesis of specific IgE, whereas calcium phosphate adsorbed TT did not (Vassilev, 1978). This is discussed further in Effects on Humans, Effects from Non-Occupational Exposure, Irritation, Irritation after Injection of Aluminium-Adsorbed Proteins (Vaccines and Hyposensitization Regimens).

There is other evidence for aluminium induction of the immune system. I.p. administered ovalbumin-adsorbed-aluminium silicate enhanced IgE antibody production (Fujimaki et al., 1984). Aluminium silicate is a component of fly ash. IgE and IgG production were increased by intratracheal instillation of ovalbumin adsorbed onto 0.02 or 0.2 mg of aluminium silicate, or onto alum or kaolin (Fujimaki et al., 1986).

Aluminium phosphate-precipitated toxoid prolonged the response to the toxoid in rabbits and guinea pigs, producing granulomas and antibody-containing cells 4 to 7 weeks after injection (White et al., 1955). The intradermal injection of alum-precipitated antigens produced lymph node infiltration of histiocytes (Turk & Heather, 1965). Intradermal injection of aluminium chlorhydrate into guinea pigs produced granulomas consisting of aggregations of undifferentiated macrophages that followed lymph drainage to the regional lymph nodes where they collected (Gaafar & Turk, 1970). Intradermal injection of 0.1 mL of alum-precipitated protein or aluminium hydroxide emulsion into Hartley guinea pig ears produced histiocyte infiltration within 4 days, persisting up to 28 days, that was mainly localized in close proximity to the entrance to the afferent lymphatics (Gaafar & Turk, 1970). I.m. injection of aluminium hydroxide or aluminium-adsorbed TT (0.1 mL containing 0.05 mg aluminium) in mice produced interstitial oedema and degenerative/necrotic changes and polymorphonuclear leukocyte infiltration at 24 hr. This acute reaction decreased over 72 hr when macrophage infiltration began, leading to a chronic granulomatous reaction beginning 1 to 2 weeks later that peaked at 8 and persisted for 16 to 20 weeks (Goto & Akama, 1982). Intradermal injections of 0.05, 0.5 or 5 mg aluminium chlorhydrate or zirconium aluminium glycinate (ZAG) or 0.065, 0.65 or 6.5 mg of aluminium hydroxide were given to Hartley strain guinea pigs. The aluminium hydroxide injections produced granulomas after the higher 2 doses. Those produced by 6.5 mg aluminium hydroxide persisted for longer than 28 days. These granulomas demonstrated undifferentiated macrophages and occasional giant cells around the injection. There was little evidence of infiltration and none of fibrosis. Aluminium chlorhydrate and ZAG injections produced skin thickness increases that reached a maximum at 28 days, and granulomas consisting of shredded bundles of basophilic collagen, giant cells and histiocytes which were pleomorphic, strongly hyperchromatic and sometimes phagocytic, followed by intense fibrosis (Turk & Parker, 1977). The authors suggested aluminium induced persistent nodule formation by a nonallergic direct toxic effect (foreign body reaction). I.m. injection of aluminium hydroxide-adsorbed TT into mice produced muscle fibre necrosis and eosinophil infiltration 4 days later (Walls, 1977). When aluminium chlorhydrate or ZAG were injected into the toe pad of New Zealand rabbits twice weekly for 6 weeks for a total dose of 1.4 mg, foreign-body granulomas, but not positive skin reactivity, were induced (Kang et al., 1977). Intradermal injection of 0.25 mL of vaccine containing ~ 0.3 mg aluminium into the backs and sides of rabbits produced s.c. nodules at all sites 8 days later, which persisted in most rabbits for 56 days and in 1 for 72 days (Pineau et al., 1992). The nodules had greater aluminium concentration than did normal skin. The infiltrate intensity and aluminium concentration in the nodules positively correlated. However, this is not the typical route for such injections. Aluminium hydroxide gel and suspension (aluminium concentration, 1 or 3 mg/mL) were injected i.m. (0.5 mL) or s.c. (1 mL) as 3 mg aluminium with ovalbumin into the hind legs of Hartley strain guinea pigs. The aluminium hydroxide gel produced granulomatous inflammatory reactions characterized by macrophages with foamy cytoplasm, small lymphocytes and giant cells at the injection sites. These effects persisted at least 8 weeks (Goto et al., 1997).

Aluminium compounds are the only adjuvants widely used in routine human vaccines and are the most commonly used adjuvants in veterinary vaccines. Two production methods have been used. One is the addition of alum to the antigen to form a precipitate of protein aluminate, termed alum-precipitated vaccines, which are similar in composition and physicochemical characteristics to aluminium phosphate adjuvants. The second is the addition of the antigen solution to preformed aluminium hydroxide, aluminium phosphate, mixed aluminium hydroxide and phosphate, or gamma aluminium oxide to produce aluminium-adsorbed vaccines (Clements & Griffiths, 2002; HogenEsch, 2002). Aluminium hydroxide (chemically: crystalline aluminium oxyhydroxide) and aluminium phosphate (chemically: aluminium hydroxyphosphate) are most commonly used (Hem, 2002). The former has an isoelectric point of 11.4 and is positively charged in interstitial fluid, at pH 7.4, thereby adsorbing negatively charged antigens by electrostatic attractive forces. Aluminium phosphate has an isoelectric point between 4.5 and 6, is negatively charged at neutral pH and this adsorbs positively charged antigens. Rational selection of the aluminium form is based on the charge of the protein to be adsorbed.

When aluminium starch octenylsuccinate was prepared in suspension and injected intracutaneously into a depilated site on the back of guinea pigs and rabbits, thrice weekly the first week and weekly for 7 more weeks, no abnormal skin reactions were observed (Nair & Yamarik, 2002). Subarachnoid (cisternal magna) injection of kaolin into foetal lambs and monkeys produced a fibrotic reaction and inflammatory cell response of the meninges and infiltration of kaolin-containing macrophages into the subarachnoid space (Edwards et al., 1984).

Ophthalmic exposure

With respect to studies relevant to industrial aluminium exposure, instillation of aluminium sulphate, potash alum, and ammonium alum into the eye resulted in conjunctivitis and purulent ophthalmitis (Grekhova et al., 1994).

Of relevance to the potential effects of human exposure to aluminium in cosmetics, instillation of aluminium starch octenylsuccinate, 70 mg in 0.1 mL, into the conjunctival sac of rabbits produced a slight reddening of the conjunctiva that was seen from 1 to 24 hr later; this was considered “unlikely” to be an ocular irritant in humans (Nair & Yamarik, 2002). When placed in the eye of rabbits as an eye shadow containing 15% of this aluminium form, the irritation potential was considered mild by the Draize classification system (Nair & Yamarik, 2002). Formulations containing 1 and 2.5% of this aluminium form were considering non-irritating in the chorioallantoic membrane vesicular assay (Nair & Yamarik, 2002). Magnesium aluminium silicate caused minimal eye irritation in a Draize eye irritation test (Hazelton Laboratories, 1968). Bentonite caused severe iritis after injection into the anterior chamber of the eyes of rabbits. When injected intralamellarly, widespread corneal infiltrates and retrocorneal membranes were recorded (Austin & Doughman, 1980).

Implantation exposure

Discs of synthetic auditory ossicle composed of aluminium oxide were implanted s.c. in the interscapular region of 16 rats and removed 1, 3, 7 and 14 days later. After 1 day, this resulted in an acute inflammatory reaction in which macrophages and neutrophils predominated and that almost disappeared after 7 days. Fibrosis began to be observed at 3 days (Ye et al., 1998).

Many reports are cited in Effects on Laboratory Mammals and In Vitro Test Systems, Irritation, Inhalation Exposure / Intratrachael Exposure, and Effects on Humans, Effects from Occupational Exposure, Irritation, Inhalation Exposure of the ability of aluminium to cause pneumoconiosis, an inflammation of the lung that can progress to fibrosis, which is typically caused by inhalation of dust. There are also many reports of negative findings. The discrepancy may be due to the chemical form (species) of the inhaled aluminium, granular vs. flake-like particles. In this section, studies addressing the mechanism(s) of action of these irritant effects are discussed.

Corrin (1963a;1963b) noted that aluminium reacts with water but is not able to do so when coated with inert aluminium oxide. Granular aluminium coated with aluminium oxide is produced without use of lubricating agents, such as spindle oil and stearine. The author attributed many of the reports of negative effects to exposure to aluminium oxide or aluminium oxide-coated aluminium. The author also found that spindle oil- or stearine-coated aluminium powder reacted with water, presumably forming reactive aluminium hydroxide, whereas stearine-coated aluminium powder did not, and noted that the substitution of mineral product for stearine coincided with the onset of aluminium-induced pneumoconiosis. The explanation offered was that respirable aluminium particles that can react with water in the lung can be toxic.

Aluminium oxide was shown to release histamine from rat peritoneal mast cells (Casarett et al., 1968). The greatest effect, seen with 4.4 μm maximal median diameter particles at pH 6.8, was comparable to that see with iron oxide but less than seen with chromium oxide. This may contribute to bronchoconstriction caused by inhaled aluminium particles. Four clays containing aluminium silicate (montmorillonite, bentonite, kaolinite and erionite), caused lysis of human umbilical vein endothelia, N1E-115 neuroblastoma and ROC-1 oligodendroglial cells (Murphy et al., 1993). The authors suggested these clays might disrupt the BBB, allowing their entry into the brain. Exposure of mouse peritoneal macrophages, human type II alveolar tumour (A549) cells and Chinese hamster V79-4 lung cells to 11 minerals, including short and long fibres of attapulgite (a hydrated magnesium aluminium silicate) revealed some dusts that were non-toxic to all three cell types, some that were toxic toward mouse peritoneal macrophages, as shown by LDH release, and some that were toxic to all 3 cell types, additionally causing increased diameter of the A549 cells and reduced survival of 79-4 cells (Chamberlain et al., 1982). The results suggest differential sensitivity of cells to toxicity produced by these dusts and that long-fibred dusts are more toxic than short-fibred dusts. Exposure of rabbit AM to hydrated aluminium silicate resulted in toxicity, as evidenced by reduced viability and ATP (Hatch et al., 1985). Hydrated aluminium silicate caused concentration-dependent haemolysis of erythrocytes (Woodworth et al., 1982). Murine neuroblastoma cells exposed to hydrated aluminium silicate showed an increase in membrane electrical conductance and loss of excitable activity, as evidence of toxicity (Banin & Meiri, 1990).

The immune system and its reactions involve interactions between various cell types and soluble mediators. These responses can be clustered into innate (natural and non-specific) and acquired (adaptive) responses for which the reaction is directed to an antigenic determinant or epitope. Non-specific responses involve effector cells such as macrophages, natural killer cells, granulocytes, and mediator systems such as the complement system. Biologically, components of the immune system are present throughout the body and interactions between the immune system and other organ systems are a normal component of immunoregulation. While a number of metals have been demonstrated to have immunotoxic properties, little has been reported for aluminium (IPCS/WHO, 1996). In addition, aluminium hydroxide has been used as an adjuvant in many human vaccines (Roit et al., 1998) (see Table 7). Vaccine efficiency is enhanced by aluminium’s capacity to absorb antigen particles forming granulomas in the point of injection. Early studies suggested altered immune responses following excess aluminium exposure. Pregnant Swiss-Webster mice exposed to aluminium (500 or 1,000 μg Al/g diet; as aluminium lactate) showed a lower resistance to bacterial Listeria monocytogene infection while non-pregnant mice showed the reverse (Yoshida et al., 1989). Acute injection of aluminium (1-10 mg/kg body weight to non-pregnant mice) resulted in a lower mortality rate to L. monocytogenes as compared to controls (Yoshida et al., 1989). In these studies, the offspring showed no differences in mortality rates. However, Golub et al. (1993) suggested that excess aluminium exposure (1000 μg Al/g diet; as aluminium lactate) in Swiss Webster mice from conception to 6 months of age resulted in alterations in immune effector cell function. Splenic lymphocytes showed a depressed response to concanavalin A. When the spleen weight was measured in mice fed 1000 ppm in the food from weaning to adulthood (4 week and 8 week exposures) no changes were detected relative to controls (Golub & Keen, 1999). Based upon these studies, Tsunoda & Sharma (1999) examined pro-inflammatory cytokine mRNA levels in the brain and immune organs of mice following a 1-month exposure to 125 ppm aluminium ammonium sulphate in the drinking water. Isolated splenic macrophages and lymphocytes showed no aluminium-related changes in the basal mRNA levels of TNFα, IL-1β, or IFNγ. However, the authors suggested that, while low and somewhat variable, basal mRNA levels for TNFα were increased in the brain of aluminium exposed mice (Tsunoda & Sharma, 1999).

With the exception of experimental studies in which the effect of aluminium exposure on the reproductive system has been examined (Effects on Laboratory Mammals and In Vitro Test Systems, Reproductive and Developmental Toxicity, Reproductive Toxicity), those designed to examine adverse effects on the endocrine system have been limited to the parathyroid response given that aluminium overload leads to PTH suppression.

Many of the PTH receptors of interest for aluminium toxicity are present in both the bone and kidney; thus, much of the data with regard to the effect of aluminium exposure on the bone discussed in Effects on Laboratory Mammals and In Vitro Test Systems, Effects On Bone is related to the alterations in serum PTH levels and calcium homeostasis. For example, Pun et al. (1990) demonstrated that lower concentrations of aluminium (4μm and 40 μM) inhibited the cyclic AMP response to PTH challenge via a decrease in PTH receptor binding in both clonal osteoblastic UMR-106 cells and in dog renal cortical membrane. Bourdeau et al. (1987) examined the endocrine response of porcine parathyroid gland tissue slices to aluminium at concentrations of 20 to 500 ng/mL. High concentrations of aluminium inhibited induced PTH release in a calcium-dependent manner. Gonzalez-Suarez et al. (2003) reported that 8 weeks of exposure to aluminium chloride (AlCl3) (i.p. daily) reduced serum PTH levels and cell proliferation in the parathyroid glands, yet did not alter serum phosphorus levels, cell apoptosis or the calcium sensing receptor expression in young adult male Wistar rats surgically nephrectomized (7/8th tissue excised). In a similar study, Diaz-Corte et al. (2001), surgically nephrectomized adult male Wistar rats maintained on a high dietary phosphorus intake received 2 daily ip. injections of AlCl3 five weeks after surgery and examined 2 weeks post-injection. While significant decreases in serum PTH levels and mRNA levels for PTH in the parathyroid gland were seen in the aluminium-injected group, no differences were seen in serum calcium and phosphorus levels, renal function or body weight. Similar decreases in plasma PTH concentrations have been reported in cats with stable chronic renal failure when maintained on a diet restricted in phosphorus and protein with aluminium hydroxide included as an intestinal phosphate binding agent (Barber et al., 1999).

Aluminium compounds have produced negative results in most short-term mutagenic assays. As early as 1976, aluminium (Al2(SO4)3) had been shown to decrease DNA synthesis without affecting replication fidelity (Sirover & Loeb, 1976). At concentrations from 20 μM to 150 mM, the accuracy of DNA synthesis in vitro was maintained. In a rat osteoblast cell line, UMR 106, DNA synthesis as determined by 3H-thimidine incorporation was shown to be decreased in the absence of an increase of protein synthesis as determined by 3H-leucine incorporation by exposure to 30 μM aluminium (Blair et al., 1989). Aluminium concentrations of 0.01 mM to 0.1 M, as AlCl3, showed no potential to induce depurination of DNA as measured by the release of adenine or guanine in calf-thymus DNA (Schaaper et al., 1987). Calf-thymus DNA was used by Ahmad et al. (1996) to examine alterations in DNA binding by AlCl3 (0.6-25 mM). These authors reported that aluminium was bound to the backbone PO2 group and the guanine N-7 site of the G-C base pairs by the process of chelation.

In bacteria, aluminium compounds have been considered, in general, to be non-mutagenic. Aluminium showed no mutagenic activity as measured by the Rec-assay using Bacillus subtilis (Nishioka, 1975). At concentrations of 1 to 10 mM, Al2O3, AlCl3, and Al2(SO4)3 were also negative in the Rec-assay with the Bacillus subtilis H17 rec+ and M45 rec- strains (Kada et al., 1980; Kanematsu et al., 1980). Both aluminium and hydrated aluminium chloride (AlCl3-6H2O) at concentrations ranging from 10 to 100 nM per plate failed to induce reverse mutations in the Salmonella typhimurium TA102 strain as identified by his gene mutations (Marzin & Phi, 1985). Positive results have been obtained in studies using dye-alumina complexes; however these (positive) results have been attributed to impurities in the complexes rather than an effect of aluminium (Brown et al., 1979). The absence of mutagenic effects of aluminium compounds on various bacterial strains including Salmonella typhimurium and Escherichia coli demonstrated in these early studies has been supported by the findings of more recent studies (Ahn & Jeffery, 1994; Gava et al., 1989; Marzin & Phi, 1985; Olivier & Marzin, 1987; Prival et al., 1991; Seo & Lee, 1993; Shimizu et al., 1985; Venier et al., 1985; Zeiger et al., 1987). In their assessment of mutagenicity, Ahn & Jeffrey (1994) failed to find positive findings with aluminium chloride (0.3 and 3.0 ppm) using the biological endpoint of his mutation induction in the absence of S9 metabolic activation in the TA98 strain. No induction of his mutations were seen by Marzin & Phi (1985) in the 102 strain exposed to aluminium chloride hexahydrate (10-100 nmol/plate), and by Gava et al. (1989) in the TA104, TA92, TA98, TA1000 strains exposed to aluminium acetylacetonate (1.9-48 μmol/plate), aluminium lactate (1.8 - 5.5 μmol/plate), or aluminium maltolate (0.5-3.7 μmol/plate). The Salmonella typhimurium strain, TA104, showed a his gene mutation to aluminium acetylacetonate (1.8 – 48 μmol/plate); however, negative responses were reported when comparisons were made between the absence and presence of S9 metabolic activation. Shimizu et al. (1985) showed no positive response to aluminium fluoride (0.02-119 μmol/plate) in TA98, TA100, TA1535, TA1537, and TA1538 strains. Zeiger et al. (1987) showed similar results in the TA98, TA100, TA1535, and TA1537 strains following exposure to sodium aluminium silicate (0.96 - 38.5 μmol/plate). Prival et al. (1991) showed no positive responses to sodium aluminium silicate (0.36 - 108.1 μmol/plate) or calcium aluminosilicate (0.033 - 10 mg/plate) in TA98, TA100, TA1535, TA1537, and TA1538 strains. Studies with Escherichia coli (WP2 strain) have shown negative responses in trp mutations with aluminium chloride (0.8 mol) (Seo & Lee, 1993); aluminium fluoride (12 nmol-1.6 mmol/plate) (Shimizu et al., 1985); calcium aluminosilicate (0.33-10 mg/plate), and sodium aluminium silicate (0.96.1 μmol/plate) (Prival et al., 1991). Using the SOS chromotest, Raabe et al. (1993) evaluated the genotoxicity potential of 36 characteristic waste products resulting from aluminium plasma etching. While a majority of the products show some genotoxic activity, a correlation between the organic constituents and biological effect could not be established. Using the common soil bacterium Rhizobium, Octive et al. (1991) reported preliminary findings showing no change in cell survival following an 18 hr exposure to 50 mM aluminium in both RDG 2002 and NZP2037 strains. In each strain, exposure to rafampicin for 3-14 days decreased cell growth; the data suggested a slight resistance in the RDG 2002 strain exposed to aluminium.

Studies have shown that aluminium compounds can inhibit cell division and produce chromosomal aberrations in plants. The relevance of data derived from plant studies to assess the carcinogenic potential in mammalian systems has come under question given that metal salts of various carcinogenic potential can give similar results in short-term plant assays (Léonard & Gerber, 1988). An early study by Gelfant (1963) showed that mammalian cell division can be inhibited by aluminium salts; however, later studies showed that this did not translate to morphological transformation of Syrian hamster embryo cells. In these cells, AlCl3 and Al2(SO4) at concentrations up to 20 μg/mL medium neither caused morphological transformation nor enhanced their transformation induced by a simian adenovirus SA7 (Casto et al., 1979; Di Paolo & Casto, 1979). In the L5178Y mouse lymphoma assay, AlCl3, 500-620 μg/mL, did not induce forward mutations at the thymidine kinase locus (Oberly et al., 1982). Chromosome aberrations have been reported in spermatocytes of grasshoppers (Phloeoba antennata) 48 – 60 hr post aluminium chloride (10 mg/0.21 g b.w.; Manna & Parida, (1965)) and in mammalian peritoneal cells (Nashed, 1975). Aberrations in the bone marrow cells of mice injected with aluminium chloride (0.1M aluminium chloride 1 mL/30 g b.w., acute ip. dose) have also been reported in a single study (Manna & Das, 1972).

Aluminium is known to act as a cross-linking agent for various cellular filaments. Using ascites hepatoma cells from Sprague-Dawley rats, Wedrychowski et al. (1986a; 1986b) reported that AlCl3 could serve as a stimulator for the crosslinking of chromosomal proteins. However, in an Epstein-Barr virus-transformed Burkitts human lymphoma cell line, AlCl3 showed no ability to crosslink DNA protein at either cytotoxic or non-cytotoxic concentration levels (Costa et al., 1996). Human blood lymphocytes showed positive responses for both micronuclei formation (Migliore et al., 1999; Roy et al., 1990) and sister chromatin exchange (Roy et al., 1990) at AlCl3 levels from 11.6 μmol/mL (Roy et al., 1990) to 500 - 4000 μM (Migliore et al., 1999). Roy et al. (1990) reported that the increase in micronuclei formation was significant only in cells obtained from adult donors, and sister chromatin exchange was significant only in cells from females. The chromatid aberrations reported in the Roy et al. (1990) study were limited to an increase in gaps and breaks and the study was done in phosphate-free media. One additional study (Alfaro Moreno et al., 1997) conducted using BALB/c mouse 3T3 cells reported anaphasic alterations as a possible step in the process of chromosomal dysfunction following exposure to Mexicali dust (98% potassium aluminium silicates and 2% sodium dioxide- 0.67 mMl/L). The work of Karlik et al. (1980a; 1980b) suggested that interactions of aluminium with DNA would be dependent upon pH.

During the 1990s, a number of investigators conducted experiments to determine the genotoxic potential of aluminium compounds administered to the whole animal. Short-term studies examining changes occurring within the first 24 - 48hr of systemic dosing with aluminium compounds showed contradictory results. Isolated DNA from the liver of male Wistar rats showed no changes in the formation of 8-hydroxydeoxyguanosine (Umemura et al., 1990) following a high dose of aluminium nitrilotriacetate complex (7 mg Al/kg [259 μmol/kg] i.p.). Takagi et al. (1990) exposed F-344 rats to 1.2% aluminium clofibrate in the diet; within 1-12 months of exposure the rats showed an elevation in hepatic peroxisomal beta-oxidation enzyme activity. One early preliminary study using high levels of aluminium chloride (0.01 - 0.1 mol/mouse, i.p.) reported the induction of chromosomal aberrations (Manna & Das, 1972). Two later published studies used high dose levels of aluminium sulphate (100 - 500 mg/kg bw (0.3 - 1.5 mmol Al/kg b.w.)) as a known inducer of either micronucleated polychromatic peripheral erythrocyte (mnPCE) formation (Roy et al., 1992) or SCEs (Dhir et al., 1993) in murine bone marrow cells. As expected, a significant increase in mnPCEs was induced 24 hrs after a second aluminium dose of 500mg/kg b.w. in Swiss albino mice. No changes were seen at the 250 mg/kg b.w. dose level (Roy et al., 1992). The work of Dhir et al. (1993) showed an induction of SCEs in bone marrow from male Swiss albino mice in a dose-related fashion 24 hr after a single dose of aluminium sulphate. The induction of SCEs was detected by bromodeoxyuridine (BrdU) pre-labelling (50 mg BrdU paraffin-coated tablet implanted subcutaenously) followed by a single dose of aluminium sulphate (100, 200, or 400 mg/kg b.w.) and a single i.p. injection of colchicine (4 mg/kg b.w.) 22 hrs later.

Studies in which in either male rats (Rattus norvegicus) or sheep were exposed to complex mixtures containing aluminium were indicative of positive changes. Bauer et al. (1995) reported mnPCE formation in male and female Wistar rats that received vacuum pump oils contaminated by waste products from a BC13/C12 aluminium plasma etching process (dose of 1000 mg/kg/day in a gavage dosing volume of 0.54 mL/kg/day). Numerous compounds and elements were identified in the waste; however, the aluminium contribution to the waste was at approximately 2000 ppb. MnPCE formation in bone marrow was not detected until the animals had been exposed for 28 days. In another mixture study, the emissions of aluminium and other ionic forms of metals from an aluminium refining plant were administered orally in distilled water for one year to sheep (Sivikova & Dianovsky, 1995). The total calculated concentration of aluminium delivered was 1.1 or 2.4 mmol Al/animal/day. A significant increase in SCEs was found in the cultured lymphocytes of the high dose group only. A mitotic delay in both dose groups was reported by the authors based upon differences in cell metaphases relative to that seen in the controls. Spotheim-Maurizot et al. (1992) reported on the antigenotoxicity of aluminium. The in vitro frequency of single- and double-stranded breaks in plasmid DNA, as induced by radiation, was significantly inhibited by low concentrations of aluminium chloride. A 50% reduction in double-stranded breaks occurred with 0.2 mM aluminium chloride. A similar reduction was seen in single-stranded breaks with 0.04 mM concentration levels. The authors speculated that the reduction was due to structural changes occurring in the DNA that prevented the access of OH+ radicals.

Overall, experimental animal studies have failed to demonstrate carcinogenicity attributable solely to aluminium compounds (for reviews, see ATSDR, 1999; Furst, 1971; Furst & Haro, 1969; Haddow & Hornig, 1960; IPCS, 1997; Shubik & Hartwell, 1969). The data that exist for aluminium compounds support the relevance of the physical characteristics of aluminium in relation to the adverse endpoint under study as was suggested by Krueger et al. (1984). As an example, in a very early study, O’Gara & Brown (1967) reported an increase in sarcomas (8 out of 18 rats) in NIH black rats implanted s.c. with 0.05 mm thick aluminium foil. However, intrapleural or i.p. administration of 3.5 μm diameter aluminium fibres to rats showed no indication of carcinogenicity (Pigott & Ishmael, 1981; 1992; Stanton, 1974). It has been proposed that the results of these studies support the hypothesis put forth by Bischoff & Gyson (1964) that the dimension of the implant rather than chemical composition is related to carcinogenicity (for review, see Krueger et al. (1984)). A similar pattern is evident in inhalation studies. Steinhagen et al. (1978) reported a dose-related increase in lung lesions in both rats (Fischer 344 males and females) and guinea pigs (Hartley) following inhalation of aluminium chlorhydrate for six months. Fifty-percent of the animals showed lesions following exposure to 2.5 mg/Al/m3 increasing to 100% of animals that had been exposed to 25 mg Al/m3. In guinea pigs, approximately 10% showed an increase in AM at a low dose of 0.25 mg Al/m3. The pathology was characterized by an increase in mononuclear inflammatory cells and large macrophages in alveoli around the termination of air passageways. These data suggest a progression in the inflammatory response of the lungs with aluminium chlorohydrate exposure that may be related to the tissue response to foreign bodies and the associated irritant response. A later study showed no increased tumour incidence in rats (male and female Wistar) following inhalation of alumina fibres (2.18 or 2.45 mg/m3; Al2O3 and approx. 4% silica) of a similar diameter for 86 weeks (Pigott & Ishmael, 1981). When Al2O3 dust was intratracheally instilled in hamsters, Stenback et al. (1973) concluded that Al2O3 was not carcinogenic for the respiratory system. Of two additional early studies Schroeder & Mitchner (1975a) reported an increased incidence in gross tumours of approximately 52% as compared to 16% in control male Long-Evans rats exposed to aluminium (KAl(SO4)2) at a concentration of 5 ppm in drinking water for approximately 2-2.5 yr. This was observed in males only. In the second study, no increase in the incidence of neoplasms in either male or female Wistar rats exposed to aluminium phosphide/ammonium carbamate in the diet for 2 years was reported (Hackenberg,1972).

A limited number of studies have been conducted in mice. Two studies examined the effects of oral exposure to aluminium potassium sulphate in male and female mice. Schroeder & Mitchener (1975b) reported an increase in the incidence of gross tumours in female Swiss Webster mice (46 vs. 30%) following exposure to 5 ppm aluminium in drinking water (1.2 mg/kg b.w./day for 2-2.5 years). A more recent study by Oneda et al. (1994) showed no increase in the incidence of gross tumours, neoplastic lesions, or other proliferative lesions in B6C3F1 mice following dietary exposure to up to 979 mg Al/kg/day for 20-24 months. Interestingly, in all groups, the incidence of spontaneous hepatocellular carcinoma was significantly decreased in the females. This was also significantly decreased in the high-dose group males (5.5 vs. 20.5% in controls) and the incidence of myocardial eosinophilic cytoplasm showed a dose-dependent decrease with aluminium exposure. When the route of delivery was changed and an i.p. injection of Al2O3 was given in male and female mice at 2 and 3 months of age, examination at the end of normal lifespan showed an increase in mesothelioma in the peritoneum (Frash et al., 1992).

Aluminium compounds have been proposed as possible chemotherapeutic agents. Experimental animal studies showed that aluminium nitrate (50 - 400 mg/kg; optimal dose: 150mg/kg b.w.) could significantly reduce the growth of i.p. transplanted Walker 256 carcinosarcomas in female Sprague-Dawley rats (Adamson et al., 1975; Hart & Adamson, 1971). A similar effect was not evident against P388 leukaemia cells, L1210 leukaemia, K1964 leukaemia, YPC-1 plasma cells, or Ehrlich ascites carcinoma cells. These effects may be related to differential uptake of aluminium by these cells (Adamson et al., 1975) or, alternatively, by direct alterations of the immune response (Pauwels et al., 1979). Pretreatment with a s.c. injection of 0.1 mL 0.2% aluminium chloride (AlCl3 - 6H2O) reduced the number of developing nodules induced by dimethyl nitrosamine (Yamane & Ohtawa, 1979).

With additional investigation, the roles of social, environmental, and biological factors as either modifiers of potential risk or susceptibility factors for adverse effects from chemical exposure are becoming more evident. With regards to genetic factors, Fosmire et al. (1993) examined the level of aluminium in the brains of 5 strains of inbred mice following dietary exposure to 260 mg Al/kg b.w. for 28 days. While no difference could be detected between the A/J, BALB/c, and C57BL/6 strains, higher levels of aluminium were seen in the brains of DBA/2 and C3H/2 strains. Interestingly, the C3H/HeJ and the C57BL/6 strain differ in bone density (Beamer et al., 1996) and calcium metabolism which is thought to occur partially via the vitamin D and PTH endocrine systems’ regulatory influence on extracellular calcium (Chen & Kalu, 1999), both of which can be influenced by aluminium. Tf plays a significant role in the biological availability of aluminium to organ systems. The ability to saturate Tf with iron was reported to be approximately 10 times greater in C57BL/6 and BALB/c mice than in DBA/2 and AKR mice; however, serum Tf levels were equivalent across these strains (Leboeuf et al., 1995). For a discussion of other potentially modifying factors such as age, and interactions with other chemical species, see Toxicokinetics.

• AAMI (Association for the Advancement of Medical Instrumentation) Water Quality for Dialysis. 3. Arlington: AAMI WQD; 1998. [Google Scholar]
• Abramson MJ, Wlodarczyk JH, Saunders NA, Hensley MJ. Does aluminum smelting cause lung disease? Am Rev Respir Dis. 1989;139:1042–1057. [PubMed] [Google Scholar]
• Abreo K, Glass J, Sella M. Aluminum inhibits hemoglobin synthesis but enhances iron uptake in friend erythroleukemia cells. Kidney Int. 1990;37:677–681. [PubMed] [Google Scholar]
• Abreo K, Jangula J, Jain S, Sella M, Glass J. Aluminum uptake and toxicity in cultured mouse hepatocytes. J Am Soc Nephrol. 1991;1:1299–1304. [PubMed] [Google Scholar]
• Abreo K, Sella M, Gautreaux S, De Samet R, Vogeleere P, Ringoir S, Vanholder R. P-cresol, a uremic compound, enhanced the uptake of aluminum in hepatocytes. J Am Soc Nephrol. 1997;8:935–942. [PubMed] [Google Scholar]
• Abreo K, Abreo F, Sella M, Jain S. Aluminum enhances iron uptake and expression of neurofibrillary tangle protein in neuroblastoma cells. J Neurochem. 1999;72:2059–2064. [PubMed] [Google Scholar]
• Abreo K, Sella M, Alvarez-Hernandez X, Jain S. Antioxidants prevent aluminum-induced toxicity in cultured hepatocytes. J Inorg Biochem. 2004;98:1129–1134. [PubMed] [Google Scholar]
• Abubakar MG, Taylor A, Ferns GA. Regional accumulation of aluminium in the rat brain is affected by dietary vitamin. Eur J Trace Elem Med Biol. 2004;18:53–59. [PubMed] [Google Scholar]
• ACGIH (American Conference of Governmental Industrial Hygienists) 1995-1996 Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists; 1996. [Google Scholar]
• ACGIH (American Conference of Governmental Industrial Hygienists) Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists; 2005. [Google Scholar]
• Ackley DC, Yokel RA. Aluminum citrate is transported from brain into blood via the monocarboxylic acid transporter located at the blood-brain barrier. Toxicology. 1997;120:89–97. [PubMed] [Google Scholar]
• Ackley DC, Yokel RA. Aluminum transport out of brain extracellular fluid is proton dependent and inhibited by mersalyl acid, suggesting mediation by the monocarboxylase transporter (MCTI) Toxicology. 1998;127:59–67. [PubMed] [Google Scholar]
• Adamis Z, Timar M, Kofler L, Tatrai E, Ungvary G. Biological effects of the respirable dusts from ore mines. Environ Res. 1986;41:319–326. [PubMed] [Google Scholar]
• Adamson RH, Canellos GP, Sieber SM. Studies on the antitumor activity of gallium nitrate (NSC-15200) and other group IIIa metal salts. Cancer Chemother Rep. 1975;59:599–610. [PubMed] [Google Scholar]
• Adler AJ, Berlyne GM. Duodenal aluminum absorption in the rat: effect of vitamin D. Am J Physiol. 1985;249:209–213. [PubMed] [Google Scholar]
• Advenier E, Landry C, Colomb V, Cognon C, Pradeau D, Florent M, Goulet O, Ricour C, Corriol O. Aluminum contamination of parenteral nutrition and aluminum loading in children on long-term parenteral nutrition. J Pediatr Gastroenterol Nutr. 2003;36:448–453. [PubMed] [Google Scholar]
• Ahmad R, Naoui M, Neault JF, Diamontoglou S, Tajmir-Riahi HA. An FTIR spectroscopic study of calf-thymus DNA complexation with Al(III) and Ga(III) cations. J Biomol Struc Dyn. 1996;13:795–802. [PubMed] [Google Scholar]
• Ahn HW, Jeffery EH. Effect of aluminum on fluoride uptake by Salmonella typhimurium TA98; implications for the Ames mutagenicity assay. J Toxicol Environ Health. 1994;4:357–368. [PubMed] [Google Scholar]
• Ahn HW, Fulton B, Moxon D, Jeffery DH. Interactive effects of fluoride and aluminum uptake and accumulation in bones of rabbits administered both agents in their drinking water. J Toxicol Environ Health. 1995;44:337–350. [PubMed] [Google Scholar]
• Akila R, Stollery BT, Riihimäki V. Decrements in cognitive performance in metal inert gas welders exposed to aluminum. Occup Environ Med. 1999;56:632–639. [PMC free article] [PubMed] [Google Scholar]
• Akyol A, Boyvat A, Kundakci N. Contact sensitivity to aluminum. Dermatology. 2004;43:942–943. [PubMed] [Google Scholar]
• Al-Suliman NN, Grabau DA, Kiaer H, Rasmussen M, Bak M. A tumour in the breast: vaccination granuloma as a differential diagnosis. Eur J Surg Oncol. 1999;25:34–37. [PubMed] [Google Scholar]
• Alberti G, Biesuz R, Profumo A, Pesavento M. Determination of the total concentration and speciation of Al(III) in tea infusions. J Inorg Biochem. 2003;97:79–88. [PubMed] [Google Scholar]
• Albina ML, Bellés M, Sanchez DJ, Domingo JL. Evaluation of the protective activity of deferiprone, an aluminum chelator, on aluminum-induced developmental toxicity in mice. Teratology. 2000;6:86–92. [PubMed] [Google Scholar]
• Albuquerque D, Seidl V, Santos V, Oliveria-Neto J, Capelloi V, Rocco P, Zin W. The effect of experimental pleurodesis caused by aluminium hydroxide on lung and chest wall mechanics. Lung. 2002;179:293–303. [PubMed] [Google Scholar]
• Alder JF, Samuel AJ, West TS. The single element determination of trace metals in hair by carbon-furnace atomic absorption spectrometry. Anal Chim Acta. 1976;87:313–321. [PubMed] [Google Scholar]
• Alessio L, Apostoli P, Ferioli A, Sipio Di I, Mussi I, Rigosa C, Albertini A. Behaviour of biological indicators of internal dose and some neuro-endocrine tests in aluminium workers. Med Lav. 1989;80:290–300. [PubMed] [Google Scholar]
• Alexander J, Gjessing E, Nordal KP, Dahl E, Halse J, Thomsassen Y. A preliminary study of aluminium in serum and other human materials in subjects from different areas of Norway. Environ Geochem Health. 1990;12:83–86. [PubMed] [Google Scholar]
• Alfaro Moreno E, Flores Rojas G, Orozco de la Huerta A, Quintana Belmares R, Osornio Vargas AR. In vitro induction of abnormal anaphases by contaminating atmospheric dust from the city of Mexicali, Baja California, and Mexico. Arch Med Res. 1997;28:549–553. [PubMed] [Google Scholar]
• Alfrey AC. Aluminum metabolism in uremia. Neurotoxicology. 1980;1:43–53. [Google Scholar]
• Alfrey AC. Aluminum metabolism. Kidney Int. 1986;29(Suppl 18):S8–S11. [PubMed] [Google Scholar]
• Alfrey AC. Physiology of aluminum in man. In: Gitelman HJ, editor. Aluminum and Health A Critical Review. New York: Marcel Dekker, Inc; 1989. pp. 101–124. [Google Scholar]
• Alfrey AC. Aluminum toxicity in patients with chronic renal failure. Ther Drug Monit. 1993;15:593–597. [PubMed] [Google Scholar]
• Alfrey AC, Hegg A, Miller N, Berl T, Berns A. Interrelationship between calcium and aluminum metabolism in dialyzed uremic patients. Miner Electrol Metab. 1979;2:81–87. [Google Scholar]
• Alfrey AC, Hegg A, Craswell P. Metabolism and toxicity of aluminum in renal failure. Am J Clin Nutr. 1980;33:1509–1516. [PubMed] [Google Scholar]
• Alfrey AC, Sedman A, Chan YL. The compartmentalization and metabolism of aluminum in uremic rats. J Lab Clin Med. 1985;105:227–233. [PubMed] [Google Scholar]
• Allain P, Gauchard F, Krari N. Enhancement of aluminum digestive absorption by fluoride in rats. Res Commun Mol Pathol Pharmacol. 1996;91:225–231. [PubMed] [Google Scholar]
• Allen DD, Yokel RA. Dissimilar aluminum and gallium permeation of the blood-brain barrier demonstrated by in vivo microdialysis. J Neurochem. 1992;58:903–908. [PubMed] [Google Scholar]
• Allen DD, Orvig C, Yokel RA. Evidence for energy-dependent transport of aluminum out of brain extracellular fluid. Toxicology. 1995;98:31–39. [PubMed] [Google Scholar]
• Allen LV, Jr, Berardi RR, Desimone EM, Engle JP, Popovich NG, Rosenthal WM, Tietze KJ. Handbook of Nonprescription Drugs. Washington: American Pharmaceutical Association; 2000. [Google Scholar]
• Allen VG, Fontenot JP. Influence of aluminium as sulfate, chloride and citrate on magnesium and calcium metabolism in sheep. J Anim Sci. 1984;59:798–804. [PubMed] [Google Scholar]
• Al-Masalkhi A, Walton SP. Pulmonary fibrosis and occupational exposure to aluminum. J Ky Med Assoc. 1994;92:59–61. [PubMed] [Google Scholar]
• Altmann P, Dhanesha U, Hamon C, Cunningham J, Blair J, Marsh F. Disturbance of cerebral function by aluminium in haemodialysis patients without overt aluminium toxicity. Lancet. 1989;2:7–12. [PubMed] [Google Scholar]
• Altmann P, Cunningham J, Dhanesha U, Ballard M, Thompson J, Marsh F. Disturbances of cerebral function in people exposed to drinking water contaminated with aluminum sulphate: retrospective study of the Camelford water incident. Br Med J. 1999;319:807–811. [PMC free article] [PubMed] [Google Scholar]
• Alvarez-Hernandez X, Madigosky SR, Stewart B, Glass J. Iron status affects aluminum uptake and transport by Caco-2 cells. J Nutr. 1994;124:1574–1580. [PubMed] [Google Scholar]
• Amador FC, Santos MS, Oliveira CR. Lipid peroxidation facilitates aluminum accumulation in rat brain synaptosomes. J Toxicol Environ Health A. 1999;58:427–435. [PubMed] [Google Scholar]
• American Academy of Pediatrics, Committee on Nutrition. Aluminum toxicity in infants and children. Pediatrics. 1996;97:413–416. [PubMed] [Google Scholar]
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Washington, D.C.: American Psychiatric Association; 1987. [Google Scholar]
• Anane R, Bonini M, Grafeille J, Creppy E. Skin absorption and hippocampal bioaccumulation of water soluble aluminum chloride in mice (abstract) Hum Exp Toxicol. 1995;14:531. [Google Scholar]
• Anane R, Bonini M, Creppy EE. Transplacental passage of aluminum from pregnant mice to fetus organs after maternal transcutaneous exposure. Hum Exp Toxicol. 1997;16:501–504. [PubMed] [Google Scholar]
• Anderson AR. Aluminum compounds: aluminum organometallic compounds. In: Mark HF, McKette JJ Jr, Othmer DF, editors. Kirk-Othmer Encyclopedia of Chemical Technology. 2. Vol. 2. New York: Interscience Publishers; 1963. pp. 226–41. [Google Scholar]
• Andrási E, Farkas E, Scheibler H, Reffy A, Bezur L. Al, Zn, Cu, Mn and Fe levels in brain in Alzheimer’s disease. Arch Gerontol Geriatr. 1995;21:89–97. [PubMed] [Google Scholar]
• Andrási E, Páli N, Molnár Z, Kösel S. Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients. J Alzheimers Dis. 2005;7:273–284. [PubMed] [Google Scholar]
• Anghileri LJ, Maincent P, Thouvenot P. Long-term oral administration of aluminum in mice. Aluminum distribution in tissues and effects on calcium metabolism. Ann Clin Lab Sci. 1994;24:22–26. [PubMed] [Google Scholar]
• Anon. Aluminium and silicosis. Lancet. 1956;271:500–501. [PubMed] [Google Scholar]
• Anthony JS, Fadl S, Mason C, Davison A, Berry J. Absorption, deposition and distribution of dietary aluminium in immature rats: effects of dietary vitamin D3 and food-borne chelating agent. J Environ Sci Health B. 1986;21:191–205. [PubMed] [Google Scholar]
• Apostoli P, Lucchini R, Maccarrone R, Alessio L. Biological monitoring of occupational exposure to aluminum. Med Lav. 1992;83:475–483. [PubMed] [Google Scholar]
• Archibald JD. Aluminum in cow’s milk. J Dairy Sci. 1955;38:159–162. [Google Scholar]
• Aremu DA, Meshitsuka S. Accumulation of aluminum by primary cultured astrocytes from aluminum amino acid complex and its apoptotic effect. Brain Res. 2005;1031:284–296. [PubMed] [Google Scholar]
• Arieff AI, Cooper JD, Armstrong D, Lazarowitz VC. Dementia, renal failure, and brain aluminum. Ann Int Med. 1979;90:741–747. [PubMed] [Google Scholar]
• Armstrong BC, Tremblay D, Baris, Theriault G. Lung cancer mortality and polynuclear aromatic hydrocarbons: a case-cohort study of aluminum production workers in Arvida, Quebec, Canada. Am J Epidemiol. 1994;139:250–262. [PubMed] [Google Scholar]
• Armstrong BE, Hutchinson E, Unwin J, Fletcher T. Lung cancer risk after exposure to polycyclic aromatic hydrocarbons: a review and meta-analysis. Environ Health Perspect. 2004;112:970–978. [PMC free article] [PubMed] [Google Scholar]
• Arnaiz NO, Kaufman JD, Daroowala FM, Quiqley S, Farin F, Checkoway H. Genetic factors and asthma in aluminum smelter workers. Arch Environ Health. 2003;58:197–200. [PubMed] [Google Scholar]
• Arnich N, Cunat L, Lanhers MC, Burnel D. Comparative in situ study of the intestinal absorption of aluminum, manganese, nickel, and lead in rats. Biol Trace Elem Res. 2004;99:157–171. [PubMed] [Google Scholar]
• Arnold CJ, Miller GG, Zello GA. Parenteral nutrition-associated cholestasis in neonates: the role of aluminum. Nutr Rev. 2003;61:306–310. [PubMed] [Google Scholar]
• Atchison WD. Effects of toxic environmental contaminants on voltage-gated calcium channel function: from past to present. J Bioeng Biomembr. 2003;35:507–532. [PubMed] [Google Scholar]
• ATSDR (Agency for Toxic Substances and Disease Registry) Toxicological Profile for Aluminum and Compounds. Atlanta, GA.: U.S Department of Health and Human Services, Public Health Service; 1992. [Google Scholar]
• ATSDR (Agency for Toxic Substances and Disease Registry) A Toxicological Profile for Aluminum. Atlanta, GA.: U.S Department of Health and Human Services, Public Health Service; 1999. [Google Scholar]
• Austin PS, Doughman DJ. Reaction to intraocular penetration of bentonite. Am J Ophthamol. 1980;89:719–723. [PubMed] [Google Scholar]
• Authier FJ, Cherin P, Creange A, Bonnotte B, Ferrer X, Abdelmoumni A, Ranoux D, Pelletier J, Figarella-Branger D, Granel B, Maisonobe T, Coquet M, Degos JD, Gherardi RK. Central nervous system disease in patients with macrophagic myofasciitis. Brain. 2001;124:974–983. [PubMed] [Google Scholar]
• Avolio G, Galietti F, Iorio M, Oliaro A. Aluminum lung as an occupational disease. Case reports. Minerva Med. 1989;80:411–414. [PubMed] [Google Scholar]
• Baes CF, Mesmer RE. The Hydrolysis of Cations. New York: John Wiley & Sons, Inc; 1976. [Google Scholar]
• Bajaj AK, Gupta SC, Pandey RK, Misra K, Rastogi S, Chatterji AK. Aluminium contact sensitivity. Contact Dermatitis. 1997;37:307–308. [PubMed] [Google Scholar]
• Ballanti P, Mocetti P, Della Rocca C, Bonucci E, Costantinit S, Giordano R, Ioppolo A, Mantovani A. Experimental aluminium intoxication and parathormone: effects on the mineralization process. Mineral Electrolyte Metab. 1989;15:233–240. [PubMed] [Google Scholar]
• Balouet G, Baret M, Relyveld E, Ravisse P, Levaditi J. Role of antigens and adjuvant substances in the histological response in experimental granulomas (immunogenic granuloma) Ann Anat Pathol. 1997;22:159–170. [PubMed] [Google Scholar]
• Bamberger PJ. Aluminum therapy in silicosis-a clinical study of the comparative effects of the metallic powder and hydrated aluminum. Ind Med Surg. 1945;14:477–479. [Google Scholar]
• Banin E, Meiri H. Toxic effects of alumino-silicates on nerve cells. Neurosci. 1990;39:171–178. [PubMed] [Google Scholar]
• Barata JD, D’Haese PC, Pires C, Lamberts LV, Simoes J, De Broe ME. Low-dose (5 mg/kg) desferrioxamine treatment in acutely aluminium-intoxicated haemodialysis patients using two drug administration schedules. Nephrol Dial Transplant. 1996;11:125–132. [PubMed] [Google Scholar]
• Barber PJ, Rawlings JM, Markwell PJ, Elliott J. Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. J Small Anim Pract. 1999;40:62–70. [PubMed] [Google Scholar]
• Barker J, Day JP, Aitken TW, Charlesworth TR, Cunningham RC, Durum PV, Lilley JS, Newton GW, Smithson MJ. Development of Al-26 accelerator mass-spectrometry for biological and toxicological applications. Nucl Instrum Methods Phys Res B. 1990;52:540–543. [Google Scholar]
• Barnard CG, McBride DI, Firth HM, Herbison GP. Assessing individual employee risk factors for occupational asthma in primary aluminium smelting. Occup Environ Med. 2004;61:604–608. [PMC free article] [PubMed] [Google Scholar]
• Barr M, Hignett S, Glenny AT, Randall KJ. Antigenic efficiency of fluid and precipitated diphtheria prophylactics in very young babies and lambs. Lancet. 1952;2:803–805. [PubMed] [Google Scholar]
• Barr M, Glenny AT, Butler NR. Immunization of babies with diphtheriatetanus-pertusis prophylactic. Br Med J. 1955;2:635–639. [PMC free article] [PubMed] [Google Scholar]
• Bast-Pettersen R, Skaug V, Ellingsen D, Thomassen Y. Neurobehavioral performance in aluminum welders. Am J Ind Med. 2000;37:184–192. [PubMed] [Google Scholar]
• Bauer S, Wolff I, Werner N, Schmidt R, Blume R, Pelzing M. Toxicological investigations in the semiconductor industry: IV. Studies on the subchronic oral toxicity and genotoxicity of vacuum pump oils contaminated by waste products from aluminum plasma etching processes. Toxicol Ind Health. 1995;11:523–541. [PubMed] [Google Scholar]
• Baxter MJ, Burrell JA, Crews HM, Massey RC. Aluminium in infant formulae and tea and leaching during cooking. In: Massey R, Taylor D, editors. Aluminium in Food and the Environment. Cambridge, UK: The Royal Society of Chemistry; 1989. pp. 77–87. [Google Scholar]
• Baxter MJ, Burrell JA, Crews H, Massey RC. Aluminum levels in milk and infant formulae. Food Addit Contam. 1991;8:653–660. [PubMed] [Google Scholar]
• Bayder T, Nagymatényi L, Isimer A, Sahin G. Effect of folic acid supplementation on aluminum accumulation in rats. Nutrition. 2005;21:406–410. [PubMed] [Google Scholar]
• Baylor NW, Egan W, Richman P. Aluminum salts in vaccines-US perspective. Vaccine. 2002;20(Suppl 3):S18–S23. [PubMed] [Google Scholar]
• Bazzoni G, Bollini A, Hernandez G, del Carmen Contini M, Chiarotto M, Rasia M. In vivo effect of aluminium upon the physical properties of the erythrocyte membrane. J Inorg Biochem. 2005;99:822–827. [PubMed] [Google Scholar]
• Beamer WG, Donahue LR, Rosen CJ, Baylink DJ. Genetic variability in adult bone density among inbred strains of mice. Bone. 1996;18:397–403. [PubMed] [Google Scholar]
• Beauville M, Pradal G, Raynaud P. Influence of fasting on the components of the gastric juice in rabbits. C R Seances Soc Biol Fil. 1966;160:404–408. [PubMed] [Google Scholar]
• Becaria A, Campbell A, Bondy SC. Aluminum as a toxicant. Toxicol Ind Health. 2002;18:309–320. [PubMed] [Google Scholar]
• Bégin R, Massé S, Rola-Pleszczynski M, Martel M, Desmarais Y, Geoffroy M, LeBouffant L, Daniel H, Martin J. Aluminum lactate treatment alters the lung biological activity of quartz. Exp Lung Res. 1986;10:385–399. [PubMed] [Google Scholar]
• Bégin R, Massé S, Sébastien P, Martel M, Bosse J, Dubois F, Geoffrey M, Labbe J. Sustained efficacy of aluminum to reduce quartz toxicity in the lung. Exp Lung Res. 1987;13:205–222. [PubMed] [Google Scholar]
• Bégin R, Massé S, Dufresne A. Further information on aluminum inhalation in silicosis. Occup Environ Med. 1995;52:778–780. [PMC free article] [PubMed] [Google Scholar]
• Bell JD, Kubal G, Radulovic S, Sadler PJ, Tucker A. Detection of aluminium(III) binding to citrate in human blood plasma by proton nuclear magnetic resonance spectroscopy. Analyst. 1993;118:241–244. [PubMed] [Google Scholar]
• Bellés M, Sanchez DJ, Gómez M, Corbella J, Domingo JL. Silicon reduces aluminum accumulation in rats: relevance to the aluminum hypothesis of Alzheimer disease. Alzheimer Dis Assoc Disord. 1998;12:83–87. [PubMed] [Google Scholar]
• Bellés M, Albina ML, Sanchez DJ, Domingo JL. Lack of protective effects of dietary silicon on aluminium-induced maternal and developmental toxicity in mice. Pharmacol Toxicol. 1999;85:1–6. [PubMed] [Google Scholar]
• Bellés M, Albina ML, Sanchez DJ, Corbella J, Domingo JL. Effects of oral aluminum on essential trace elements metabolism during pregnancy. Biol Trace Elem Res. 2001;79:67–81. [PubMed] [Google Scholar]
• Bellia JP, Newton K, Davenport A, Birchall JD, Roberts NB. Silicon and aluminium and their inter-relationship in serum and urine after renal transplantation. Eur J Clin Invest. 1994;24:703–710. [PubMed] [Google Scholar]
• Bellia JP, Birchall JD, Roberts NB. The role of silicic acid in the renal excretion of aluminum. Ann Clin Lab Sci. 1996;26:227–233. [PubMed] [Google Scholar]
• Bellows CG, Aubin JE, Heersche JNM. Aluminium inhibits both initiation and progression of mineralization of osteoid nodules formed in differentiating rat calvaria cell cultures. J Bone Mineral Res. 1995;10:2011–2016. [PubMed] [Google Scholar]
• Bellows CG, Heersche JN, Aubin JE. Aluminum accelerates osteoblastic differentiation but is cytotoxic in long-term rat calvaria cell cultures. Calcif Tissue Int. 1999;65:59–65. [PubMed] [Google Scholar]
• Belt TF, King EJ. Failure of aluminium to prevent experimental silicosis. J Path Bact. 1943;55:69–73. [Google Scholar]
• Benet LZ, Kroetz DL, Sheiner LB. Pharmacokinetics. The dynamics of drug absorption, distribution, and elimination. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, editors. Pharmacological Basis of Therapeutics. New York: McGraw-Hill; 1996. pp. 3–28. [Google Scholar]
• Benke G, Abramson M, Sim M. Exposures in the alumina and primary aluminium industry: a historical review. Ann Occup Hyg. 1998;42:173–189. [PubMed] [Google Scholar]
• Berend K, van der Voet G, Boer WH. Acute aluminum encephalopathy in a dialysis center caused by a cement mortar water distribution pipe. Kidney Int. 2001;59:746–753. [PubMed] [Google Scholar]
• Berend K, van der Voet G, de Wolff A. Acute aluminum intoxication. In: Roesky H, Atwood D, editors. Structure and Bonding. Berlin: Springer; 2002. pp. 1–58. [Google Scholar]
• Bergerioux G, Boivert J. Rapid neutron activation method for the determination of minerals in milk. Int J Nucl Med Biol. 1979;6:128–131. [PubMed] [Google Scholar]
• Bergfors E. 406 children with contact allergy to aluminium after the use of adsorbed vaccines. Sixth Keele Meeting on Aluminium; February 26-March 2, 2005; Bussaco, Portugal. 2005. [Google Scholar]
• Bergfors E, Trollfors B, Inerot A. Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer. Vaccine. 2003;22:64–69. [PubMed] [Google Scholar]
• Bergomi M, Vinceti M, Nacci G, Pietrini V, Bratter P, Alber D, Ferrari A, Vescovi L, Guidetti D, Sola P, Malagu S, Aramini C, Vivoli G. Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: a population-based case-control study. Environ Res. 2002;89:116–123. [PubMed] [Google Scholar]
• Berlyne GM, Yagil R, Ari JB, Weinberger G, Knopf E, Danovitch GM. Aluminium toxicity in rats. Lancet. 1972a;1:564–568. [PubMed] [Google Scholar]
• Berlyne GM, Yagil RJ, Ben Ari J, Danovitch GM. Aluminium toxicity. Lancet. 1972b;1:1070–1071. [PubMed] [Google Scholar]
• Bernier RH, Frank JA, Nolan TF. Abcesses complicating DTP vacccination. Am J Dis Child. 1981;135:826–828. [PubMed] [Google Scholar]
• Berry JW. Aluminum therapy in advanced silicosis. Amer Rev Tuberc. 1948;57:557–573. [PubMed] [Google Scholar]
• Bertholf RL, Herman MM, Savory J, Carpenter RM, Sturgill B, Katsetos CD, Vandenberg SR, Wills MR. A long-term intravenous model of aluminum maltol toxicity in rabbits: tissue distribution, hepatic, renal, and neuronal cytoskeletal changes associated with systemic exposure. Toxicol Appl Pharmacol. 1989;98:58–74. [PubMed] [Google Scholar]
• Bertram L, Tanzi RE. The current status of Alzheimer’s disease genetics: what do we tell the patients? Pharmacol Res. 2004;50:385–396. [PubMed] [Google Scholar]
• Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Invest. 2005;115:1449–1457. [PMC free article] [PubMed] [Google Scholar]
• Berubé D. Speciation analysis and the occurrence of aluminium turbidity. J Toxicol Environ Health A. 2004;67:1655–1666. [PubMed] [Google Scholar]
• Beynon H, Cassidy MJ. Gastrointestinal absorption of aluminum. Nephron. 1990;55:235–236. [PubMed] [Google Scholar]
• Bia MJ, Cooper K, Schnall S, Duffy T, Hendler E, Malluche H, Solomon L. Aluminum induced anemia: pathogenesis and treatment in patients on chronic hemodialysis. Kidney Int. 1989;36:852–858. [PubMed] [Google Scholar]
• Biego GH, Joyeux M, Hartemann P, Debry G. Daily intake of essential minerals and metallic micropollutants from foods in France. Sci Total Environ. 1998;217:27–36. [PubMed] [Google Scholar]
• Bilkei-Gorzó A. Neurotoxic effect of enteral aluminum. Food Chem Toxicol. 1993;31:357–361. [PubMed] [Google Scholar]
• Birchall JD, Chappell JS. Aluminum water chemistry, and Alzheimer’s disease. Lancet. 1989;1:953. [PubMed] [Google Scholar]
• Birchall JD, Bellia JP, Roberts NB. On the mechanisms underying the essentiality of silicon-interactions with aluminum and copper. Coor Chem Rev. 1996;149:231–240. [Google Scholar]
• Bischoff R, Gyson G. Carcinogenesis through solid state surfaces. Proc Exp Tumor Res. 1964;5:85–133. [PubMed] [Google Scholar]
• Bishop NJ, Morley R, Day JP, Lucas A. Aluminum neurotoxicity in preterm infants receiving intravenous-feeding solutions. N Eng J Med. 1997;336:1557–1561. [PubMed] [Google Scholar]
• Bjertness E, Candy JM, Torvik A, Ince P, McArthur F, Taylor GA, Johansen SW, Alexander J, Grønnesby JK, Bakketeig LS, Edwardson JA. Content of brain aluminum is not elevated in Alzheimer disease. Alzheimer Dis Assoc Disord. 1996;10:171–174. [PubMed] [Google Scholar]
• Blahos J, Care AD, Abbas M, Corlett SC. Auminium induced decrease in osteocalcin levels in the chick. Horm Metab Res. 1991;23:50–51. [PubMed] [Google Scholar]
• Blair HC, Finch JL, Avioli R, Crouch LL, Slatopolisky L, Teitelbaum SL. Micromolar aluminum levels reduce 3H-thymidine incorporation by cell line UMR 106-01. Kidney Int. 1989;35:1119–1125. [PubMed] [Google Scholar]
• Blank IH, Jones JL, Gould E. A study of the penetration of aluminum salts into excised skin. Proc Sci Sect Toilet Goods Assoc. 1958;29:32–35. [Google Scholar]
• Blumenthal NC, Posner AS. In vitro model of aluminium induced osteomalacia: inhibition of hydroxyapatite formation and growth. Calcif Tissue Int. 1984;36:439–441. [PubMed] [Google Scholar]
• Böhler-Sommeregger K, Lindemayr H. Contact sensitivity to aluminium. Contact Dermatitis. 1986;15:278–281. [PubMed] [Google Scholar]
• Bordet AL, Michenet P, Cohen C, Arbion F, Ekindi N, Bonneau C, Kerdraon R, Coville M. Post-vaccination granuloma due to aluminium hydroxide. Ann Pathol. 2001;21:149–152. [PubMed] [Google Scholar]
• Boudey MF, Bureau C, Place D, Neuville M, Drosdowsky, Arhan P, Bougle D. Effect of small variations of aluminum intake on calcium metabolism in young rats. J Pediatr Gastroenterol Nutr. 1997;24:124–127. [PubMed] [Google Scholar]
• Bougle D, Bureau F, Voirin J, Neuville D, Duhamel JF. A cross-sectional study of plasma and urinary aluminum levels in term and preterm infants. J Parenter Enteral Nutr. 1992;16:157–159. [PubMed] [Google Scholar]
• Bougle D, Bureau F, Morello R, Guillow B, Sabatier JP. Aluminum in the premature infant. Trace Elem Electrolytes. 1997;14:24–26. [Google Scholar]
• Bouras C, Giannakopoulos P, Good PF, Hsu A, Hof PR, Perl DP. A laser microprobe mass analysis of brain aluminum and iron in dementia pugilistica: comparison with Alzheimer’s disease. Eur Neurol. 1997;38:53–58. [PubMed] [Google Scholar]
• Bourdeau AM, Plachot JJ, Cournet-Witmer G, Pointillart A, Balsan S, Sachs C. Parathyroid response to aluminum in vitro: ultrastructural changes and PTH release. Kidney Int. 1987;31:15–24. [PubMed] [Google Scholar]
• Bowen HJM. Environmental Chemistry of the Elements. London: Academic Press; 1979. [Google Scholar]
• Boyce BF, Eider HY, Fell SG, Nicholson WA, Smith GD, Dempster DW, Gray CC, Boyle IT. Quantitation and localisation of aluminum in human cancellous bone in renal osteodystrophy. Scan Electron Microsc. 1981;3:329–337. [PubMed] [Google Scholar]
• Bozynski ME, Sedman AB, Naglie RA, Wright EJ. Serial plasma and urinary aluminum levels and tissue loading in preterm twins. J Parenter Enteral Nutr. 1989;13:428–431. [PubMed] [Google Scholar]
• Bradberry SM, Beer ST, Vale JA. UKPID monograph Aluminium oxide. 1997. [online] Cited 24 January 2007 www.intox.org/databank/documents/chemical/alumoxde/ukpid33.htm.
• Bradbury MW. Transport of iron in the blood-brain-cerebrospinal fluid system. J Neurochem. 1997;69:443–454. [PubMed] [Google Scholar]
• Bradley C, Leung FY. Aluminum determined in plasma and urine by atomic absorption spectroscopy with a transversely heated graphite atomizer furnace. Clin Chem. 1994;40:431–434. [PubMed] [Google Scholar]
• Bräunlich H, Fleck C, Kersten L, Stein G, Laske V, Müller A, Keil E. Renal effects of aluminium in uraemic rats and rats with intact kidney function. J Appl Toxicol. 1986;6:55–59. [PubMed] [Google Scholar]
• Brown GM, Donaldson K, Brown DM. Bronchoalveolar leukocyte response in experimental silicosis: modulation by a soluble aluminum compound. Toxicol Appl Pharmacol. 1989;101:95–105. [PubMed] [Google Scholar]
• Brown JP, Dietrich PS, Bakner CM. Mutagenicity testing of some drug and cosmetic dye lakes with the Salmonella/mammalian microsome assay. Mutat Res. 1979;66:181–185. [PubMed] [Google Scholar]
• Brown TS, Schwartz R. Aluminum accumulation in serum, liver and spleen of Fe-depleted and Fe-adequate rats. Biol Trace Elem Res. 1992;34:1–10. [PubMed] [Google Scholar]
• Browning E. Aluminum. In: Browning E, editor. Toxicity of Industrial Metals. New York: Appleton-Century-Crofts; 1969. pp. 3–22. [Google Scholar]
• Brudevold F, Bakhos Y, Gron P. Fluoride in human saliva after ingestion of aluminium chloride and sodium fluoride or sodium monofluorophosphate. Arch Oral Biol. 1973;18:699–706. [PubMed] [Google Scholar]
• Brunton LL. Agents for control of gastric acidity and treatment of peptic ulcers. In: Hardman JG, Limbird LE, editors. The Pharmacological Basis of Therapeutics. 9. New York: McGraw-Hill; 1996. pp. 901–915. [Google Scholar]
• Brusewitz S. Aluminum vol 203. Stockholm, Sweden: University of Stockholm Institute of Theoretical Physics; 1984. [Google Scholar]
• Buchanan MRC, Ihle BU, Dunn CM. Haemodialysis related osteomalacia: a staining method to demonstrate aluminum. J Clin Pathol. 1981;34:1352–1354. [PMC free article] [PubMed] [Google Scholar]
• Buchta M, Kiesswetter E, Otto A, Schaller KH, Seeber A, Hilla W, Windorfer K, Stork J, Kuhlmann A, Gefeller O, Letzel S. Longitudinal study examining the neurotoxicity of occupational exposure to aluminium-containing welding fumes. Int Arch Occup Environ Health. 2003;76:539–548. [PubMed] [Google Scholar]
• Buchta M, Kiesswetter E, Schaper M, Zchiesche W, Schaller KH, Kuhlmann A, Letzel S. Neurotoxicity of exposures to aluminium welding fumes in the truck trailer construction industry. Environ Toxicol Pharmacol. 2005;19:677–685. [PubMed] [Google Scholar]
• Budavari S, O’Neil MJ, Smith A, Heckelman PE. The Merck Index. 11. Rathway, N.J.: Merck & Co. Inc; 1989. [Google Scholar]
• Bugiani O, Ghetti B. Progressing encephalomyelopathy with muscular athropy, induced by aluminum powder. Neurobiol Aging. 1982;3:209–222. [PubMed] [Google Scholar]
• Burge PS, Scott JA, McCoach J. Occupational asthma caused by aluminum. Allergy. 2000;55:779–780. [PubMed] [Google Scholar]
• Burnatowska-Hledin MA, Mayor GH. The effects of aluminum loading on selected tissue calcium and magnesium concentrations in rats. Biol Trace Elem Res. 1984;6:531–535. [PubMed] [Google Scholar]
• Burnatowska-Hledin MA, Mayor GH, Lau K. Renal handling of aluminum in the rat: clearance and micropuncture studies. Am J Physiol. 1985;249:F192–F197. [PubMed] [Google Scholar]
• Burnatowska-Hledin MA, Doyle TM, Eadie MJ, Mayor GH. 1,25 Dihydroxy-vitamin D increases serum and tissue accumulation of aluminum in rats. J Lab Clin Med. 1986;108:96–102. [PubMed] [Google Scholar]
• Burwen DR, Olsen SM, Bland LA, Arduino MJ, Reid MH, Jarvis WR. Epidemic aluminum intoxication in hemodialysis patients traced to use of an aluminum pump. Kidney Int. 1995;48:469–474. [PubMed] [Google Scholar]
• Bushinsky DA, Sprague SM, Hallegot P, Girod C, Chabala JM, Levisetti R. Effects of aluminium on bone surface ion composition. J Bone Mineral Res. 1995;10:1988–1997. [PubMed] [Google Scholar]
• Butler NR, Voyce MA, Burland WL, Hilton ML. Advantages of aluminium hydroxide adsorbed combined diptheria, tetanus, and pertussis vaccines for the immunization of infants. Br Med J. 1969;1:663–666. [PMC free article] [PubMed] [Google Scholar]
• Cam JM, Luck VA, Eastwood JB, De Wardener HE. The effect of aluminium hydroxide orally on calcium, phosphorus and aluminium in normal subjects. Clin Sci Mol Med. 1976;51:407–414. [PubMed] [Google Scholar]
• Campbell A. The potential role of aluminum in Alzheimer’s disease. Nephrol Dial Transplant. 2002;17:17–20. [PubMed] [Google Scholar]
• Campbell A. Inflammation, neurodegnerative diseases, and environmental exposures. Ann N Y Acad Sci. 2004;1035:117–132. [PubMed] [Google Scholar]
• Campbell A, Bondy SC. Aluminum induced oxidative events and its relation to inflammation: a role for the metal in Alzheimer’s disease. Cell Mol Biol. 2000;46:721–730. [PubMed] [Google Scholar]
• Campbell A, Prasad KN, Bondy SC. Aluminum-induced oxidative events in cell lines: glioma are more responsive than neuroblastoma. Free Radic Biol Med. 1999;26:1166–1171. [PubMed] [Google Scholar]
• Candy J, Klinowski J, Perry R, Perry E, Fairbain A, Oakley A, Carpenter T, Atack J, Blessed G, Edwardson J. Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet. 1986;1:354–357. [PubMed] [Google Scholar]
• Cannata Andía JB. Aluminium toxicity: its relationship with bone and iron metabolism. Nephrol Dial Transplant. 1996;11(Suppl 3):69–73. [PubMed] [Google Scholar]
• Cannata Andía JB. Adynamic bone and chronic renal failure: an overview. Am J Med Sci. 2000;320:81–84. [PubMed] [Google Scholar]
• Cannata JB, Suarez C, Cuesta V, Roza RR, Allende MT, Herrera J, Llanderal JP. Gastrointestinal aluminum absorption: is it modulated by the iron-absorptive mechanism? Proc Eur Dial Transplant Assoc Eur Ren Assoc. 1984;21:354–359. [PubMed] [Google Scholar]
• Cannata JB, Diaz Lopez JB, Fernandez Menendez MJ, Virgos MJ. The parathyroid gland and aluminum overload: an overview. Contrib Nephrol. 1988;64:113–119. [PubMed] [Google Scholar]
• Cannata JB, Fernandez-Soto I, Fernandez-Menendez MJ, Fernandez-Martin JL, McGregor SJ, Brock JH, Halls D. Role of iron metabolism in absorption and cellular uptake of aluminum. Kidney Int. 1991;39:799–803. [PubMed] [Google Scholar]
• Cannata JB, Olaizola IR, Gomez-Alonso C, Menendez-Fraga P, Alonso-Suarez M, Diaz-Lopez JB. Serum aluminum transport and aluminum uptake in chronic renal failure: role of iron and aluminum metabolism. Nephron. 1993;65:141–146. [PubMed] [Google Scholar]
• Cannata-Andía JB, Fernadez-Martin JL. The clinical impact of aluminum overload in renal failure. Nephrol Dial Transplant. 2002;17(Suppl 2):9–12. [PubMed] [Google Scholar]
• Caramelo CA, Cannata JB, Rodeles MR, Fernandez Martin JL, Mosquera JR, Monzu B, Outeirino J, Blum J, Andrea C, Lopez Farre AJ, Acuna J, Casado S, Hernando L. Mechanisms of aluminum-induced microcytosis: lessons from accidental aluminum intoxication. Kidney Int. 1995;47:164–168. [PubMed] [Google Scholar]
• Cardillo P, Nebuloni M. Reactivity limits of aluminium and halohydrocarbon mixtures: determination by the ASTM CHETAH program. J Loss Prev Process Ind. 1992;5:81–88. [Google Scholar]
• Carlisle EM, Curran MJ. Effect of dietary silicon and aluminum on silicon and aluminum levels in rat brain. Alzheimer Dis Assoc Disord. 1987;1:83–89. [PubMed] [Google Scholar]
• Caroli S, Alimonti A, Coni E, Petrucci F, Senofonte O, Violante N. The assessment of reference values for elements in human biological tissues and fluids: a systematic review. Crit Rev Anal Chem. 1994;24:363–398. [Google Scholar]
• Caruso JA, Klaue B, Michalke B, Rocke DM. Group assessment: elemental speciation. Ecotoxicol Environ Saf. 2003;56:32–44. [PubMed] [Google Scholar]
• Caruso JA, Wuilloud RG, Altamirano JC, Harris WR. Modeling and separation-detection methods to evaluate the speciation of metals for toxicity assessment. J Toxicol Environ Health B Crit Rev. 2005;9:41–61. [PubMed] [Google Scholar]
• Casarett MG, Casarett LJ, Hodge HC. An in vitro study of mast cell response to praticulate materials. Pharmacology. 1968;1:271–282. [PubMed] [Google Scholar]
• Castelain PY, Castelain M, Vervloet D, Garbe L, Mallet B. Sensitization to aluminium by aluminium precipitated dust and pollen extracts. Contact Dermatitis. 1988;19:58–60. [PubMed] [Google Scholar]
• Casto BC, Meyers J, DiPaolo JA. Enhancement of viral transformation for evaluation of the carcinogenic or mutagenic potential of inorganic metal salts. Cancer Res. 1979;39:193–198. [PubMed] [Google Scholar]
• Cech I, Montera J. Spatial variations in total aluminum concentrations in drinking water supplies studied by geographic information system (GIS) methods. Wat Res. 2000;34:2703–2712. [Google Scholar]
• Cefali EA, Nolan JC, McConnell WR, Walters DL. Pharmacokinetic study of zeolite A, sodium aluminosilicate, magnesium silicate, and aluminum hydroxide in dogs. Pharm Res. 1995;12:270–274. [PubMed] [Google Scholar]
• Cefali EA, Nolan JC, McConnell WR, Walters DL. Bioavailability of silicon and aluminum from Zeolite A in dogs. Int J Pharm. 1996;127:147–154. [Google Scholar]
• CFTA. Safety data of magnesium aluminum silicate. 1970 Unpublished data. [Google Scholar]
• Chafi AH, Hauw JJ, Rancurel G, Berry J-P, Galle C. Absence of aluminium in Alzheimer’s disease brain tissue: electron microprobe and ion microprobe studies. Neurosci Lett. 1991;123:61–64. [PubMed] [Google Scholar]
• Chamberlain M, Davies R, Brown RC, Griffiths DM. In vitro tests for the pathogenicity of mineral dusts. Ann Occup Hyg. 1982;26:583–592. [PubMed] [Google Scholar]
• Chan WS, Marshall JF, Hart IR. Photodynamic therapy of a murine tumor following sensitisation with chloro aluminum sulfonated phthalocyanine. Photochem Photobiol. 1987;46:867–871. [PubMed] [Google Scholar]
• Chan YC, Simpson RW, Mctainsh GH, Vowles PD, Cohen DD, Bailey GM. Characterisation of chemical species in PM2.5 and PM10 aerosols in Brisbane, Australia. Atmos Environ. 1997;31:3773–3785. [Google Scholar]
• Chan YL, Alfrey AC, Posen S, Lissner D, Hills E, Dunstan CR, Evans RA. Effect of aluminum on normal and uremic rats: tissue distribution, vitamin D metabolites, and quantitative bone histology. Calcif Tissue Int. 1983;35:344–351. [PubMed] [Google Scholar]
• Chan-Yeung M, Wong R, MacLean L, Tan F, Dorken E, Schulzer M, Dennis R, Grzybowski S. Epidemiologic health study of workers in an aluminum smelter in British Columbia, Canada: Effects on respiratory system. Am Rev Respir Dis. 1983;127:465–469. [PubMed] [Google Scholar]
• Channon SM, Arfeen S, Ward MK. Long-term accumulation of aluminium in patients with renal failure. Trace Elem Med. 1988;5:154–157. [Google Scholar]
• Chappuis P, Duhaux L, Paolaggi F, De Vernejoul MC, Rousselet F. Analytical problems encountered in determining aluminum status from hair in controls and hemodialyzed patients. Clin Chem. 1988;34:2253–2255. [PubMed] [Google Scholar]
• Chappuis P, de Vernejoul MC, Paolaggi F, Rousselet F. Relationship between hair, serum and bone aluminium in hemodialyzed patients. Clin Chim Acta. 1989;179:271–278. [PubMed] [Google Scholar]
• Charlet P, Deloume JP, Duc G, Thomas-David G. Chelation of aluminum(3+) ions by succinic, aspartic, and glutamic acids and 1-histidine. Potentiometric study. Bull Soc Chimique France. 1984;N7:222–226. [Google Scholar]
• Chen C, Kalu DN. Strain differences in bone density and calcium metabolism between C3H/HeJ and C57BL/6J mice. Bone. 1999;25:413–420. [PubMed] [Google Scholar]
• Chen J, Huang C, Hu B, Jiang Z. Speciation of aluminum in drink samples by 8-hydroxyquinoline loaded silylanization silica gel microcolumn separation with off-line ICP-MS detection. J Agric Food Chem. 2004;52:6843–6847. [PubMed] [Google Scholar]
• Chen WJ, Monnat RJ, Chen M, Mottet NK. Aluminum induced pulmonary granulomatosis. Hum Pathol. 1978;9:705–712. [PubMed] [Google Scholar]
• Chernov VK, Lazareva V, Asmolov AI, Markova SB. Content of some trace elements in plasma and erythrocytes. Zdravookhranenie Kazakhstana. 1977;4:80–81. [Google Scholar]
• Chiba J, Kusumoto M, Shirai S, Ikawa K, Sakamoto S. The influence of fluoride ingestion on urinary aluminum excretion in humans. Tohoku J Exp Med. 2002;196:139–149. [PubMed] [Google Scholar]
• Chmielnicka J, Nasiadek M, Lewandowska-zyndul E, Pinkowski R. Effect of aluminum on hematopoiesis after intraperitoneal exposure in rats. Ecotoxicol Environ Saf. 1996;33:201–206. [PubMed] [Google Scholar]
• Cho SW, Joshi JG. Inactivation of glucose-6-phosphate dehydrogenase isozymes from human and pig brain by aluminum. J Neurochem. 1989;53:616–621. [PubMed] [Google Scholar]
• Chow HS, Chen Z, Matsuura GT. Direct transport of cocaine from the nasal cavity to the brain following intranasal cocaine administration in rats. J Pharm Sci. 1999;88:754–758. [PubMed] [Google Scholar]
• Chow JC, Watson JG, Lu Z, Lowenthal DH, Frazier CA, Solomon PA, Thuillier RH, Magliano K. Descriptive analysis of PM(2.5) and PM(10) at regionally representative locations during SJVAQS/AUSPEX. Atmos Envrion. 1996;30:2079–2112. [Google Scholar]
• Christie H, Mackay RJ, Fisher AM. Pulmonary effects of inhalation of aluminum by rats and hamsters. Ind Hyg J. 1963;24:47–56. [PubMed] [Google Scholar]
• Clark RA, Krueger GL. Aluminon: its limited application as a reagent for the detection of aluminum species. J Histochem Cytochem. 1985;33:729–732. [PubMed] [Google Scholar]
• Clarkson EM, Luck VA, Hynson WV, Bailey RR, Eastwood JR, Woodhead JS, Clemets VR, O’Riordan JL, De Wardener HE. The effect of aluminum hydroxide on calcium, phosphorus and aluminum balances, the serum parathyroid hormone concentration and the aluminum content of bone in patients with chronic renal failure. Clin Sci. 1972;43:519–531. [PubMed] [Google Scholar]
• Clements CJ, Griffiths E. The global impact of vaccines containing aluminium adjuvants. Vaccine. 2002;20(Suppl 3):S24–S33. [PubMed] [Google Scholar]
• Clemmensen O, Knudsen HE. Contact sensitivity to aluminium in a patient hyposensitized with aluminium precipitated grass pollen. Contact Dermatitis. 1980;6:305–308. [PubMed] [Google Scholar]
• Clonfero E, Cortese S, Saia B, Marcer G, Crepet M. Pulmonary pathology in a plant of electrolytic reduction of aluminum. Med Lav. 1978;69:613–619. [PubMed] [Google Scholar]
• Clonfero E, Caroldi S, Cortese M, Zambon P. Health problems in aluminum foundry workers of Porto Marghera [Italy]. Part II. Chronic bronchitis. Securitas. 1980a;64:60–62. [Google Scholar]
• Clonfero E, Caroldi S, Cortese M, Zambon P. Health problems in aluminum foundry workers of Porto Marghera [Italy]. Part III. Alumina-induced pneumoconiosis. Securitas. 1980b;64:63–66. [Google Scholar]
• Coburn JW, Mischel MG, Goodman WG, Salusky IB. Calcium citrate markedly enhances aluminum absoprtion from aluminum hydroxide. Am J Kidney Dis. 1991;17:708–711. [PubMed] [Google Scholar]
• Cochran M, Chawtur V. Interaction of horse-spleen ferritin with aluminium citrate. Clin Chim Acta. 1988;178:79–84. [PubMed] [Google Scholar]
• Cochran M, Goddard G, Ludwigson N. Aluminum absorption by rat duodenum: further evidence of energy-dependent uptake. Toxicol Lett. 1990;51:287–294. [PubMed] [Google Scholar]
• Cochran M, Chawtur V, Phillips JW, Dilena B. Effect of citrate infusion on urinary aluminium excretion in the rat. Clin Sci. 1994;86:223–226. [PubMed] [Google Scholar]
• Coggon D. Camelford revisited. Br Med J. 1991;303:1280–1281. [PMC free article] [PubMed] [Google Scholar]
• Cogne M, Ballet JJ, Schmitt C, Bizzini B. Total and IgE antibody levels following booster immunization with aluminium absorbed and nonabsorbed tetanus toxoid in humans. Ann Allergy. 1985;54:148–151. [PubMed] [Google Scholar]
• Cointry GR, Capozza RF, Negri AL, Ferretti JL. Biomechanical impact of aluminium accumulation on the pre and post yield behavior of rat cortical bone. J Bone Miner Metab. 2005;23:15–23. [PubMed] [Google Scholar]
• Colomina M, Gomez TM, Domingo JL, Llobet M, Corbella J. Concurrent ingestion of lactate and aluminum can result in developmental toxicity in mice. Res Commun Chem Pathol Pharmacol. 1992;77:95–106. [PubMed] [Google Scholar]
• Colomina MT, Gómez M, Domingo JL, Llobet JM, Corbella J. Lack of maternal and developmental toxicity in mice given high doses of aluminium hydroxide and ascorbic acid during gestation. Pharmacol Toxicol. 1994;74:236–239. [PubMed] [Google Scholar]
• Colomina MT, Esparza JL, Corbella J, Domingo JL. The effect of maternal stress on developmental toxicity of aluminum in mice. Neurotoxicol Teratol. 1998;20:651–656. [PubMed] [Google Scholar]
• Colomina MT, Sanchez DJ, Domingo JL, Sanchez-Turet M. Exposure of pregnant mice to aluminum and restraint stress: Effects on postnatal development and behaviour of the offspring. Psychobiol. 1999;27:521–529. [Google Scholar]
• Colomina MT, Roig JL, Torrente M, Vicens P, Domingo JL. Concurrent exposure to aluminum and stress during pregnancy in rats: Effects on postnatal development and behavior of the offspring. Neurotoxicol Teratol. 2005;27:565–574. [PubMed] [Google Scholar]
• Cominos D, Strutton G, Busmanis I. Granulomas associated with tetanus toxoid immunization. Am J Dermatopathol. 1993;15:114–117. [PubMed] [Google Scholar]
• CFASD (Committee on Food Additives Survey Data) Poundage Update of Food Chemicals, 1982. Washington D.C.: National Academy Press; 1984. [Google Scholar]
• Comsa CD, Prestwich WV, McNeil FE, Byun SH. Application of spectral decomposition analysis to in vivo quantification of aluminum by neutron activation analysis. Appl Radiat Isot. 2004;61:1353–1360. [PubMed] [Google Scholar]
• Coni E, Stacchini A, Caroli S, Falconieri P. Analytical approach to obtaining reference values for minor and trace elements in human milk. J Anal At Spectrom. 1990;5:581–586. [Google Scholar]
• Conway EL, O’Callaghan C, Drummer OH, Howes LG, Louis WG. A single-dose comparison of the bioavailability of aluminum from two formulations of sucralphate in normal volunteers. Biopharm Drug Dispos. 1994;15:253–261. [PubMed] [Google Scholar]
• Corrin B. Aluminium pneumoconiosis. II. Effect on the rat lung of intratracheal injections of stamped aluminium powders containing different lubricating agents and of a granular aluminium powder. Br J Ind Med. 1963a;20:268–276. [PMC free article] [PubMed] [Google Scholar]
• Corrin B. Aluminium pneumoconiosis. I. In vitro comparison of stamped aluminium powders containing different lubricating agents and a granular aluminium powder. Br J Ind Med. 1963b;20:264–267. [PMC free article] [PubMed] [Google Scholar]
• Cosnes A, Flechet M-L, Revuz J. Inflammatory nodular reactions after hepatitis B vaccination due to aluminium sensitization. Contact Dermatitis. 1990;23:65–67. [PubMed] [Google Scholar]
• Costa M, Zhitkovich A, Gargas M, Paustenbach D, Finley B, Kuykendall J, Billings R, Carlson TJ, Wetterhahn K, Xu J, Pateirno S, Bogdanffy M. Interlaboratory validation of a new assay for DNA-protein crosslinks. Mutat Res. 1996;369:13–21. [PubMed] [Google Scholar]
• Costantini S, Giordano R, Ioppolo A, Mantovani A, Ballanti P, Mocetti P, Bonucci E. Distribution of aluminium following intraperitoneal injection of aluminium lactate in the rat. Pharmacol Toxicol. 1989;64:47–50. [PubMed] [Google Scholar]
• Cotton FA, Wilkinson G. Advanced Inorganic Chemistry. 4. New York: John Wiley & Sons, Inc; 1980. [Google Scholar]
• Council on Industrial Health. JAMA. 1946;130:1223. [Google Scholar]
• Cournot-Witmer G, Zinngraff J, Plachot JJ, Escaig F, Lefevre R, Boumati P, Bourdeau A, Garadedian M, Galle P, Bourdon R, Drüeke T, Balsan S. Aluminium localization in bone from hemodialyzed patients: Relationship to matrix mineralization. Kidney Int. 1981;20:375–378. [PubMed] [Google Scholar]
• Cox NH, Moss C, Forsyth A. Allergy to non-toxoid constituents of vaccines and implications for patch testing. Contact Dermatitis. 1988a;18:143–146. [PubMed] [Google Scholar]
• Cox NH, Moss C, Forsyth A. Cutaneous reactions to aluminium in vaccines: an avoidable problem. Lancet. 1988b;2:43. [PubMed] [Google Scholar]
• Cranmer JM, Wilkins JD, Cannon DJ, Smith L. Fetal-placental-maternal uptake of aluminum in mice following gestational exposure: Effect of dose and route of administration. Neurotoxicology. 1986;7:601–608. [PubMed] [Google Scholar]
• Crapper DR, Krishnan SS, Dalton AJ. Brain aluminum distribution in Alzheimer’s disease and experimental neurofibrillary degeneration. Science. 1973;180:511–513. [PubMed] [Google Scholar]
• Crapper DR, Krishnan SS, Quittkat S. Aluminum, neurofibrillary degeneration and Alzheimer’s disease. Brain. 1976;99:67–80. [PubMed] [Google Scholar]
• Crapper D, Quittkat S, Krishnan S, Dalton A, De Boni U. Intranuclear aluminum content in Alzheimer’s disease, dialysis encephalopathy and experimental aluminum encephalopathy. Acta Neuropathol. 1980;50:19–24. [PubMed] [Google Scholar]
• Crombie DW, Blaisdell JL, MacPherson G. The treatment of silicosis by aluminum powder. Can Med Assoc J. 1944;50:318–328. [PMC free article] [PubMed] [Google Scholar]
• Cronin RE, Henrich WL. UpToDate® 2004. [online] https://store.utdol.com/app/index.asp.
• Crowther RS, Marriott C. Counter-ion binding to mucus glycoproteins. J Pharm Pharmacol. 1984;36:21–26. [PubMed] [Google Scholar]
• Csoti T, Gyori J, Salanki J, Erdelyi L. pH-dependent actions of aluminum on voltage-activated sodium currents in snail neurons. Neurotoxicology. 2001;22:109–116. [PubMed] [Google Scholar]
• Culora GA, Ramsay AD, Theaker JM. Aluminum and injection site reactions. J Clin Pathol. 1996;49:844–847. [PMC free article] [PubMed] [Google Scholar]
• Cunat L, Lanhers MC, Joyeux M, Burnel D. Bioavailability and intestinal absorption of aluminum in rats: effects of aluminum compounds and some dietary constituents. Biol Trace Elem Res. 2000;76:31–55. [PubMed] [Google Scholar]
• Cunha-Melo JR, Gonzaga HM, Alzamora F, Freire-Maia L. Effects of purified scorpion toxin (tityustoxin) on gastric secretion in the rat. Toxicology. 1983;21:843–848. [PubMed] [Google Scholar]
• Cutrufo C, Caroli S, Delle FP, Ortolani E, Palazzesi S, Violante N, Zapponi GA, Loizzo A. Experimental aluminium encephalopathy: quantitative EEG analysis of aluminium bioavailability. J Neurol Neurosurg Psych. 1984;47:204–206. [PMC free article] [PubMed] [Google Scholar]
• Cyrys J, Hochadel M, Gehring U, Hoek G, Diegmann V, Brunekreef B, Heinrich J. GIS-based estimation of exposure to particulate matter and NO2 in an urban area: stochastic versus dispersion modeling. Environ Health Perspect. 2005;113:987–992. [PMC free article] [PubMed] [Google Scholar]
• Dabeka RW, McKenzie AD. Graphite-furnace atomic absorption spectrometric determination and survey of total aluminum, copper, manganese, molybdenum, and tin in infant formulas and evaporated milks. J Assoc Off Anal Chem Int. 1992;75:954–963. [Google Scholar]
• Dalbey W, Pulkowski C. Comparison of synthetic zeolite catalysts and alumina binders administered intratracheally to rats. J Toxicol Environ Health A. 2000;60:355–374. [PubMed] [Google Scholar]
• Daniela B, Antonella D, Antonela L. Aluminum contamination in home parenteral nutrition patients. J Parenter Enteral Nutr. 2002;26:S30–S31. [Google Scholar]
• DaSilva JJ, Williams RJ. The Biological Chemistry of the Elements. Oxford: Clarenden Press; 1991. [Google Scholar]
• Dave KR, Syal AR, Katyare SS. Effect of long-term aluminum feeding on kinetics attributes of tissue cholinesterases. Brain Res Bull. 2002;58:225–233. [PubMed] [Google Scholar]
• Davenport A, Williams PS, Roberts NB, Bone JM. Sepsis: a cause of aluminum release from tissue stores associated with acute neurological dysfunction and mortality. Clin Nephrol. 1988;30:48–51. [PubMed] [Google Scholar]
• Davenport A, Davison AM, Will EJ, Toothill C, Newton KE, Giles GR. Aluminium accumulation and immunosuppression. BMJ. 1989;298:458–459. [PMC free article] [PubMed] [Google Scholar]
• David A. Cerebral dysfunction after water pollution incident in Camelford: Results were biased by self selection of cases. Br Med J. 2000;320:1337. [PMC free article] [PubMed] [Google Scholar]
• Davis WM. Is aluminum an etiologic contributor to alcoholic amnesia and dementia? Med Hypotheses. 1993;41:341–343. [PubMed] [Google Scholar]
• Dawson EB, Ritter S, Harris WA, Evans DR, Powell LC. Comparison of sperm viability with seminal plasma metal levels. Biol Trace Elem Res. 1998;64:215–219. [PubMed] [Google Scholar]
• Dawson EB, Evans DR, Harris WA, Powell LC. Seminal plasma trace metal levels in industrial workers. Biol Trace Elem Res. 2000;74:97–105. [PubMed] [Google Scholar]
• Day JP, Barker J, Evans LJ, Perks J, Seabright PJ, Ackrill P, Lilley JS, Drumm PV, Newton GW. Aluminium absorption studied by 26Al tracer. Lancet. 1991;337:1345. [PubMed] [Google Scholar]
• Day JP, Barker J, King SJ, Miller RV, Templar J, Lilley JS, Drumm PV, Newton GWA, Fifield LK, Stone JOH, Allan GL, Edwardson JA, Moore PB, Ferrier IN, Priest ND, Newton D, Talbot RJ, Brock JH, Sanchez L, Dobson CB, Itzhaki RF, Radunovic A, Bradbury MWB. Biological chemistry of aluminium studied using 26Al and accelerator mass spectrometry. Nucl Instrum Methods Phys Res. 1994;B29:463–468. [Google Scholar]
• Daydé S, Brumas V, Champmartin D, Rubini P, Berthon G. Aluminum speciation studies in biological fluids. Part 9. A quantitative investigation of aluminum(III)-glutamate complex equilibria and their potential implications for aluminum metabolism and toxicity. J Inorg Biochem. 2003;97:104–117. [PubMed] [Google Scholar]
• De la Torre JC. Alzheimer disease as a vascular disorder: nosological evidence. Stroke. 2002;33:1152–1162. [PubMed] [Google Scholar]
• De Marchi J. Uber experimentelle aluminium-staubungen. Grenzgeb Einzeldarst. 1947;4:28. [Google Scholar]
• De Stasio G, Dunham D, Tonner BP, Mercanti D, Ciotti MT, Angelini A, Coluzza C, Perfetti P, Margaritondo G. Aluminum in rat cerebellar neural cultures. Neuroreport. 1993;4:1175–1178. [PubMed] [Google Scholar]
• De Stasio G, Mercanti D, Ciotti MT, Dunham D, Droubay TC, Tonner BP, Perfetti P, Margaritondo G. Aluminium in rat cerebellar primary cultures: glial cells and GABAergic neurones. Neuroreport. 1994;5:1973–1976. [PubMed] [Google Scholar]
• De Vernejoul MC, Marchais S, London G, Morieux C, Bielakoff J, Miravet L. Increased bone aluminum deposition after subtotal parathyroidectomy in dialyzed patients. Kidney Int. 1985;27:785–791. [PubMed] [Google Scholar]
• De Vernejoul MC, Marchais S, London G, Bielakoff J, Chappuis P, Morieux C, Llach F. Deferoxamine test and bone disease in dialysis patients with mild aluminum accumulation. Am J Kidney Dis. 1989;14:124–130. [PubMed] [Google Scholar]
• De Vuyst P, Dumortier P, Rickaert F, Van De Weyer R, Lenclud C, Yernault JC. Occupational lung fibrosis in an aluminium polisher. Eur J Respir Dis. 1986;68:131–140. [PubMed] [Google Scholar]
• De Vuyst P, Dumortier P, Schandené L, Estenne M, Verhest A, Yernault JC. Sarcoid-like lung granulomatosis induced by aluminum dust. Am Rev Respir Dis. 1987;135:493–497. [PubMed] [Google Scholar]
• Dedman DJ, Treffry A, Harrison PM. Interaction of aluminium citrate with horse spleen ferritin. Biochem J. 1992a;287:515–520. [PMC free article] [PubMed] [Google Scholar]
• Dedman DJ, Treffry A, Candy JM, Taylor GA, Morris CM, Bloxham CA, Perry MH, Edwardson JA. Iron and aluminum in relation to brain ferritin in normal individuals and Alzheimer’s-disease and chronic renal-dialysis patients. Biochem J. 1992b;287:509–514. [PMC free article] [PubMed] [Google Scholar]
• Del’va VA. Changes in the concentration of aluminum of the blood and cerebrospinal fluid in some pathologic processes. Ref Zh Khim Biol Khim. 1962;19:193–195. [Google Scholar]
• Deloncle R, Guillard O, Huguet F, Clanet F. Modification of the blood-brain barrier through chronic intoxication by aluminum glutamate. Possible role in the etiology of Alzheimer’s disease. Biol Trace Elem Res. 1995;47:227–233. [PubMed] [Google Scholar]
• Deloncle R, Huguet F, Babin P, Fernandez B, Quellard N, Guillard O. Chronic administration of aluminum L-glutamate in young mature rats: effects on iron levels and lipid peroxidation in selected brain areas. Toxicol Lett. 1999;104:65–73. [PubMed] [Google Scholar]
• Deloncle R, Huguet F, Fernandez B, Quellard N, Babin P, Guillard O. Ultrastructural study of rat hippocampus after chronic administration of aluminum L-glutamate: an acceleration of the aging process. Exp Gerontol. 2001;36:231–244. [PubMed] [Google Scholar]
• Deloncle R, Fauconneau B, Piriou A, Huguet F, Guillard O. Aluminum L-glutamate complex in rat brain cortex: in vivo prevention of aluminum deposit by magnesium D-aspartate. Brain Res. 2002;946:247–252. [PubMed] [Google Scholar]
• Delves HT, Sieniawaska CE, Suchak B. Total and bioavailable aluminium in foods and beverages. Anal Proc (London) 1993;30:358–360. [Google Scholar]
• Deng ZY, Coudray C, Gouzoux L, Mazur A, Rayssiguier Y, Pepin D. Effect of oral aluminum citrate on blood level and short-term tissue distribution of aluminum in the rat. Biol Trace Elem Res. 1998;63:139–147. [PubMed] [Google Scholar]
• Deng Z, Coudray C, Gouzoux L, Mazur A, Rayssiguier Y, Pepin D. Effects of acute and chronic coingestion of AlCl3 with citrate or polyphenolic acids on tissue retention and distribution of aluminum in rats. Biol Trace Elem Res. 2000;76:245–256. [PubMed] [Google Scholar]
• Denny JJ, Robson WD, Irwin DA. The prevention of silicosis by metallic aluminum. Can Med Assoc J. 1937;37:1–11. [PMC free article] [PubMed] [Google Scholar]
• Denny JJ, Robson WD, Irwin DA. The prevention of silicosis by metallic aluminum II. Can Med Assoc J. 1939;40:213–228. [PMC free article] [PubMed] [Google Scholar]
• Dhir H, Roy AK, Sharma A. Relative efficiency of Phyllanthus emblica fruit extract and ascorbic acid in modifying lead and aluminum-induced sister-chromatid exchanges in mouse bone marrow. Environ Mol Mutagen. 1993;21:229–236. [PubMed] [Google Scholar]
• Di Muzio A, Capasso M, Verrotti A, Trotta D, Lupo S, Pappalepore N, Manzoli C, Chiarelli F, Uncini A. Macrophagic myofasciitis: an infantile Italian case. Neuromuscul Disord. 2004;14:175–177. [PubMed] [Google Scholar]
• Di Paolo N, Masti A, Comparini IB, Garosi G, Di Paolo M, Centini F, Brardi S, Monaci G, Finato V. Uremia, dialysis and aluminium. Int J Artif Organs. 1997;20:547–552. [PubMed] [Google Scholar]
• Di Paolo JA, Casto BC. Quantitative studies of in vitro morphological transformation of Syrian hamster cells by inorganic metal salts. Cancer Res. 1979;39:1008–1013. [PubMed] [Google Scholar]
• Díaz-Corte C, Fernández-Martin JL, Barreto S, Gómez C, Fernández-Coto T, Braga S, Cannata JB. Effect of aluminium load on parathyroid hormone synthesis. Nephrol Dial Transplant. 2001;16:742–745. [PubMed] [Google Scholar]
• Dinman BD. Aluminium, alloys and compounds. In: Parmeggiani L, editor. Encyclopedia of Occupational Health and Safety. Geneva: International Labour Organisation; 1983. pp. 131–135. [Google Scholar]
• Dinman BD. Aluminum in the lung: the pyropowder conundrum. J Occup Med. 1987;29:869–876. [PubMed] [Google Scholar]
• Dinman BD. Alumina-related pulmonary disease. J Occup Med. 1988;30:328–335. [PubMed] [Google Scholar]
• Discher DP, Breitenstein BD. Prevalence of chronic pulmonary disease in aluminum potroom workers. J Occup Med. 1976;18:379–386. [Google Scholar]
• Divine KK, Lewis JL, Grant PG, Bench G. Quantitative particle-induced x-ray emission imaging of rat olfactory epithelium applied to the permeability of rat epithelium to inhaled aluminum. Chem Res Toxicol. 1999;12:575–581. [PubMed] [Google Scholar]
• Dlugaszek M, Fiejka MA, Graczyk A, Aleksandrowicz JC. Effects of various aluminium compounds given orally to mice on Al tissue distribution and tissue concentrations of essential elements. Pharmacol Toxicol. 2000;86:135–139. [PubMed] [Google Scholar]
• Dobson CB, Day JP, King SJ, Itzhaki RF. Location of aluminium and gallium in human neuroblastoma cells treated with metal-chelating agent complexes. Toxicol Appl Pharmacol. 1998;152:145–152. [PubMed] [Google Scholar]
• Dockery DW, Pope CA, Xu X, Spengler JD, Ware JH, Fay ME, Ferris BG, Speizer FE. An association between air pollution and motality in six U.S. cities. N Engl J Med. 1993;329:1753–1759. [PubMed] [Google Scholar]
• Doese M. Industrial medicine studies on injury to health caused by aluminium, in particular lung disease from aluminium dust. Arch Gewerbepathol. 1938;8:501–531. [Google Scholar]
• Doll R. Review: Alzheimer’s disease and environmental aluminium. Age Ageing. 1993;22:138–153. [PubMed] [Google Scholar]
• Domingo JL. Reproductive and developmental toxicity of aluminum: a review. Neurotoxicol Teratol. 1995;17:515–521. [PubMed] [Google Scholar]
• Domingo JL. Adverse effects of aluminum-chelating compounds for clinical use. Adv Drug React Toxicol Rev. 1996;15:145–165. [PubMed] [Google Scholar]
• Domingo JL, Llobet JM, Gómez M, Tomás JM, Corbella J. Nutritional and toxicological effects of short-term ingestion of aluminum by the rat. Res Commun Chem Pathol Pharmacol. 1987;56:409–419. [PubMed] [Google Scholar]
• Domingo JL, Gómez M, Bosque MA, Corbella J. Lack of teratogenicity of aluminum hydroxide in rats. Life Sci. 1989;45:243–247. [PubMed] [Google Scholar]
• Domingo JL, Gómez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Intl. 1991a;39:598–601. [PubMed] [Google Scholar]
• Domingo JL, Gómez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminium absorption. Lancet. 1991b;338:1467. [PubMed] [Google Scholar]
• Domingo JL, Gómez M, Sanchez DJ, Llobet JM, Corbella J. Effect of various dietary constituents on gastrointestinal absorption of aluminum from drinking water and diet. Res Commun Chem Pathol Pharmacol. 1993;79:377–380. [PubMed] [Google Scholar]
• Domingo JL, Gómez M, Llobet JM, del Castillo D, Corbella J. Influence of citric, ascorbic and lactic acids on the gastrointestinal absorption of aluminum in uremic rats. Nephron. 1994;66:108–109. [PubMed] [Google Scholar]
• Domingo JL, Llorens J, Sanchez DJ, Gómez M, Llobet JM, Corbella J. Age-related effects of aluminum ingestion on brain aluminum accumulation and behavior in rats. Life Sci. 1996;58:1387–1395. [PubMed] [Google Scholar]
• Donald JM, Golub MS, Gershwin ME, Keen CL. Neurobehavioral effects in offspring of mice given excess aluminum in diet during gestation and lactation. Neurotoxicol Teratol. 1989;11:345–351. [PubMed] [Google Scholar]
• Dorman DC, Brenneman KA, McElveen AM, Lynch SE, Roberts KC, Wong BA. Olfactory transport: a direct route of delivery of inhaled manganese phosphate to the rat brain. J Toxicol Environ Health A. 2002;65:1493–1511. [PubMed] [Google Scholar]
• Drabek O, Mladkova L, Boruvka L, Szakova J, Nikodem A, Nemecek K. Comparison of water-soluble and exchangeable forms of Al in acid forest soils. J Inorg Biochem. 2005;99:1788–1795. [PubMed] [Google Scholar]
• Drabløs PA, Hetland S, Schmidt F, Thomassen Y. Uptake and Excretion of Aluminum in Workers Exposed to Aluminum Fluoride and Aluminum Oxide. Aluminum Association. Aluminum and Health, 2nd International Conference; Tampa, Florida. 1992. pp. 157–160. [Google Scholar]
• Drew RT, Gupta BN, Bend JR, Hook GE. Inhalation studies with a glycol complex of aluminum-chloride-hydroxide. Arch Environ Health. 1974;28:321–326. [PubMed] [Google Scholar]
• Drewitt PN, Butterworth KR, Springall CD, Moorhouse SR. Plasma levels of aluminium after tea ingestion in healthy volunteers. Food Chem Toxicol. 1993;31:19–23. [PubMed] [Google Scholar]
• Driscoll CT, Letterman RD. Chemistry and fate of aluminum (III) in treated drinking water. J Environ Eng. 1988;114:21–37. [Google Scholar]
• Driscoll CT, Letterman RD. Factors regulating residual aluminium concentrations in treated waters. Environmetrics. 1995;6:287–309. [Google Scholar]
• Driscoll CT, Schecher WD. Aqueous chemistry of aluminum. In: Gitelman HJ, editor. Aluminum and Health a Critical Review. New York: Marcel Dekker; 1989. pp. 27–65. [Google Scholar]
• Drüeke T. Hyporesponsiveness to recombinant human erythropoietin. Nephrol Dial Transplant. 2001;16:25–28. [PubMed] [Google Scholar]
• Drüeke TB. Intestinal absorption of aluminium in renal failure. Nephrol Dial Transplant. 2002;17(Suppl 2):13–16. [PubMed] [Google Scholar]
• Drüeke T, Lacour B, Touam M, Basile C, Bourdon R. Oral aluminum administration to uremic, hyperparathyroid, or vitamin D-supplemented rats. Nephron. 1985;39:10–17. [PubMed] [Google Scholar]
• Drüeke TB, Jouhanneau P, Banide H, Lacour B, Yiou F, Raisbeck G. Effects of silicon, citrate and the fasting state on the intestinal absorption of aluminium in rats. Clin Sci. 1997;92:63–67. [PubMed] [Google Scholar]
• Dubois F, Bégin R, Cantin A, Massé S, Martel M, Bilodeau G, Dufresne A, Perreault G, Sébastien P. Aluminum inhalation reduces silicosis in a sheep model. Am Rev Respir Dis. 1988;137:1172–1179. [PubMed] [Google Scholar]
• Duckett S, Galle P. Electron microscope-microprobe studies of aluminum in the brains of cases of Alzheimer’s disease and ageing patients. J Neuropathol Exp Neurol. 1980;39:350. [Google Scholar]
• Duffield JR, Edwards K, Evans DA, Morrish DM, Vobe A, Williams D. Low molecular mass aluminum complex speciation in biofluids. J Coord Chem. 1991;23:277–290. [Google Scholar]
• Dufresne A, Sébastien P, Michaud D, Perrault G, Bégin R. Influence of aluminum treatments on pulmonary retention of quartz in sheep silicosis. Exp Lung Res. 1994;20:157–168. [PubMed] [Google Scholar]
• Durand M, Florkowski C, George P, Walmsley T, Weinstein P, Cole J. Elevated trace element output in urine following acute volcanic gas exposure. J Volcanol Geotherm Res. 2004;134:139–148. [Google Scholar]
• DuVal G, Brubb B, Bentley P. Aluminum accumulation in the crystalline lens of humans and domestic animals. Trace Elem Med. 1986;3:100–104. [Google Scholar]
• Dworski M. Prophylaxis and treatment of experimental silicosis by means of aluminum; an experimental study. Arch Ind Health. 1955;12:229–246. [PubMed] [Google Scholar]
• Dwyer CM, Kerr RE. Contact allergy to aluminum in 2 brothers. Contact Dermatitis. 1993;29:36–38. [PubMed] [Google Scholar]
• Eastwood JB, Levin GE, Pazianas M, Taylor AP, Denton J, Freemont AJ. Aluminum deposition in bone after contamination of drinking water supply. Lancet. 1990;336:462–464. [PubMed] [Google Scholar]
• Ebina Y, Okada S, Hamazaki S, Midorikawa O. Liver, kidney, and central nervous system toxicity of aluminum given intraperitoneally to rats: a multiple-dose subchronic study using aluminum nitrilotriacetate. Toxicol Appl Pharmacol. 1984;72:211–218. [PubMed] [Google Scholar]
• Ecelbarger CA, Greger JL. Dietary citrate and kidney function affect aluminum, zinc, and iron utilization in rats. J Nutr. 1991;121:1755–1762. [PubMed] [Google Scholar]
• Ecelbarger CA, MacNeil GG, Greger JL. Tissue aluminum accumulation and toxic consequences in rats chronically fed aluminum with and without citrate. J Agric Food Chem. 1994a;42:2220–2224. [Google Scholar]
• Ecelbarger CA, MacNeil GG, Greger JL. Aluminum retention by aged rats fed aluminum and treated with desferrioxamine. Toxicol Lett. 1994b;73:249–257. [PubMed] [Google Scholar]
• Edling NPG. Aluminum pneumoconiosis: A roentgendiagnostic study of five cases. Acta Radiol. 1961;56:170–178. [PubMed] [Google Scholar]
• Edling C, Jarvholm B, Andersson L, Axelson O. Mortality and cancer incidence among workers in an abrasive manufacturing industry. Br J Ind Med. 1987;44:57–59. [PMC free article] [PubMed] [Google Scholar]
• Edwards MS, Harrison MR, Halks-Miller M, Nakayama DK, Berger MS, Glick PL, Chinn DH. Kaolin-induced congenital hydrocephalus in utero in fetal lambs and rhesus monkeys. J Neurosurg. 1984;60:115–122. [PubMed] [Google Scholar]
• Edwardson JA, Candy JM, Ince PG, McArthur FK, Morris CM, Oakley AE, Taylor GA, Bjertness E. Aluminium accumulation, beta-amyloid deposition and neurofibrillary changes in the central nervous system. In: Chadwick DJ, Whelan J, editors. Aluminium in Biology and Medicine. New York: John Wiley; 1992. pp. 165–179. discussion 179-185. [PubMed] [Google Scholar]
• Edwardson JA, Moore PB, Ferrier IN, Lilley JS, Newton GW, Barker J, Templar J, Day JP. Effect of silicon on gastrointestinal absorption of aluminium. Lancet. 1993;342:211–212. [PubMed] [Google Scholar]
• EEC (European Economic Union Council) EEC directive 67/548/EEC of 27 June 1967 on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. 1967:1–98. [Google Scholar]
• Eickhoff TC, Myers M. Aluminum in vaccines. Vaccine. 2002;20:S1–S4. [PubMed] [Google Scholar]
• El-Rahman SS. Neuropathology of aluminum toxicity in rats (glutamate and GABA impairment) Pharmacol Res. 2003;47:189–194. [PubMed] [Google Scholar]
• Elinder CG, Ahrengart L, Lidums V, Pettersson E, Sjögren B. Evidence of aluminium accumulation in aluminium welders. Br J Ind Med. 1991;48:735–738. [PMC free article] [PubMed] [Google Scholar]
• Ellen G, Egmond E, Van Loon JW, Sahertian ET, Tolsma K. Dietary intakes of some essential and non-essential trace elements, nitrate, nitrite and N-nitrosamines, by Dutch adults: estimated via a 24-hour duplicate portion study. Food Addit Contam. 1990;7:207–221. [PubMed] [Google Scholar]
• Ellis H, Scurr JH. Axillary hyperhidrosis - topical treatment with aluminum chloride hexahydrate. Postgrad Med J. 1979;55:868–869. [PMC free article] [PubMed] [Google Scholar]
• Ellis HA, McCarthy JH, Herrington J. Bone aluminium in haemodialysed patients and in rats injected with aluminium chloride: relationship to impaired bone mineralisation. J Clin Pathol. 1979;32:832–844. [PMC free article] [PubMed] [Google Scholar]
• Ellis KJ, Keleher S, Raciti A, Savory J, Wills M. In vivo monitoring of skeletal aluminum burden in patients with renal failure. J Radioanal Nucl Chem. 1988;124:85–95. [Google Scholar]
• Elmore AR. Cosmetic ingredient review expert panel. Final report on the safety assessment of aluminum silicate, calcium silicate, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, sodium magnesium aluminum silicate, zirconium silicate, attapulgite, bentonite, Fuller’s earth, hectorite, kaolin, lithium magnesium silicate, lithium magnesium sodium silicate, montmorillonite, pyrophyllite, and zeolite. Int J Toxicol. 2003;22(Suppl 1):S37–S102. [PubMed] [Google Scholar]
• Elorriaga R, Fernández Martin JL, Menéndez Fraga PM, Naves ML, Braga S, Cannata JB. Aluminium removal: short and long-term preliminary results with L1 in rats. Drugs Today. 1992;28:177–182. [Google Scholar]
• Emmett M. A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. Kidney Int Suppl. 2004;90:S25–S32. [PubMed] [Google Scholar]
• Eng PJ, Trainor TP, Brown GE, Waychunas GA, Newville M, Sutton SR. Structure of the hydrated α–Al2O3 (0001) surface. Science. 2000;288:1029–1033. [PubMed] [Google Scholar]
• Englert N. Fine particles and human health-a review of epidemiological studies. Toxicol Lett. 2004;149:235–242. [PubMed] [Google Scholar]
• EPA (Environmental Protection Agency) U.S. Environmental Protection Agency. Code of Federal Regulations. 1979 40 CFR 143.3. [Google Scholar]
• EPA (Environmental Protection Agency) National ambient air quality standards for particulate matter; final rule. Fed Reg. 1997;62:38651. [Google Scholar]
• Epstein SG. A summary of findings from twenty years of molten metal incident reporting. Light Metals 2005 2005 [Google Scholar]
• Erdohazi M, Newman RL. Aluminium hydroxide granuloma. Br Med J. 1971;3:621–623. [PMC free article] [PubMed] [Google Scholar]
• Eschbach JW, Varma A, Stivelman JC. Is it time for a paradigm shift? Is erythropoietin deficiency still the main cause of renal anaemia? Nephrol Dial Transplant. 2002;17(Suppl 5):2–7. [PubMed] [Google Scholar]
• ESIS (European Chemical Substances Information System) 2007. [online]. Cited 24 January 2007. http://ecb.jrc.it/esis.
• Esmonde TF. Cerebral dysfunction after a water pollution incident in Camelford: Study has several methodological errors. Br Med J. 2000;320:1337–1338. [PubMed] [Google Scholar]
• Esparza JL, Gómez M, Romeu M, Mulero M, Sanchez DJ, Mallol J, Domingo JL. Aluminum-induced pro-oxidant effects in rats: protective role of exogenous melatonin. J Pineal Res. 2003;35:32–39. [PubMed] [Google Scholar]
• Ess S, Steinegger A, Ess H, Schlatter C. Experimental study on the fibrogenic properties of different types of alumina. Am Ind Hyg Assoc J. 1993;45:360–370. [PubMed] [Google Scholar]
• Eticha D, Stass A, Horst WJ. Localization of aluminum in the maize root apex: can morin detect cell wall-bound aluminum? J Exp Bot. 2005;56:1351–1357. [PubMed] [Google Scholar]
• European Commission. Technical guidance document on risk assessment. 2003. [online] Cited 24 January 2007 http://ecb.jrc.it/tgd/
• Evans SM, Zeit W. Tissue responses to physical forces. II. The response of connective tissue to piezoelectrically active crystals. J Lab Clin Med. 1949;34:592–609. [PubMed] [Google Scholar]
• Evans WJ, Martin CJ. Heat of complex formation of Al(III) and Cd(II) with phytic acid. IX. J Inorg Biochem. 1988;34:11–18. [PubMed] [Google Scholar]
• Exley C. Does antiperspirant use increase the risk of aluminium-related disease, including Alzheimer’s disease? Molec Med Today. 1998;4:107–109. [PubMed] [Google Scholar]
• Exley C. A molecular mechanism of aluminum-induced Alzheimer’s disease? J Inorg Biochem. 1999;76:133–140. [PubMed] [Google Scholar]
• Exley C. Aluminum in antiperspirants: more than just skin deep. Am J Med. 2004;117:969–970. [PubMed] [Google Scholar]
• Exley C. The aluminium-amyloid cascade hypothesis and Alzheimer’s disease. Subcell Biochem. 2005;38:225–234. [PubMed] [Google Scholar]
• Exley C, Birchall JD. Aluminium and Alzheimer’s disease. Age Ageing. 1993;22:391–392. [PubMed] [Google Scholar]
• Fairweather-Tait SJ, Piper Z, Fatemi SJ, Moore GR. The effect of tea on iron and aluminium metabolism in the rat. Br J Nutr. 1991;65:61–68. [PubMed] [Google Scholar]
• Fairweather-Tait S, Hickson K, McGaw B, Reid M. Orange juice enhances aluminum absorption from antacid preparations. Eur J Clin Nutr. 1994;48:71–73. [PubMed] [Google Scholar]
• FAO/WHO (Food and Agriculture Organization/World Health Organization) Aluminium. Evaluation of Certain Food Additives and Contaminants; Thirty-third report of the Joint FAO/WHO Expert Committee on Food Additives; Geneva: World Health Organization; 1989. pp. 28–31. WHO Technical Report Series No. 776. [PubMed] [Google Scholar]
• FAO/WHO (Food and Agriculture Organization/World Health Organization) Summary and conclusions of the sixty-seventh meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) 2006. [online] Cited 24 January 2007 http://www.who.int/ipcs/food/jecfa/summaries/summary67.pdf.
• Farina M, Lara FS, Brandao R, Jacques R, Rocha JB. Effects of aluminum sulfate on erythropoiesis in rats. Toxicol Lett. 2002;132:131–139. [PubMed] [Google Scholar]
• Farina M, Rotta LN, Soares FA, Jardim F, Jacques R, Souza DO, Rocha JB. Hematological changes in rats chronically exposed to oral aluminum. Toxicology. 2005;209:29–37. [PubMed] [Google Scholar]
• Farrar G, Morton AP, Blair JA. The intestinal absorption and tissue distribution of aluminium, gallium and scandium: a comparative study. Biochem Soc Trans. 1987;15:1164–1165. [Google Scholar]
• Farrar G, Altmann P, Welch S, Wychrij O, Ghose B, Lejeune J, Corbett J, Prasher V, Blair JA. Defective gallium-transferrin binding in Alzheimer’s disease and Down’s syndrome: possible mechanism for accumulation of aluminum in brain. Lancet. 1990;335:747–750. [PubMed] [Google Scholar]
• FASEB (Federation of American Societies for Experimental Biology) Evaluation of the Health Aspects of Aluminum Compounds as Food Ingredients. NTIS Report No-262 665. Springfield VA: 1975. p. 26. National Technical Information Service Sponsored by the US Food and Drug Administration. US FDA Report FDA/BF-77/24. [Google Scholar]
• Fattoretti P, Bertoni-Freddari C, Balietti M, Giorgetti B, Solazzi M, Zatta P. Chronic aluminum administration to old rats results in increased levels of brain metal ions and enlarged hippocampal mossy fibers. Ann N Y Acad Sci. 2004;1019:44–47. [PubMed] [Google Scholar]
• Favarato M, Zanoni S, Zatta PF. Unambiguous aluminum(III) localization in senile plaque core from Alzheimer’s disease brains. Neurobiol Aging. 1992;13(Suppl 1):S40. [Google Scholar]
• Favaro RM, Silva HC, Vannucchi H. Bioavailability of vitamin A in the rat following ingestion of neomycin sulfate or aluminium hydroxide. Int J Vit Nutr Res. 1994;64:98–103. [PubMed] [Google Scholar]
• Fawcett HA, Smith NP. Injection-site granuloma due to aluminum. Arch Dermatol. 1984;120:1318–1322. [PubMed] [Google Scholar]
• Fawcett HA, McGibbon D, Cronin E. Persistent vaccination granuloma due to aluminium hypersensitivity. Br J Dermatol. 1985;113(Suppl 29):101–102. [Google Scholar]
• Federal-Provincial-Territorial Committee on Drinking Water. Summary of guidelines for Canadian drinking water quality. 2006. [online] Cited 24 January 2007 www.healthcanada.gc.ca/waterquality.
• Feinroth M, Feinroth MV, Berlyne GM. Aluminum absorption in the rat everted gut sac. Miner Electrolyte Metab. 1982;8:29–35. [PubMed] [Google Scholar]
• Feldman GV. Pertussin antibody response after triple antigen. Arch Dis Child. 1957;32:111–113. [PMC free article] [PubMed] [Google Scholar]
• Feng TL, Gurian PL, Healy MD, Barron AR. Aluminum citrate: isolation and structural characterization of a stable trinuclear complex. Inorg Chem. 1990;29:408–411. [Google Scholar]
• Fenwick S, Roberts EA, Mahesh BS, Roberts NB. In end-stage renal failure, does infection lead to elevated plasma aluminium and neurotoxicity? Implications for monitoring. Ann Clin Biochem. 2005;42:149–152. [PubMed] [Google Scholar]
• Fernández F, Bernaola G, Muñoz DG, Fernandez de Corres L. Nodulos subcutáneous por sensibilización a aluminio en pacientes tratados mediante inmunoterapia con extratos semidepot. Dermititis Contacto. 1990;16:57–60. [Google Scholar]
• Fernández I, Fernández JL, Rodriquez R, Sanz-Medel A, Cannata JB. The influence of iron stores on aluminum gastrointestinal absorption. Rev Esp Fisiol. 1989;45:33–39. [PubMed] [Google Scholar]
• Fernández-Martin JL, Canteros A, Alles A, Massari P, Cannata-Andia J. Aluminum exposure in chronic renal failure in iberoamerica at the end of the 1990s: overview and perspectives. Am J Med Sci. 2000;320:96–99. [PubMed] [Google Scholar]
• Fernandez Menendez MJ, Fell GS, Brock JH, Cannata JB. Aluminium uptake by intestinal cells: effect of iron status and precomplexation. Nephrol Dial Transplant. 1991;6:672–674. [PubMed] [Google Scholar]
• Fiejka M, Aleksandrowicz J. Aluminum as an adjuvant in vaccines and post-vaccine reactions. Rocz Panstw Zakl Hig. 1993;44:73–80. [PubMed] [Google Scholar]
• Fiejka M, Fiejka E, Dlugaszek M. Effect of aluminum hydroxide administration on normal mice: tissue distribution and ultrastructural localization of aluminum in liver. Pharmacol Toxicol. 1996;78:123–128. [PubMed] [Google Scholar]
• Field GB. Pulmonary function in aluminum smelters. Thorax. 1984;39:743–751. [PMC free article] [PubMed] [Google Scholar]
• Fifield LK, Day JP, Oldham C, Carling RS. Department of Nuclear Physics, Annual Report. Canberra: Australian National University; 1997. Study of the kinetics of aluminium absorption and excretion in humans; pp. 97–101. [Google Scholar]
• Filov VA. Vrednie Chemichescie Veshestva Neorganicheskie Soedinenia Elementov I-IV Groopp [Hazardous Substances Inorganic Substances Containing I-IV Group Elements] Leningrad: Chemistry; 1988. [Google Scholar]
• Fimreite N, Hansen OO, Pettersen HC. Aluminum concentrations in selected foods prepared in aluminum cookware, and its implications for human health. Bull Environ Contam Toxicol. 1997;58:1–7. [PubMed] [Google Scholar]
• Findlow JA, Duffield JR, Williams DR. The chemical speciation of aluminum in milk. Chem Speciat Bioavail. 1990;2:3–32. [Google Scholar]
• Finelli VN, Que Hee SS, Niemeier RW. Influence of exposure to aluminum chloride and fluoride dusts on some biochemical and physiological parameters in rats. In: Brown SS, Davies DS, editors. Organ-Directed Toxicity Chemical Indices and Mechanisms. New York: Pergamon Press; 1981. pp. 291–295. [Google Scholar]
• Fink D, Walton J, Hotchkis MA, Jacobsen GE, Lawson EM, Smith AM, Tuniz C, Wilcox D. First 26Al analyses at the ANATARES AMS Centre: uptake via oral ingestion of 26Al in rats. Nucl Instr Meth Phys Res Sect B. 1994;92:473–477. [Google Scholar]
• Firling CE, Hill TA, Severson AR. Aluminum toxicity perturbs long bone calcification in the embryonic chick. Arch Toxicol. 1999;73:359–366. [PubMed] [Google Scholar]
• Fischer T, Rystedt I. A case of contact sensitivity to aluminium. Contact Dermatitis. 1982;8:343. [PubMed] [Google Scholar]
• Fisher AA. Reactions to aluminum and its salts. Cutis. 1984;33:154–159. [PubMed] [Google Scholar]
• Flarend RE, Hem SL, White JL, Elmore D, Suckow MA, Rudy AC, Dandashli EA. In vivo absorption of aluminum-containing vaccine adjuvants using 26Al. Vaccine. 1997;15:1314–1318. [PubMed] [Google Scholar]
• Flarend R, Bin T, Elmore D, Hem SL. A preliminary study of the dermal absorption of aluminum from antiperspirants using aluminum-26. Food Chem Toxicol. 2001;39:163–168. [PubMed] [Google Scholar]
• Flaten TP. Geographical associations between aluminium in drinking water and death rates with dementia (including Alzheimer’s disease), Parkinson’s disease and amyotrophic lateral sclerosis in Norway. Environ Geochem Health. 1990;12:152–167. [PubMed] [Google Scholar]
• Flaten TP. Aluminium as a risk factor in Alzheimer’s disease, with emphasis on drinking water. Brain Res Bull. 2001;55:187–196. [PubMed] [Google Scholar]
• Flaten TP, Odegard M. Tea, aluminium and Alzheimer’s disease. Food Chem Toxicol. 1988;26:959–960. [PubMed] [Google Scholar]
• Flaten TP, Glattre E, Viste A, Sooreide O. Mortality from dementia among gastroduodenal ulcer patients. J Epidemiol Community Health. 1991;45:203–206. [PMC free article] [PubMed] [Google Scholar]
• Fleming J, Joshi JG. Ferritin: Isolation of aluminum-ferritin complex from brain. Proc Natl Acad Sci. 1987;84:7866–7870. [PMC free article] [PubMed] [Google Scholar]
• Flora SJ, Dhawan M, Tandon SK. Effects of combined exposure to aluminium and ethanol on aluminium body burden and some neuronal, hepatic and haematopoietic biochemical variables in the rat. Hum Exp Toxicol. 1991;10:45–48. [PubMed] [Google Scholar]
• Flora SJ, Mehta A, Satsangi K, Kannan GM, Gupta M. Aluminum-induced oxidative stress in rat brain: response to combined administration of citric acid and HEDTA. Comp Biochem Physiol C Toxicol Pharmacol. 2003;134:319–328. [PubMed] [Google Scholar]
• Florence AL, Gauthier A, Ponsar C, Van den Bosch de Aguilar P, Crichton RR. An experimental animal model of aluminium overload. Neurodegeneration. 1994;3:315–323. [PubMed] [Google Scholar]
• Foley CM, Polinsky MS, Gruskin AB, Baluarte HJ, Grover WD. Encephalopathy in infants and children with chronic renal disease. Arch Neurol. 1981;38:656–658. [PubMed] [Google Scholar]
• Folstein MF, Folstein SE, McHugh PR. “Mini-Mental State:” a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–198. [PubMed] [Google Scholar]
• Forbes WF, Agwani N. Geochemical risk factors for mental functioning, based on the Ontario, Longitudinal study of aging (LSA). III. The effects of different aluminum-containing compounds. Can J Aging. 1994a;13:488–498. [Google Scholar]
• Forbes WF, Agwani N. A suggested mechanism for aluminum biotoxicity. J Theor Biol. 1994b;171:207–214. [PubMed] [Google Scholar]
• Forbes WF, Gentleman JF. Risk factors, causality, and policy initiatives: the case of aluminum and mental impairment. Exp Gerontol. 1998;33:141–154. [PubMed] [Google Scholar]
• Forbes WF, Hayward LM, Agwani N. Dementia, aluminum, and fluoride. Lancet. 1991;338:1592–1593. [PubMed] [Google Scholar]
• Forbes WF, Hayward LM, Agwani N. Geochemical risk factors for mental functioning, based on the Ontario Longitudial Study of Aging (LAS). I. Results from a preliminary investigation. Can J Aging. 1992;11:269–280. [Google Scholar]
• Forbes WF, McAiney CA, Hayward LM, Agwani N. Geochemical risk factors for mental functioning, based on the Ontario longitudinal study of aging (LSA): II. The role of pH. Can J Aging. 1994;13:249–267. [Google Scholar]
• Forbes WF, Agwani N, Lachmaniuk P. Geochemical risk factors for mental functioning, based on the Ontario Longitudinal Study of Aging (LAS) IV. The role of silicon-containing compounds. Can J Aging. 1995;14:630–641. [Google Scholar]
• Forster DP, Newens AJ, Kay DW, Edwardson JA. Risk factors in clinically diagnosed presenile dementia of the Alzheimer type: a case-control study in northern England. J Epidemiol Commun Health. 1995;49:253–258. [PMC free article] [PubMed] [Google Scholar]
• Fosmire GJ, Focht SJ, McClearn GE. Genetic influences on tissue deposition of aluminum in mice. Biol Trace Elem Res. 1993;37:115–121. [PubMed] [Google Scholar]
• Fox JL, Lamson ML. RSTRIP: Pharmacokinetic Data Stripping/Least Squares Parameter Optimization. Salt Lake City: MicroMath, Inc; 1989. [Google Scholar]
• Frash VN, Vanchugova NN, Rukoleeva SN, Zykova VA, Grebennikov SA, Shcherbakov SV. Carcinogenic effects of some nonfibrous mineral dusts. Byull Eksp Biol Med. 1992;114:648–651. [PubMed] [Google Scholar]
• Frecker MF. Dementia in Newfoundland: Identification of a geographical isolate? J Epidemiol Comm Health. 1991;45:307–311. [PMC free article] [PubMed] [Google Scholar]
• French P, Gardner MJ, Gunn AM. Dietary aluminium and Alzheimer’s disease. Food Chem Toxicol. 1989;27:495–498. [PubMed] [Google Scholar]
• Freour P, Germouty J, Jault D, Plancel F, Warin JF. A case of pneumoconiosis due to aluminum dust. La Presse Medicale. 1966;74:2547–2549. [PubMed] [Google Scholar]
• Fritschi L, Beach J, Sim M, Abramson M, Benke G, Musk AW, de Klerk N, McNeil J. Respiratory symptoms and lung function in two prebake aluminum smelters. Am J Ind Med. 1999;35:491–498. [PubMed] [Google Scholar]
• Fritschi L, Sim MR, Forbes A, Abramson MJ, Benke G, Musk AW, de Klerk NH. Respiratory symptoms and lung-function changes with exposure to five substances in aluminium smelters. Int Arch Occup Environ Health. 2003;76:103–110. [PubMed] [Google Scholar]
• Froment DH, Buddington B, Miller NL, Alfrey AC. Effect of solubility on the gastrointestinal absorption of aluminum from various aluminum compounds in the rat. J Lab Clin Med. 1989a;114:237–242. [PubMed] [Google Scholar]
• Froment DP, Molitoris BA, Buddington B, Miller N, Alfrey AC. Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate. Kidney Int. 1989b;36:978–984. [PubMed] [Google Scholar]
• Frost L, Johansen P, Pedersen S, Veien N, Aabel Östergaard P, Nielsen MH. Persistent subcutaneous nodules in children hyposensitized with aluminium-containing allergen extracts. Allergy. 1985;40:368–372. [PubMed] [Google Scholar]
• Frostad AW. Fluorine intoxication in Norwegian aluminium plant workers. Tidskr Nor Laegenforen. 1936;56:179–182. [Google Scholar]
• Fujimaki H, Ozawa MT, Kubota K, Watanabe N. Adjuvant effects of aluminum silicate on IgE and IgG1 antibody production in mice. Int Arch Allergy Appl Immunol. 1984;75:351–356. [PubMed] [Google Scholar]
• Fujimaki H, Ozawa M, Ashikawa T, Kubota K, Watanabe N. Induction of IgE antibody production to aerosolized ovalbumin in mice treated intratracheally with aluminum silicate. Int Arch Allergy Appl Immunol. 1986;79:206–210. [PubMed] [Google Scholar]
• Fulton B, Jeffery EH. Absorption and retention of aluminum from drinking water.1. Effect of citric and ascorbic acids on aluminum tissue levels in rabbits. Fundam Appl Toxicol. 1990;14:788–796. [PubMed] [Google Scholar]
• Fulton B, Jaw S, Jeffery EH. Bioavailability of aluminum from drinking water. Fundam Appl Toxicol. 1989;12:144–150. [PubMed] [Google Scholar]
• Furst A. Trace elements related to specific chronic diseases. Cancer Geol Soc Am Mem. 1971;123:109–114. [Google Scholar]
• Furst A, Haro RT. A survey of metal carcinogenesis. Prog Exp Tumor Res. 1969;12:102–133. [PubMed] [Google Scholar]
• Gaafar SM, Turk JL. Granuloma formation in lymph-nodes. J Pathol. 1970;100:9–20. [PubMed] [Google Scholar]
• Gaffuri E, Donna A, Pietra R, Sabbioni E. Pulmonary changes and aluminum levels following inhalation of alumina dust: A study on four exposed workers. Med Lav. 1985;76:222–227. [PubMed] [Google Scholar]
• Gafter U, Mamet R, Korzets A, Malachi T, Schoenfeld N. Bullous dermatosis of end-stage renal disease: a possible association between abnormal porphyrin metabolism and aluminium. Nephrol Dial Transplant. 1996;11:1787–1791. [PubMed] [Google Scholar]
• Galceran T, Finch J, Bergfeld M, Coburn JW, Martin K, Teitelbaum S, Slatopolsky E. Biological effects of aluminum on normal dogs: studies on the isolated perfused bone. Endocrinology. 1987;121:406–413. [PubMed] [Google Scholar]
• Gallon C, Munger C, Permont S, Campbell PG. Hydroponic study of aluminum accumulation by aquatic plans: effects of fluoride and pH. Water Air Soil Poll. 2004;153:135–155. [Google Scholar]
• Ganrot PO. Metabolism and possible health effects of aluminum. Environ Health Perspect. 1986;65:363–441. [PMC free article] [PubMed] [Google Scholar]
• Garbossa G, Galvez G, Castro ME, Nesse A. Oral aluminum administration to rats with normal renal function. 1. Impairment of erythropoiesis. Hum Exp Toxicol. 1998a;17:312–317. [PubMed] [Google Scholar]
• Garbossa G, Galvez G, Perez G, Stripeikis J, Tudino M, Nesse A. Oral aluminum administration to rats with normal renal function. 2. Body distribution. Hum Exp Toxicol. 1998b;17:318–322. [PubMed] [Google Scholar]
• Garcia-Patos V, Pujol RM, Alomar A, Cistero A, Curell R, Fernandez-Figueras MT, de Moragas JM. Persistent subcutaneous nodules in patients hyposensitized with aluminum-containing allergen extracts. Arch Dermatol. 1995;131:1421–1424. [PubMed] [Google Scholar]
• Gardner LU, Dworski M, Delahant AB. Aluminum therapy in silicosis: An experimental study. J Ind Hyg Toxicol. 1944;26:211–223. [Google Scholar]
• Gardner MJ, Gunn AM. Bioavailability of aluminium from food and drinking water. Alzheimer’s Disease and the Environment; Proceedings of the conference, Royal Society of Medicine, Round Table Series No 26, ed Lord Walton of Detchant; London UK. 1991. pp. 78–86. [Google Scholar]
• Gardner MJ, Gunn AM. Speciation and bioavailability of aluminum in drinking waer. Chem Speciat Bioavail. 1995;7:9–16. [Google Scholar]
• Garrett P. Aluminium accumulation and immunosuppression. BMJ. 1989;298:755. [PMC free article] [PubMed] [Google Scholar]
• Garruto RM. Pacific paradigms of environmentally-induced neurological disorders: clinical, epidemiological and molecular perspectives. Neurotoxicology. 1991;12:347–377. [PubMed] [Google Scholar]
• Garruto RM, Yase Y. Neurodegenerative disorders of the Western Pacific: the search for mechanisms of pathogenesis. Trends Neurosci. 1986;9:368–374. [Google Scholar]
• Garruto RM, Fukatsu R, Yanagihara R, Gajdusek DC, Hook G, Fiori CE. Imaging of calcium and aluminum in neurofibrillary tangle-bearing neurons in parkinsonism-dementia of Guam. Proc Natl Acad Sci. 1984;81:1875–1879. [PMC free article] [PubMed] [Google Scholar]
• Garruto RM, Shankar SK, Yanagihara R, Salazar AM, Amyx HL, Gajdusek DC. Low-calcium high-aluminum diet-induced motor neuron pathology in cynomolgus monkeys. Acta Neuropathol. 1989;78:210–219. [PubMed] [Google Scholar]
• Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006;63:168–174. [PubMed] [Google Scholar]
• Gauthier E, Fortier I, Courchesne F, Pepin P, Mortimer J, Gauvreau D. Aluminium forms in drinking water and risk of Alzheimer’s disease. Environ Res A. 2000;84:234–246. [PubMed] [Google Scholar]
• Gava C, Perazzolo M, Zentilin L, Levis AG, Corain B, Bombi GG, Palumbo M, Zatta P. Genotoxic potentiality and DNA binding properties of acetylacetone, maltol, and their aluminum (III) and chromium (III) neutral complexes. Toxicol Environ Chem. 1989;22:149–157. [Google Scholar]
• Gelfant S. Inhibition of cell division: a critical and experimental analysis. In: Bourne GH, Danielli JF, editors. International Review of Cytology. New York: Academic Press; 1963. pp. 1–39. [PubMed] [Google Scholar]
• Gherardi RK, Cherin P. Macropagic fascitis: a new entity. Groupe d’etudes et recherche surles maladies musculaires acquises et disimmunitaires (GERMMAD) de l’association francaise contre les myopathies (AFM) Rev Med Interne. 1998;19:617–618. [PubMed] [Google Scholar]
• Gherardi RK, Coquet M, Cherin P, Belec L, Moretto P, Dreyfus PA, Pellissier JF, Chariot P, Authier FJ. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain. 2001;124:1821–1831. [PubMed] [Google Scholar]
• Ghetti B, Ohcs S. On the relation between microtubule denisty and axoplasmic transport in nerves treated with maytansine in vitro. In: Canal N, Pozza G, editors. Periferal Neuropathies. Amsterdam: Elsevier/North Holland Biomedical Press; 1978. pp. 177–186. [Google Scholar]
• Ghribi O, Herman MM, Savory J. The endoplasmic reticulum is the main site for caspase-3 activation following aluminum-induced neurotoxicity in rabbit hippocampus. Neurosci Lett. 2002;324:217–221. [PubMed] [Google Scholar]
• Gibbs GW. Mortality of aluminum reduction plant workers, 1950 through 1977. J Occup Med. 1985;27:761–770. [PubMed] [Google Scholar]
• Gidden H, Holland FF, Klein E. Trace metal protein binding in normal and dialyzed uremic serum. Trans Am Soc Artif Intern Organs. 1980;26:133–138. [PubMed] [Google Scholar]
• Gilbert-Barness E, Barness LA, Wolff J, Harding C. Aluminum toxicity. Arch Pediatr Adolesc Med. 1998;152:511–512. [PubMed] [Google Scholar]
• Gilks B, Churg A. Aluminum-induced pulmonary fibrosis: do fibers play a role? Am Rev Respir Dis. 1987;136:176–179. [PubMed] [Google Scholar]
• Gillette-Guyonnet S, Andrieu S, Nourhashemi F, de La Guéronnierè VH, Grandjean H, Vellas B. Cognitive impairment and composition of drinking water in women: findings of the EPIDOS study. Am J Clin Nutr. 2005;81:897–902. [PubMed] [Google Scholar]
• Gitelman HJ. Aluminum exposure and excretion. Sci Total Environ. 1995;163:129–135. [PubMed] [Google Scholar]
• Gitelman HJ, Alderman FR, Kurs-Lasky M, Rockette HE. Serum and urinary aluminium levels of workers in the aluminium industry. Ann Occup Hyg. 1995;39:181–191. [PubMed] [Google Scholar]
• Glenny AT, Popk CG, Waddington H, Wallace U. Immunological notes. XXIII. The antigenic value of toxoid precipitated by potassium alum. J Pathol Bacteriol. 1926;29:38–39. [Google Scholar]
• Glenny AT, Buttle GA, Stevens MF. Rate of disappearance of diphtheria toxoid injected into rabbits and guinea pigs: toxoid precipitated with alum. J Pathol Bacteriol. 1931;34:267–275. [Google Scholar]
• Gloxhuber C, Potokar M, Pittermann W, Wallat S, Bartnik F, Reuter H, Braig S. Zeolithe A--A phosphate substitute for detergents: toxicological investigation. Food Chem Toxicol. 1983;21:209–220. [PubMed] [Google Scholar]
• Glynn AW, Sparen A, Danielsson LG, Haegglund G, Jorhem L. Bioavailability of labile aluminum in acidic drinking water: A study in the rat. Food Chem Toxicol. 1995;33:403–408. [PubMed] [Google Scholar]
• Glynn AW, Sparen A, Danielsson LG, Sundstrom B, Jorhem L. Concentration-dependent absorption of aluminum in rats exposed to labile aluminum in drinking water. J Toxicol Environ Health A. 1999;56:501–512. [PubMed] [Google Scholar]
• Glynn AW, Sparen A, Danielsson LG, Sundstrom B, Jorhem L. The influence of complexing agents on the solubility and absorption of aluminium in rats exposed to aluminium in water. Food Addit Contam. 2001;18:515–523. [PubMed] [Google Scholar]
• Goh CL. Aluminum choride hexahydrate versus palmar hyperhidrosis. Evaporimeter assessment. Int J Dermatol. 1990;29:368–370. [PubMed] [Google Scholar]
• Gokal R, Ramos JM, Ellis HA, Parkinson I, Sweetman V, Dewar J, Ward MK, Kerr DN. Histological renal osteodystrophy, and 25 hydroxycholecalciferol and aluminum levels in patients on continuous ambulatory peritoneal dialysis. Kidney Int. 1983;23:15–21. [PubMed] [Google Scholar]
• Golub MS, Domingo JL. What we know and what we need to know about developmental aluminum toxicity. J Toxicol Environ Health. 1996;48:585–597. [PubMed] [Google Scholar]
• Golub MS, Keen CL. Effects of dietary aluminum on pubertal mice. Neurotoxicol Teratol. 1999;21:595–602. [PubMed] [Google Scholar]
• Golub MS, Gershwin ME, Donald JM, Negri S, Keen CL. Maternal and developmental toxicity of chronic aluminum exposure in mice. Fundam Appl Toxicol. 1987;8:346–357. [PubMed] [Google Scholar]
• Golub MS, Donald JM, Gershwin ME, Keen CL. Effects of aluminum ingestion on spontaneous motor activity of mice. Neurotoxicol Teratol. 1989;11:231–235. [PubMed] [Google Scholar]
• Golub MS, Han B, Keen CL. Al and Mn: Interactions in adult and developing mice. Teratology. 1991;43:490. [Google Scholar]
• Golub MS, Takeuchi PE, Gershwin ME, Yoshida SH. Influence of dietary aluminum on cytokine production by mitogen-stimulated spleen cells, from Swiss Webster mice. Immunopharmacol Immunotoxicol. 1993;15:605–619. [PubMed] [Google Scholar]
• Golub MS, Han B, Keen CL, Gershwin ME, Tarara RP. Behavioral performance of Swiss Webster mice exposed to excess dietary aluminum during development or during development and as adults. Toxicol Appl Pharmacol. 1995;133:64–72. [PubMed] [Google Scholar]
• Golub MS, Han B, Keen CL. Developmental patterns of aluminum and five essential mineral elements in the central nervous system of the fetal and infant guinea pig. Biol Trace Elem Res. 1996a;55:241–251. [PubMed] [Google Scholar]
• Golub MS, Han B, Keen CL. Aluminum alters iron and manganese uptake and regulation of surface transferrin receptors in primary rat oligodendrocyte cultures. Brain Res. 1996b;719:72–77. [PubMed] [Google Scholar]
• Golub MS, Han B, Keen CL. Aluminum uptake and effects on transferrin mediated iron uptake in primaary cultures of rat neurons, astrocytes and oligodendrocytes. Neurotoxicology. 1999;20:961–970. [PubMed] [Google Scholar]
• Golub MS, Germann SL, Han B, Keen CL. Lifelong feeding of a high aluminum diet to mice. Toxicology. 2000;150:107–117. [PubMed] [Google Scholar]
• Gomez-Alonso C, Mendez-Rodriquez P, Virgos-Soriano MJ, Fernandez-Martin JL, Fernandez-Coto MT, Cannata-Andia JB. Aluminum-induced osteogenesis in ostopenic rats with normal renal function. Calcif Tissue Int. 1999;64:534–541. [PubMed] [Google Scholar]
• Gómez M, Domingo JL, Llobet JM, Tomas JM, Corbella J. Short-term oral toxicity study of aluminium in rats. Arch Farmacol Toxicol. 1986;12:145–151. [PubMed] [Google Scholar]
• Gómez M, Bosque MA, Domingo JL, Llobet JM, Corbella J. Evaluation of the maternal and developmental toxicity of aluminum from high doses of aluminum hydroxide in rats. Vet Hum Toxicol. 1990;32:545–548. [PubMed] [Google Scholar]
• Gómez M, Domingo JL, Llobet JM. Developmental toxicity evaluation of oral aluminum in rats: Influence of citrate. Neurotoxicol Teratol. 1991;13:323–328. [PubMed] [Google Scholar]
• Gómez M, Domingo JL, Llobet JM, Richart C, Corbella J. Effect of frequent dietary organic constituents on the gastrointestinal absorption of aluminum. In: Collery P, Poirier LA, Littlefield NA, Etienne JC, editors. Metal Ions in Biology and Medicine. Paris: John Libbey Eurotext; 1994. pp. 91–95. [Google Scholar]
• Gómez M, Sanchez DJ, Llobet JM, Corbella J, Domingo JL. The effect of age on aluminum retention in rats. Toxicology. 1997;116:1–8. [PubMed] [Google Scholar]
• Gómez M, Esparza JL, Nogues MR, Giralt M, Cabre M, Domingo JL. Pro-oxidant activity of aluminum in the rat hippocampus: gene expression of antioxidant enzymes after melatonin administration. Free Radic Biol Med. 2005;38:104–111. [PubMed] [Google Scholar]
• Gonda Z, Lehotzky K, Miklosi A. Neurotoxicity induced by prenatal aluminum exposure in rats. Neurotoxicology. 1996;17:459–469. [PubMed] [Google Scholar]
• Gonzalez MA, Roma MG, Bernal CA, Alvarez L, Carrillo MC. Biliary secretory function in rats chronically intoxicated with aluminum. Toxicol Sci. 2004;79:189–195. [PubMed] [Google Scholar]
• Gonzalez-Suarez I, Naves M, Diaz-Corte C, Fernandez-Martin JL, Menendez-Rodriguez P, Cannata-Andia JB. Effect of aluminium on calcium-sensing receptor expression, proliferation, and apoptosis of parathyroid glands from rats with chronic renal failure. Kidney Int. 2003;85:S39–S43. [PubMed] [Google Scholar]
• Good PF, Perl DP, Bierer LM, Schmeidler J. Selective accumulation of aluminium and iron in the neurofibrillary tangles of Alzheimer’s disease: a laser microprobe (LAMMA) study. Ann Neurol. 1992;31:286–292. [PubMed] [Google Scholar]
• Goodman WG. Short-term aluminum administration in the rat: reductions in formation without osteomalacia. J Lab Clin Med. 1984;103:749–757. [PubMed] [Google Scholar]
• Goodman WG, Gilligan J, Horst R. Short-term aluminum administration in the rat: effects on bone formation and relationship with renal osteomalacia. J Clin Invest. 1984a;73:171–181. [PMC free article] [PubMed] [Google Scholar]
• Goodman WG, Henry DA, Horst R, Nudelman RK, Alfrey AC, Coburn JW. Parenteral aluminum administration in the dog: II. Induction of osteomalacia and effect on vitamin D metabolism. Kidney Int. 1984b;25:370–375. [PubMed] [Google Scholar]
• Goralewski G. Klinische und tierexperimentelle studien sur frage der aluminum-staublunge. [Clinical and animal experimental studies and the question of the aluminum-dusty lung] Arch Gewerbepathol Gewerbehyg. 1939;9:676–688. [Google Scholar]
• Goralewski G. Zur symptomalogie der aluminum-staublunge. [The symptomatology of the aluminum dust lung] Arch Gewerbepathol Gewerbehyg. 1940;10:384–408. [Google Scholar]
• Goralewski G. Zur klinik der aluminumlunge [Clinical examination of the aluminum lung] Arch Gewerbepathol Gewerbehyg. 1941;11:108–116. [Google Scholar]
• Goralewski G. Weitere erfahrungen zum krankheitsbild der aluminumlunge. Dtsch Tuberk Bl. 1943;17:2–10. [Google Scholar]
• Goralewski G. Die aluminiumlunge-eine neue gewerbeerkrankung. [The aluminum lung: a new industrial disease] Z Gesamte Inn Med. 1947;2:665–673. [Google Scholar]
• Goralewski G. The aluminium lung: A new industrial disease. Br J Ind Med. 1948;6:53–54. Abstract of Goralewski, 1947. [Google Scholar]
• Gorsky JE, Dietz AA, Spencer H, Osis D. Metabolic balance of aluminum studied in six men. Clin Chem. 1979;25:1739–1743. [PubMed] [Google Scholar]
• Goto N, Kato H, Maeyama J, Shibano M, Saito T, Yamaguchi J, Yoshihara S. Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties. Vaccine. 1997;15:1364–1371. [PubMed] [Google Scholar]
• Goto N, Akama K. Histopathological studies of reactions in mice injected with aluminum-adsorbed tetanus toxoid. Microbiol Immunol. 1982;26:1121–1132. [PubMed] [Google Scholar]
• Gough J, Hale LW, King EJ, Nagelschmidt G. Pneumoconiosis of kaolin workers. Br J Ind Med. 1956;13:251–259. [PMC free article] [PubMed] [Google Scholar]
• Goyens P, Brasseur D. Aluminum and infants. Pediatrics. 1990;86:650–652. [PubMed] [Google Scholar]
• Graf H, Stummvoll HK, Meisinger V, Kovarik J, Wolf A, Pinggera WF. Aluminum removal by hemodialysis. Kidney Int. 1981;19:587–592. [PubMed] [Google Scholar]
• Gramiccioni L, Ingrao G, Milana MR, Santaroni P, Tomassi G. Aluminium levels in Italian diets and in selected foods from aluminium utensils. Food Addit Contam. 1996;13:767–774. [PubMed] [Google Scholar]
• Grandjean P, Hörder M, Thomassen Y. Fluoride, aluminum, and phosphate kinetics in cryolite workers. J Occup Med. 1990;32:58–63. [PubMed] [Google Scholar]
• Graske A, Thuvander A, Johannisson A, Gadhasson I, Schutz A, Festin R, Wicklund Glynn A. Influence of aluminium on the immune system--an experimental study on volunteers. Biometals. 2000;13:123–133. [PubMed] [Google Scholar]
• Graves AB, White E, Koepsell TD, Reifler BV, Van Belle G, Larson EB. The association between aluminum-containing products and Alzheimer’s disease. J Clin Epidemiol. 1990;43:35–44. [PubMed] [Google Scholar]
• Greenberg L, Benoit R. Control of potency and the dosage of diphtheria and tetanus toxoids. J Am Med Assoc. 1956;160:108–113. [PubMed] [Google Scholar]
• Greenberg S. The pulmonary effects of pure aluminum in the Swiss mouse. Lab Invest. 1977;36:339. [Google Scholar]
• Greger JL. Aluminum content of the American diet. Food Technol. 1985;39:73–80. [Google Scholar]
• Greger JL, Baier MJ. Excretion and retention of low or moderate levels of aluminium by human subjects. Food Chem Toxicol. 1983;21:473–477. [PubMed] [Google Scholar]
• Greger JL, Donnabauer S. Retention of aluminium in the tissue of rats after the discontinuation of oral exposure to aluminium. Food Chem Toxicol. 1986;24:1331–1334. [PubMed] [Google Scholar]
• Greger JL, Powers CF. Assessment of exposure to parenteral and oral aluminum with and without citrate using a desferrioxamine test in rats. Toxicology. 1992;76:119–132. [PubMed] [Google Scholar]
• Greger JL, Radzanowski GM. Tissue aluminium distribution in growing, mature and ageing rats: relationship to changes in gut, kidney and bone metabolism. Food Chem Toxicol. 1995;33:867–875. [PubMed] [Google Scholar]
• Greger JL, Sutherland JE. Aluminum exposure and metabolism. Crit Rev Clin Lab Sci. 1997;34:439–474. [PubMed] [Google Scholar]
• Greger JL, Bula EN, Gum ET. Mineral metabolism of rats fed moderate levels of various aluminum compounds for short periods of time. J Nutr. 1985;115:1708–1716. [PubMed] [Google Scholar]
• Greger JL, Chang MM, MacNeil GG. Tissue turnover of aluminum and Ga-67: effect of iron status. Proc Soc Exp Biol Med. 1994;207:89–96. [PubMed] [Google Scholar]
• Grekhova TD, Neizvestnova EM, Konstantinova LI, Dobroliubova LP, Babakova OM, Petelina EV, Fomina AS. Rationale for maximum allowable exposure level of aluminum sulfate and its coagulants in the air of the workplace. Med Tr Prom Ekol. 1994;1:26–28. [PubMed] [Google Scholar]
• Gross P, Harley RA, Detreville RT. Pulmonary reaction to metallic aluminum powders. Arch Environ Health. 1973;26:227–236. [PubMed] [Google Scholar]
• Guibaud G, Gauthier C. Aluminium speciation in the Vienne river on its upstream catchment (Limousin Region, France) J Inorg Biochem. 2005;99:1817–1821. [PubMed] [Google Scholar]
• Guillard O, Fauconneau B, Olichon D, Dedieu G, Deloncle R. Hyperaluminemia in a woman using an aluminum-containing antiperspirant for 4 years. Am J Med. 2004;117:956–959. [PubMed] [Google Scholar]
• Gun RT, Korten AE, Jorm AF, Hendersen AS, Broe GA, Creasy H, McCusker E, Mylvaganam A. Occupational risk factors for Alzheimer disease: A case control study. Alzheimer Dis Assoc Disord. 1997;11:21–27. [PubMed] [Google Scholar]
• Gundersen HJ, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, West MJ. The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS. 1988;96:857–881. [PubMed] [Google Scholar]
• Gupta RK. Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev. 1998;32:155–172. [PubMed] [Google Scholar]
• Gupta RK, Siber GR. Adjuvants for human vaccines-current status, problems and future prospects. Vaccine. 1995;13:1263–1276. [PubMed] [Google Scholar]
• Gupta SK, Waters DH, Gwilt PR. Absorption and disposition of aluminium in the rat. J Pharm Sci. 1986;75:586–589. [PubMed] [Google Scholar]
• Gupta VB, Anitha S, Hegde ML, Zecca L, Garruto RM, Ravid R, Shankar SK, Stein R, Shanmugavelu P, Jagannatha Rao KS. Aluminium in Alzheimer’s disease: are we still at a crossroad? Cell Mol Life Sci. 2005;62:143–158. [PubMed] [Google Scholar]
• Gusev VA, Danilovskaja YV, Vatolkina OY, Lomonosova OS, Velichkovsky BT. Effects of quartz and alumina dust on generation of superoxide radicals and hydrogen peroxide by alveolar macrophages, granulocytes, and monocytes. Br J Ind Med. 1993;50:732–735. [PMC free article] [PubMed] [Google Scholar]
• Guy SP, Seabright PJ, Day JP, Itzhaki RF. Uptake of aluminium by human neuroblastoma cells. Biochem Soc Transactions. 1990;18:392–393. [PubMed] [Google Scholar]
• Gylseth B, Bjoerseth O, Dugstad O, Gjoennes J. Occurrence of fibrous sodium aluminum tetrafluoride particles in potrooms of the primary aluminum industry. Scand J Work Environ Health. 1984;10:189–195. [PubMed] [Google Scholar]
• Hackenberg U. Chronic ingestion by rats of standard diet treated with aluminum phosphide. Toxicol Appl Pharmacol. 1972;23:147–158. [PubMed] [Google Scholar]
• Haddow A, Hornig ES. On the carcinogenicity of an iron-dextran complex. J Natl Cancer Inst. 1960;24:109–147. [PubMed] [Google Scholar]
• Halatek T, Opalska B, Lao I, Stetkiewicz J, Rydzynski K. Pneumotoxicity of dust from aluminum foundry and pure alumina: a comparative study of morphology and biomarkers in rats. Int J Occup Med Environ Health. 2005;18:59–70. [PubMed] [Google Scholar]
• Hall AF. Occupational contact dermatitis among aircraft workers. J Am Med Assoc. 1944;125:179–185. [Google Scholar]
• Hamilton E, Minski M. Abundance of the chemical elements in man’s diet and possible relations with environmental factors. Sci Total Environ. 19721973;1:375–394. [Google Scholar]
• Hamilton JA, Byrne R, Whitty G. Particulate adjuvants can induce macrophage survival, DNA synthesis, and a synergistic proliferative response to GM-CSF and CSF-1. J Leukoc Biol. 2000;67:226–232. [PubMed] [Google Scholar]
• Han J, Han J, Dunn MA. Effect of dietary aluminum on tissue nonheme iron and ferritin levels in the chick. Toxicology. 2000;142:97–109. [PubMed] [Google Scholar]
• Han SH, Sakinci U, Kose SK, Yazkan R. The relationship between aluminum and spontaneous pneumothorax: treatment, prognosis, follow-up? Interact Cardiovas Thorac Surg. 2004;3:79–82. [PubMed] [Google Scholar]
• Hanninen H, Matikainen E, Kovala T, Valkonen S, Riihmahki V. Internal load of aluminum and the central nervous system function of aluminum welders. Scand J Work Environ Health. 1994;20:279–285. [PubMed] [Google Scholar]
• Hannon JW. Aluminum therapy in silicosis. Trans Canad Min. 1944;47:180. [Google Scholar]
• Hannon JW. Proceedings of the 5th Conference of McIntyre Research Foundation on silicosis.1953. [Google Scholar]
• Hantson P, Mahieu P, Gersdorff M, Sindic SJ, Lauwerys R. Encephalopathy with seizures after use of aluminum containing bone cement. Lancet. 1994;344:1647. [PubMed] [Google Scholar]
• Haram EM, Weberg R, Berstad A. Urinary excretion of aluminum after ingestion of sucralfate and an aluminum-containing antacid in man. Scand J Gastroenterol. 1987;22:615–618. [PubMed] [Google Scholar]
• Harris WR. Equilibrium model for speciation of aluminum in serum. Clin Chem. 1992;38:1809–1818. [PubMed] [Google Scholar]
• Harris WR, Messori L. A comparative study of aluminum (III), gallium (III), indium (III), and thallium (III) binding to human serum transferrin. Coord Chem Rev. 2002;228:237–262. [Google Scholar]
• Harris WR, Berthon G, Day JP, Exley C, Flaten TP, Forbes WF, Kiss T, Orvig C, Zatta PF. Speciation of aluminum in biological systems. J Toxicol Environ Health. 1996;48:543–568. [PubMed] [Google Scholar]
• Hart MM, Adamson RH. Antitumor activity and toxicity of salts of inorganic group IIIa metals: aluminum, gallium, indium, and thallium. Proc Natl Acad Sci. 1971;68:1623–1626. [PMC free article] [PubMed] [Google Scholar]
• Hatch GE, Boykin E, Graham JA, Lewtas J, Pott F, Loud K, Mumford JL. Inhalable particles and pulmonary host defense: in vivo and in vitro effects of ambient air and combustion particles. Environ Res. 1985;36:67–80. [PubMed] [Google Scholar]
• Hawkins NM, Coffey S, Lawson MS, Delves HT. Potential aluminum toxicity in infants fed special infant formula. J Pediatr Gastroenterol Nutr. 1994;19:377–381. [PubMed] [Google Scholar]
• Hazelton Laboratories. Acute ocular and dermal testing with magnesium aluminum silicate. 1968 Unpublished data. [Google Scholar]
• Hdez-Jaras J, Galan A, Sanchez P. Accidental aluminum intoxication in patients undergoing acetate-free biofiltration. Nephron. 1998;78:274–277. [PubMed] [Google Scholar]
• He BP, Strong MJ. Motor neuronal death in sporadic amyotrophic lateral sclerosis (ALS) is not apoptotic. A comparative study of ALS and chronic aluminium chloride neurotoxicity in New Zealand white rabbits. Neuropathol Appl Neurobiol. 2000a;26:150–160. [PubMed] [Google Scholar]
• He BP, Strong MJ. A morphological analysis of the motor neuron degeneration and microglial reaction in acute and chronic in vivo aluminum chloride neurotoxicity. J Chem Neuroanat. 2000b;17:207–215. [PubMed] [Google Scholar]
• Healy J, Bradley SD, Northage C, Scobbie E. Inhalation exposure in secondary aluminum smelting. Ann Occup Hyg. 2001;45:217–225. [PubMed] [Google Scholar]
• Heimlich JM, Regnier FE, White JL, Hem SL. The in vitro displacement of adsorbed model antigens from aluminium-containing adjuvants by interstitial proteins. Vaccine. 1999;17:2873–2881. [PubMed] [Google Scholar]
• Hellström HO, Mjöberg B, Mallmin H, Michaëlsson K. The aluminum content of bone increases with age, but is not higher in hip fracture cases with and without dementia compared to controls. Osteoporos Int. 2005;16:1982–1988. [PubMed] [Google Scholar]
• Helmboldt O, Hudson LK, Misra C, Wefers K, Stark H, Danner M. Aluminum compounds, inorganic. In: Gerhartz W, Yamamoto YS, Campbell FT, Pfefferkorn R, Rounsaville JF, editors. Ullmann’s Encyclopedia of Industrial Chemistry - Volume A1: Abrasives to Aluminum Oxide. Weinheim: Verlag Chemie; 1985. pp. 527–541. [Google Scholar]
• Hem SL. Elimination of aluminium adjuvants. Vaccine. 2002;20(Suppl 3):S40–S43. [PubMed] [Google Scholar]
• Hem SL, White JL. Pharmaceutical uses of aluminum. In: Gitelman HJ, editor. Aluminum and Health A Critical Review. New York: Marcel Dekker; 1989. pp. 257–282. [Google Scholar]
• Hemadi M, Miquel G, Kahn PH, Hage Chahine JM. Aluminum exchange between citrate and human serum transferrin and interaction with transferrin receptor 1. Biochem. 2003;42:3120–3130. [PubMed] [Google Scholar]
• Hemmer W, Wantke F, Focke M, Gotz M, Jarisch R. Evaluation of cutaneous hypersenstivity to aluminum by routine path testing with AlCl. Contact Dermatitis. 1996;34:217–218. [PubMed] [Google Scholar]
• Henry DA, Goodman WG, Nudelman RK, Didomenico NC, Alfrey AC, Slatopolsky E, Stanley TM, Coburn JW. Parenteral aluminum administration in the dog: I. Plasma kinetics, tissue levels, calcium metabolism, and para-thyroid hormone. Kidney Int. 1984;25:362–369. [PubMed] [Google Scholar]
• Herbert A, Sterling G, Abraham J, Corrin B. Desquamative interstitial pneumonia in an aluminum welder. Hum Pathol. 1982;13:694–699. [PubMed] [Google Scholar]
• Herman SJ, Olscamp GC, Weisbrod GL. Pulmonary kaolin granulomas. J Can Assoc Radiol. 1982;33:279–280. [PubMed] [Google Scholar]
• Hertzberg M, Zlochower IA, Cashdollar KL. Explosibility of metal dusts. Comb Sci Tech. 1991;75:161–165. [Google Scholar]
• Hicks JS, Hackett DS, Sprague GL. Toxicity and aluminium concentration in bone following dietary administration of two sodium aluminium phosphate formulations in rats. Food Chem Toxicol. 1987;25:533–538. [PubMed] [Google Scholar]
• Hirschberg R, von Herrath D, Voss R, Bossaller W, Mauelshagen U, Pauls A, Schaefer K. Organ distribution of aluminium in uremic rats: influence of parathyroid hormone and 1,25-dihydroxyvitamin D3. Miner Electrolyte Metab. 1985;11:106–110. [PubMed] [Google Scholar]
• Hjortsberg U, Ørbæk P, Arborelius M, Karlsson JE. Upper airway irritation and small airways hyperreactivity due to exposure to potassium aluminium tetrafluoride flux: an extended case report. Occup Environ Med. 1994;51:706–709. [PMC free article] [PubMed] [Google Scholar]
• Hobbs CS, Moorman RP, Griffith JM, West JL, Merriman GM, Hansard SL, Chamberlain CC. The University of Tennessee Agricultural Exeriment Station Knoxville, Report No 235. Knoxville, Tennessee: University of Tennessee; 1954. Fluorosis in cattle and sheep. [Google Scholar]
• Höflich BL, Wentzel M, Ortner HM, Weinbruch S, Skogstad A, Hetland S, Thomassen Y, Chaschin VP, Nieboer E. Chemical composition of individual aerosol particles from working areas in a nickel refinery. J Environ Monit. 2000;2:213–217. [PubMed] [Google Scholar]
• Höflich BL, Weinbruch S, Theissmann R, Gorzawski H, Ebert M, Ortner HM, Skogstad A, Ellingsen DG, Drablos PA, Thomassen Y. Characterization of individual aerosol particles in workroom air of aluminum smelter potrooms. J Environ Monit. 2005;7:419–424. [PubMed] [Google Scholar]
• HogenEsch H. Mechanisms of stimulation of the immune response by aluminium adjuvants. Vaccine. 2002;20(Suppl 3):S34–S39. [PubMed] [Google Scholar]
• Hohl C, Gerisch P, Korschinek G, Nolte E, Ittel TH. Medical application of 26Al. Nucl Instr Meth Phys Res B. 1994;92:478–482. [Google Scholar]
• Höhr D, Abel J, Wilhelm M. Renal clearance of aluminium: studies in the isolated perfused rat kidney. Toxicol Lett. 1989;45:165–174. [PubMed] [Google Scholar]
• Hong SH, Kim BK. Effects of lifter bars on the ball motion and aluminum foil milling in tumbler ball mill. Mater Lett. 2002;57:275–279. [Google Scholar]
• Hosovski E, Mastelica Z, Sunderic D, Radulovic D. Mental abilities of workers exposed to aluminium. Med Lav. 1990;81:119–123. [PubMed] [Google Scholar]
• Hosovski E, Vidakovic A, Hosovski M. Dermal and bronchial responsiveness of aluminum smelter workers. J Occup Health. 1998;40:44–49. [Google Scholar]
• Hostynek JJ, Hinz RS, Lorence CR, Price M, Guy RH. Metals and the skin. Crit Rev Toxicol. 1993;23:171–235. [PubMed] [Google Scholar]
• House RA. Factors affecting plasma aluminum concentrations in nonexposed workers. J Occup Med. 1992;34:1013–1017. [PubMed] [Google Scholar]
• Hovatta O, Venalainen ER, Kuusimaki L, Heikkila J, Hirvi T, Reima I. Aluminium, lead and cadmium concentrations in seminal plasma and spermatozoa, and semen quality in Finnish men. Hum Reprod. 1998;13:115–119. [PubMed] [Google Scholar]
• HSDB (Hazardous Substances Data Bank) National Library of Medicine, National Toxicology Program. Bethesda MD: 1995. [Google Scholar]
• Huang JY, Huang CC, Lim PS, Wu MS, Leu ML. Effect of body iron stores on serum aluminum level in hemodialysis patients. Nephron. 1992;61:158–162. [PubMed] [Google Scholar]
• Huang Y, Herman MM, Liu J, Katsetos CD, Wills MR, Savory J. Neurofibrillary lesions in experimental aluminum-induced encephalopathy and Alzheimer’s disease share immunoreactivity for amyloid precursor protein, A beta, alpha1-antichymotrypsin and ubiquitin-protein conjugates. Brain Res. 1997;771:213–220. [PubMed] [Google Scholar]
• Hunter D, Milton R, Perry KMA, Thompson DR. Effects of aluminum and alumina on the lung in grinders of duralumin aeroplane propellers. Br J Ind Med. 1944;1:159–164. [Google Scholar]
• Hunter RL. Overview of vaccine adjuvants: present and future. Vaccine. 2002;20(Suppl 3):S7–S12. [PubMed] [Google Scholar]
• Hussain RI, Ballard CG, Edwardson JA, Morris CM. Transferrin gene polymorphism in Alzheimer’s disease and dementia with Lewy bodies in humans. Neurosci Lett. 2002;317:13–16. [PubMed] [Google Scholar]
• Hütteroth TH, Quast U. Aluminum hydroxide granuloma following hepatitis B vaccination. Dtsch Med Wochenschr. 1990;115:476. [PubMed] [Google Scholar]
• Hyry H, Hook-Nikanne J. Aluminium and milk allergies in an adult. Contact Dermatitis. 2004;50:107. [PubMed] [Google Scholar]
• IAEA (International Atomic Energy Agency) Activation analysis of hair as an indicator of contamination of man by environmental trace element pollutants. Vienna. 1978 Report No IAEA/RL/50. [Google Scholar]
• IAI (International Aluminium Institute) Alternative source data, Aluminium recovered from purchased or tolled scrap. 2005. [online] Cited 27 November 2005 Available from www.world-aluminium.org/iai/stats/
• IAI (International Aluminium Institute) IAI statistics. 2006a. [online] Cited 24 January 2007 http://world-aluminium.org/iai/stats/index.asp.
• IAI (International Aluminium Institute) Aluminium applications. 2006b. [online] Cited 24 January 2007 http://www.world-aluminium.org/applications/index.html.
• IAI (International Aluminium Institute) Consolidated IAI primary aluminium production reports, 20 December, 2006. 2006c. [online] Cited 24 January 2007 http://www.world-aluminium.org/iai/stats/formServer.asp?form=16.
• IARC (International Agency for Research on Cancer) Polynuclear Aromatic Compounds, Part 3, Industrial Exposures in Aluminum Production, Coal Gasification, Coke Production, and Iron and Steel Founding. Lyon, France: World Health Organization, International Agency for Research on Cancer; 1984. [Google Scholar]
• IARC (International Agency for Research on Cancer) Polynuclear aromatic compounds. Part 4: Bitumens, coal-tars and derived products, shale oils and soots. IARC Monogr Eval Carcinog Risks Hum. 1985;35:1–271. [PubMed] [Google Scholar]
• IARC (International Agency for Research on Cancer) Overall Evaluation of Carcinogenicity: An Updating of IARC Monographs (Volumes 1 to 42) Lyon, France: World Health Organization, International Agency for Research on Cancer; 1987. [Google Scholar]
• ICRP (International Commission of Radiological Protection) Limits on Intakes of Radionuclides by Workers. Oxford: Pergamon; 1975. Metabolic data for aluminium; pp. 12–13. [Google Scholar]
• ICRP (International Commission of Radiological Protection) Limits for Intakes of Radionuclides by Workers. Oxford: Pergamon Press; 1981. [Google Scholar]
• Ilyin A, Gromov A, An F, Faubert V, de Izarra C, Espagnscq A, Brunet L. Characterization of aluminum powders I. Parameters of reactivity of aluminum powders. Propell Explos Pyrot. 2002;27:361–364. [Google Scholar]
• Imahori A, Fukushima I, Shiobara S, Yanagida Y, Tomura K. Multielement neutron activation analysis of human scalp hair. A local population survey in the Tokyo metropolitan area. J Radioanal Chem. 1979;52:167–180. [Google Scholar]
• IPAI (International Primary Aluminium Institute) Statistical Summary - Volume 5. London: International Primary Aluminium Institute; 1993. [Google Scholar]
• IPCS (International Programme on Chemical Safety) Methylmercury Environmental Health Criteria 144. Geneva: World Health Organization; 1990. [Google Scholar]
• IPCS (International Programme on Chemical Safety) Aluminum Environmental Health Criteria 194. Geneva: World Health Organization; 1997. [Google Scholar]
• IPCS/WHO (International Programme on Chemical Safety/World Health Organization) Principles and Methods for Assessing Direct Immunotoxicity Associated with Exposure to Chemicals Environmental Health Criteria 180. Geneva: World Health Organization; 1996. [Google Scholar]
• Iregren A, Sjögren B, Gustafsson K, Hagman M, Nylen L, Frech W, Andersson M, Ljunggren KG, Wennberg A. Effects on the nervous system in different groups of workers exposed to aluminum. Occup Environ Med. 2001;58:453–460. [PMC free article] [PubMed] [Google Scholar]
• IRIS (Integrated Risk Information System) Cincinnati, OH: U.S. Environmental Protection Agency; 1997. [Google Scholar]
• IRIS (Integrated Risk Information System) Cincinnati, OH: U.S. Environmental Protection Agency; 1999. [Google Scholar]
• Ittel TH, Buddington B, Miller NL, Alfrey AC. Enhanced gastrointestinal absorption of aluminum in uremic rats. Kidney Int. 1987;32:821–826. [PubMed] [Google Scholar]
• Ittel TH, Kluge R, Sieberth HG. Enhanced gastrointestinal absorption of aluminium in uraemia: time course and effect of vitamin D. Nephrol Dial Transplant. 1988;3:617–623. [PubMed] [Google Scholar]
• Ittel TH, Koppe BK, Sieberth HG. Differential effect of steroids and chloroquine on the intestinal absorption of aluminium and calcium. Nephrol Dial Transplant. 1990;5:860–867. [PubMed] [Google Scholar]
• Ittel TH, Gladziwa U, Mück W, Sieberth HG. Hyperaluminaemia in critically ill patients: role of antacid therapy and impaired renal function. Eur J Clin Invest. 1991a;21:96–102. [PubMed] [Google Scholar]
• Ittel TH, Griessner A, Sieberth HG. Effect of lactate on the absorption and retention of aluminum in the remnant kidney rat model. Nephron. 1991b;57:332–339. [PubMed] [Google Scholar]
• Ittel TH, Paulus CP, Handt S, Hofstadter F, Sieberth HG. Induction of intestinal mucosal atrophy by difluoromethylornithine: a nonuremic model of enhanced aluminum absorption. Miner Electrolyte Metab. 1992a;18:15–23. [PubMed] [Google Scholar]
• Ittel TH, Gruber E, Heinrichs A, Handt S, Hofstädter F, Sieberth HG. Effect of fluoride on aluminum-induced bone disease in rats with renal failure. Kidney Int. 1992b;41:1340–1348. [PubMed] [Google Scholar]
• Ittel TH, Gladziwa U, Sieberth HG. Synergistic effect of 1,25-vitamin D3 and fluoride on bone aluminum accumulation. Bone. 1993a;14:427–432. [PubMed] [Google Scholar]
• Ittel TH, Gerisch P, Nolte E, Sieberth HG. Fractional absorption of aluminium is dose-dependent: A 26Al tracer study. Nephrol Dial Transplant. 1993b;8:993. [Google Scholar]
• Ittel TH, Kinzel S, Ortmanns A, Sieberth HG. Effect of iron status on the intestinal absorption of aluminum: a reappraisal. Kidney Int. 1996;50:1879–1888. [PubMed] [Google Scholar]
• Ittel TH, Steinhausen C, Kislinger G, Kinzel S, Nolte E, Sieberth HG. Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry. Nephrol Dial Transplant. 1997;12:1369–1375. [PubMed] [Google Scholar]
• Iwata S, Kasajima K, Yase Y, Yoshimasu F, Kamiayashi Y. Radioactivation analysis of amyotrophic lateral sclerosis. Kyoto Daigaku Genshiro Jikkensho Gakujutsu Koenkai Koen Yoshishu. 1976;10:33–38. [Google Scholar]
• Jackson ML, Huang PM. Aluminum of acid soils in the food chain and senility. Sci Total Environ. 1983;28:269–276. [PubMed] [Google Scholar]
• Jackson RTJ, Tigges J, Arnold W. Subarachnoid space of the CNS, nasal mucosa, and lymphatic system. Arch Otolaryngol. 1979;105:180–184. [PubMed] [Google Scholar]
• Jacobs RW, Duong T, Jones RE, Trapp GA, Scheibel AB. A re-examination of aluminium in Alzheimer’s disease: Analysis by energy dispersive x-ray microprobe and flameless atomic absorption spectrophotometry. Can J Neurol Sci. 1989;16:498–503. [PubMed] [Google Scholar]
• Jacqmin H, Commenges D, Letenneur L, Barberger-Gateau P, Dartigues JF. Components of drinking water and risk of cognitive impairment in the elderly. Am J Epidemiol. 1994;139:48–57. [PubMed] [Google Scholar]
• Jacqmin-Gadda H, Commenges D, Letenneur L, Dartigues JF. Silica and aluminum in drinking water and cognitive impairment in the elderly. Epidemiology. 1996;7:281–285. [PubMed] [Google Scholar]
• Jagannatha Rao K, Rao R, Shanmgaveu P, Menon R. Trace elements in the cerebrospinal fluid in Alzheier’s disease. Alz Rep. 1999;2:333–338. [Google Scholar]
• Jäger DE, Wilhelm M, Witte G, Ohnesorge FK. Intestinal absorption of aluminium: studies in the isolated perfused rat intestinal preparation. J Trace Elem Electrolytes Health Dis. 1991;5:81–85. [PubMed] [Google Scholar]
• Jäger R, Jäger F. Colloid chemistry and histochemistry in the problem of pulmonary disease caused by aluminum dust. Archiv fuer Gewerbepathologie und Gewerbehygiene. 1941;11:117–130. [Google Scholar]
• James DM, Morris TG, Marks J. Drug treatment of experimental silicosis. Br J Ind Med. 1960;17:36–40. [PMC free article] [PubMed] [Google Scholar]
• James JD, Pounds CA, Wilshire B. Production and characterization of flake metal powders for fingerprint detection. Powder Metall. 1991;34:39–43. [Google Scholar]
• Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Borchelt DR. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 2004;13:159–170. [PubMed] [Google Scholar]
• Jederlinic PJ, Abraham JL, Churg A, Himmelstein JS, Epler GR, Gaensler EA. Pulmonary fibrosis in aluminum oxide workers. Investigation of nine workers, with pathologic examination and microanalysis in three of them. Am Rev Respir Dis. 1990;142:1179–1184. [PubMed] [Google Scholar]
• Jeffery EH, Abreo K, Burgess E, Cannata J, Greger JL. Systemic aluminum toxicity: effects on bone, hematopoietic tissue, and kidney. J Toxicol Environ Health. 1996;48:649–665. [PubMed] [Google Scholar]
• Jensen OM, Koch C. On the effect of Al(OH)3 as an immunological adjuvant. APMIS. 1988;96:257–264. [PubMed] [Google Scholar]
• Johannessen H, Bergan-Skar B. Itching problems among potroom workers in factories using recycled alumina. Contact Dermatitis. 1980;6:42. [PubMed] [Google Scholar]
• Johns DR, Petronella SJ. Aluminum therapy for silicosis. Monthly Bull Indiana State Board Health. 1945;43:203. [Google Scholar]
• Johnson KE, Treble RG. Determination of aluminum in biological fluids by furnace atomic absorption spectrophotometry. J Clin Lab Anal. 1992;6:264–268. [PubMed] [Google Scholar]
• Johnsson C, Schutz A, Sallsten G. Impact of consumption of freshwater fish on mercury levels in hair, blood, urine, and alveolar air. J Toxicol Environ Health A. 2005;68:129–140. [PubMed] [Google Scholar]
• Jones KC, Bennett BG. Exposure of man to environmental aluminum-An exposure commitment assessment. Sci Total Environ. 1986;52:65–82. [PubMed] [Google Scholar]
• Jones KR, Oorschot DE. Do aluminium and/or glutamate induce Alz-50 reactivity? A light microscopic immunohistochemical study. J Neurocytol. 1998;27:45–57. [PubMed] [Google Scholar]
• Jones P, Ebdon L, Williams T. Determination of trace amounts of aluminum by ion chromatography with fluorescence detection. Analyst. 1988;113:641–644. [Google Scholar]
• Jordan JW. Pulmonary fibrosis in a worker using an aluminum powder. Br J Ind Med. 1961;18:21–23. [Google Scholar]
• Jorhem L, Haegglund G. Aluminium in foodstuffs and diets in Sweden. Zeitschrift für Lebensmittel-Untersuchung und-Forschung. 1992;194:38–42. [PubMed] [Google Scholar]
• Jötten KW, Eickhoff W. Risk of lung damage by Al dust. I. Literature and discussion of hygienic technique. Archiv Fuer Hygiene und Backteriologie. 1942;127:344–367. [Google Scholar]
• Jouhanneau P, Lacour B, Raisbeck G, Yiou F, Banide H, Brown E, Drüeke T. Gastrointestinal absorption of aluminum in rats using 26Al and accelerator mass spectrometry. Clin Nephrol. 1993;40:244–248. [PubMed] [Google Scholar]
• Jouhanneau P, Raisbeck GM, Yiou F, Lacour B, Banide H, Drüeke TB. Gastrointestinal absorption, tissue retention, and urinary excretion of dietary aluminum in rats determined by using 26Al. Clin Chem. 1997a;43:1023–1028. [PubMed] [Google Scholar]
• Jouhanneau P, Raisbeck GM, Yiou F, Lacour B, Banide H, Drüeke TB. Gastrointestinal absorption, tissue retention, and urinary excretion of dietary aluminum in rats determined by using 26Al. Clin Chem. 1997b;43:1023–1028. [PubMed] [Google Scholar]
• Jugdaohsingh R, Reffitt DM, Oldham C, Day JP, Fifield LK, Thompson RP, Powell JJ. Oligomeric but not monomeric silica prevents aluminum absorption in humans. Am J Clin Nutr. 2000;71:944–949. [PubMed] [Google Scholar]
• Julka D, Gill KD. Altered calcium homeostasis: a possible mechanisms of aluminium-induced neurotoxicity. Biochimica et Biophysica Acta. 1996;1315:47–54. [PubMed] [Google Scholar]
• Jullien G, Vallecalle E, Leandri M. Harmful effect of aluminium hydroxide in inhalation and its effect on the pulmonary tissue. Arch Mal Prof. 1952;13:31–38. [PubMed] [Google Scholar]
• Kaaber K, Nielsen AO, Veien NK. Vaccination granulomas and aluminum allergy: course and prognostic factors. Contact Dermatitis. 1992;26:304–306. [PubMed] [Google Scholar]
• Kada T, Hirano K, Shirasu Y. Screening of environmental chemical mutagens by the rec(-) assay system with Bacillus subtilis. In: Hollaender A, Serres FJ, editors. Chemical Mutagens: Principles and Methods for their Detection. New York: Plenum Press; 1980. pp. 149–173. [Google Scholar]
• Kaehny WD, Hegg AP, Alfrey AC. Gastrointestinal absorption of aluminum from aluminum-containing antacids. N Engl J Med. 1977;296:1389–1390. [PubMed] [Google Scholar]
• Kagan BL, Hirakura Y, Azimov R, Azimova R, Lin MC. The channel hypothesis of Alzheimer’s disease: current status. Peptides. 2002;23:1311–1315. [PubMed] [Google Scholar]
• Kales SN, Goldman RH. Mercury exposure: current concepts, controversies, and a clinic’s experience. J Occup Environ Med. 2002;44:143–154. [PubMed] [Google Scholar]
• Kallio A, Kiilunen M, Kivisto H, Pekari K, Valkonen S. Results of biomonitoring analyses in Biomonitoring Laboratory, Helsinki, Finland in 1997. Toxicol Lett. 1999;108:249–257. [PubMed] [Google Scholar]
• Kalveram KJ, Rapp-Frick C, Sorck G. Misleading patch test results with aluminium Finn chambers and mercury salts. Contact Dermatitis. 1980;6:507–508. [PubMed] [Google Scholar]
• Kamboj VP, Kar AB. Antitesticular effect of metallic and rare earth salts. J Reprod Fertil. 1964;7:21–28. [PubMed] [Google Scholar]
• Kammer C. Aluminum Handbook. Dusseldorf: Aluminium Verlag; 1999. [Google Scholar]
• Kandiah J, Kies C. Aluminum concentrations in tissues of rats: effect of soft drink packaging. Biometals. 1994;7:57–60. [PubMed] [Google Scholar]
• Kanematsu N, Hara M, Kada T. Rec assay and mutagenicity studies on metal compounds. Mutat Res. 1980;77:109–116. [PubMed] [Google Scholar]
• Kang KY, Bice D, Hoffman E, D’Amato R, Salvaggio J. Experimental studies of sensitization to beryllium, zirconium, and aluminum compounds in the rabbit. J Allergy Clin Immunol. 1977;59:425–436. [PubMed] [Google Scholar]
• Kapaki EN, Zourmas CP, Segdistsa IT, Xenos DS, Papageorgiou CT. Cerebrospinal fluid aluminum levels in Alzheimer’s disease. Biol Psych. 1993;33:679–681. [PubMed] [Google Scholar]
• Kaplan HM, Timmons EH. The Rabbit A Model for the Principles of Mammalian Physiology and Surgery. New York: Academic Press; 1979. [Google Scholar]
• Karlik SJ, Eichhorn GL, Crapper DR. Molecular interactions of aluminum with DNA. Neurotoxicology. 1980a;1:83–88. [Google Scholar]
• Karlik SJ, Eichhorn GL, Levis PN, Crapper DR. Interaction of aluminum species with deoxyribonucleic acid. Biochemistry. 1980b;19:5991–5998. [PubMed] [Google Scholar]
• Kasa P, Szerdahelyi P, Wisniewski HM. Lack of topographical relationship between sites of aluminum deposition and senile plaques in the Alzheimer’s disease brain. Acta Neuropathol. 1995;90:526–531. [PubMed] [Google Scholar]
• Kassem M, Eriksen EF, Melsen F, Mosekilde L. Antacid-induced osteomalacia: a case report with a histomorphometric analysis. J Intern Med. 1991;229:275–279. [PubMed] [Google Scholar]
• Katz AC, Frank DW, Sauerhoff MW, Zwicker GM, Freudenthal RI. A 6-month dietary toxicity study of acidic sodium aluminium phosphate in beagle dogs. Food Chem Toxicol. 1984;22:7–9. [PubMed] [Google Scholar]
• Kawahara M, Muramoto K, Kobayashi K, Mori H, Kuroda Y. Aluminum promotes the aggregation of Alzheimer’s amyloid beta-protein in vitro. Biochem Biophys Res Commun. 1994;198:531–535. [PubMed] [Google Scholar]
• Kawahara M, Kato M, Kuroda Y. Effects of aluminum on the neurotoxicity of primary cultured neurons and on the aggregation of beta-amyloid protein. Brain Res Bull. 2001;55:211–217. [PubMed] [Google Scholar]
• Keith LS, Jones DE, Chou CH. Aluminum toxicokinetics regarding infant diet and vaccinations. Vaccine. 2002;20(Suppl 3):S13–S17. [PubMed] [Google Scholar]
• Kennedy MC. Aluminium powder inhalations in the treatment of silicosis of pottery workers and pneumoconiosis of coal-miners. Br J Ind Med. 1956;13:85–101. [PMC free article] [PubMed] [Google Scholar]
• Kida S, Pantazis A, Weller RO. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol. 1993;19:480–488. [PubMed] [Google Scholar]
• Kihira T, Yoshida S, Yase Y, Ono S, Kondo T. Chronic low-Ca/Mg high-Al diet induces neuronal loss. Neuropathology. 2002;22:171–179. [PubMed] [Google Scholar]
• Kihira T, Yoshida S, Kondo T, Yase Y, Ono S. ALS-like skin changes in mice on a chronic low-Ca/Mg high-Al diet. J Neurol Sci. 2004;219:7–14. [PubMed] [Google Scholar]
• Kilburn KH, Warshaw RH. Irregular opacities in the lung, occupational asthma, and airways dysfunction in aluminum workers. Am J Ind Med. 1992;21:845–853. [PubMed] [Google Scholar]
• King EJ, Wright BM. Effect of aluminium on the silicosis-producing action of inhaled quartz. Br J Ind Med. 1950;7:27–36. [PMC free article] [PubMed] [Google Scholar]
• King EJ, Rogers N, Gilchrist M. Attempts to prevent silicosis with aluminium. J Pathol Bacteriol. 1945;57:281. [Google Scholar]
• King EJ, Harrison C, Mohanty G, Nagelschmidt G. The effect of various forms of alumina on the lungs of rats. J Pathol Bacteriol. 1955;69:81–93. [PubMed] [Google Scholar]
• King EJ, Harrison CV, Mohanty GP, Yoganathan M. The effect of aluminum and of aluminum containing 5 per cent. of quartz in the lungs of rats. J Pathol Bacteriol. 1958;75:429–434. [PubMed] [Google Scholar]
• King J, Day RS, Milne FJ, Bezwoda WR, Viljoen JD, Kramer S. Delayed onset of overt porphyria cutanea tarda in a patient on long-term haemodialysis. A case report. S Afr Med J. 1983;63:743–746. [PubMed] [Google Scholar]
• King SJ, Templar J, Miller RV, Day JP, Itzhaki RF, Fifield LK, Allan G. Aluminium and Alzheimer’s disease: sites of aluminium binding in human neuroblastoma cells determined using 26Al and accelerator mass spectrometry. Nuc Instr Meth Phys Res B. 1994;92:469–472. [Google Scholar]
• King SJ, Day JP, Oldham C, Popplewell JF, Ackrill P, Moore P, Taylor G, Edwardson JA, Fifield LK, Liu K, Cresswell RG. The influence of dissolved silicate on the physiological chemistry of aluminium, studies in humans using tracer 26Al and accelerator mass spectrometry. Nuc Instr Meth Phys Res. 1997;123:254–258. [Google Scholar]
• Kislinger G, Steinhausen C, Alvarez-Bruckmann M, Winklhofer C, Ittel T, Nolte E. Investigations of the human aluminium biokinetics with 26Al and AMS. Nuc Instr Meth Phys Res B. 1997;123:259–265. [Google Scholar]
• Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissinen A. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol. 2005;62:1556–1560. [PubMed] [Google Scholar]
• Klatzo I, Wisniewski H, Streicher E. Experimental production of neurofibrillary degeneration: 1. Light microscopic observation. J Neuropathol Exp Neurol. 1965;24:187–199. [PubMed] [Google Scholar]
• Klein GL. Aluminum contamination of parenteral nutrition solutions and its impact on the pediatric patient. Nutr Clin Pract. 2003;18:302–307. [PubMed] [Google Scholar]
• Klein GL, Ott SM, Alfrey AC, Sherrard DJ, Hazlet TK, Miller NL, Maloney NA, Berquist WE, Ament ME, Coburn JW. Aluminum as a factor in the bone disease of long-term parenteral nutrition. Trans Assoc Am Physicians. 1982;95:155–164. [PubMed] [Google Scholar]
• Klein GL, Sedman AB, Heyman MB, Marathe G, Battifora HA, Worrall JL, Horst RL, Brewer GJ, Miller NL, Alfrey AC. Hepatic abnormalities associated with aluminum loading in piglets. J Parenter Enteral Nutr. 1987;11:293–297. [PubMed] [Google Scholar]
• Klein GL, Goldblum RM, Moslen MT, Pyron DL, Mann PA, Lee TC, Alfrey AC. Increased biliary transferrin excretion following parenteral aluminum administration to rats. Pharmacol Toxicol. 1993;72:373–376. [PubMed] [Google Scholar]
• Klosterkötter W. Effects of ultramicroscopic gamma-aluminum oxide on rats and mice. AMA Arch Ind Health. 1960;21:458–472. [PubMed] [Google Scholar]
• Knodel L, Kendall S, Young L, Hickey M. Nonprescription Products: Formulations and Features ’96-97. Washington: American Pharmaceutical Association; 1996. [Google Scholar]
• Knoll O, Kellinghaus H, Bertram HP, Zumkley H, Graefe U. Gastrointestinal absorption of aluminum in chronic renal insufficiency. Contrib Nephrol. 1984;38:24–31. [PubMed] [Google Scholar]
• Knutti R, Zimmerli B. Investigation of the daily portions of Swiss food establishments: III. Lead, cadmium, mercury, nickel and aluminium. Mitt Geb Lebensm Hyg. 1985;76:206–232. [Google Scholar]
• Kobayashi S, Hirota N, Saito K, Utsuyama M. Aluminum accumulation in tangle-bearing neurons of Alzheimer’s disease with Balint’s syndrome in a long-term aluminum refiner. Acta Neuropathol. 1987;74:47–52. [PubMed] [Google Scholar]
• Kobayashi S, Fujiwara S, Arimoto S, Koide H, Fukuda J, Shimode K, Yamaguchi S, Okada K, Tsunematsu T. Hair aluminium in normal aged and senile dementia of Alzheimer type. Prog Clin Biol Res. 1989;317:1095–1109. [PubMed] [Google Scholar]
• Kobayashi K, Yumoto S, Nagai H, Hosoyama Y, Imamura M, Masuzawa S, Koizumi Y, Yamashita H. 26Al tracer experiment by accelerator mass spectrometry and its application to the studies for amyotrophic lateral sclerosis and Alzheimer’s disease. I Proc Jpn Acad B. 1990;66:189–192. [Google Scholar]
• Koch KR, Pougnet MA, de Villiers S, Monteagudo F. Increased urinary excretion of Al after drinking tea. Nature. 1988;333:122. [PubMed] [Google Scholar]
• Koelsch F. Pulmonary disease caused by aluminum dust. Beitr Klin Tuberk. 1942;97:688–693. [Google Scholar]
• Kohila T, Parkkonen E, Tahti H. Evaluation of the effects of aluminium, ethanol and their combination on rat brain synaptosomal integral proteins in vitro and after 90-day oral exposure. Arch Toxicol. 2004;78:276–282. [PubMed] [Google Scholar]
• Kongerud J, Samuelsen SO. A longitudinal study of respiratory symptoms in aluminium potroom workers. Am Rev Respir Dis. 1991;144:10–16. [PubMed] [Google Scholar]
• Kongerud J, Gronnesby JK, Magnus P. Respiratory symptoms and lung function of aluminium potroom workers. Scand J Work Environ Health. 1990;16:270–277. [PubMed] [Google Scholar]
• Kongerud J, Boe J, Soyseth V, Naalsund A, Magnus P. Aluminum potroom asthma: The Norwegian experience. Eur Resp J. 1994;7:165–172. [PubMed] [Google Scholar]
• Koo WW, Kaplan LA. Aluminum and bone disorders with specific reference to aluminum contamination of infant nutrients. J Am Coll Nutr. 1988;7:199–214. [PubMed] [Google Scholar]
• Koo WW, Kaplan LA, Bendon R, Succop T, Tsang RC, Horn J, Steichen JJ. Response to aluminum in parenteral nutrition during infancy. J Pediatr. 1986;109:877–883. [PubMed] [Google Scholar]
• Koo WW, Kaplan LA, Krug-Wispe SK. Aluminum contamination of infant formulas. J Parenter Enteral Nutr. 1988;12:170–173. [PubMed] [Google Scholar]
• Kotovirta ML, Salo OP, Visa-Tolvanen K. Contact sensitivity to aluminium. Contact Dermatitis. 1984;11:135. [PubMed] [Google Scholar]
• Kovalchik MT, Kaehny WD, Hegg AP, Jackson JT, Alfrey AC. Aluminum kinetics during hemodialysis. J Lab Clin Med. 1978;92:712–720. [PubMed] [Google Scholar]
• Krachler M, Prohaska T, Koellensperger G, Rossipal E, Stingeder G. Concentrations of selected trace elements in human milk and in infant formulas determined by magnetic sector field inductively coupled plasma-mass spectrometry. Biol Trace Elem Res. 2000;76:97–112. [PubMed] [Google Scholar]
• Kralj B, Krizaj I, Bukovec P, Slejko S, Milacic R. Speciation of aluminium in tea infusions by use of SEC and FPLC with ICP-OES and ES-MS-MS detection. Anal Bioanal Chem. 2005;383:467–475. [PubMed] [Google Scholar]
• Krasnukhina AV, Laptev SF, Vakhramova SP. Reactions of some metal cations with oleic acid in water. Sb Tr Tsent Nauch Issled-Inst Olovyan Prom. 1971;1:69–71. [Google Scholar]
• Krasovskii GN, Vasukovich LY, Chariev OG. Experimental study of biological effects of lead and aluminum following oral administration. Environ Health Perspect. 1979;30:47–51. [PMC free article] [PubMed] [Google Scholar]
• Kraus AS, Forbes WF. Aluminum, fluoride and the prevention of Alzheimer’s disease. Can J Pub Health. 1992;83:97–100. [PubMed] [Google Scholar]
• Kraus T, Schaller KH, Angerer J, Letzel S. Aluminium dust-induced lung disease in the pyro-powder-producing industry: detection by high-resolution computed tomography. Int Arch Occup Environ Health. 2000;73:61–64. [PubMed] [Google Scholar]
• Krueger GL, Morris TK, Suskind RR, Widner EM. The health effects of aluminum compounds in mammals. Crit Rev Toxicol. 1984;13:1–24. [PubMed] [Google Scholar]
• Kruglikov GG, Velichkovskii BT, Garmash TI. Morphology of pneumoconiosis induced by natural zeolite. Gig Tr Prof Zabol. 1990;5:14–17. [PubMed] [Google Scholar]
• Kukhtina AP. Effect of age and the functional condition of the central nervous system on the level of some trace elements in the skeletal muscles and blood of white rats. Mikroelementy v Meditsine. 1972;3:123–126. [Google Scholar]
• Kumar S. Aluminum-induced biphasic effect. Med Hypotheses. 1999;52:557–559. [PubMed] [Google Scholar]
• Kushelevsky A, Yagil R, Alfasi Z, Berlyne GM. Uptake of aluminium ion by the liver. Biomed. 1976;25:59–60. [PubMed] [Google Scholar]
• Kvech S, Edwards M. Solubility controls on aluminium in drinking water at relatively low and high pH. Water Res. 2002;36:4356–4368. [PubMed] [Google Scholar]
• L’vov BV, Polzik LK, Weinbruch S, Ellingsen DG, Thomassen Y. Theoretical aspects of fluoride air contaminant formation in aluminium smelter potrooms. J Environ Monit. 2005;7:425–430. [PubMed] [Google Scholar]
• Lacson AG, D’Cruz CA, Gilbert-Barness E, Sharer L, Jacinto S, Cuenca R. Aluminum phagocytosis in quadriceps muscle following vaccination in children: relationship to macrophagic myofasciitis. Pediatr Dev Pathol. 2002;5:151–158. [PubMed] [Google Scholar]
• Laden F, Neas LM, Dockery DW, Schwartz J. Association of fine particulate matter from different sources with daily mortality in six U.S. cities. Environ Health Perspect. 2000;108:941–947. [PMC free article] [PubMed] [Google Scholar]
• Lakatos A, Banyai I, Decock P, Kiss T. Time-dependent solution speciation of the AlIII-citrate system: potentiometric and NMR studies. Eur J Inorg Chem. 2001;2001:461–469. [Google Scholar]
• Landau AJ, Eberhardt RT, Frishman WH. Intranasal delivery of cardiovascular agents: an innovative approach to cardiovascular pharmacotherapy. Am Heart J. 1994;127:1594–1599. [PubMed] [Google Scholar]
• Landsberg JP, McDonald B, Watt F. Absence of aluminium in neuritic plaque cores in Alzheimer’s disease. Nature. 1992;360:65–68. [PubMed] [Google Scholar]
• Landsberg J, McDonald B, Grime G, Watt F. Microanalysis of senile plaques using nuclear microscopy. J Geriatr Psychiatry Neurol. 1993;6:97–104. [PubMed] [Google Scholar]
• Lansdown AB. Production of epidermal damage in mammalian skins by some simple aluminum compounds. Br J Dermatol. 1973;89:67–76. [PubMed] [Google Scholar]
• Lapenas DJ, Gale PN. Kaolin pneumoconiosis. A case report. Arch Pathol Lab Med. 1983;107:650–653. [PubMed] [Google Scholar]
• Larsen S, Lund R, Nielsen D, Thygesen P, Poulsen O. Adjuvant effect of di-n-butyl-, di-n-octyl-, di-iso-nonyl and di-iso-decyl phtalate in a subcutaneous injection model using BALB/c mice. Pharmacol Toxicol. 2002;91:264–272. [PubMed] [Google Scholar]
• Larsson NPO, Tapper UAS, Sturesson K, Odselius R, Brun A. Technical aspects of nuclear microprobe analysis of senile plaques from Alzheimer patients. Nuc Inst Meth Phys Res B. 1990;49:472–475. [Google Scholar]
• Lawley A. Modern powder metallurgy science and technology. JOM. 1986;38:15–26. [Google Scholar]
• Lazerte BD, Van Loon G, Anderson B. Aluminum in water. In: Yokel RA, Golub M, editors. Research Issues in Aluminum Toxicity. Washington DC: Taylor & Francis; 1997. pp. 17–45. [Google Scholar]
• Le Bouffant L, Daniel H, Martin JC. The therapeutic action of aluminium compounds on the development of experimental lesions produced by pure quartz or mixed dust. Inhaled Part. 1975;4:389–401. [PubMed] [Google Scholar]
• Leblondel G, Allain P. Blood and brain aluminium concentrations in mice after intraperitoneal injection of different aluminium compounds. Res Commun Chem Pathol Pharmacol. 1980;27:579–586. [PubMed] [Google Scholar]
• Leboeuf RC, Tolson D, Heinecke JW. Dissociation between tissue iron concentrations and transferrin saturation among inbred mouse strains. J Lab Clin Med. 1995;126:128–136. [PubMed] [Google Scholar]
• Lee DS, Garland JA, Fox AA. Atmospheric concentrations of trace elements in urban areas of the United Kingdom. Atmos Environ. 1994;28:2691–2713. [Google Scholar]
• Lee PK, Brook JR, Dabek-Zlotorzynska E, Mabury SA. Identification of the major sources contributing to PM2.5 observed in Toronto. Environ Sci Technol. 2003;37:4381–4840. [PubMed] [Google Scholar]
• Lemaire I. Selective differences in macrophage populations and monokine production in resolving pulmonary granuloma and fibrosis. Am J Pathol. 1991;138:487–495. [PMC free article] [PubMed] [Google Scholar]
• Lemaire I, Dionne PG, Nadeau D, Dunnigan J. Rat lung reactivity to natural and man-made fibrous silicates following short-term exposure. Environ Res. 1989;48:193–210. [PubMed] [Google Scholar]
• Lenntech. EU’s drinking water standards. 2004. [online] Cited 24 January 2007 http://www.lenntech.com/EU’s-drinking-water-standards.htm.
• Lenz TR. Foreign body granuloma caused by jet injection of tetanus toxoid. Rocky Mt Med J. 1966;63:48. [PubMed] [Google Scholar]
• Léonard A, Gerber GB. Mutagenicity, carcinogenicity and teratogenicity of aluminium. Mutat Res. 1988;196:247–257. [PubMed] [Google Scholar]
• Lesnikovich AI, Shunkevich TM, Vorob’eva JA, Maumenko VN. Interaction of highly dispersed aluminum with oleic acid. Vestnik Belorusskogo Gosudarstvennogo Universiteta, Seriya 2: Khimiya Biologiya Geografiya. 1993;1:7–9. [Google Scholar]
• Letzel S, Schaller KH, Angerer J, Drexler H, Weber A, Schmid K, Weltle D. Biological monitoring of occupational aluminum powder exposure. Occup Hyg. 1996;3:271–280. [Google Scholar]
• Letzel S, Lang C, Schaller KH, Angerer J, Fuchs S, Neudörfer B, Lehnert G. Longitudinal study of neurotoxicity with occupational exposure to aluminium dust. Neurology. 2000;54:997–1000. [PubMed] [Google Scholar]
• Leung FY, Hodsman AB, Muirhead N, Henderson AR. Ultrafiltration studies in vitro of serum aluminum in dialysis patients after deferoxamine chelation therapy. Clin Chem. 1985;31:20–23. [PubMed] [Google Scholar]
• Levatidi J, Guibert L, Wolfromm R. Experimental study of tissue reactions following repeated injections of aluminium hydroxide. Ann Inst Pasteur. 1968;114:511–517. [PubMed] [Google Scholar]
• Lévesque L, Mizzen CA, McLachlan DR, Fraser PE. Ligand specific effects on aluminum incorporation and toxicity in neurons and astrocytes. Brain Res. 2000;877:191–202. [PubMed] [Google Scholar]
• Lewis CW, Macias ES. Composition of size-fractioned aerosols in Charleston, WV. Atmos Environ. 1980;14:185–194. [Google Scholar]
• Lewis JL, Hahn FF, Dahl AR. Transport of inhaled toxicants to the central nervous system. Characteristics of a nose-brain barrier. In: Isaacson RL, Jensen KF, editors. The Vulnerable Brain and Environmental Risks, Vol 3: Toxins in Air and Water. New York: Plenum Press; 1994. pp. 77–103. [Google Scholar]
• Li D, Xiao B, Dong Q, Li S, Zhan C. Aluminum and fluorine absorption in a perfusion system of rat small intestine in vivo. J West China Univ Med Sci. 1991;22:189–191. [PubMed] [Google Scholar]
• Liang L, D’Haese PC, Lamberts LV, De Broe ME. Direct calibration for determining aluminum in bone and soft tissues by graphite furnace atomic absorption spectrometry. Clin Chem. 1991;37:461–466. [PubMed] [Google Scholar]
• Liao YH, Yu HS, Ho CK, Wu MT, Yang CY, Chen JR, Chang CC. Biological monitoring of exposures to aluminium, gallium, indium, arsenic, and antimony in optoelectronic industry workers. J Occup Environ Med. 2004;46:931–936. [PubMed] [Google Scholar]
• Liddiard PD. Aluminum powder metallurgy in perspective. Powder Metall. 1984;27:193–200. [Google Scholar]
• Lie DR, editor. CRC Handbook of Chemistry and Physics. 71. Boca Raton, FL: The Chemical Rubber Publishing Company; 19901991. [Google Scholar]
• Lieuallen WG, Weisbrode SE. Effects of systemic aluminium on the resolution of a uremic and dieteary phosphorus-dependent model of uremic osteomalacia in rats. J Bone Mineral Res. 1991;6:751–757. [PubMed] [Google Scholar]
• Lindberg JS, Copley JB, Koenig KG, Cushner HM. Effect of citrate on serum aluminum concentrations in hemodialysis patients: a prospective study. South Med J. 1993;86:1385–1388. [PubMed] [Google Scholar]
• Lindenschmidt RC, Driscoll KE, Perkins MA, Higgins JM, Maurer JK, Belfiore KA. The comparison of a fibrogenic and two nonfibrogenic dusts by bronchoalveoar lavage. Toxicol Appl Pharmacol. 1990;102:268–281. [PubMed] [Google Scholar]
• Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002;156:445–453. [PubMed] [Google Scholar]
• Linse R, Hadlich J, Kirsten D. Cutaneous foreign body granulomas casued by aluminium hydroxide after desensitization with Mischpollen-Depotallergen. Dermatol Monatsschr. 1979;165:653–657. [PubMed] [Google Scholar]
• Linss VW, Martin R, Stein G, Bräunlich H, Fleck C. Electron microscopic evidence of aluminium in lysosomes of kidney cells by electron energy loss spectroscopy. Acta Histochem. 1991;90:65–73. [PubMed] [Google Scholar]
• Linss W, Martin R, Stein G, Bräunlich H, Fleck C. The occurrence of aluminum-containing lysosomes in the kidney of experimentally treated rats. Acta Histochem Suppl. 1992;42:273–276. [PubMed] [Google Scholar]
• Linton RW, Bryan SR, Griffis DP, Shelburne JD, Fiori CE, Garruto RM. Digital imaging studies of aluminum and calcium in neurofibrillary tangle-bearing neurons using secondary ion mass spectrometry. Trace Elem Med. 1987;4:99–104. [Google Scholar]
• Lione A. The prophylactic reduction of aluminium intake. Food Chem Toxicol. 1983;21:103–109. [PubMed] [Google Scholar]
• Lione A, Smith JC. The mobilization of aluminum from three brands of chewing gum. Food Chem Toxicol. 1982;20:945–946. [PubMed] [Google Scholar]
• Litov RE, Sickles VS, Chan GM, Springer MA, Cordano A. Plasma aluminum measurements in term infants fed human milk or a soy-based infant formula. Pediatrics. 1989;84:1105–1107. [PubMed] [Google Scholar]
• Liu P, Yao YN, Wu SD, Dong HJ, Feng GC, Yuan XY. The efficacy of deferiprone on tissues aluminum removal and copper, zinc, manganese level in rabbits. J Inorg Biochem. 2005;99:1733–1737. [PubMed] [Google Scholar]
• Liu SM, Chung C. Trace elements in Taiwanese diet in different seasons. J Radioanal Nucl Chem. 1992;161:27–38. [Google Scholar]
• Liu SM, Chung C, Chan CC. Daily dietary intake of Pratas islanders in the South China Sea. J Radioanal Nucl Chem. 1992;162:363–370. [Google Scholar]
• Ljunggren KG, Lidums V, Sjögren B. Blood and urine concentrations of aluminum among workers exposed to aluminum flake powders. Br J Ind Med. 1991;48:106–109. [PMC free article] [PubMed] [Google Scholar]
• Lleo A, Blesa R, Angelopoulos C, Pastor-Rubio P, Villa M, Oliva R, Bufill E. Transferrin C2 allele, haemochromatosis gene mutations, and risk for Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2002;72:820–821. [PMC free article] [PubMed] [Google Scholar]
• Llobet JM, Colomina MT, Sirvent JJ, Domingo JL, Corbella J. Reproductive toxicology of aluminum in male mice. Fundam Appl Toxicol. 1995;25:45–51. [PubMed] [Google Scholar]
• Long JF, Renkes G, Steinmeyer CL, Nagode LA. Effect of calcitriol infusions on serum aluminum in vitamin D-depleted rabbits fed an aluminum-supplemented ration. Res Commun Chem Pathol Pharmacol. 1991;74:89–104. [PubMed] [Google Scholar]
• Long JF, Nagode LA, Stemeyer CL, Renkes G. Comparative effects of calcitriol and parathyroid hormone on serum aluminum in vitamin D-depleted rabbits fed an aluminum-supplemented diet. Res Commun Chem Pathol Pharmacol. 1994;83:3–14. [PubMed] [Google Scholar]
• López FF, Cabrera C, Lorenzo ML, López M. Aluminium content of drinking waters, fruit juices and soft drinks: contribution to dietary intake. Sci Total Environ. 2002;292:205–213. [PubMed] [Google Scholar]
• Lopez S, Pelaez A, Navarro LA, Montesinos E, Morales C, Carda C. Aluminum allergy in patients hyposensitized with aluminum-precipitated antigen extracts. Contact Dermatitis. 1994;31:37–40. [PubMed] [Google Scholar]
• Lorusso A, Sama B, Giacomazzi G, Magarotto G. A retrospective assessment of 19 subjects compensated for the inhalation of aluminum powders (item 48, D.P.R. 482/75) Med Lav. 1992;83:451–455. [PubMed] [Google Scholar]
• Lote CJ, Wood JA, Saunders HC. Renal filtration, reabsorption and excretion of aluminium in the rat. Clin Sci. 1992;82:13–18. [PubMed] [Google Scholar]
• Lovell MA, Ehmann WD, Markesbery WR. Laser microprobe analysis of brain aluminium in Alzheimer’s disease. Ann Neurol. 1993;33:36–42. [PubMed] [Google Scholar]
• Lu ZY, Gong H, Amemiya T. Aluminum chloride induces retinal changes in the rat. Toxicol Sci. 2002;66:253–260. [PubMed] [Google Scholar]
• Lukiw WJ, Krishnan B, Wong L, Kruck TP, Bergeron C, Crapper McLachlan DR. Nuclear compartmentalization of aluminum in Alzheimer’s disease (AD) Neurobiol Aging. 1991;13:115–121. [PubMed] [Google Scholar]
• Lum KR, Betteridge JS, Macdonald RR. The potential availability of P, Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn in urban particulate matter. Env Technol Lett. 1982;3:57–62. [Google Scholar]
• Lynch KM, McIver FA. Pneumoconiosis from exposure to kaolin dust kaolinosis. Am J Pathol. 1954;30:1117–1127. [PMC free article] [PubMed] [Google Scholar]
• Lysiak M. Somatotropic hormone and pH of the gastric juice. Patol Pol. 1963;14:477–478. [PubMed] [Google Scholar]
• MacFarland HN, Hornstein N. An experimental investigation of the effects of the inhalation of alumina and other fumes. Can Chem Process Industries. 1949;33:145. [Google Scholar]
• Mackay IR, Oliphant RC, Laby B, Smith MM, Fisher JN, Mitchell RJ, Propert PN, Tait BD. An immunologic and genetic study of asthma in workers in an aluminum smelter. J Occup Med. 1990;32:1022–1026. [PubMed] [Google Scholar]
• Maenhaut W, Ducastel G, Leck C, Nilsson ED, Heintzenberg J. Multi-elemental composition and sources of the high arctic atmospheric aerosol during summer and autumn. Tellus B. 1996;48:300–321. [Google Scholar]
• Mahieu S, Calvo ML. Effect of chronic poisoning with aluminum on the renal handling of phosphate in the rat. Toxicol Lett. 1998;94:47–56. [PubMed] [Google Scholar]
• Mahieu S, Calvo ML, Millen N, Gonzalez M, Contini MC. Growth and metabolism of calcium in rats chronically poisoned with aluminium hydroxide. Acta Physiol Pharmacol Ther Latinoam. 1998;48:32–40. [PubMed] [Google Scholar]
• Mahieu S, del Carmen Contini M, Gonzalez M, Millen N, Elias MM. Aluminum toxicity. Hematological effects. Toxicol Lett. 2000;111:235–242. [PubMed] [Google Scholar]
• Mahieu ST, Navoni J, Millen N, del Carmen CM, Gonzalez M, Elias MM. Effects of aluminum on phosphate metabolism in rats: a possible interaction with vitamin D3 renal production. Arch Toxicol. 2004;78:609–616. [PubMed] [Google Scholar]
• Maitani T, Kubota H, Hori N, Yoshihira K, Takeda M. Distribution and urinary excretion of aluminum injected with several organic acids into mice: Relationship with chemical state in serum studied by the HPLC-ICP method. J Appl Toxicol. 1994;14:257–261. [PubMed] [Google Scholar]
• Makjanic J, McDonald B, Li-Hsian Chen CP, Watt F. Absence of aluminum in neurofibrillary tangles in Alzheimer’s disease. Neurosci Lett. 1998;240:123–126. [PubMed] [Google Scholar]
• Malluche HH. Aluminum and bone disease in chronic renal failure. Nephrol Dial Tranplant. 2002;172(Suppl 2):21–24. [PubMed] [Google Scholar]
• Malluche HH, Faugere MC, Friedler RM, Matthews C, Fanti P. Calcitriol, parathyroid hormone, and accumulation of aluminum in bone in dogs with renal failure. J Clin Invest. 1987;79:754–761. [PMC free article] [PubMed] [Google Scholar]
• Mandic ML, Grgic J, Grgic Z, Seruga M, Hasenay D. Aluminum levels in human milk. Sci Total Environ. 1995;170:165–170. [PubMed] [Google Scholar]
• Manna GK, Das RK. Chromosome aberration in mice induced by aluminum chloride. Nucleus. 1972;15:180–186. [Google Scholar]
• Manna GK, Parida BB. Aluminum chloride induced meiotic chromosome aberrations in the grasshopper. Phloeoba antennata Naturwissenschaften. 1965;52:647–648. [Google Scholar]
• Mantyh PW, Ghilardi JR, Rogers S, Demaster E, Allen CJ, Stimson ER, Maggio JE. Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. J Neurochem. 1993;61:1171–1174. [PubMed] [Google Scholar]
• Marchante-Gayon JM, Muniz CS, Alonson JI, Sanz-Medel A. Multielemental trace analysis of biological materials using double focusing inductively coupled plasma mass spectrometry detection. Analyt Chim Acta. 1999;400:307–320. [Google Scholar]
• Marcus DL, Wong S, Freedman ML. Dietary aluminum and Alzheimer’s disease. J Nutr Elder. 1992;12:55–61. [PubMed] [Google Scholar]
• Marek J, Blaha V. Some methodical and morphological aspects of the bentonite-induced inflammatory reaction in rat. Acta Univ Palacki Olomuc Fac Med. 1985;108:151–170. [PubMed] [Google Scholar]
• Mark A, Björkstén B, Granström M. Immunoglobulin E responses to diptheria and tetanus toxoids after booster with aluminium-adsorbed and fluid DT-vaccines. Vaccine. 1995;13:669–673. [PubMed] [Google Scholar]
• Markesbery W, Ehmann W, Hossain T, Alauddin M, Goodin D. Instrumental neutron activation analysis of brain aluminum in Alzheimer disease and aging. Ann Neurol. 1981;10:511–516. [PubMed] [Google Scholar]
• Markesbery WR, Ehmann WD, Alauddin M, Hossain TIM. Brain trace element concentrations in aging. Neurobiol Aging. 1984;5:19–28. [PubMed] [Google Scholar]
• Martin JC, Daniel H, Le Bouffant L. Short-and long-term experimental study of the toxicity of coal-mine dust and of some of its constituents. Inhaled Part. 1975;4(Pt 1):361–371. [PubMed] [Google Scholar]
• Martin RB. The chemistry of aluminum as related to biology and medicine. Clin Chem. 1986;32:1797–1806. [PubMed] [Google Scholar]
• Martin RB. Aluminum: a neurotoxic product of acid rain. Acc Chem Res. 1994;27:204–210. [Google Scholar]
• Martin RB. Ternary complexes of Al3+ and F with a third ligand. Coord Chem Rev. 1996;141:23–32. [Google Scholar]
• Martyn CN, Barker DJ, Osmond O, Harris EC, Edwardson JA, Lacey RF. Geographical relation between Alzheimer’s disease and aluminium in drinking water. Lancet. 1989;1:59–62. [PubMed] [Google Scholar]
• Martyn CN, Coggon DN, Inskip H, Lacey RF, Young WF. Aluminum concentrations in drinking water and risk of Alzheimer’s disease. Epidemiology. 1997;8:281–286. [PubMed] [Google Scholar]
• Marumo F, Tsukamoto Y, Iwanami S, Kishimoto T, Yamagami S. Trace element concentrations in hair, fingernails and plasma of patients with chronic renal failure on hemodialysis and hemofiltration. Nephron. 1984;38:267–272. [PubMed] [Google Scholar]
• Marzin DR, Phi HV. Study of the mutagenicity of metal derivatives with Salmonella typhimurium TA102. Mutat Res. 1985;155:49–51. [PubMed] [Google Scholar]
• Massie HR, Aiello VR, Tuttle RS. Aluminum in the organs and diet of ageing C57BL/6J mice. Mech Ageing Dev. 1988;45:145–156. [PubMed] [Google Scholar]
• Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 1985;4:2757–2763. [PMC free article] [PubMed] [Google Scholar]
• Mastrangelo G, Fadda E, Marzia V. Polycyclic aromatic hydrocarbons and cancer in man. Environ Health Perspect. 1996;104:1166–1170. [PMC free article] [PubMed] [Google Scholar]
• Mathias R, Salusky I, Harman W, Paredes A, Emans J, Segre G, Goodman W. Renal bone disease in pediatric and young adult patients on hemodialysis in a children’s hospital. J Am Soc Nephrol. 1993;3:1938–1946. [PubMed] [Google Scholar]
• Matsuda R, Sasaki K, Sakai H, Aoyagi Y, Saeki M, Hasegawa Y, Hidaka T, Ishii K, Mochizuki E, Yamamoto T, Miyabe M, Tamura Y, Hori S, Ikebe K, Tsuji M, Kojima M, Saeki K, Matsuoka S, Nishioka C, Fujita H, Shiroma H, Oshiro Z, Toyoda M. Estimation of daily dietary intake of aluminum. Shokuhin Eiseigaku Zasshi. 2001;42:18–23. [PubMed] [Google Scholar]
• Matsuno K, Tanaka I, Kodama Y. Pulmonary deposition and clearance of a coal fly ash aerosol by inhalation. Environ Res. 1986;41:195–200. [PubMed] [Google Scholar]
• Mattson MP, Lovell MA, Ehmann WD, Markesbery WR. Comparison of the effects of elevated intracellular aluminum and calcium levels on neuronal survival and tau immunoreactivity. Brain Res. 1993;602:21–31. [PubMed] [Google Scholar]
• Mauro LS, Kuhl DA, Kirchhoff JR, Mauro VF, Hamilton RW. Impact of oral bases on aluminum absorption. Am J Therap. 2001;8:21–25. [PubMed] [Google Scholar]
• Maynard EA. Gold, silver, manganese, and other minor metals. In: DiPalma JR, editor. Drill’s Pharacology in Medicine. 3. New York: McGraw-Hill Book Company; 1965. pp. 872–887. [Google Scholar]
• Mayor GH, Keiser JA, Makdani D, Ku PK. Aluminum absorption and distribution: Effect of parathyroid hormone. Science. 1977;197:1187–1189. [PubMed] [Google Scholar]
• Mazzaferro S, Coen G, Ballanti P, Costantini S, Bondatti F, Giordano R, Manni M, Pasquali M, Perruzza I, Sardella A. Deferoxamine test and PTH serum levels are useful not to recognize but to exclude aluminum-related bone disease. Nephron. 1992;61:151–157. [PubMed] [Google Scholar]
• Mazzera DM, Lowenthal DH, Chow JC, Watson JG, Grubisic V. PM10 measurements at McMurdo station, Antarctica. Atmos Environ. 2001;35:1891–1902. [Google Scholar]
• McColl KE, Simpson K, Laiwah AY, Thompson GG, McDougall A, Moore MR. Hemodialysis-related porphyria cutanea tarda-treatment failure with charcoal hemoperfusion. Photdermatol. 1986;3:169–173. [PubMed] [Google Scholar]
• McCullough ML, Hsu N. Metabolic bone disease in home total parenteral nutrition. J Am Diet Assoc. 1987;87:915–920. [PubMed] [Google Scholar]
• McDermott JR, Smith A, Ward MK, Parkinson IS, Kerr DN. Brain-aluminium concentration in dialysis encephalopathy. Lancet. 1978;1:901–904. [PubMed] [Google Scholar]
• McDermott JR, Smith I, Iqbal K, Wisniewski HM. Brain aluminum in aging and Alzheimer disease. Neurology. 1979;27:809–814. [PubMed] [Google Scholar]
• McDonald B, Haszard R, Spence A, Osbourne K. A mortality study of Alzheimer’s disease and aluminum exposure through inhalation of McIntyre powder in Cornish tin miners. Neurobiol Aging. 1996;17:S122–S123. [Google Scholar]
• McFadden N, Lyberg T, Hensten-Pettersen A. Aluminum-induced granulomas in a tattoo. J Am Acad Dermatol. 1989;20:903–908. [PubMed] [Google Scholar]
• McGrath KG. An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving. Eur J Cancer Prev. 2003;12:479–485. [PubMed] [Google Scholar]
• McGregor SJ, Brock JH, Halls D. The role of transferrin and citrate in cellular uptake of aluminium. Biol Metals. 1991;4:173–175. [PubMed] [Google Scholar]
• McGregor SJ, Fernandez Menendez MJ, Naves ML, Elloriaga R, Brock JH, Cannata JB. The uptake of aluminum and its effect on iron metabolism in the osteoblast like cell line MG-63. Trace Elem Electrolytes. 1994;11:187–191. [Google Scholar]
• McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34:939–944. [PubMed] [Google Scholar]
• McKinney TD, Basinger, Dawson E, Jones MM. Serum aluminum levels in dialysis dementia. Nephron. 1982;32:53–56. [PubMed] [Google Scholar]
• McLachlan DR, Crapper McLachlan CD, Krishnan B, Krishnan SS, Dalton AJ, Steele JC. Aluminum and calcium in soil and food from Guam, Palau and Jamaica: implications for amyotrophic lateral sclerosis and parkinsonism-dementia syndromes of Guam. Environ Geochem Health. 1989;11:45–53. [PubMed] [Google Scholar]
• McLachlan DR, Bergeron C, Smith JE, Boomer D, Rifat SL. Risk for neuropathologically confirmed Alzheimer’s disease and residual aluminum in municipal drinking water employing weighted residential histories. Neurology. 1996;46:401–405. [PubMed] [Google Scholar]
• McLaughlin AIG, Kazantzis G, King E, Teare D, Porter RJ, Owen R. Pulmonary fibrosis and encephalopathy associated with the inhalation of aluminium dust. Br J Ind Med. 1962;19:253–263. [PMC free article] [PubMed] [Google Scholar]
• McMillan TM, Freemont AJ, Herxheimer A, Denton J, Taylor AP, Pazianas M, Cummin AR, Eastwood JB. Camelford water poisoning accident: serial neuropsychological assessments and further observations on bone aluminium. Hum Exp Toxicol. 1993;12:37–42. [PubMed] [Google Scholar]
• McNall AD, Fosmire GJ. Zinc status does not affect aluminum deposition in tissues of rats. Biol Trace Elem Res. 1996;53:7–18. [PubMed] [Google Scholar]
• Meda L, Marra G, Galfetti L, Inchingalo S, Severini F, De Luca L. Nano-composites for rocket and solid propellants. Compos Sci Technol. 2004;65:769–773. [Google Scholar]
• Medical Research Council. Medical Research Council’s Committee on Clinical Trials of Influenza, V., Second progress report by the 1955 Antibody responses and clinical reactions with saline and oil adjuvant influenza virus vaccines. Br Med J. 1955;2:1229–1232. [PMC free article] [PubMed] [Google Scholar]
• Meding B, Augustsson A, Hansson C. Short communications. Patch test reactions to aluminium. Contact Dermatitis. 1984;10:107. [PubMed] [Google Scholar]
• Meirav O, Sutton RA, Fink D, Middleton R, Klein J, Walker VR, Halabe A, Vetterli D, Johnson RR. Accelerator mass spectrometry: application to study of aluminum kinetics in the rat. Am J Physiol. 1991;260:F466–469. [PubMed] [Google Scholar]
• Meshitsuka S, Inoue M. Urinary excretion of aluminum from antacid ingestion and estimation of its apparent biological half-time. Trace Elem Electrolytes. 1998;15:132–135. [Google Scholar]
• Meshitsuka S, Matsushima F, Nose T. Absorption of aluminum from aspirin preparations with aluminum glycinate. Trace Elem Electrolytes. 1999;16:175–176. [Google Scholar]
• Meyer FA, Kasper W. Examination of the effects of aluminium on the lung. Dtsch Arch Klin Med. 1942a;189:471–495. [Google Scholar]
• Meyer FA, Kasper W. Results of examination of workers in an aluminum-stamping works. Sitzber physik -med Sozietat Erlangen. 1942b;73:71–75. [Google Scholar]
• Migliore L, Cocchi L, Nesti C, Sabbioni E. Micronuclei assay and FISH analysis in human lymphocytes treated with six metal salts. Environ Mol Mutagen. 1999;34:279–284. [PubMed] [Google Scholar]
• Miliauskas JR, Mukherjee T, Dixon B. Postimmunization (vaccination) injection-site reactions. A report of four cases and review of the literature. Am J Surg Pathol. 1993;17:516–524. [PubMed] [Google Scholar]
• Miller RR, Churg AM, Hutcheon M, Lom S. Pulmonary alveolar proteinosis and aluminum dust exposure. Am Rev Respir Dis. 1984;130:312–315. [PubMed] [Google Scholar]
• Mineralogy Database. 2006. [online] Cited 24 January 2007. http://webmineral.com.
• MAFF (Ministry of Agriculture Fisheries and Food) Fifteenth report of the Steering Group on Food Surveillance, the working party on the monitoring of foodstuffs for heavy metals Food Surveillance Paper No 15. London, UK: The Ministry; 1985. Survey of Aluminium, Antimony, Chromium, Cobalt, Indium, Nickel, Thallium and Tin in Food. [Google Scholar]
• Ministry of Agriculture, Fisheries and Food (MAFF) The thirty-ninth report of the Steering Group on Chemical Aspects of Food Surveillance (MAFF) Food Surveillance Paper No 39. London, UK: The Ministry; 1993. Aluminium in Food. [Google Scholar]
• Mirick DK, Davis S, Thomas DB. Antiperspirant use and the risk of breast cancer. J Natl Cancer Inst. 2002;94:1578–1580. [PubMed] [Google Scholar]
• Misawa T, Shigeta S. Effects of prenatal aluminum treatment on development and behavior in the rat. J Toxicol Sci. 1993;18:43–48. [PubMed] [Google Scholar]
• Mitchell J. Pulmonary fibrosis in an aluminium worker. Br J Ind Med. 1959;16:123–125. [PMC free article] [PubMed] [Google Scholar]
• Mitchell J, Manning GB, Molyneux M, Lane RE. Pulmonary fibrosis in workers exposed to finely powdered aluminium. Br J Ind Med. 1961;18:10–23. [PMC free article] [PubMed] [Google Scholar]
• Mitrovic B, Milacic R. Speciation of aluminum in forest soil extracts by size exclusion chromatography with UV and ICP-AES detection and cation exchange fast protein liquid chromatography with ETAAS detection. Sci Total Environ. 2000;258:183–194. [PubMed] [Google Scholar]
• Miu AC, Andreescu CE, Vasiu R, Olteanu AI. A behavioral and histological study of the effects of long-term exposure of adult rats to aluminum. Int J Neurosci. 2003;113:1197–1211. [PubMed] [Google Scholar]
• Miu AC, Olteanu AI, Miclea M. A behavioral and ultrastructural dissection of the interference of aluminum with aging. J Alzheimers Dis. 2004;6:315–328. [PubMed] [Google Scholar]
• Mizumoto Y, Iwata S, Sasajima K, Yoshimasu F, Yase Y. X-ray florescence analysis for trace elements in frontal cortex in amytrophic lateral sclerosis. Kinki Daigaku Genshiryoku Kenkyusho Nenpo. 1983;20:1–4. [Google Scholar]
• Mjoberg B, Hellquist E, Mallmin H, Lindh U. Aluminum, Alzheimer’s disease and bone fragility. Acta Orthop Stand. 1997;68:511–514. [PubMed] [Google Scholar]
• Mladenovic J. Aluminum inhibits erythropoiesis in vitro. J Clin Invest. 1988;81:1661–1665. [PMC free article] [PubMed] [Google Scholar]
• Mödder H, Schmitt T. Spreading of aluminosis. Dtsch Med Wochenschr. 1951;76:84–87. [PubMed] [Google Scholar]
• Monteagudo FS, Isaacson LC, Wilson G, Hickman R, Folb PI. Aluminum excretion by the distal tubule of the pig kidney. Nephron. 1988;49:245–250. [PubMed] [Google Scholar]
• Moore PB, Edwardson JA, Ferrier IN, Taylor GA, Lett D, Tyrer SP, Day JP, King SJ, Lilley JS. Gastrointestinal absorption of aluminum is increased in Down’s syndrome. Biol Psychiatry. 1997;41:488–492. [PubMed] [Google Scholar]
• Moore PB, Day JP, Taylor GA, Ferrier IN, Fifield LK, Edwardson JA. Absorption of aluminium-26 in Alzheimer’s disease, measured using accelerator mass spectrometry. Dem Geriatr Cognitive Dis. 2000;11:66–69. [PubMed] [Google Scholar]
• More J, Fioramonti J, Bueno L. Aluminium hydroxide uptake in the stomach and in the intestine of the rat: a histochemical study. Acta Anatom. 1992;145:50–54. [PubMed] [Google Scholar]
• Moreno A, Dominguez P, Dominguez C, Ballabriga A. High serum aluminum levels and acute reversible encephalopathy in a 4-year-old boy with acute renal failure. Eur J Pediatr. 1991;150:513–514. [PubMed] [Google Scholar]
• Moretz RC, Iqbal K, Wisniewski HM. Microanalysis of Alzheimer disease NFT and plaques. Environ Geochem Health. 1990;12:15–16. [PubMed] [Google Scholar]
• Morgan WK, Donner A, Higgins IT, Pearson MG, Rawlings W. The effects of kaolin on the lung. Am Rev Respir Dis. 1988;138:813–820. [PubMed] [Google Scholar]
• Mori H, Swyt C, Smith QR, Atack JR, Rapoport SI. In situ x-ray microanalysis of senile plaques in Alzheimer’s disease. Neurology. 1988;38(Suppl 1):230. [Google Scholar]
• Morie T, Iwamoto M, Harada N, Masumoto S, Yamada M, Kusunose Y. Urinary excretion of aluminium: effects of aging and diurnal variation. Arch Gerontol Geriatr. 1996;22:287–295. [PubMed] [Google Scholar]
• Morrissey J, Slatopolsky E. The effect of aluminum on parathyroid hormone secretion. Kidney Int Suppl. 1986;29(Suppl 18):S41–S44. [PubMed] [Google Scholar]
• Morrissey J, Rothstein M, Mayor GH, Slatopolsky E. Suppression of parathyroid hormone secretion by aluminum. Kidney Int. 1983;2:699–704. [PubMed] [Google Scholar]
• Morris CM, Candy JM, Court JA, Whitford CA, Edwardson JA. The role of transferrin in the uptake of aluminum and manganese by the IMR 32 neuroblastoma cell line. Biochem Soc Trans. 1987;15:498. [Google Scholar]
• Morris CM, Candy JM, Oakley AE, Taylor GA, Mountfort S, Bishop H, Ward MK, Bloxham CA, Edwardson J. Comparison of the regional distribution of transferrin receptors and aluminium in the forebrain of chronic renal dialysis patients. J Neurol Sci. 1989;94:295–306. [PubMed] [Google Scholar]
• Morrow PE, Haseman KJ, Hobbs CH, Driscoll KW, Vu V, Oberdorster G. The maximum tolerated dose for inhalation bioassays: toxicity vs overload. Fundam Appl Toxicol. 1996;29:155–167. [PubMed] [Google Scholar]
• Moulin JJ, Clavel T, Buclez B, Laffitte-Rigaud G. A mortality study among workers in a french aluminum reduction plant. Int Arch Occup Environ Health. 2000;73:323–330. [PubMed] [Google Scholar]
• Mouser JF, Wu AH, Herson VC. Aluminum contamination of neonatal parenteral nutrient solutions and additives. Am J Health Syst Pharm. 1998;55:1071–1072. [PubMed] [Google Scholar]
• Mrak RE. Muscle granulomas following intramuscular injection. Muscle Nerve. 1982;5:637–639. [PubMed] [Google Scholar]
• Muller G, Hutin MF, Burnel D, Lehr PR. Aluminum transfer through milk in female rats intoxicated by aluminum chloride. Biol Trace Elem Res. 1992;34:79–87. [PubMed] [Google Scholar]
• Muller L, Wilhelm M. Uptake and distribution of aluminium in rat hepatocytes and its effect on enzyme leakage and lactate formation. Toxicology. 1987;44:203–212. [PubMed] [Google Scholar]
• Müller M, Anke M, Illing-Günther H. Oral aluminium exposure of adults in Germany - A long-term survey. In: Fischer P, L’Abbé M, Cockell K, Gibson R, editors. Trace Elements in Man and Animals -9: Proceedings of the Ninth International Symposium on Trace Elements in Man and Animals. Ottawa, Canada: NRC Research Press; 1997. pp. 177–178. [Google Scholar]
• Müller M, Anke M, Illing-Günther H. Aluminium in foodstuffs. Food Chem. 1998;61:419–428. [Google Scholar]
• Muma NA, Singer SM. Aluminum-induced neuropathology: transient changes in microtubule-associated proteins. Neurotoxicol Teratol. 1996;18:679–690. [PubMed] [Google Scholar]
• Mur JM, Moulin JJ, Meyer-Bisch C, Massin N, Couloun JP, Loulergue J. Mortality of aluminum reduction plant workers in France. Int J Epidemiol. 1987;16:257–264. [PubMed] [Google Scholar]
• Mur JM, Wild P, Rapp R, Vautrin JP, Coulon JP. Demographic evaluation of the fertility of aluminium industry workers: influence of exposure to heat and static magnetic fields. Hum Reprod. 1998;13:2016–2019. [PubMed] [Google Scholar]
• Murphy EJ, Roberts E, Horrocks LA. Aluminum silicate toxicity in cell cultures. Neuroscience. 1993;55:597–605. [PubMed] [Google Scholar]
• Musk AW, Greville HW, Tribe AE. Pulmonary disease from occupational exposure to an artificial aluminum silicate used for cat litter. Br J Ind Med. 1980;37:367–372. [PMC free article] [PubMed] [Google Scholar]
• Musk AW, Beck BD, Greville HW, Brain JD, Bohannon DE. Pulmonary disease from exposure to an artificial aluminium silicate: further observations. Br J Ind Med. 1988;45:246–250. [PMC free article] [PubMed] [Google Scholar]
• Mussi I, Calzaferri G, Buratti M, Alessio L. Behaviour of plasma and urinary aluminum levels in occupationally exposed subjects. Int Arch Occup Environ Health. 1984;54:155–161. [PubMed] [Google Scholar]
• Nagasawa K, Ito S, Kakuda T, Nagai K, Tamai T, Tsuji A, Fujimoto S. Transport mechanism for aluminum citrate at the blood-brain barrier: kinetic evidence implies involvement of system Xc- in immortalized rat brain endothelial cells. Toxicol Lett. 2005;155:289–296. [PubMed] [Google Scholar]
• Nagel J, Svec D, Waters T, Fireman P. IgE synthesis in man-I. Development of specific IgE antibodies after immunization with tetanus-diphtheria (Td) toxoids. J Immunol. 1977;118:334–341. [PubMed] [Google Scholar]
• Nagore E, Martinez-Escribano JA, Tato A, Sabater V, Vilata JJ. Subcutaneous nodules following treatment with aluminium-containing allergen extracts. Eur J Dermatol. 2001;11:138–140. [PubMed] [Google Scholar]
• Nagy E, Jobst K. The kinetics of aluminum-containing antacid absorption in man. Eur J Clin Chem Clin Biochem. 1994;32:119–121. [PubMed] [Google Scholar]
• Nair B, Yamarik TA. Final report on the safety assessment of aluminum starch octenylsuccinate. Int J Toxicol. 2002;21(Suppl 1):1–7. [PubMed] [Google Scholar]
• Nakamura H, Rose PG, Blumer JL, Reed MD. Acute encephalopathy due to aluminum toxicity successfully treated by combined intravenous deferoxamine and hemodialysis. J Clin Pharmacol. 2000;40:296–300. [PubMed] [Google Scholar]
• Namekata KM, Imagawa M, Terashi A, Ohta S, Oyama F, Ihara Y. Association of transferrin C2 allele with late-onset Alzheimer’s disease. Hum Genet. 1997;101:126–129. [PubMed] [Google Scholar]
• Nashed N. Preparation of peritoneal cell metaphases of rats, mice and Chinese hamsters after mitogenic stimulation with magnesium sulfate and/or aluminium hydroxide. Mutat Res. 1975;30:407–416. [PubMed] [Google Scholar]
• National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(Suppl 3):S1–S201. [PubMed] [Google Scholar]
• Navarro-Blasco I, Alvarez-Galindo JI. Aluminium content of Spanish infant formula. Food Addit Contam. 2003;20:470–481. [PubMed] [Google Scholar]
• Nayak P, Chatterjee AK. Effects of aluminum exposure on brain glutamate and GABA systems: an experimental study in rats. Food Chem Toxicol. 2001;39:1285–1289. [PubMed] [Google Scholar]
• Nayan R, Dey AK. Avidity of folic acid for carcinogenic metal ions aluminium(3), chromium(3), beryllium(II), lead(II) and uranium(VI) Z Naturforsch B. 1970;25:1453–1457. [PubMed] [Google Scholar]
• Naylor GJ, Sheperd B, Treliving L, McHarg A, Smith A, Ward N, Harper M. Tissue aluminum concentrations stability over time, relationship to age, and dietary intake. Biol Psychiatry. 1990;27:884–890. [PubMed] [Google Scholar]
• Neelam M, Bamji S, Kaladhar M. Risk of increased aluminium burden in the Indian population: contribution of aluminium from cookware. Food Chem. 2000;70:57–61. [Google Scholar]
• Nemery B. Metal toxicity and the respiratory tract. Eur Respir J. 1990;3:202–219. [PubMed] [Google Scholar]
• Neri LC, Hewitt D. Aluminum, Alzheimer’s disease, and drinking water. Lancet. 1991;338:390. [PubMed] [Google Scholar]
• Nestel AW, Meyers AM, Paiker J, Rollin HB. Effect of calcium supplement preparation containing small amounts of citrate on the absorption of aluminium in normal subjects and in renal failure patients. Nephron. 1994;68:197–201. [PubMed] [Google Scholar]
• Netter P, Kessler M, Burnel D, Hutin MF, Delones S, Benoit J, Gaucher A. Aluminum in the joint tissues of chronic renal failure patients treated with regular hemodialysis and aluminum compounds. J Rheumatol. 1984;11:66–70. [PubMed] [Google Scholar]
• Netter P, Kessler M, Gaucher A, Gillet P, Delons S, Burnel D, Benoit J, Got C. Aluminium and dialysis arthropathy. Lancet. 1988;1:886–887. [PubMed] [Google Scholar]
• Netterlid E, Bruze M, Hindsén M, Isaksson M, Olin P. Persistent itching nodules after the fourth dose of diphtheria-tetanus toxoid vaccines without evidence of delayed hypersensitivity to aluminium. Vaccine. 2004;22:3698–3706. [PubMed] [Google Scholar]
• Nevo Y, Kutai M, Jossiphov J, Livne A, Neeman A, Arad T, Popovitz-Biro R, Atsmon J, Shapira Y, Soffer D. Childhood macrophagic myofasciitis-consanguinity and clinicopathological features. Neuromuscul Disord. 2004;14:246–252. [PubMed] [Google Scholar]
• NFA (National Food Authority) The 1992 Australian Market Basket Survey - A Total Diet Survey of Pesticides and Contaminants. Canberra: The Authority; 1993. [Google Scholar]
• Ng AH, Hercz G, Kandel R, Grynpas MD. Association between fluoride, magnesium, aluminum and bone quality in renal osteodystrophy. Bone. 2004;34:216–224. [PubMed] [Google Scholar]
• Nieboer E, Fletcher GG. Determinants of reactivity in metal toxicology. In: Chang LW, editor. Toxicology of Metals. Boca Raton, FL: CRC Publishing; 1996. pp. 113–132. [Google Scholar]
• Nieboer E, Richardson DHS. The replacement of the nondescript term ‘heavy metals’ by a biologically and chemically significant classification of metal ions. Env Pollut (Series B) 1980;1:3–26. [Google Scholar]
• Nieboer E, Gibson BL, Oxman AD, Kramer JR. Health effects of aluminum: A critical review with emphasis on aluminum in drinking water. Environ Rev. 1995;3:29–81. [Google Scholar]
• Nieboer E, Fletcher GG, Thomassen Y. Relevance of reactivity determinants to exposure assesssment and biological monitoring of the elements. J Environ Monit. 1999;1:1–14. [PubMed] [Google Scholar]
• Nieboer E, Thomassen Y, Chashchin V, Odland JO. Occupational exposure assessment. J Environ Monit. 2005;7:411–415. [PubMed] [Google Scholar]
• Nielsen AO, Kaaber K, Veien NK. Aluminum allergy caused by DTP vaccine. Ugeskr Laeger. 1992;154:1900–1901. [PubMed] [Google Scholar]
• Nielsen J, Dahlqvist M, Welinder H, Thomassen Y, Alexandersson R, Skerfving S. Small airways function in aluminum and stainless steel welders. Int Arch Occup Environ Health. 1993;65:101–105. [PubMed] [Google Scholar]
• Nielsen VT, Hjorth L, Moller JC. Vaccination granuloma in the breast region-differential diagnosis. Ugesker Laeger. 1991;153:2180–2182. [PubMed] [Google Scholar]
• Nikaido T, Austin J, Trueb L, Rinehart R. Studies in ageing of the brain. II. Microchemical analyses of the nervous system in Alzheimer patients. Arch Neurol. 1972;27:549–554. [PubMed] [Google Scholar]
• NIOSH (National Institute for Occupational Safety and Health) Recommendations for Occupational Safety and Health -- Copendium of Policy Documents and Statements. Cincinnati, OH: Department of Health and Human Services, National Institute for Occupational Safety and Health; 1992. [Google Scholar]
• NIOSH (National Institute for Occupational Safety and Health) Pocket guide to chemical hazards, aluminum. 2005. [online] Cited 24 January 2007 http://www.cdc.gov/niosh/npg/npgd0022.html.
• Nishioka H. Mutagenic activities of metal compounds in bacteria. Mutat Res. 1975;31:185–189. [PubMed] [Google Scholar]
• Nolan CR, Califano JR, Butzin CA. Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int. 1990;38:937–941. [PubMed] [Google Scholar]
• Nolte E, Beck E, Winklhofer C, Steinhausen C. Compartmental model for aluminium biokinetics. Hum Exp Toxicol. 2001;20:111–117. [PubMed] [Google Scholar]
• Nordal KP, Dahl E, Sorhus K, Berg KJ, Thomassen Y, Kofstad J, Halse J. Gastrointestinal absorption and urinary excretion of aluminium in patients with predialysis chronic renal failure. Pharmacol Toxicol. 1988a;63:351–354. [PubMed] [Google Scholar]
• Nordal KP, Dahl E, Thomassen Y, Brodwall EK, Halse J. Seasonal variations in serum aluminium concentrations. Pharmacol Toxicol. 1988b;62:80–83. [PubMed] [Google Scholar]
• Nordal KP, Dahl E, Albrechtsen D, Halse J, Leivestad T, Tretli S, Flatmark A. Aluminium accumulation and immunosuppressive effect in recipients of kidney transplants. BMJ. 1988c;297:1581–1582. [PMC free article] [PubMed] [Google Scholar]
• Norimatsu M, Ogikubo Y, Aoki A, Takahasi T, Watanabe G, Taya K, Sasamoto S, Tsuchiya M, Tamura Y. Effects of aluminium adjuvant on systemic reactions of lipopolysaccharides in swine. Vaccine. 1995;13:1325–1329. [PubMed] [Google Scholar]
• Norris KC, Crooks PW, Nebeker HG, Hercz G, Milliner DS, Gerszi K, Slatopolsky E, Andress DL, Sherrard DJ, Coburn JW. Clinical and laboratory features of aluminum-related bone disease: differences between sporadic and “epidemic” forms of the syndrome. Am J Kidney Dis. 1985;6:342–347. [PubMed] [Google Scholar]
• NRC (National Research Council) Airborne Particles. Baltimore: University Park Press; 1979. [Google Scholar]
• NRC (National Research Council) Risk Assessment in the Federal Government: Managing the Process. Washingon D.C.: National Academy Press; 1983. [Google Scholar]
• O’Donnell TV, Welford B, Coleman ED. Potroom asthma: New Zealand experience and follow-up. Am J Ind Med. 1989;15:43–49. [PubMed] [Google Scholar]
• O’Driscoll JB, Beck M, Kesseler E, Ford G. Contact sensitivity to aluminium acetate eardrops. Contact Dermatitis. 1991;24:156–157. [PubMed] [Google Scholar]
• O’Gara R, Brown J. Comparison of the carcinogenic actions of subcutaneous implants of iron and aluminium in rodents. J Nat Cancer Inst. 1967;38:947–957. [PubMed] [Google Scholar]
• Oberdorster G, Ferin J, Morrow PE. Volumetric loading of alveolar macrophages (AM): A possible basis for diminished AM-mediated particle clearance. Exp Lung Res. 1992;18:87–104. [PubMed] [Google Scholar]
• Oberly TJ, Piper CE, McDonald DS. Mutagenicity of metal salts in the L5178Y mouse lymphoma assay. J Toxicol Environ Health. 1982;9:367–376. [PubMed] [Google Scholar]
• Occupational Disease Panel (Industrial Disease Standards Panel) Annual Report 1997/98. 1998. [online] Cited 24 January 2007 http://www.canoshweb.org/odp/html/an98.htm.
• Octive JC, Wood M, Johnson AC. Mutagenic effects of aluminium. Mutat Res. 1991;264:135–137. [PubMed] [Google Scholar]
• Odelram H, Granström M, Hedenskog S, Duchen K, Björkstén B. Immunoglobulin E and G responses to pertussis toxin after booster immunization in relation to atopy, local reactions and aluminium content of the vaccines. Allergy Immunol. 1994;5:118–123. [PubMed] [Google Scholar]
• Office of the Federal Register, National Archives and Records Administration. Code of Federal Regulations, Title 21- Food and Drugs. College Park, MD: Center for Food Safety and Applied Nutrition, U.S Food and Drug Administration; 2003. [Google Scholar]
• Ogasawara Y, Sakamoto T, Ishii K, Takanasi H, Tanabe S. Effects of the administration routes and chemical form of aluminium on aluminium accumulation in the rat brain. Biol Trace Element Res. 2002;86:269–278. [PubMed] [Google Scholar]
• Ogugbuaja VO, Onyeyili PA, Gadam AA, William A. The bioaccumulation of aluminium from coal ash on the tissue of rabbits: an environmental toxicology study. J Chem Soc Nigeria. 2004;29:1–4. [Google Scholar]
• Ohman LO, Martin RB. Citrate as the main small molecule binding Al3+ in serum. Clin Chem. 1994;40:598–601. [PubMed] [Google Scholar]
• Olaizola I, Fernández Martin JL, Fernández Menéndez MJ, Vizoso Piñeiro FJ, Virgós MJ, Fernández Soto I, Roza Suárez M, Cannata JB. Aluminium hydroxide absorption: Effect of age, renal failure and aluminium overload. Kidney Int. 1989;36:147. [Google Scholar]
• Olaizola Ottonello I, Serrano AM, Vizoso PF, Rodrigo SL, Garcia MM, Cannata Andia JB. Aluminum absorption in the presence of normal kidney function: the effect of the pH. Revista Clinica Espanola. 1991;188:442–445. [PubMed] [Google Scholar]
• Olivier P, Marzin D. Study of the genotoxic potential of 48 inorganic derivatives with the SOS chromotest. Mutat Res. 1987;189:263–269. [PubMed] [Google Scholar]
• Oller A, Bates H. Metals in perspective. J Environ Monit. 2005;6:411–412. [Google Scholar]
• Omokhodion FO, Howard JM. Trace elements in the sweat of acclimatized persons. Clin Chim Acta. 1994;231:23–28. [PubMed] [Google Scholar]
• Ondreicka R, Kortus J, Ginter E. Aluminum, its aborption, distribution and effects on phosphous metabolism. In: Skoryna SC, Waldron-Edward D, editors. Intestinal Absorption of Metal Ions, Trace Elements and Radionuclides. Oxford: Pergamon; 1971. pp. 293–305. [Google Scholar]
• Oneda S, Takasaki T, Kuriwaki K, Ohi Y, Umekita Y, Hatanaka S, Fujiyoshi T, Yoshida A, Yoshida H. Chronic toxicity and tumorigenicity study of aluminum potassium sulfate in B6C3F1 mice. In Vivo. 1994;8:271–278. [PubMed] [Google Scholar]
• Orell SR. Subcutaneous granulomata following inoculation of influenza vaccine. Acta Pathol Microbiol Scand. 1962;56:127–134. [PubMed] [Google Scholar]
• Orfan NA, Dykewicz MS, Barnowsky L. Extensive subcutaneous fibrosis in a patient treated with alum precipitated allergenic extract. Ann Allergy Asthma Immunol. 1995;75:453–456. [PubMed] [Google Scholar]
• Orlans D, Verbov J. Skin reactions after triple vaccine. Practit. 1982;226:1295–1296. [PubMed] [Google Scholar]
• Orlic I, Wen X, Ng TH, Tang SM. Two years of aerosol pollution monitoring in Singapore. A review. Nucl Instrum Meth B. 1999;150:457–464. [Google Scholar]
• Osmond LH. Experiences with the control of silicosis in a foundry. A M A Arch Ind Health. 1955;12:221–225. [PubMed] [Google Scholar]
• Oteiza PI, Mackenzie GG, Verstraeten SV. Metals in neurodegeneration: involvement of oxidants and oxidant-sensitive transcription factors. Mol Aspects Med. 2004;25:103–115. [PubMed] [Google Scholar]
• Ortner HM, Hoffman P, Stadermann FJ, Weinbruch S, Wentzel M. Chemical characterization of environmental and industrial particulate samples. Analyst. 1998;123:833–842. [Google Scholar]
• Ott SM, Maloney NA, Coburn JW, Alfrey AC, Sherrard DJ. The prevalence of bone aluminum deposition in renal osteodystrophy and its relation to the response to calcitriol therapy. N Engl J Med. 1982;307:709–713. [PubMed] [Google Scholar]
• Ott SM, Maloney NA, Klein GL, Alfrey AC, Ament ME, Coburn JW, Sherrard DJ. Aluminum is associated with low bone formation in patients receiving chronic parenteral nutrition. Ann Intern Med. 1983;98:910–914. [PubMed] [Google Scholar]
• Ott SM, Feist E, Andress DL, Liu CC, Sherrard DJ, Alfrey AC, Slatopolsky E, Howard GA. Development and reversibility of aluminum-induced bone lesions in the rat. J Lab Clin Med. 1987;109:40–47. [PubMed] [Google Scholar]
• Ott SM. Sources of aluminium. In: de Broe ME, Coburn JW, editors. Aluminum and Renal Failure. Dordrecht, Netherlands: Kluwer Academic; 1990. pp. 189–201. [Google Scholar]
• Owen LM, Crews HM, Bishop NJ, Massey RC. Aluminum uptake from some foods by guinea pigs and the characterization of aluminum in in vivo intestinal digesta by SEC-ICP-MS. Food Chem Toxicol. 1994;32:697–705. [PubMed] [Google Scholar]
• Pai SM, Melethil S. Kinetics of aluminum in rats I: Dose-dependent elimination from blood after intravenous administration. J Pharmac Sci. 1989;78:200–202. [PubMed] [Google Scholar]
• Park HS, Uh ST, Park CS. Increased neutrophil chemotactic activity is noted in aluminum induced occupational asthma. Kor J Int Med. 1996;11:69–73. [PMC free article] [PubMed] [Google Scholar]
• Parkinson IS, Ward MK, Kerr DN. Dialysis encephalopathy, bone disease and anaemia: the aluminum intoxication syndrome during regular haemodialysis. J Clin Pathol. 1981;34:1285–1294. [PMC free article] [PubMed] [Google Scholar]
• Parry R, Plowman D, Delves HT, Roberts NB, Birchall JD, Bellia JP, Davenport A, Ahmad R, Fahal I, Altmann P. Silicon and aluminium interactions in haemodialysis patients. Nephrol Dial Transplant. 1998;13:1759–1762. [PubMed] [Google Scholar]
• Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int. 1989;35:1413–1417. [PubMed] [Google Scholar]
• Partridge NA, Regnier FE, Reed WM, White JL, Hem SL. Contribution of soluble aluminium species to absorption of aluminium from the rat gut in situ. Clin Sci. 1992;83:425–30. [PubMed] [Google Scholar]
• Passi P, Zadro A, Galassini S, Rossi P, Moschini G. PIXE micro-beam maping of materials in human peri-implant tissues. J Mat Sci Mater Med. 2002;13:1083–1089. [PubMed] [Google Scholar]
• Paternain JL, Domingo JL, Llobet JM, Corbella J. Embryotoxic and teratogenic effects of aluminum nitrate in rats upon oral administration. Teratology. 1988;38:253–257. [PubMed] [Google Scholar]
• Pattaragarn A, Alon US. Antacid-induced rickets in infancy. Clin Pediatr. 2001;40:389–393. [PubMed] [Google Scholar]
• Pauwels R, Bazin H, Platteau B, Van der Straeten M. The influence of different adjuvants on the production of IgE and IgE antibodies. Ann Immunol. 1979;130C:49–58. [PubMed] [Google Scholar]
• Pearson A. Aluminum oxide (alumina) In: Kroschwitz JI, Howe-Grant M, editors. Othmer Encyclopedia of Chemical Technology. New York: John Wiley & Sons Inc; 1992. [Google Scholar]
• Pei Y, Hercz G, Greenwood C, Sherrard D, Segre G, Manuel A, Saiphoo C, Fenton S. Non-invasive prediction of aluminum bone disease in hemo- and peritoneal dialysis patients. Kidney Int. 1992;41:1374–1382. [PubMed] [Google Scholar]
• Pejovi-Mili A, Byun SH, Comsa DC, McNeill FE, Prestwich WV. In vivo measurement of bone aluminium: recent developments. Sixth Keele Meeting on Aluminium; February 26-March 2, 2005; Bussaco, Portugal. 2005. [Google Scholar]
• Pembroke AC, Marten RH. Unusual cutaneous reactions following diphtheria and tetanus immunization. Clin Exp Dermatol. 1979;4:345–348. [PubMed] [Google Scholar]
• Pennington JA. Aluminium content of foods and diets. Food Addit Contam. 1988;5:161–232. [PubMed] [Google Scholar]
• Pennington JA, Jones J. Aluminum in american diets. In: Gitelman HJ, editor. Aluminum in Health, A Critical Review. New York: Marcel Dekker; 1989. pp. 67–100. [Google Scholar]
• Pennington JA, Schoen SA. Estimates of dietary exposure to aluminium. Food Addit Contam. 1995;12:119–128. [PubMed] [Google Scholar]
• Perez Parajon J, Gonzalez FB, Cannata JB, Sanz Medel A. A critical appraisal of the speciation of aluminum in serum b ultrafiltration. Trace Elem Med. 1989;6:41–46. [Google Scholar]
• Perl DP, Brody AR. Alzheimer’s disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science. 1980;208:297–299. [PubMed] [Google Scholar]
• Perl DP, Good PF. Uptake of aluminum into central nervous system along nasal-olfactory pathways. Lancet. 1987;1:1028. [PubMed] [Google Scholar]
• Perl DP, Pendlebury WW. Aluminum neurotoxicity--potential role in the pathogenesis of neurofibrillary tangle formation. Can J Neurol Sci. 1986;13:S441–S445. [PubMed] [Google Scholar]
• Perl DP, Gajdusek DC, Garruto RM, Yanagihara RT, Gibbs CJ. Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam. Science. 1982;217:1053–1055. [PubMed] [Google Scholar]
• Perry KM. Diseases of the lung resulting from occupational dusts other than silica. Thorax. 1947;2:91–120. [PMC free article] [PubMed] [Google Scholar]
• Peserico A. Pathogenesis of Porphyria cutanea tarda-like syndrome. Nephron. 1979;24:51. [PubMed] [Google Scholar]
• Peters T, Hani N, Kirchberg K, Gold H, Hunzelmann N, Scharffetter-Kochanek K. Occupational contact sensitivity to aluminium in a machine construction plant worker. Contact Dermatitis. 1998;39:322–323. [PubMed] [Google Scholar]
• Pettersen JC, Hackett DS, Zwicker GM. Twenty-six week toxicity study with kasal (basic sodium aluminum phosphate) in beagle dogs. Environ Geochem Health. 1990;12:121–123. [PubMed] [Google Scholar]
• Phelps KR, Naylor K, Brien TP, Wilbur H, Haqqie SS. Encephalopathy after bladder irrigation with alum: case report and literature review. Am J Med. 1999;318:181–185. [PubMed] [Google Scholar]
• Piccardo P, Yanagihara R, Garruto RM, Gibbs CJ, Gajdusek CD. Histochemical and X-ray microanalytical localization of aluminum in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam. Acta Neuropathol. 1988;77:1–4. [PubMed] [Google Scholar]
• Pichichero ME, Edwards KM, Anderson EL, Rennels MB, Englund JA, Yerg DE, Blackwelder WC, Jansen DL, Meade BD. Safety and imunogenicity of six acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fifth dose in four to six year old children. Pediatrics. 2000;105:e11. [PubMed] [Google Scholar]
• Pierre F, Baruthio F, Diebold F, Biette P. Effect of different exposure compounds on urinary kinetics of aluminum and fluoride in industrially exposed workers. Occup Environ Med. 1995;52:396–403. [PMC free article] [PubMed] [Google Scholar]
• Pierre F, Diebold F, Baruthio F. Biomonitoring of aluminium in production workers. In: Priest ND, O’Donnell TV, editors. Health in the Aluminium Industry. London, UK: Middlesex University Press; 1998. pp. 68–69. [Google Scholar]
• Pigott GH, Ishmael J. An assessment of the fibrogenic potential of two refractory fibres by intraperitoneal injection in rats. Toxicol Lett. 1981;8:153–163. [PubMed] [Google Scholar]
• Pigott GH, Ishmael J. The effects of intrapleural injections of alumina and aluminoosilicate (ceramic) fibres. Int J Exp Pathol. 1992;73:137–146. [PMC free article] [PubMed] [Google Scholar]
• Pigott GH, Gaskell BA, Ishmael J. Effects of long term inhalation of alumina fibres in rats. Br J Exp Pathol. 1981;62:323–331. [PMC free article] [PubMed] [Google Scholar]
• Pineau A, Chappuis P, Arnaud J, Baruthio F, Zawislak R, Jaudon MC. Interlaboratory tests: completion of a method of aluminum assay in serum by electrothermal atomic absorption spectrometry. Annales de Biologie Clinique. 1992;50:577–585. [PubMed] [Google Scholar]
• Pinto JP, Stevens RK, Willis RD, Kellogg R, Mamane Y, Novak J, Santroch J, Benes I, Bures V, Lenicek J. Czech air quality monitoring and receptor modeling study. Environ Sci Technol. 1998;32:843–854. [Google Scholar]
• Pittman PR. Aluminum-containing vaccine associated adverse events: role of route of administration and gender. Vaccine. 2002;20(Suppl 3):S48–S50. [PubMed] [Google Scholar]
• Platt B, Fiddler G, Riedel G, Henderson Z. Aluminum toxicity in the rat brain: histochemical and immunocytochemical evidence. Brain Res Bull. 2001;55:257–267. [PubMed] [Google Scholar]
• Polizzi S, Pira E, Ferrara M, Bugiani M, Papaleo A, Albera R, Palmi S. Neurotoxic effects of aluminium among foundry workers and Alzheimer’s disease. Neurotoxicology. 2002;23:761–774. [PubMed] [Google Scholar]
• Pope CA, 3rd, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. J A M A. 2002;287:1132–1141. [PMC free article] [PubMed] [Google Scholar]
• Posner AS, Blumenthal NC. Model of aluminium-induced osteomalacia. Inhibition of apatite formation and growth. In: Ornoy A, Harell A, Sela J, editors. Current Advances in Skeletogenesis. Amsterdam: Exerpta Medica; 1985. pp. 299–304. [Google Scholar]
• Poulos BK, Perazzolo M, Lee MY, Rudelli R, Wisniewski HM, Soifer D. Oral aluminum administration during pregnancy and lactation produces gastric and renal lesions in rat mothers and delay in CNS development in their pups. Mol Chem Neuropathol. 1996;29:15–25. [PubMed] [Google Scholar]
• Powell JJ, Thompson RP. The chemistry of aluminium in the gastrointestinal lumen and its uptake and absorption. Proc Nutr Soc. 1993;52:241–253. [PubMed] [Google Scholar]
• Powell JJ, Greenfield SM, Parkes HG, Nicholson JK, Thompson RP. Gastro-intestinal availability of aluminum from tea. Food Chem Toxicol. 1993;31:449–454. [PubMed] [Google Scholar]
• Powell JJ, Ainley CC, Evans R, Thompson RP. Intestinal perfusion of dietary levels of aluminium: association with the mucosa. Gut. 1994;35:1053–1057. [PMC free article] [PubMed] [Google Scholar]
• Powell JJ, Whitehead MW, Ainley CC, Kendall MD, Nicholson JK, Thompson RP. Dietary minerals in the gastrointestinal tract: hydroxypolymerization of aluminum is regulated by luminal mucins. J Inorg Biochem. 1999;75:167–180. [PubMed] [Google Scholar]
• Pratico D, Uryu K, Sung S, Tang S, Trojanowski JQ, Lee VM. Aluminum modulates brain amyloidosis through oxidative stress in APP transgenic mice. FASEB J. 2002;16:1138–1140. [PubMed] [Google Scholar]
• Pratt PC. 6th Saranac Laboratory Symposium. New York: 1950. Pneumoconiosis. [Google Scholar]
• Priest ND. The bioavailability and metabolism of aluminium compounds in man. Proc Nutr Soc. 1993;52:231–240. [PubMed] [Google Scholar]
• Priest ND. A Human Volunteer Feeding Study using Aluminium-26 Labelled Aluminium Citrate, Aluminium Hydroxide and Aluminium Hydroxide in the Presence of Citrate. Harwell, Oxfordshire: AEA Technology; 1994. Report No AEA-TPD-268. [Google Scholar]
• Priest ND. The biological behaviour and bioavailability of aluminium in man, with special reference to studies employing aluminium-26 as a tracer: review and study update. J Environ Monitor. 2004;6:375–403. [PubMed] [Google Scholar]
• Priest ND, Newton D, Day JP, Talbot RJ, Warner AJ. Human metabolism of aluminium-26 and gallium-67 injected as citrates. Hum Exp Toxicol. 1995;14:287–293. [PubMed] [Google Scholar]
• Priest ND, Talbot RJ, Austin JG, Day JP, King SJ, Fifield K, Cresswell RG. The bioavailability of 26Al-labelled aluminium citrate and aluminium hydroxide in volunteers. BioMetals. 1996;9:221–228. [PubMed] [Google Scholar]
• Priest ND, Talbot RJ, Newton D, Day JP, King SJ, Fifield LK. Uptake by man of aluminium in a public water supply. Hum Exp Toxicol. 1998;17:296–301. [PubMed] [Google Scholar]
• Prival MJ, Simmon VF, Mortelmans KE. Bacterial mutagenicity testing of 49 food ingredients gives very few positive results. Mutat Res. 1991;260:321–329. [PubMed] [Google Scholar]
• Provan SD, Yokel RA. Aluminum uptake by the in situ rat gut preparation. J Pharmacol Exp Therap. 1988a;245:928–931. [PubMed] [Google Scholar]
• Provan SD, Yokel RA. Influence of calcium on aluminum accumulation by the rat jejunal slice. Res Commun Chem Pathol Pharmacol. 1988b;59:79–92. [PubMed] [Google Scholar]
• Provan SD, Yokel RA. Reduced intestinal calcium and dietary calcium intake increase aluminum absorption and tissue concentrations in the rat. Biol Trace Elem Res. 1990;23:119–132. [PubMed] [Google Scholar]
• Pun KK, Ho PW, Lau P. Effects of aluminum on the parathyroid hormone receptors of bone and kidney. Kidney Int. 1990;37:72–78. [PubMed] [Google Scholar]
• Putterman GJ, Strassburger J, Fitzgerald JJ. In vitro sorption of aluminum complex to guinea pig stratum corneum. J Invest Dermatol. 1981;77:319–324. [PubMed] [Google Scholar]
• Quarles LD. Attenuated bone aluminum deposition in nonuremic beagles with reduced bone remodeling. Am J Physiol. 1990;258:E576–E581. [PubMed] [Google Scholar]
• Quarles LD, Dennis VW, Gitelman HJ, Harrelson JM, Drezner MK. Aluminum deposition at the osteoid-bone interface. J Clin Invest. 1985;75:1441–1447. [PMC free article] [PubMed] [Google Scholar]
• Quarles LD, Gitelman HJ, Drezner MK. Induction of bone formation in the beagle: a novel effect of aluminum. J Clin Invest. 1988;81:1056–1066. [PMC free article] [PubMed] [Google Scholar]
• Quarles LD, Gitelman HJ, Drezner MK. Aluminium-induced de novo bone formation in the beagle: a parathyroid hormone-dependent event. J Clin Invest. 1989;83:1644–1650. [PMC free article] [PubMed] [Google Scholar]
• Quartley B, Essehnont G, Taylor A, Dobrota M. Effect of oral aluminum citrate on short-term tissue distribution of aluminum. Food Chem Toxicol. 1993;31:543–548. [PubMed] [Google Scholar]
• Quatrale RP. Mechanism of antiperspirant action. Cosmet Toiletries. 1985;100:23–26. [Google Scholar]
• Quatrale R, Waldman A, Rogers J, Felger C. The mechanism of antiperspirant action by aluminum salts. I. The effect of cellophane tape stripping on aluminum salt-inhibited eccrine sweat glands. J Soc Cos Chem. 1981a;32:67–73. [Google Scholar]
• Quatrale R, Coble D, Stoner K, Felger C. The mechanism of antiperspirant action by aluminum salts. II. Histological observation of human eccrine sweat glands inhibited by aluminum chlorohydrate. J Soc Cos Chem. 1981b;32:107–136. [Google Scholar]
• Queensland Government. Public health guidance note Aluminum. 2002. [online] Cited 24 January 2007 http://www.health.qld.gov.au/phs/Documents/ehu/4177.pdf.
• Raabe OG, Yeh H, Newton GJ, Phalen RF, Velasquez DJ. Deposition of inhaled monodisperse aerosols in small rodents. In: Walton WH, editor. Inhaled Particles. IV. New York: Pergamon Press; 1977. pp. 3–21. [PubMed] [Google Scholar]
• Raabe OG, Tyler WS, Last JA, Schwartz LW, Lollini LO, Fisher GL, Wilson FD, Dungworth DL. Studies of the chronic inhalation of coal fly ash by rats. Ann Occup Hyg. 1982;26:189–211. [PubMed] [Google Scholar]
• Raabe R, Janz S, Wolff G, Merten H, Landrock A, Birkenfeld T, Herzschuh R. Genotoxicity assessment of waste products of aluminum plasma etching wih SOS chromotest. Mutat Res. 1993;300:99–109. [PubMed] [Google Scholar]
• Radon K, Nowak D, Heinrich-Ramm R, Szadkowski D. Respiratory health and fluoride exposure in different parts of the modern primary aluminum industry. Int Arch Occup Environ Health. 1999;72:297–303. [PubMed] [Google Scholar]
• Radunovic A, Ueda F, Raja KB, Simpson RJ, Templar J, King SJ, Lilley JS, Day JP, Bradbury MW. Uptake of 26-Al and 67-Ga into brain and other tissues of normal and hypotransferrinaemic mice. BioMetals. 1997;10:185–191. [PubMed] [Google Scholar]
• Radunovic A, Delves HT, Bradbury MW. Uptake of aluminum and gallium into tissues of the rat: influence of antibody against the transferrin receptor. Biol Trace Elem Res. 1998;62:51–64. [PubMed] [Google Scholar]
• Rahman H, Skillen AW, Channon SM, Ward MK, Kerr DN. Methods for studying the binding of aluminum by serumprotein. Clin Chem. 1985;31:1969–1973. [PubMed] [Google Scholar]
• Rahnema S, Jennings F. Accumulation and depletion of aluminum from various tissues of rats following aluminum citrate ingestion. Ohio J Sci. 1999;99:98–101. [Google Scholar]
• Rajan MT, Jagannatha Rao KS, Mamatha BM, Rao RV, Shanmugavelu P, Menon RB, Pavithran MV. Quantification of trace elements in normal human brain by inductively coupled plasma atomic emission spectrometry. J Neurol Sci. 1997;146:153–166. [PubMed] [Google Scholar]
• Rajasekaran K. Effects of combined exposure to aluminium and ethanol on food intake, motor behaviour and a few biochemical parameters in pubertal rats. Environ Toxicol Pharmacol. 2000;9:25–30. [PubMed] [Google Scholar]
• Rajwanshi P, Singh V, Gupta MK, Kumari V, Shrivastav R, Ramanamurthy M, Dass S. Studies on aluminum leaching from cookware in tea and coffee and estimation of aluminum content in toothpaste, baking powder, and paan masala. Sci Total Environ. 1997;193:243–249. [PubMed] [Google Scholar]
• Ranau R, Oehlenchälger SH. Aluminium levels of fish fillets backed and grilled in aluminium foil. Food Chem. 2001;73:1–6. [Google Scholar]
• Rao JK, Katsetos CD, Herman MM, Savory J. Experimental aluminum encephalomyelopathy. Relationship to human neurodegenerative disease. Clin Lab Med. 1998;18:687–698. [PubMed] [Google Scholar]
• Rauch H, Fleischer F, Bohrer H, Jurs G, Wilhelm M, Krier C. Serum aluminium levels of intensive care patients treated with two different antacids for prevention of stress ulceration. Intensive Care Med. 1989;15:84–86. [PubMed] [Google Scholar]
• Razniewska G, Trzcinka-Ochocka M, Gazewski A. Serum aluminum concentration in dialyzed patients. Sixth Keele Meeting on Aluminium; February 26-March 2, 2005; Bussaco, Portugal. 2005. [Google Scholar]
• Recker RR, Blotcky AJ, Leffler JA, Rack EP. Evidence of aluminum absorption from the gastrointestinal tract and bone deposition by aluminum carbonate ingestion with normal renal function. J Lab Clin Med. 1977;90:810–815. [PubMed] [Google Scholar]
• Rees EL. Aluminum toxicity as indicated by hair analysis. J Orthomol Psych. 1979;8:37–43. [Google Scholar]
• Reffitt DM, Jugdaohsingh R, Thompson RP, Powell JJ. Silicic acid: its gastrointestinal uptake and urinary excretion in man and effects on aluminium excretion. J Inorg Biochem. 1999;76:141–147. [PubMed] [Google Scholar]
• Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, Duff K, Pappolla MA. Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis. 2000;7:321–331. [PubMed] [Google Scholar]
• Reiber S, Kukull W, Standish-Lee P. Drinking water aluminum and bioavailability. J Am Water Works Assoc. 1995;87:86–100. [Google Scholar]
• Reid SD, McDonald DG, Rhem RR. Acclimation of sublethal aluminum; modifications of metal-gill surface interactins of juvenile rainbow trout (Oncorhynchus mykiss) Can J Fish Aquat Sci. 1991;48:1996–2005. [Google Scholar]
• Reinke CM, Breitkreutz J, Leuenberger H. Aluminium in over-the-counter drugs: risks outweigh benefits? Drug Saf. 2003;26:1011–1025. [PubMed] [Google Scholar]
• Remillard S, Rebhun LI, Howie GA, Kupchan SM. Antimitotic activity of the potent tumor inhibitor maytanisine. Science. 1975;189:1002–1005. [PubMed] [Google Scholar]
• Renard JL, Felten D, Bequet D. Post-otoneurosurgery aluminum encephalopathy. Lancet. 1994;344:63–64. [PubMed] [Google Scholar]
• Reusche E. Argyrophilic inclusions distinct from Alzheimer neurofibrillary changes in one case of dialysis-associated encephalopathy. Acta Neuropathol. 1997;94:612–616. [PubMed] [Google Scholar]
• Reusche E, Koch V, Friedrich HJ, Nunninghoff D, Stein P, Rob PM. Correlation of drug-related aluminum intake and dialysis treatment with deposition of argyrophilic aluminum-containing inclusions in CNS and in organ systems of patients with dialysis-associated encephalopathy. Clin Neuropathol. 1996;15:342–347. [PubMed] [Google Scholar]
• Reusche E, Koch V, Lindner B, Harrison AP, Friedrich HJ. Alzheimer morphology is not increased in dialysis-associated encephalopathy and long-term hemodialysis. Acta Neuropathol. 2001a;101:211–216. [PubMed] [Google Scholar]
• Reusche E, Pilz P, Oberascher G, Lindner B, Egensperger R, Gloeckner K, Trinka E, Iglseder B. Subacute fatal aluminum encephalopathy after reconstructive otoneurosurgery: a case report. Hum Pathol. 2001b;32:1136–1140. [PubMed] [Google Scholar]
• Riddell AR. Pulmonary changes encountered in employees engaged in the manufacture of alumina abrasives. Occup Med. 1948;5:710–717. [PubMed] [Google Scholar]
• Rifat SL. Cognitive deficit after exposure to McIntyre powder: exposure effect or artifact?. Second international conference on aluminum and health; Tampa, Florida. 1992. [Google Scholar]
• Rifat SL, Eastwood MR, McLachlan DR, Corey PN. Effect of exposure of miners to aluminium powder. Lancet. 1990;336:1162–1165. [PubMed] [Google Scholar]
• Riihimaki V, Hanninen H, Akila R, Kovala T, Kuosma E, Paakkulainen H, Valkonen S, Engstrom B. Body burden of aluminum in relation to central nervous system function among metal inert-gas welders. Scan J Work Environ Health. 2000;26:118–130. [PubMed] [Google Scholar]
• Rimaniol AC, Gras G, Verdier F, Capel F, Grigoriev VB, Porcheray F, Sauzeat E, Fournier JG, Clayette P, Siegrist CA, Dormont D. Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type. Vaccine. 2004;22:3127–3135. [PubMed] [Google Scholar]
• Rob PM, Niederstadt C, Reusche E. Dementia in patients undergoing long-term dialysis: aetiology, differential diagnoses, epidemiology and management. CNS Drugs. 2001;15:691–699. [PubMed] [Google Scholar]
• Roberts NB, Williams P. Silicon measurement in serum and urine by direct current plasma emission spectrometry. Clin Chem. 1990;36:1460–1465. [PubMed] [Google Scholar]
• Roberts NB, Clough A, Bellia JP, Kim JY. Increased absorption of aluminum from a normal dietary intake in dementia. J Inorg Biochem. 1998;69:171–176. [PubMed] [Google Scholar]
• Roberts RJ. Dolomite as a source of toxic metals. N Engl J Med. 1981;304:423. [PubMed] [Google Scholar]
• Robertson JA, Felsenfeld AJ, Haygood CC, Wilson P, Clarke C, Llach F. Animal model of aluminum-induced osteomalacia: role of chronic renal failure. Kidney Int. 1983;23:327–335. [PubMed] [Google Scholar]
• Robertson JA, Salusky IB, Goodman WG, Norris KC, Coburn JW. Sucralfate, intestinal aluminum absorption, and aluminum toxicity in a patient on dialysis. Ann Intern Med. 1989;111:179–181. [PubMed] [Google Scholar]
• Robillard E, Alarie Y. Static volume-pressure relations in guinea pig lungs after inhalation of aluminum or iron oxide particles and bronchodilator aerosols. Can J Biochem Physiol. 1963a;41:461–468. [PubMed] [Google Scholar]
• Robillard E, Alarie Y. Pressure-volume curves in isolated atelectatic rat lungs after aluminum oxide microparticle inhalation. Can J Biochem Physiol. 1963b;41:1257–1265. [PubMed] [Google Scholar]
• Rockette HE, Arena VC. Mortality studies of aluminum reduction plant workers: Potroom and carbon department. J Occup Med. 1983;25:549–557. [PubMed] [Google Scholar]
• Rodella L, Rezzani R, Lanzi R, Bianchi R. Chronic exposure to aluminium decreases NADPH-diaphorase positive neurons in the rat cerebral cortex. Brain Res. 2001;889:229–233. [PubMed] [Google Scholar]
• Rodger RS, Muralikrishna GS, Halls DJ, Henderson JB, Forrest JA, MacDougall AI, Fell GS. Ranitidine suppresses aluminum absorption in man. Clin Sci. 1991;80:505–508. [PubMed] [Google Scholar]
• Rodushkin I, Odman F. Application of ICP-MS for elemental analysis of urine. J Trace Elem Med Biol. 2001;14:241–247. [PubMed] [Google Scholar]
• Rogers MA, Simon DG. A preliminary study of dietary aluminum intake and risk of Alzheimer’s disease. Age Aging. 1999;28:205–209. [PubMed] [Google Scholar]
• Roider G, Drasch G. Concentration of aluminum in human tissues-investigations on an ocupationally non-exposed population in Southern Bavaria (Germany) Trace Elem Electrolytes. 1999;16:77–86. [Google Scholar]
• Roig JL, Fuentes S, Colomina MT, Vicens P, Domingo JL. Aluminum, restraint stress and aging: behavioral effects in rats after 1 and 2 years of aluminum exposure. Toxicology. 2006;218:112–124. [PubMed] [Google Scholar]
• Roit I, Brostoff J, Male D. Vaccination, Immunology. London: Mosby; 1998. [Google Scholar]
• Rollin HB, Nogueira CM. Identification of aluminium fractions in serum using the techniques of high performance liquid chromatography, ultrafiltration and Zeeman atomic absorption spectrometry. Eur J Clin Chem Clin Biochem. 1997;35:215–222. [PubMed] [Google Scholar]
• Rollin HB, Theodorou P, Kilroe-Smith TA. The effect of exposure to aluminium on concentrations of essential metals in serum of foundry workers. Br J Ind Med. 1991a;48:243–246. [PMC free article] [PubMed] [Google Scholar]
• Rollin HB, Theodorou P, Kilroe-Smith TA. Deposition of aluminum in tissues of rabbits exposed to inhalation of low concentrations of Al203 dust. Br J Ind Med. 1991b;48:389–391. [PMC free article] [PubMed] [Google Scholar]
• Rollin HB, Theodorou P, Cantrell AC. Biological indicators of exposure to total and respirable aluminum dust fractions in a primary aluminum smelter. Occup Environ Med. 1996;53:417–421. [PMC free article] [PubMed] [Google Scholar]
• Rollin HB, Theodorou P, Nogueir CM, Levin J. Aluminium uptake and excretion in potroom workers of a new primary aluminium smelter during the construction stage. J Environ Monit. 2001;3:560–564. [PubMed] [Google Scholar]
• Romundstad P, Haldorsen T, Andersen A. Lung and bladder cancer among workers in a Norwegian aluminum reduction plant. Occup Environ Med. 2000a;57:495–499. [PMC free article] [PubMed] [Google Scholar]
• Romundstad P, Andersen A, Haldorsen T. Cancer incidence among workers in six Norwegian aluminum plants. Scand J Work Environ Health. 2000b;26:461–469. [PubMed] [Google Scholar]
• Rondeau V, Commenges D, Jacqmin-Gadda H, Dartigues JF. Relation between aluminum concentrations in drinking water and Alzheimer’s disease: an 8-year follow-up study. Am J Epidemiol. 2000;152:59–66. [PMC free article] [PubMed] [Google Scholar]
• Rondeau V, Jacqmin-Gadda H, Commenges D, Dartiques JF. Aluminum in drinking water and cognitive decline in elderly subjects: the Paquid cohort. Am J Epidemiol. 2001;154:288–290. [PMC free article] [PubMed] [Google Scholar]
• Rondeau V, Iron, Letenneur L, Commenges D, Duchene F, Arveiller B, Dartiques JF. Analysis of the effect of aluminum in drinking water and transferrin C2 allele on Alzheimer’s disease. Eur J Neurol. 2006;13:1022–1025. [PMC free article] [PubMed] [Google Scholar]
• Ronneberg A, Haldorsen T, Romundstad P, Andersen A. Occupational exposure and cancer incidence among workers from an aluminum smelter in western Norway. Scand J Work Environ Health. 1999;25:207–214. [PubMed] [Google Scholar]
• Rosborg I, Nihlgard B, Gerhardsson L, Gernersson ML, Ohlin R, Olsson T. Concentrations of inorganic elements in bottled waters on the Swedish market. Environ Geochem Health. 2005;27:217–227. [PubMed] [Google Scholar]
• Roskams AJ, Connor JR. Aluminum access to the brain: a role for transferrin and its receptor. Proc Natl Acad Sci. 1990;87:9024–9027. [PMC free article] [PubMed] [Google Scholar]
• Ross RA, Takacs A. Heterogeneous reactions of aluminum and copper surfaces with stearic acid. Ind Eng Chem Prod Res Dev. 1983;22:280–286. [Google Scholar]
• Rowland M, Tozer TM. Clinical Pharmacokinetics Concepts and Applications. 3. Philadelphia: Williams & Wilkins, Media; 1995. [Google Scholar]
• Roy AJ, Talukder G, Sharma A. Effects of aluminium sulphate on human leukocyte chromosomes in vitro. Mutat Res. 1990;244:179–183. [PubMed] [Google Scholar]
• Roy AJ, Talukder G, Sharma A. Similar effects in vivo of two aluminum salts on the liver, kidney, bone, and brain of Rattus norvegicus. Bull Environ Contam Toxicol. 1991;47:288–295. [PubMed] [Google Scholar]
• Roy AJ, Dhir H, Sharma A. Modification of metal induced micronuclei formation in mouse bone marrow erythrocytes by Phyllanthus fruit extract and ascorbic acid. Toxicol Lett. 1992;62:9–17. [PubMed] [Google Scholar]
• Roychowdhury M. A review of safety and health hazards of metalorganic compounds. Am Ind Hyg Assoc J. 1993;54:607–614. [Google Scholar]
• RTECS (Registry of Toxic Effects of Chemical Substances) Aluminum oxide. 2006. [online] Cited 24 January 2007 www.cdc.gov/niosh/rtecs/bd124f80.html.
• Rudy D, Sica DA, Comstock T, Davis J, Savory J, Schoolwerth AC. Aluminum-citrate interaction in end-stage renal disease. Int J Artif Organs. 1991;14:625–629. [PubMed] [Google Scholar]
• Ruster M, Abendroth K, Lehmann G, Stein G. Aluminum deposition in the bone of patients with chronic renal failure--detection of aluminum accumulation without signs of aluminum toxicity in bone using acid solochrome azurine. Clin Nephrol. 2002;58:305–312. [PubMed] [Google Scholar]
• Sahin G, Varol I, Temizer A, Benli K, Demirdamar R, Duru S. Determination of aluminum levels in the kidney, liver, and brain of mice treated with aluminum hydroxide. Biol Trace Elem Res. 1994;41:129–135. [PubMed] [Google Scholar]
• Saia B, Cortese S, Piazza G, Camposampietro A, Clonfero E. Chest x-ray findings among aluminium production plant workers. Med Lav. 1981;72:323–329. [PubMed] [Google Scholar]
• Saiyed SM, Yokel RA. Aluminium content of some foods and food products in the USA, with aluminium food additives. Food Addit Contam. 2005;22:234–244. [PubMed] [Google Scholar]
• Sakamoto T, Ogasawara Y, Ishii K, Takahashi H, Tanabe S. Accumulation of aluminum in ferritin isolated from rat brain. Neurosci Lett. 2004;366:264–267. [PubMed] [Google Scholar]
• Sakhaee K, Wabner CL, Zerwekh JE, Copley JB, Pak L, Poindexter JR, Pak CY. Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys. Bone Miner. 1993;20:87–97. [PubMed] [Google Scholar]
• Sakiewicz P, Paganini E. The use of iron in patients on chronic dialysis: mistake and misconceptions. J Nephrol. 1998;11:5–15. [PubMed] [Google Scholar]
• Sakula A. Pneumoconiosis due to Fuller’s earth. Thorax. 1961;16:176–179. [PMC free article] [PubMed] [Google Scholar]
• Salib E, Hillier V. A case-control study of Alzheimer’s disease and aluminum occupation. Br J Psychiatry. 1996;168:244–249. [PubMed] [Google Scholar]
• Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. Fine particulate air pollution and mortality in 20 U.S. cities, 1987-1994. N Engl J Med. 2000;343:1742–1749. [PubMed] [Google Scholar]
• San LN, Uysal H, Gokbel H, Bediz LS, Sayal A. Pulmonary function of workers in the aluminum industry. Am J Ind Med. 1997;33:305–307. [PubMed] [Google Scholar]
• Sanchez DJ, Gómez M, Llobet JM, Corbella J, Domingo JL. Effects of aluminum on the mineral metabolism of rats in relation to age. Pharmacol Toxicol. 1997;80:11–17. [PubMed] [Google Scholar]
• Sanei H, Goodarzi F, Flier-Keller EV. Historical variation of elements with respect to different geochemical fractions in recent sediments from Pigeon Lake, Alberta, Canada. J Environ Monit. 2001;3:27–36. [PubMed] [Google Scholar]
• Santaroni P. Ingestion of aluminum in the diet and evaluation of safety levels in Italy. Rivista di Tossicologia: Sperimentale e Clinica. 1990;20:25–30. [Google Scholar]
• Sanz-Medel A, Cabezuelo ABS, Milacic R, Polak TB. The chemical speciation of auminium in human serum. Coord Chem Rev. 2002;228:373–383. [Google Scholar]
• Saric M, Godnic-Cvar J, Gomzi M, Stillnovic L. The role of atopy in potroom workers asthma. Am J Ind Med. 1986;9:239–242. [PubMed] [Google Scholar]
• Savage J. Proceedings: Aluminium hydroxide granuloma. Proc R Soc Med. 1973;66:984–985. [PMC free article] [PubMed] [Google Scholar]
• Savory J. Iatrogenic aluminum poisoning. Clin Chem. 1994;40:1477–1478. [PubMed] [Google Scholar]
• Savory J, Wills MR. Analysis of aluminum in biological materials. In: Siegel H, Siegel A, editors. Metal Ions in Biological Systems, Vol 24: Aluminum and its Role in Biology. New York: Marcel Dekker; 1988. pp. 347–371. [Google Scholar]
• Savory J, Brown S, Bertholf RL, Mendoza N, Wills MR. Aluminum. Methods Enzymol. 1988;158:289–301. [PubMed] [Google Scholar]
• Savory J, Ghribi O, Forbes MS, Herman MM. Aluminium and neuronal cell injury: inter-relationships between neurofilamentous arrays and apoptosis. J Inorg Biochem. 2001;87:15–19. [PubMed] [Google Scholar]
• Savory J, Herman MM, Ghribi O. Intracellular mechanisms underlying aluminum-induced apoptosis in rabbit brain. J Inorg Biochem. 2003;15:151–154. [PubMed] [Google Scholar]
• Sax NI, Lewis RJ Sr, editors. Hawley’s Condensed Chemical Dictionary. 11. New York, NY: Van Nostrand Reinhold; 1987. pp. 1248–1249. [Google Scholar]
• Schaaper RM, Koplitz RM, Tkeskelashvili LK, Loeb LA. Metal-induced lethality and mutagenesis: possible role of apurinic intermediates. Mutat Res. 1987;177:179–188. [PubMed] [Google Scholar]
• Schijns VE. Immunological concepts of vaccine adjuvant activity. Curr Opin Immunol. 2000;12:456–463. [PubMed] [Google Scholar]
• Schintu M, Meloni P, Contu A. Aluminum fractions in drinking water from reservoirs. Ecotoxicol Environ Saf. 2000;46:29–33. [PubMed] [Google Scholar]
• Schlatter C, Steinegger A. Limitations of biological monitoring of aluminium exposure. Second international conference on aluminum and health; Tampa, Florida. 1992. [Google Scholar]
• Schlatter C, Steinegger A, Rickenbacher U, Hans C, Lengyel A. Aluminum levels in the blood plasma of persons working in the aluminum industry. Environ Geochem Health. 1990;12:59–64. [PubMed] [Google Scholar]
• Schlesinger RB, Snyder CA, Chen LC, Gorchzynski JE, Menarche M. Clearance and translocation of aluminium oxide (alumina) from the lungs. Inhal Toxicol. 2000;12:927–939. [PubMed] [Google Scholar]
• Schmid K, Angerer J, Letzel S, Sturm G, Lehnert G. Use of bone mineral content determination by x-ray absorptiometry in the evaluation of osteodystrophy among workers exposed to aluminum powders. Sci Total Environ. 1995;163:147–151. [PubMed] [Google Scholar]
• Schmidt PF, Zumkley H, Bertram H, Lison A, Winterberg B, Barckhaus R. Localization of aluminum in bone of patients with dialysis osteomalacia. In: Bratter P, Schramel P, editors. Trace Elements-Analytical Chemistry in Medicine and Biology. Vol. 3. New York: Walter de Gruyter & Co; 1984. pp. 475–482. [Google Scholar]
• Schönholzer K, Sutton R, Walker V, Sossi V, Schulzer M, Venczel E, Johnson R, Vetterli D, Dittrich B, Suter M. Is intestinal aluminum absorption enhanced in the renal failure rat? J Am Soc Nephrol. 1992;3:676. abstract. [Google Scholar]
• Schönholzer KW, Sutton RA, Walker VR, Sossi V, Schulzer M, Orvig C, Venczel E, Johnson RR, Vetterli D, Dittrich-Hannen B, Kubik P, Sutter M. Intestinal absorption of trace amounts of aluminium in rats studied with 26aluminium and accelerator mass spectrometry. Clin Sci. 1997;92:379–383. [PubMed] [Google Scholar]
• Schreider JP, Culbertson MR, Raabe OG. Comparative pulmonary fibrogenic potential of selected particles. Environ Res. 1985;38:256–274. [PubMed] [Google Scholar]
• Schroeder HA, Mitchener M. Life-term effects of mercury, methyl mercury, and nine other trace metals on mice. J Nutr. 1975a;105:452–458. [PubMed] [Google Scholar]
• Schroeder HA, Mitchener M. Life-term studies in rats: effects of aluminum, barium, beryllium, and tungsten. J Nutr. 1975b;105:421–427. [PubMed] [Google Scholar]
• Schroeder JC, Tolbert PE, Eisen EA, Monson RR, Hallock MF, Smith TJ, Woskie SR, Hammond SK, Milton DK. Mortality studies of machining fluid exposure in the automobile industry. IV: A case-control study of lung cancer. Am J Ind Med. 1997;31:525–533. [PubMed] [Google Scholar]
• Schulz W, Deuber HJ, Popperl G. On the differential diagnosis and therapy of dialysis osteomalacia under special consideration to a therapy with oral phosphate binders. Trace Elem Med. 1984;1:120–127. [Google Scholar]
• Schuurmans Stekhoven JH, Renkawek K, Otte-Holler I, Stols A. Exogenous aluminum accumulates in the lysosomes of cultured rat cortical neurons. Neurosci Lett. 1990;119:71–74. [PubMed] [Google Scholar]
• Schwarze HP, Giordano-Labadie F, Loche F, Gorguet MB, Bazex J. Delayed-hypersensitivity granulomatous reaction induced by blepharopigmentation with aluminum-silicate. J Am Acad Dermatol. 2000;42:888–891. [PubMed] [Google Scholar]
• Sedman AB, Wilkening GN, Warady BA. Clinical and laboratory observations. Encephalopathy in childhood secondary to aluminum toxicity. J Pediatr. 1984;105:836–838. [PubMed] [Google Scholar]
• Sedman AB, Klein GL, Merritt RJ, Miller NL, Weber KO, Gill WL, Anand H, Alfrey AC. Evidence of aluminum loading in infants receiving intravenous therapy. N Engl J Med. 1985;312:1337–1343. [PubMed] [Google Scholar]
• Sedman AB, Alfrey AC, Miller NL, Goodman WG. Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig. J Clin Invest. 1987;79:86–92. [PMC free article] [PubMed] [Google Scholar]
• Seko Y, Nakamura I, Sugamata M, Nonaka K, Miura T. A possible increase in the concentration of aluminum in the brain of rats infected with Japanese encephalitis virus; an investigation by neutron activation analysis. Igaku to Seibutsugaku. 1986;113:367–370. [Google Scholar]
• Selden AI, Westberg HB, Axelson O. Cancer morbidity in workers at aluminum foundries and secondary aluminum smelters. Am J Ind Med. 1997;32:467–477. [PubMed] [Google Scholar]
• Senitz D, Bluthner K. The presence of aluminum in cerebral vessels in Alzheimer’s disease. Zentralblatt allg Pathology. 1990;136:329–335. [PubMed] [Google Scholar]
• Seo KS, Lee CS. Mutagenicity of metal compounds using Escherichia coli WP2 UVRA. Misaengmul Hakhoechi. 1993;31:527–531. [Google Scholar]
• Shah NR, Oberkircher OR, Lobel JS. Aluminum-induced microcytosis in a child with moderate renal insufficiency. Am J Pediatr Hematol Oncol. 1990;12:77–79. [PubMed] [Google Scholar]
• Sharif AAM, Ghafourian H, Ahmadiniar A, Waqif Husain S, Saber-Tehrani M, Ghods H. Determination of aluminum levels in serum and red blood cells from long-term haemodialysis patients using instrumental neutron activation analysis. J Radioanal Nucl Chem. 2004;262:473–477. [Google Scholar]
• Sharpe FR, Vobe RA, Williams DR. Chemical speciation of aluminum in beers. Chem Spec Bioavail. 1995;7:49–55. [Google Scholar]
• Shaver CG. Pulmonary changes encountered in employees engaged in the manufacture of alumina abrasives. Occup Med. 1948;5:718–728. [PubMed] [Google Scholar]
• Shaver CG, Riddell AR. Lung changes associated with the manufacture of alumina abrasives. J Ind Hyg Toxicol. 1947;29:145–157. [PubMed] [Google Scholar]
• Sherrard DJ, Walker JV, Boykin JL. Precipitation of dialysis dementia by deferoxamine treatment of aluminum-related bone disease. Am J Kidney Dis. 1988;12:126–130. [PubMed] [Google Scholar]
• Sherwin RP, Barman ML, Abraham JL. Silicate pneumoconiosis of farm workers. Lab Invest. 1979;40:576–582. [PubMed] [Google Scholar]
• Shi B, Haug A. Aluminum uptake by neuroblastoma cells. J Neurochem. 1990;55:551–558. [PubMed] [Google Scholar]
• Shi Y, HogenEsch H, Regnier FE, Hem SL. Detoxification of endotoxin by aluminium hydroxide adjuvant. Vaccine. 2001;19:1747–1752. [PubMed] [Google Scholar]
• Shimizu H, Suzuki Y, Takemura N, Goto S, Matsushita H. Results of microbial mutation test for forty-three industrial chemicals. Sangyo Igaku. 1985;27:400–419. [PubMed] [Google Scholar]
• Shimizu H, Mori T, Koyama M, Sekiya M, Ooami H. A correlative study of the aluminum content and aging changes of the brain in non-demented elderly subjects. Nippon Ronen Igakkai Zasshi. 1994;31:950–960. [PubMed] [Google Scholar]
• Shin RW, Lee VM, Trojanowski JQ. Neurofibrillary pathology and aluminum in Alzheimer’s disease. Histol Histopathol. 1995;10:969–978. [PubMed] [Google Scholar]
• Shirley DG, Walter MF, Walter SJ, Thewles A, Lote CJ. Renal aluminium handling in the rat: a micropuncture assessment. Clin Sci. 2004;107:159–165. [PubMed] [Google Scholar]
• Shore D, Wyatt RJ. Aluminum and Alzheimer’s disease. J Nerv Ment Dis. 1983;171:553–558. [PubMed] [Google Scholar]
• Shore D, Sprague SM, Mayor GH, Moreno EC, Apostoles PS, Wyatt RJ. Aluminum-fluoride complexes: preclinical studies. J Environ Pathol Toxicol Oncol. 1985;6:9–13. [PubMed] [Google Scholar]
• Shubik P, Hartwell JL. Survey of compounds which have been tested for carcinogenic activity. 1969;(Suppl 2) U.S. Public Health Service Publication, No. 149. [Google Scholar]
• Siegrist CA. Vaccine adjuvants and macrophagic myofasciitis. Arch Pediatr. 2005;12:96–101. [PubMed] [Google Scholar]
• Sighinolfi GP, Gorgoni C, Bonori O, Cantoni E, Martelli M, Simonetti L. Comprehensive determination of trace elements in human saliva by ETA-AAS. Microchimica Acta. 1989;97:171–179. [Google Scholar]
• Silva VS, Cordeiro JM, Matos MJ, Oliveira CR, Goncalves PP. Aluminum accumulation and membrane fluidity alteration in synaptosomes isolated from rat brain cortex following aluminum ingestion: effect of cholesterol. Neurosci Res. 2002;44:181–193. [PubMed] [Google Scholar]
• Silwood CJ, Grootveld M. Evaluation of the speciation status of aluminium(III) ions in isolated osteoarthritic knee-joint synovial fluid. Biochim Biophys Acta. 2005;1725:327–339. [PubMed] [Google Scholar]
• Sim M, Benke G. World at work: hazards and controls in aluminium potrooms. Occup Environ Med. 2003;60:989–992. [PMC free article] [PubMed] [Google Scholar]
• Simmer K, Fudge A, Teubner J, James SL. Aluminum concentrations in infant formulae. J Paediatr Child Health. 1990;26:9–11. [PubMed] [Google Scholar]
• Simonsson BG, Sjöberg A, Rolf C, Haeger-Aronsen B. Acute and long-term airway hyperreactivity in aluminium-salt exposed workers with nocturnal asthma. Eur J Respir Dis. 1985;66:105–118. [PubMed] [Google Scholar]
• Simonyte S, Cherkashin G, Sadauskiene I, Planciuniene R, Stapulionis R, Ivanov L. Effects of lead and aluminum on the specific immune response of growing mice. Ekologija. 2004;2:16–20. [Google Scholar]
• Sinczuk-Walczak H, Szymczak M, Razniewska G, Matczak W, Szymczak W. Effects of occupational exposure to aluminum on nervous system: clinical and electroencephalographic findings. Int J Occup Med Environ Health. 2003;16:301–310. [PubMed] [Google Scholar]
• Sinigaglia F. The molecular basis of metal recognition by T cells. J Invest Dermatol. 1994;102:398–401. [PubMed] [Google Scholar]
• Sirover MA, Loeb LA. Infidelity of DNA synthesis in vitro: screening for potential metal mutagens or carcinogens. Science. 1976;194:1434–1436. [PubMed] [Google Scholar]
• Sivikova K, Dianovsky J. Sister-chromatid exchanges after exposure to metal-containing emissions. Mutat Res. 1995;327:17–22. [PubMed] [Google Scholar]
• Sjögren B. Occupational aluminum exposure. Neurotoxicology. 2000;21:871. [Google Scholar]
• Sjögren B, Elinder CG. Proposal of a dose-response relationship between aluminium welding fume exposure and effect on the central nervous system. Med Lav. 1992;83:484–488. [PubMed] [Google Scholar]
• Sjögren B, Ulfvarson U. Respiratory symptoms and pulmonary function among welders working with aluminum, stainless steel and railroad tracks. Ulfnd J Work Environ Health. 1985;11:27–32. [PubMed] [Google Scholar]
• Sjögren B, Lundberg I, Lidums V. Aluminium in the blood and urine of industrially exposed workers. Br J Ind Med. 1983;40:301–304. [PMC free article] [PubMed] [Google Scholar]
• Sjögren B, Lidums V, Hakansson M, Hedstrom L. Exposure and urinary excretion of aluminum during welding. Scand J Work Environ Health. 1985;11:39–43. [PubMed] [Google Scholar]
• Sjögren B, Elinder CG, Lidums V, Chang G. Uptake and urinary excretion of aluminum among welders. Int Arch Occup Environ Health. 1988;60:77–79. [PubMed] [Google Scholar]
• Sjögren B, Gustavsson P, Hogstedt C. Neuropsychiatric symptoms among welders exposed to neurotoxic metals. Br J Ind Med. 1990;47:704–707. [PMC free article] [PubMed] [Google Scholar]
• Sjögren B, Iregren A, Frechn W, Hagman M, Johansson L, Tesarz M, Wennberg A. Effects on the nervous system among welders exposed to aluminum and maganese. Occup Environ Med. 1996a;53:32–40. [PMC free article] [PubMed] [Google Scholar]
• Sjögren B, Ljunggren KG, Almkvist O, Frech W, Basun H. A follow-up study of five cases of aluminosis. Int Arch Occup Environ Health. 1996b;68:161–164. [PubMed] [Google Scholar]
• Sjögren B, Elinder CG, Iregren A, McLachlan DRC, Riihimaki V. Occupational aluminum exposure and its health effects. In: Yokel RA, Golub MS, editors. Aluminum Toxicity. Washington DC.: Taylor & Francis; 1997. pp. 165–183. [Google Scholar]
• Skaugset NP, Elingsen DG, Jordbekken L, Notø H, Thomassen Y. Measurement strategies for peak exposure to gases and aerosols. Abstract 0-60, Fifth International Symposium on Modern Principles of Air Monitoring (Including Biomonitoring), Airmon 2005; Loen, Norway. 2005. [Google Scholar]
• Skelton HG, 3rd, Smith KJ, Johnson FB, Cooper CR, Tyler WF, Lupton GP. Zirconium granuloma resulting from an aluminum zirconium complex: a previously unrecognized agent in the development of hypersensitivity granulomas. J Am Acad Dermatol. 1993;28:874–876. [PubMed] [Google Scholar]
• Skowron F, Grezard P, Berard F, Balme B, Perrot H. Persistent nodules at sites of hepatitis B vaccination due to aluminium sensitization. Contact Dermatitis. 1998;39:135–136. [PubMed] [Google Scholar]
• Slanina P, Falkeborn Y, Frech W, Cedergren A. Aluminium concentrations in the brain and bone of rats fed citric acid, aluminium citrate or aluminium hydroxide. Food Chem Toxicol. 1984;22:391–397. [PubMed] [Google Scholar]
• Slanina P, Frech W, Bernhardson A, Cedergren A, Mattsson P. Influence of dietary factors on aluminium absorption and retention in the brain and bone of rats. Acta Pharmacol Toxicol. 1985;56:331–336. [PubMed] [Google Scholar]
• Slanina P, Frech W, Ekström LG, Lööf L, Slorach S, Cedergren A. Dietary citric acid enhances absorption of aluminium in antacids. Clin Chem. 1986;32:539–541. [PubMed] [Google Scholar]
• Slater DN, Underwood JC, Durrant TE, Gray T, Hopper IP. Aluminium hydroxide granulomas: light and electron microscopic studies and X-ray microanalysis. Br J Dermatol. 1982;107:103–108. [PubMed] [Google Scholar]
• Sleppy WC. Aluminum compounds. In: Kroschwitz JI, Howe-Grant M, editors. Kirk-Othmer Encylopedia of Chemical Technology. Vol. 2. New York: John Wiley & Sons; 1992. pp. 252–267. [Google Scholar]
• Smans KA, D’Haese PC, Van Landeghem GF, Andries LJ, Lamberts LV, Hendy GN, De Broe ME. Transferrin-mediated uptake of aluminium by human parathyroid cells results in reduced parathyroid hormone secretion. Nephrol Dial Transplant. 2000;15:1328–1336. [PubMed] [Google Scholar]
• Smichowski P, Gomez DR, Dawidowski LE, Gine MF, Bellato AC, Reich SL. Monitoring trace metals in urban aerosols from Buenos Aires city. Determination by plasma-based techniques. J Environ Monit. 2004;6:286–294. [PubMed] [Google Scholar]
• Smith CC, Hyatt PJ, Stanyer L, Betteridge DJ. Platelet secretion of beta-amyloid is increased in hypercholesterolaemia. Brain Res. 2001;896:161–164. [PubMed] [Google Scholar]
• Smith GD, Winney RJ, McLean A, Robson JS. Aluminium-related osteomalacia: response to reverse osmosis water treatment. Kidney Int. 1987;32:96–101. [PubMed] [Google Scholar]
• Smith PS, McClure J. Localization of aluminum by histochemical and electron probe x-ray microanalytical techniques in bone tissue of cases of renal osteodystrophy. J Clin Pathol. 1982;35:1283–1293. [PMC free article] [PubMed] [Google Scholar]
• Smith Q, Mori H, Swyt C, Atack J, Rapoport S. Electron probe microanalysis of aluminum and silicon in Alzheimer’s disease senile palques using unfixed, unstained tissue. Aluminum Association. Aluminum and Health, 2 nd International Conference; Tampa, Florida. 1992. [Google Scholar]
• Smith Q, Deng Q, Brady D, Swyt C, Nguyen J, Gillen G. Aluminum localization and analysis in stained and unstained human brain tissue using X-ray microanalysis and secondary ion mass spectrometry. Aluminum Association. Aluminum and Health, 3 rd International Conference; Miami, Florida. 1994. [Google Scholar]
• Snipes MB, Boecker BB, McClellan RO. Retention of monodisperse or polydisperse aluminosilicate particles inhaled by dogs, rats, and mice. Toxicol Appl Pharmacol. 1983;69:345–362. [PubMed] [Google Scholar]
• Sohn SJ, Shin JH, Park YS, Rhee JA, Choi JS. Components of drinking water and risk of cognitive impairment in the rural elderly. Chonnam J Med Sci. 1996;9:189–193. [Google Scholar]
• Solfrizzi V, Panza F, Capurso A. The role of diet in cognitive decline. J Neural Transm. 2003;110:95–110. [PubMed] [Google Scholar]
• Soliman K, Zikovsky L. Concentrations of Al in food sold in Montreal, Canada, and its daily dietary intake. J Radioanal Nucl Chem. 1999;242:807–809. [Google Scholar]
• Soni MG, White SM, Flamm WG, Burdock GA. Safety evaluation of dietary aluminum. Regul Toxicol Pharmacol. 2001;33:66–79. [PubMed] [Google Scholar]
• Sorgdrager B, Pal TM, de Looff AJ, Dubois AE, de Monchy JG. Occupational asthma in aluminium potroom workers related to pre-employment eosinophil count. Eur Respir J. 1995;8:1520–1524. [PubMed] [Google Scholar]
• Sorgdrager B, de Looff AJ, de Monchy JG, Pal TM, Dubois AE, Rijcken B. Occurrence of occupational asthma in aluminum potroom workers in relation to preventive measures. Int Arch Occup Environ Health. 1998;71:53–59. [PubMed] [Google Scholar]
• Søyseth V, Kongerud J. Prevalence of respiratory disorders among aluminum potroom workers in relation to exposure to fluoride. Br J Ind Med. 1992;49:125–130. [PMC free article] [PubMed] [Google Scholar]
• Søyseth V, Kongerud J, Kjuus H, Boe J. Bronchial responsiveness and decline in FEV in aluminum potroom workers. Eur Resp J. 1994;7:888–894. [PubMed] [Google Scholar]
• Søyseth V, Kongerud J, Aalen OO, Botten G, Boe J. Bronchial responsiveness decreases in relocated aluminum potroom workers compared with workers who continue their potroom exposure. Int Arch Occup Environ Health. 1995;67:53–57. [PubMed] [Google Scholar]
• Søyseth V, Kongerud J, Boe J. Increased variability in bronchial responsiveness in aluminum potroom workers with work-related asthma-like symptoms. Occup Environ Med. 1996;38:66–69. [PubMed] [Google Scholar]
• Søyseth V, Boe J, Kongerud J. Relation between decline in FEV1 and exposure to dust and tobacco smoke in aluminum potroom workers. Occup Environ Med. 1997;54:27–31. [PMC free article] [PubMed] [Google Scholar]
• Sparkman DR. X-ray probe microanalysis of Alzheimer disease soluble and insoluble paired helical filaments. Neurosci Lett. 1993;151:153–157. [PubMed] [Google Scholar]
• Spencer H, Kramer L. Osteoporosis: calcium, fluoride, and aluminum interactions. J Am Coll Nutr. 1985;4:121–128. [PubMed] [Google Scholar]
• Spencer H, Lender M. Adverse effects of aluminum-containing antacids on mineral metabolism. Gastroenterology. 1979;76:603–606. [PubMed] [Google Scholar]
• Spencer H, Kramer L, Norris C, Wiatrowski E. Effect of aluminum hydroxide on fluoride metabolism. Clin Pharmacol Therap. 1980a;28:529–535. [PubMed] [Google Scholar]
• Spencer H, Kramer L, Osis D, Wiatrowski E, Norris C, Lender M. Effect of calcium, phosphorus, magnesium, and aluminum on fluoride metabolism in man. Ann N Y Acad Sci. 1980b;355:181–194. [PubMed] [Google Scholar]
• Spencer H, Kramer L, Norris C, Wiatrowski E. Effect of aluminum hydroxide on plasma fluoride and fluoride excretion during a high fluoride intake in man. Toxicol Appl Phamacol. 1981;58:140–144. [PubMed] [Google Scholar]
• Spencer H, Kramer L, Osis D, Wiatrowski E. Effects of aluminum hydroxide on fluoride and calcium metabolism. J Environ Pathol Toxicol Oncol. 1985;6:33–41. [PubMed] [Google Scholar]
• Spencer PS. Aluminum and its compounds. In: Spencer PS, Schaumburg HH, editors. Experimental and Clinical Neurotoxicology. New York: Oxford University Press; 2000. pp. 142–151. [Google Scholar]
• Speziali M, Orvini E. Metals distribution and regionalization in the brain. In: Zatta P, editor. Metal Ions and Neurodegenerative Disorders. Singapore: World Scientific Publishing Co. Pte. Ltd; 2003. pp. 15–65. [Google Scholar]
• Spinelli JJ, Band PR, Svirchev LM, Gallagher RP. Mortality and cancer incidence in aluminum reduction plant workers. J Occup Med. 1991;33:1150–1155. [PubMed] [Google Scholar]
• Spotheim-Maurizot M, Garnier F, Sabattier R, Charlier M. Metal ions protect DNA against strand breakage induced by fast neutrons. Int J Radiat Biol. 1992;62:659–666. [PubMed] [Google Scholar]
• Sreekumaran E, Ramakrishna T, Madhav TR, Anandh D, Prabhu BM, Sulekha S, Bindu PN, Raju TR. Loss of dendritic connectivity in CA1, CA2, and CA3 neurons in hippocampus in rat under aluminum toxicity: antidotal effect of pyridoxine. Brain Res Bull. 2003;59:421–427. [PubMed] [Google Scholar]
• Srivastava RA, Jain JC. Scavenger receptor class B type I expression and elemental analysis in cerebellum and parietal cortex regions of the Alzheimer’s disease brain. J Neurol Sci. 2002;196:45–52. [PubMed] [Google Scholar]
• Stables GI, Forsyth A, Lever RS. Patch testing in children. Contact Dermatitis. 1996;34:341–344. [PubMed] [Google Scholar]
• Stacy BD, King EJ, Harrison CV, Nagelschmidt G, Nelson S. Tissue changes in rats’ lungs caused by hydroxides, oxides and phosphates of aluminium and iron. J Pathol Bacteriol. 1959;77:417–426. [PubMed] [Google Scholar]
• Staley JT, Haupin W. Aluminum and aluminum alloys. In: Kroschwitz JI, Howe-Grant M, editors. Kirk-Othmer Encyclopedia of Chemical Technology. Vol. 2. New York: John Wiley & Sons; 1992. [Google Scholar]
• Stanton MF. Fiber carcinogenesis: is asbestos the only hazard? J Natl Cancer Inst. 1974;52:633–634. [PubMed] [Google Scholar]
• Stauber JL, Florence TM, Davies CM, Adams MS, Buchanan SJ. Bioavailability of Al in alum-treated drinking water. J Am Water Works Assoc. 1999;91:84–93. [Google Scholar]
• Steel M. On the absorption of aluminium from aluminized food. Am J Physiol. 1911;28:94–102. [Google Scholar]
• Steinhagen WH, Cavender FL, Cockrell BY. Six month inhalation exposures of rats and guinea pigs to aluminum chlorhydrate. J Environ Pathol Toxicol. 1978;1:267–277. [PubMed] [Google Scholar]
• Steinhausen C, Kislinger G, Winklhofer C, Beck E, Hohl C, Nolte E, Ittel TH, Alvarez-Bruckmann MJ. Investigation of the aluminium biokinetics in humans: a 26Al tracer study. Food Chem Toxicol. 2004;42:363–371. [PubMed] [Google Scholar]
• Stenback F, Ferrero A, Shubik P. Synergistic effects of diethylnitrosamine and different dusts on respiratory carcinogenesis in hamsters. Cancer Res. 1973;33:2209–2214. [PubMed] [Google Scholar]
• Stern AJ, Perl DP, Munoz-Garcia D, Good PF, Abraham C, Selkoe DJ. Investigation of silicon and aluminum content in isolated senile plaque cores by laser microprobe mass analysis (LAMMA) J Neuropathol Exp Neurol. 1986;45:361. [Google Scholar]
• Stevens BJ, Willis GL, Humphrey TJ, Atkins RC. Combined toxicity of aluminum and fluoride in the rat: possible implications in hemodialysis. Trace Elem Med. 1987;4:61–66. [Google Scholar]
• Stevens RK, Dzubay TG, Russwurm G, Rickel D. Sampling and analysis of atmospheric sulfates and related species. Atmos Environ. 1978;12:55–68. [Google Scholar]
• Stitch SR. Trace elements in human tissue. I. A semi-quantitative spectrographic survey. Biochem J. 1957;67:97–103. [PMC free article] [PubMed] [Google Scholar]
• Stone CJ, McLaurin DA, Steinhagen WH, Cavender FL, Haseman JK. Tissue deposition patterns after chronic inhalation exposures of rats and guinea pigs to aluminum chlorhydrate. Toxicol Appl Pharmacol. 1979;49:71–76. [PubMed] [Google Scholar]
• Straif K, Baan R, Gross Y, Secretan B, El Ghissassi F, Cogliano V. on behalf of the WHO International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of polycyclic aromatic hydrocarbons. Lancet Oncol. 2005;6:931–932. [PubMed] [Google Scholar]
• Struys-Ponsar C, Kerkhofs A, Gauthier A, Soffie M, van den Bosch de Aguilar P. Effects of aluminum exposure on behavioral parameters in the rat. Pharmacol Biochem Behav. 1997;56:643–648. [PubMed] [Google Scholar]
• Stumm W, Morgan JJ. Aquatic Chemistry: Chemical Equilibria and Rates in Natural Waters. New York: John Wiley & Sons, Inc; 1996. [Google Scholar]
• Suarez-Fernandez MB, Soldado AB, Sanz-Medel A, Vega JA, Novelli A, Fernandez-Sanchez MT. Aluminum-induced degeneration of astrocytes occurs via apoptosis and results in neuronal death. Brain Res. 1999;835:125–136. [PubMed] [Google Scholar]
• Subra JF, Krari N, Tirot P, Mauras Y, Balit G, Van-Weydevelt FC, Allain P. Aluminum determination in the skin of patients with and without end-stage renal failure. Nephron. 1991;58:170–173. [PubMed] [Google Scholar]
• Suga C, Ikezawa Z. Porphyria cutanea tarda in hemodialyzed patients. Nippon Rinsho. 1995;53:1484–1490. [PubMed] [Google Scholar]
• Sugawara C, Sugawara N, Kiyosawa H, Miyake H. Decrease of serum triglyceride in normal rat fed with 2000 ppm aluminum diet for 67 days. II. Feeding young and adult rats a sucrose diet with addition of aluminum hyroxide and aluminum potassium sulfate. Fundam Appl Toxicol. 1988;10:616–623. [PubMed] [Google Scholar]
• Sunami K, Yamadroi I, Kishimoto T, Ozaki S, Kawabata Y. Unilateral mixed-dust pneumoconiosis with aluminum deposition associated with interstitial pneumonia. Nihon Kyobu Shikkan Gakkai Zasshi. 1997;35:189–195. [PubMed] [Google Scholar]
• Sutherland JE, Greger JL. Kinetics of aluminum disposition after ingestion of low to moderate pharmacological doses of aluminum. Toxicology. 1998;126:115–125. [PubMed] [Google Scholar]
• Sutherland JE, Radzanowski GM, Greger JL. Bile is an important route of elimination of ingested aluminum by conscious male Sprague-Dawley rats. Toxicology. 1996;109:101–109. [PubMed] [Google Scholar]
• Suwalsky M, Norris B, Villena F, Cuevas F, Sotomayor P, Zatta P. Aluminum fluoride affects the structure and functions of cell membranes. Food Chem Toxicol. 2004;42:925–933. [PubMed] [Google Scholar]
• Suzuki Y, Kohyama N. Malignant mesothelioma induced by asbestos and zeolite in the mouse peritoneal cavity. Environ Res. 1984;35:277–292. [PubMed] [Google Scholar]
• Swartz R, Dombrouski J, Burnatowska-Hledin M, Mayor G. Microcytic anemia in dialysis patients: reversible marker of aluminum toxicity. Am J Kidney Dis. 1987;9:217–223. [PubMed] [Google Scholar]
• Swensson A, Nordenfelt O, Forssman S, Lundgren KD, Öhman H. Aluminum dust pneumoconiosis: A clinical study. Int Arch Gewerbepathol Gewerbehyg. 1962;19:131–148. [Google Scholar]
• Swegert CV, Dave KR, Katyare SS. Effect of aluminum induced Alzheimer’s like condition on oxidative energy metabolism in rat liver, brain and heart mitochondria. Mech Ageing Dev. 1999;112:27–42. [PubMed] [Google Scholar]
• Sykes SE, Morgan A, Evans JC, Evans N, Holmes A, Moores SR. Use of an in vivo test system to investigate the acute and subacute responses of the rat lung to mineral dusts. Ann Occup Hyg. 1982;26:593–605. [PubMed] [Google Scholar]
• Szerdahelyi P, Kasa P. Intraventricular administration of the cholinotoxin AF64A increases the accumulation of aluminum in the rat parietal cortex and hippocampus, but not in the frontal cortex. Brain Res. 1988;444:356–360. [PubMed] [Google Scholar]
• Szutowicz A. Aluminum, NO, and nerve growth factor neurotoxicity in cholinergic neurons. J Neurosci Res. 2001;66:1009–1018. [PubMed] [Google Scholar]
• Takagi A, Sai K, Umemura T, Hasegawa R, Kurokawa K. Relationship between hepatic peroxisome proliferation and 8-hydroxydeoxyguanosine formation in liver DNA of rats following long-term exposure to three peroxisome proliferators; di(2-ethylhexyl)phthalate, aluminium clofibrate and simfibrate. Cancer Lett. 1990;53:33–38. [PubMed] [Google Scholar]
• Takahashi S, Takahashi I, Sato H, Kubota Y, Yoshida S, Muramatsu Y. Age-related changes in the concentrations of major and trace elements in the brain of rats and mice. Biol Trace Elem Res. 2001;80:145–158. [PubMed] [Google Scholar]
• Talbot RJ, Newton D, Priest ND, Austin JG, Day JP. Inter-subject variability in the metabolism of aluminium following intravenous injection as citrate. Hum Exp Toxicol. 1995;14:595–599. [PubMed] [Google Scholar]
• Tamada T. Fluorimetric determination of aluminum in human serum and whole blood. Bunseki Kagaku. 2004;53:435–440. [Google Scholar]
• Tanaka A. Toxicity of indium arsenide, gallium arsenide, and aluminium gallium arsenide. Toxicol Appl Pharmacol. 2004;198:405–411. [PubMed] [Google Scholar]
• Tanaka I, Matsuno K, Kodama Y, Akiyama T. Pulmonary deposition of a fly ash aerosol by inhalation. J UOEH. 1983;5:423–431. [PubMed] [Google Scholar]
• Taneda M. Effect of aluminum on rat brain. Enhancement by calcium deficiency. Hokkaido Igaku Zasshi. 1984;59:312–337. [PubMed] [Google Scholar]
• Tang S, Parsons PJ, Slavin W. Effect of acids, modifiers and chloride on the atomization of aluminum in electrothermal atomic absorption spectrometry. J Anal At Spectrom. 1995;10:521–526. [Google Scholar]
• Tatrai E, Adamis Z, Timar M, Ungvary G. Comparative histopathological and biochemical analysis of early stages of exposure to non-silicogenic aluminium silicate- and strongly silicogenic quartz-dust in rats. Exp Pathol. 1983;23:163–171. [PubMed] [Google Scholar]
• Tatrai E, Ungvary G, Adamis Z, Timar M. Short term in vivo method for prediction of the fibrogenic effect of different mineral dusts. Exp Pathol. 1985;28:111–118. [PubMed] [Google Scholar]
• Tatrai E, Wojnarovits I, Ungvary G. Non-fibrous zeolite induced experimental pneumoconiosis in rats. Exp Pathol. 1991;43:41–46. [PubMed] [Google Scholar]
• Taylor A, Walker AW. Measurement of aluminum in clinical samples. Ann Clin Biochem. 1992;29:377–389. [PubMed] [Google Scholar]
• Taylor GA, Ferrier IN, McLoughlin IJ, Fairbairn AF, McKeith IG, Lett D, Edwardson JA. Gastrointestinal absorption of aluminium in Alzheimer’s disease: Response to aluminium citrate. Age Aging. 1992;21:81–90. [PubMed] [Google Scholar]
• Taylor GA, Newens AJ, Edwardson JA, Kay DW, Forster DP. Alzheimer’s disease and the relationship between silicon and aluminium in water supplies in northern England. J Epidemiol Community Health. 1995;49:323–324. [PMC free article] [PubMed] [Google Scholar]
• Taylor GA, Moore PB, Ferrier IN, Tyrer SP, Edwardson JA. Gastrointestinal absorption of aluminium and citrate in man. J Inorg Biochem. 1998;69:165–169. [PubMed] [Google Scholar]
• Teagarden DL, Radavich JF, White JL, Hem SL. Aluminum chlorohydrate II: Physicochemical properties. J Pharm Sci. 1981;70:762–764. [PubMed] [Google Scholar]
• Templeton DM, Ariese F, Cornelis R, Danielsson LG, Muntau H, van Leeuwen HP, Lobinski R. Guidelines for terms related to chemical speciation and fractionation of elements. Definitions, structural aspects, and methodological approaches (IUPAC recommendations 2000) Pure Appl Chem. 2000;72:1453–1470. [Google Scholar]
• Teraoka H. Distribution of 24 elements in the internal organs of normal males and metallic workers in Japan. Arch Environ Health. 1981;36:155–165. [PubMed] [Google Scholar]
• Teraoka H, Morii F, Kobayashi J. The concentrations of 24 elements in foodstuffs and the estimate of their daily intake. J Jap Soc Nutr Food Sci. 1981;34:221–239. [Google Scholar]
• Tercedor J, Lopez-Hernandez B, Rodenas JM. Bullous dermatosis of end-stage renal disease and aluminium. Nephrol Dial Transplant. 1997;12:1083. [PubMed] [Google Scholar]
• Terry RD, Pena C. Experimental production of neurofibrillary degeneration. 2. Electron microscopy, phosphatase histochemistry, and electron probe analysis. J Neuropathol Exp Neurol. 1965;24:200–210. [PubMed] [Google Scholar]
• Testolin G, Erba D, Ciappellano S, Bermano G. Influence of organic acids on aluminium absorption and storage in rat tissues. Food Addit Contam. 1996;13:21–27. [PubMed] [Google Scholar]
• The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 13. Whitehouse Station, NJ: Merck & Co., Inc; 2001. [Google Scholar]
• Thierry-Carstensen B, Stellfeld M. Itching nodules and hypersensitivity to aluminium after the use of adsorbed vaccines from SSI. Vaccine. 2004;22:1845. [PubMed] [Google Scholar]
• Thomas P, Barnstorf S, Summer B, Willmann G, Przybilla B. Immuno-allergological properties of aluminium oxide (Al2O3) ceramics and nickel sulfate in humans. Biomaterials. 2003;24:959–966. [PubMed] [Google Scholar]
• Thomassen Y, Koch W, Dunkhorst W, Ellingsen DG, Skaugset NP, Jordbekken L, Arne Drabløs P, Weinbruch S. Ultrafine particles at workplaces of a primary aluminium smelter. J Environ Monit. 2006;8:127–133. [PubMed] [Google Scholar]
• Thomson SM, Burnett DC, Bergmann JD, Hixson CJ. Comparative inhalation hazards of aluminum and brass powders using bronchopulmonary lavage as an indicator of lung damage. J Appl Toxicol. 1986;6:197–209. [PubMed] [Google Scholar]
• Thorne BM, Donohoe T, Lin KN, Lyon S, Mederios DM, Weaver ML. Aluminum ingestion and behavior in the Long-Evans rat. Physiol Behav. 1986;36:63–67. [PubMed] [Google Scholar]
• Thurston H, Gilmore GR, Swales JD. Aluminium retention and toxicity in chronic renal failure. Lancet. 1972;1:881–883. [PubMed] [Google Scholar]
• Tielemans C, Collart F, Wens R, Smeyers-Verbeeke J, van Hoff I, Dratwa M, Verbeelen D. Improvement of anemia with deferoxamine in hemodialysis patients with aluminum-induced bone disease. Clin Nephrol. 1985;24:237–241. [PubMed] [Google Scholar]
• Tikhov SF, Potapova YV, Sadykov VA, Fenelonov VB, Tsybulya SV, Salanov AN, Ivanov VP, Kolomiichuk VN. Porous Al2O3 /Al metal ceramics prepared by the oxidation of aluminum powder under hydrothermal conditions followed by thermal dehydration: III. The reactivity of aluminum, the reaction mechanism of its oxidation with water vapour, and the microtexture of cermets. Kinet Catal. 2003;44:297–308. [Google Scholar]
• Tipper JL, Hatton A, Nevelos JE, Ingham E, Doyle C, Streicher R, Nevelos AB, Fisher J. Alumina-alumina artificial hip joints. Part II: characterization of the wear debris from in vitro hip joint simulations. Biomaterials. 2002;23:3441–3448. [PubMed] [Google Scholar]
• Tipton IH, Shafer JJ. Statistical analysis of lung trace element levels. Arch Environ Health. 1964;8:58–67. [PubMed] [Google Scholar]
• Tipton IH, Stewart PL, Martin PG. Trace elements in diets and excretia. Health Phys. 1966;12:1683–1689. [Google Scholar]
• Tjälve H, Henriksson J. Uptake of metals in the brain via olfactory pathways. Neurotoxicology. 1999;20:181–195. [PubMed] [Google Scholar]
• Tjälve H, Henriksson J, Tallkvist J, Larsson BS, Lindquist NG. Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. Pharmacol Toxicol. 1996;79:347–356. [PubMed] [Google Scholar]
• Tokutake S, Nagase H, Morisaki S, Oyanagi S. Aluminium detected in senile plaques and neurofibrillary tangles is contained in lipofuscin granules with silicon, probably as aluminosilicate. Neurosci Lett. 1995;185:99–102. [PubMed] [Google Scholar]
• Topi GC, Alessandro GL, Cancarini GC, De Costanza F, Griso D, Ravelli M. Porphyria cutanea tarda in a haemodialysed patient. Br J Dermatol. 1981;104:579–580. [PubMed] [Google Scholar]
• Tornling G, Blaschke E, Eklund A. Long term effects of alumina on components of bronchioalveolar lavage fluid from rats. Br J Ind Med. 1993;50:172–175. [PMC free article] [PubMed] [Google Scholar]
• Tosti A, Vincenzi C, Peluso AM. Accidental diagnosis of aluminium sensitivity with Finn Chambers. Contact Dermatitis. 1990;23:48–49. [PubMed] [Google Scholar]
• Townsend MC, Enterline PE, Sussman NB, Bonney TB, Rippey LL. Pulmonary function in relation to total dust exposure at a bauxite refinery and alumina-based chemical products plant. Am Rev Respir Dis. 1985;132:1174–1180. [PubMed] [Google Scholar]
• Trapp GA, Miner GD, Zimmermann RL, Mastri AR, Heston LL. Aluminum levels in brain in Alzheimer’s disease. Biol Psychiatry. 1978;13:709–718. [PubMed] [Google Scholar]
• Traub RD, Rains TC, Garruto RM, Gajdusek DC, Gibbs CJ., Jr Brain destruction alone does not elevate brain aluminum. Neurology. 1981;31:986–990. [PubMed] [Google Scholar]
• Trentini PL, Ascanelli M, Zanforlini B, Venturini F, Buci G, Fagioli F. Determination of aluminium by inductively coupled plasma mass spectrometry in serum of patients treated by haemodialysis, dialysis solutions and tap water, and a comparison with atomic absorption spectrometry. J Anal At Spectrom. 1993;8:905–909. [Google Scholar]
• Tripathi RM, Mahapatra S, Raghunath R, Vinod Kumar A, Sadasivan S. Daily intake of aluminium by adult population of Mumbai, India. Sci Total Environ. 2002;299:73–77. [PubMed] [Google Scholar]
• Trollfors B, Bergfors E, Inerot A. Vaccine related itching nodules and hypersensitivity to aluminium. Vaccine. 2005;23:975–976. [PubMed] [Google Scholar]
• Trunov MA, Schoenitz M, Zhu X, Dreizin EL. Effect of polymorphic phase transformations in Al2O3 film on oxidation kinetics of aluminum powders. Combust Flame. 2005;140:310–318. [Google Scholar]
• Trzcinka-Ochocka M, Razniewska G, Sinczuk-Walczak H, Gazewski A. Urinary aluminum levels of workers in the aluminium foundry. Sixth Keele Meeting on Aluminium; February 26-March 2, 2005; Bussaco, Portugal. 2005. [Google Scholar]
• Tsou VM, Young RM, Hart MH, Vanderhoof JA. Elevated plasma aluminum levels in normal infants receiving antacids containing aluminum. Pediatrics. 1991;87:148–151. [PubMed] [Google Scholar]
• Tsukamoto Y, Iwanami S, Marumo F. Study of trace elements in patients with chronic renal failure by neutron activation analysis. Proc Eur Dial Transplant Assoc. 1979;16:665–667. [PubMed] [Google Scholar]
• Tsunoda M, Sharma RP. Modulation of tumor necrosis factor alpha expression in mouse brain after exposure to aluminum in drinking water. Arch Toxicol. 1999;73:419–426. [PubMed] [Google Scholar]
• Turgut G, Kaptanoglu B, Turgut S, Enli Y, Genc O. Effects of chronic aluminum administration on blood and liver iron-related parameters in mice. Yonsei Med J. 2004;45:135–139. [PubMed] [Google Scholar]
• Turk JL, Heather CJ. A histological study of lymph nodes during the development of delayed hypersensitivity to soluble antigens. Int Arch Allergy Appl Immunol. 1965;27:199–212. [PubMed] [Google Scholar]
• Turk JL, Parker D. Granuloma formation in normal guinea pigs injected intradermally with aluminum and zirconium compounds. J Invest Dermatol. 1977;68:336–340. [PubMed] [Google Scholar]
• Turner DR. Problems in trace metal speciation modeling. In: Tessier A, Turner DR, editors. Metal Speciation and Bioavailability in Aquatic Systems. Chichester, England: John Wiley & Sons; 1995. pp. 149–203. [Google Scholar]
• Turnquest EM, Hallenbeck WH. Blood aluminum levels as a function of aluminum intake from drinking water. Bull Environ Contam Toxicol. 1991;46:554–560. [PubMed] [Google Scholar]
• Tytgat GN, Heading RC, Muller-Lissner S, Kamm MA, Scholmerich J, Berstad A, Fried A, Chaussade S, Jewell D, Briggs A. Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting. Aliment Pharacol Ther. 2003;18:291–301. [PubMed] [Google Scholar]
• Ueda M, Mizoi Y, Maki Z, Maeda R, Takada R. A case of aluminum dust lung: A necropsy report. Kobe J Med Sci. 1958;4:91–99. [Google Scholar]
• Uemura E. Intranuclear aluminum accumulation in chronic animals with experimental neurofibrillary changes. Exp Neurol. 1984;85:10–18. [PubMed] [Google Scholar]
• Uitti RJ, Rajput AH, Rozdilsky B, Bickis M, Wollin T, Yuen WK. Regional metal concentrations in Parkinson’s disease, other chronic neurological diseases, and control brains. Can J Neurol Sci. 1989;16:310–314. [PubMed] [Google Scholar]
• Ulfvarson U, Wold S. Trace-element concentrations in blood samples from welders of stainless steel or aluminium and a reference group. Scand J Work Environ Health. 1977;3:183–191. [PubMed] [Google Scholar]
• Umemura T, Sai K, Takagi A, Hasegawa R, Kurokawa Y. Formation of 8-hydroxydeoxyguanosine (8-OH-dG) in rat kidney DNA after intraperitoneal administration of ferric nitrilotriacetate (Fe-NTA) Carcinogenesis. 1990;11:345–347. [PubMed] [Google Scholar]
• Underhill FP, Peterman FI, Steel SL. Studies in the metabolism of aluminium. IV. The fate of intravenously injected aluminium. Am J Physiol. 1929;90:52–61. [Google Scholar]
• US FDA (US Food and Drug Administration) Aluminum in large and small volume parenterals used in total parenteral nutrition. Code of Federal Regulations, Vol 21CFR201.323 [Docket No 90N-056] and Fed Regist 1998. 2000;63:176–185. [Google Scholar]
• USGS (US Geological Survey) US Geological Survey Minerals Yearbook: Aluminum. 1997. [online] Cited 24 January 2007 http://minerals.er.usgs.gov/minerals/pubs/commodity/aluminum/050497 pdf.
• USGS (US Geological Survey) US Geological Survey Minerals Yearbook: Bauxite and Alumina. 2002. [online] Cited 24 January 2007 http://minerals.usgs.gov/minerals/pubs/commodity/bauxite/bauximyb02 pdf.
• USGS (US Geological Survey) US Geological Survey Minerals Yearbook: Aluminum. 2004. [online] Cited 24 January 2007 http://minerals.usgs.gov/minerals/pubs/commodity/aluminum/alumimyb 04.pdf.
• USGS (US Geological Survey) Mineral Commodity Summaries. 2005a. [online] Cited 24 January 2007 http://minerals.usgs.gov/minerals/pubs/commodity/bauxite/bauximcs05 pdf.
• USGS (US Geological Survey) US Geological Survey Minerals Yearbook: Bauxite & Alumina. 2005b. [online] Cited 24 January 2007 http://minerals.usgs.gov/minerals/pubs/commodity/bauxite/bauximyb04 pdf.
• USGS (US Geological Survey) US Geological Survey Minerals Yearbook: Aluminum. 2005c. [online] Cited 24 January 2007 http://minerals.usgs.gov/minerals/pubs/commodity/aluminum/alumimyb 04.pdf.
• USGS (US Geological Survey) US Geological Survey Minerals Yearbook: Bauxite & Alumina. 2006a. [online] Cited 24 January 2007 http://minerals.usgs.gov/minerals/pubs/commodity/bauxite/bauximyb05 pdf.
• USGS (US Geological Survey) US Geological Survey Minerals Yearbook: Aluminum. 2006b. [online] Cited 24 January 2007 http://minerals.usgs.gov/minerals/pubs/commodity/aluminum/alumimyb 05.pdf.
• Uversky VN, Li J, Fink AL. Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkison’s disease and heavy metal exposure. J Biol Chem. 2001;276:44284–44296. [PubMed] [Google Scholar]
• Valkonen S, Aitio A. Analysis of aluminium in serum and urine for the biomonitoring of occupational exposure. Sci Total Environ. 1997;199:103–110. [PubMed] [Google Scholar]
• Vallyathan V, Bergeron WN, Robichaux PA, Craighead JE. Pulmonary fibrosis in an aluminum arc welder. Chest. 1982;81:372–374. [PubMed] [Google Scholar]
• Valtulini S, Macchi C, Ballanti P, Cherel Y, Laval A, Theaker JM, Bak M, Ferretti E, Morvan H. Aluminium hydroxide induced granulomas in pigs. Vaccine. 2005;23:3999–4004. [PubMed] [Google Scholar]
• Van der Voet GB, de Wolff FA. Intestinal absorption of aluminium in rats. Arch Toxicol Suppl. 1985;8:316–318. [PubMed] [Google Scholar]
• Van der Voet GB, de Wolff FA. Intestinal absorption of aluminium from antacids: a comparison between hydrotalcite and algeldrate. J Toxicol Clin Toxicol. 19861987;24:545–553. [PubMed] [Google Scholar]
• Van der Voet GB, de Wolff FA. Intestinal absorption of aluminium in rats: effect of sodium. Arch Toxicol Suppl. 1987a;11:231–235. [PubMed] [Google Scholar]
• Van der Voet GB, de Wolff FA. The effect of di- and trivalent iron on the intestinal absorption of aluminum in rats. Toxicol Appl Pharmacol. 1987b;90:190–197. [PubMed] [Google Scholar]
• Van der Voet GB, De Wolff FA. Intestinal absorption of aluminum: effect of sodium and calcium. Arch Toxicol. 1998;72:110–114. [PubMed] [Google Scholar]
• Van der Voet GB, van Ginkel MF, de Wolff FA. Intestinal absorption of aluminum in rats: stimulation by citric acid and inhibition by dinitrophenol. Toxicol Appl Pharmacol. 1989;99:90–97. [PubMed] [Google Scholar]
• Van Ginkel MF, van der Voet GB, de Wolff FA. Improved method of analysis for aluminum in brain tissue. Clin Chem. 1990;36:658–661. [PubMed] [Google Scholar]
• Van Ginkel MF, van der Voet GB, D’Haese PC, De Broe ME, de Wolff FA. Effect of citric acid and maltol on the accumulation of aluminum in rat brain and bone. J Lab Clin Med. 1993;121:453–460. [PubMed] [Google Scholar]
• Van Landeghem GF, de Broe ME, D’Haese PC. Al and Si: their speciation, distribution, and toxicity. Clin Biochem. 1998;31:385–397. [PubMed] [Google Scholar]
• Van Marwyck C, Eickhoff W. Result of further experiments on the pulmonary pathogenicity of aluminum dusts. Arch Hyg Bakteriol. 1950;133:139–157. [PubMed] [Google Scholar]
• Van Oostdam JC, Zwanenburg H, Harrison JR. Canadian perspectives on aluminum. Environ Geochem Health. 1990;12:71–74. [PubMed] [Google Scholar]
• Vandenplas O, Delwiche JP, Vanbilsen ML, Joly J, Roosels D. Occupational asthma caused by aluminium welding. Eur Resp J. 1998;11:1182–1184. [PubMed] [Google Scholar]
• Varo P, Koivistoinen P. Mineral element composition of Finnish foods: XII. General discussion and nutritional evaluation. Acta Agric Scand Suppl. 1980;22:165–171. [Google Scholar]
• Vassilev TL. Aluminium phosphate but not calcium phosphate stimulates the specific IgE response in guinea pigs to tetanus toxoid. Allergy. 1978;33:155–159. [PubMed] [Google Scholar]
• Veien NK, Hattel T, Justesen O, Norholm A. Aluminium allergy. Contact Dermatitis. 1986;15:295–297. [PubMed] [Google Scholar]
• Veien NK, Hattel T, Laurberg G. Systemically aggravated contact dermatitis caused by aluminium in toothpaste. Contact Dermatitis. 1993;28:199–200. [PubMed] [Google Scholar]
• Venier P, Montaldi A, Busi L, Gava C, Zentilin L, Tecchio G, Bianchi V, Levis AG. Genetic effects of chromium tannins. Carcinogenesis. 1985;6:1327–1335. [PubMed] [Google Scholar]
• Verbueken AH, van de Vyver FL, Van Grieken RE, De Broe ME. Microanalysis in biology and medicine ultrastructural localization of aluminum. Clin Nephrol. 1985;24:S58–S77. [PubMed] [Google Scholar]
• Verdier F, Burnett R, Michelet-Habchi C, Moretto P, Fievet-Groyne F, Sauzeat E. Aluminium assay and evaluation of the local reaction at several time points after intramuscular administration of aluminium containing vaccines in the Cynomolgus monkey. Vaccine. 2005;23:1359–1367. [PubMed] [Google Scholar]
• Verreault R, Laurin D, Lindsay J, DeSerres G. Past exposure to vaccines and subsequent risk of Alzheimer’s disease. CMAJ. 2001;165:1495–1498. [PMC free article] [PubMed] [Google Scholar]
• Versieck J, Cornelis R. Measuring aluminum levels. N Engl J Med. 1980;302:468–469. [PubMed] [Google Scholar]
• Versieck J, Cornelis R. Trace Elements in Human Plasma or Serum. Boca Raton, Florida: CRC Press; 1989. [Google Scholar]
• Villain M, Cirimele V, Kintz P. Hair analysis in toxicology. Clin Chem Lab Med. 2004;42:1265–1272. [PubMed] [Google Scholar]
• Vinas P, Campillo N, Lopez-Garcia I, Hernandez-Cordoba M. Electrothermal atomic absorption spectrometric determination of molybdenum, aluminium, chromium and manganese in milk. Anal Chim Acta. 1997;356:267–276. [Google Scholar]
• Vincent JH. Perspectives on international standards for health-related sampling of airborne contaminants. Appl Occup Environ Hyg. 1993;8:233–238. [Google Scholar]
• Vincent JH. Measurement of coarse aerosols in workplaces. A review. Analyst. 1994;119:13–18. [PubMed] [Google Scholar]
• Vincent JH. Aerosol Science for Industrial Hygienists. Oxford: Elsevier Science Ltd; 1995. [Google Scholar]
• Vincent JH. Health-related aerosol measurement: a review of existing sampling criteria and proposals for new ones. J Env Monit. 2005;7:1037–1053. [PubMed] [Google Scholar]
• Vittori D, Nesse A, Perez G, Garbossa G. Morphologic and functional alterations of erythroid cells induced by long-term ingestion of aluminium. J Inorg Biochem. 1999;76:113–120. [PubMed] [Google Scholar]
• Vittori D, Garbossa G, Lafourcade C, Perez G, Nesse A. Human erythroid cells are affected by aluminium. Alteration of membrane band 3 protein. Biochim Biophys Acta. 2002;1558:142–150. [PubMed] [Google Scholar]
• Vogelbruch M, Nuss B, Korner M, Kapp A, Kiehl P, Bohm W. Aluminium-induced granulomas after inaccurate intradermal hyposensitization injections of aluminium-adsorbed depot preparations. Allergy. 2000;55:883–887. [PubMed] [Google Scholar]
• Voisin C, Fisekci F, Buclez B, Didier A, Couste B, Bastien F, Bouchard P, Pairon JC. Mineralogical analysis of the respiratory tract in aluminium oxide-exposed workers. Eur Resp J. 1996;9:1874–1879. [PubMed] [Google Scholar]
• Volk VK, Bunney WE. Diphtheria immunization with fluid toxoid and alum-precipitated toxoid. Am J Public Health Nations Health. 1942;32:690–699. [PMC free article] [PubMed] [Google Scholar]
• von Stockhausen HB, Schrod L, Bratter P, Rosick U. Aluminum loading in premature infants during intensive care as related to clinical aspects. J Trace Elem Electrolytes Health Dis. 1990;4:209–213. [PubMed] [Google Scholar]
• Voss H, Tolki U. On a vaccine granuloma approximately one year old in man. Arch Hyg Bakteriol. 1960;178:291–299. [PubMed] [Google Scholar]
• Wachi M, Aikawa K. Serum aluminum assay by flameless atomic absorption spectroscopic method and oral absorption of some aluminum compounds by rats. Oyo Yakuri. 1975;10:359–363. [Google Scholar]
• Wagner JC, Pooley FD, Gibbs A, Lyons J, Sheers G, Moncrieff CB. Inhalation of china stone and china clay dusts: relationship between the mineralogy of dust retained in the lungs and pathological changes. Thorax. 1986;41:190–196. [PMC free article] [PubMed] [Google Scholar]
• Wagner W. Canadian Minerals Yearbook. Ottawa: Natural Resources Canada; 1999. [Google Scholar]
• Wakayama I, Nerurkar VR, Strong MJ, Garruto RM. Comparative study of chronic aluminum-induced neurofilamentous aggregates with intracytoplasmic inclusions of amyotrophic lateral sclerosis. Acta Neuropathol. 1996;92:545–554. [PubMed] [Google Scholar]
• Walker JA, Sherman RA, Cody RP. The effect of oral bases on enteral aluminum absorption. Arch Intern Med. 1990;150:2037–2039. [PubMed] [Google Scholar]
• Walker VR, Sutton RA, Meirav O, Sossi V, Johnson R, Klein J, Fink D, Middleton R. Tissue disposition of 26aluminum in rats measured by accelerator mass spectrometry. Clin Invest Med. 1994;17:420–425. [PubMed] [Google Scholar]
• Walls RS. Eosinophil response to alum adjuvants: involvement of T cells in non-antigen-dependent mechanisms. Proc Soc Exp Biol Med. 1977;156:431–435. [PubMed] [Google Scholar]
• Walton J, Hams G, Wilcox D. Bioavailability of Aluminium From Drinking Water: Co-exposure with Foods and Beverages. Melbourne, Australia: Urban Water Research Association of Australia, Melbourne Water Corporation; 1994. Research Report No 83. [Google Scholar]
• Walton J, Tuniz C, Fink D, Jacobsen G, Wilcox D. Uptake of trace amounts of aluminum into the brain from drinking water. Neurotoxicology. 1995;16:187–190. [PubMed] [Google Scholar]
• Wang M, Chen JT, Ruan DY, Xu YZ. The influence of developmental period of aluminum exposure on synaptic plasticity in the adult rat dentate gyrus in vivo. Neuroscience. 2002;113:411–419. [PubMed] [Google Scholar]
• Ward NI, Mason JA. Neutron activation analysis techniques for identifying elemental status in Alzheimer’s disease. J Radioanal Nucl Chem. 1987;113:515–526. [Google Scholar]
• Ward RJ, Zhang Y, Crichton RR. Aluminium toxicity and iron homeostasis. J Inorg Biochem. 2001;87:9–14. [PubMed] [Google Scholar]
• Warshawsky D, Reilman R, Cheu J, Radike M, Rice C. Influence of particle dose on the cytotoxicity of hamster and rat pulmonary alveolar macrophage in vitro. J Toxicol Environ Health. 1994;42:407–421. [PubMed] [Google Scholar]
• Weberg R, Berstad A. Gastrointestinal absorption of aluminium from single doses of aluminium containing antacids in man. Eur J Clin Invest. 1986;16:428–432. [PubMed] [Google Scholar]
• Weberg R, Berstad A, Ladehaug B, Thomassen Y. Are aluminum containing antacids during pregnancy safe? Acta Pharmacol Toxicol. 1986;59:63–65. [PubMed] [Google Scholar]
• Wedrychowski A, Schmidt WN, Hnilica LS. The in vivo cross-linking of proteins and DNA by heavy metals. J Biol Chem. 1986a;261:3370–3376. [PubMed] [Google Scholar]
• Wedrychowski A, Schmidt WN, Hnilica LS. DNA-protein crosslinking by heavy metals in Novikoff hepatoma. Arch Biochem Biophys. 1986b;251:397–402. [PubMed] [Google Scholar]
• Weed DL. Weight of evidence: a review of concept and methods. Risk Anal. 2005;25:1545–1557. [PubMed] [Google Scholar]
• Weinbrüch S, van Aken P, Ebert M, Thomassen Y, Skogstad A, Chashchin VP, Nikonov A. The heterogeneous composition of working place aerosols in a nickel refinery: a transmission and scanning electron microscope study. J Environ Monit. 2002;4:344–350. [PubMed] [Google Scholar]
• Weintraub R, Hams G, Meerkin M, Rosenberg AR. High aluminum content of infant milk formulas. Arch Dis Child. 1986;61:914–916. [PMC free article] [PubMed] [Google Scholar]
• Weller W, Reif E, Ulmer WT. Long term inhalation studies on rats on the problem of silicosis prophylaxis with McIntyre aluminum powder. Histology, determination of oxyproline and dust content, examination of respiration and circulation. Int Arch Arbeitsmed. 1966;22:77–94. [PubMed] [Google Scholar]
• Wen GY, Wisniewski HM. Histochemical localization of aluminum in the rabbit CNS. Acta Neuropathol. 1985;68:175–184. [PubMed] [Google Scholar]
• Wettstein A, Aeppli J, Gautschi K, Peter M. Failure to find a relationship between mnestic skills of octogenarians and aluminium in drinking water. Int Arch Occup Environ Health. 1991;63:97–103. [PubMed] [Google Scholar]
• White DM, Longstreth WT, Jr, Rosenstock L, Claypoole KH, Brodkin CA, Townes BD. Neurologic syndrome in 25 workers from an aluminum smelting plant. Arch Intern Med. 1992;152:1443–1448. [PubMed] [Google Scholar]
• White LR, Steinegger AF, Schlatter C. Pulmonary response following intratracheal instillation of potroom dust from an aluminum reduction plant into rat lung. Environ Res. 1987;42:534–545. [PubMed] [Google Scholar]
• White RG, Coons AH, Connolly JM. Studies on antibody production. III. The alum granuloma. J Exp Med. 1955;102:73–82. [PMC free article] [PubMed] [Google Scholar]
• Whitehead MW, Farrar G, Christie GL, Blair JA, Thompson RP, Powell JJ. Mechanisms of aluminum absorption in rats. Am J Clin Nutr. 1997;65:1446–1452. [PubMed] [Google Scholar]
• WHO (World Health Organization) Guidelines for Drinking-Water Quality. 3. Vol. 1. Geneva: World Health Organization; 2004. Recommendations. [Google Scholar]
• Wilcock LK, Francis JN, Durham SR. Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells. Clin Exp Allergy. 2004;34:1373–1378. [PubMed] [Google Scholar]
• Wilhelm M, Ohnesorge FK. Influence of storage conditions on aluminum concentrations in serum dialysis fluid, urine, and tap water. J Anal Toxicol. 1990;14:206–210. [PubMed] [Google Scholar]
• Wilhelm M, Sprenger KB, Vossas U, Ohnesorge FK. Aluminum load in chronic intermittent plasma exchange. J Toxicol Clin Toxicol. 1987;25:209–220. [PubMed] [Google Scholar]
• Wilhelm M, Passlick J, Busch T, Szydlik M, Ohnesorge FK. Scalp hair as an indicator of aluminium exposure: comparison to bone and plasma. Hum Toxicol. 1989a;8:5–9. [PubMed] [Google Scholar]
• Wilhelm M, Ohnesorge FK, Lombeck I, Hafner D. Uptake of aluminum, cadmium, copper, lead, and zinc by human scalp hair and elution of the adsorbed metals. J Anal Toxicol. 1989b;13:17–21. [PubMed] [Google Scholar]
• Wilhelm M, Jäger DE, Ohnesorge FK. Aluminium toxicokinetics. Pharmacol Toxicol. 1990;66:4–9. [PubMed] [Google Scholar]
• Wilhelm M, Zhang XJ, Hafner D, Ohnesorge FK. Single-dose toxicokinetics of aluminum in the rat. Arch Toxicol. 1992;66:700–705. [PubMed] [Google Scholar]
• Wilkinson KJ, Bertsch PM, Jagoe CH, Campbell PGC. Surface complexation of aluminum on isolated fish gill cells. Environ Sci Technol. 1993;27:1132–1138. [Google Scholar]
• Williams JW, Vera SR, Peters TG, Luther RW, Bhattacharya S, Spears H, Graham A, Pitcock JA, Crawford AJ, Palmieri GM. Biliary excretion of aluminum in aluminum osteodystrophy with liver disease. Ann Intern Med. 1986;104:782–786. [PubMed] [Google Scholar]
• Williams RJ, Fraústo da Silva JJ. The Natural Selection of the Chemical Elements. New York: Oxford University Press; 1996. [Google Scholar]
• Winearls CG. Recombinant human erythropoietin: 10 years of clinical experience. Nephrol Dial Transplant. 1998;13:S3–S8. [PubMed] [Google Scholar]
• Winklhofer C, Steinhausen C, Beck E, Alvarez-Bruckmann M, Kinzel S, Ittel TH, Nolte E. Effect of iron status on the absorption, speciation and tissue distribution of aluminium in rats. Nuc Inst Meth Phys Res B. 2000;172:920–924. [Google Scholar]
• Winterberg B, Bertram H, Rolf N, Roedig N, Kisters K, Remmers S, Spieker C, Zumkley H. Differences in plasma and tissue aluminum concentrations due to different aluminum-containing drugs in patients with renal insufficiency and with normal renal function. J Trace Elem Electrolytes Health Dis. 1987a;1:69–72. [PubMed] [Google Scholar]
• Winterberg B, Bertram H, Korte R, Niederlain G, Remmers S, Remmers J, Zumkley H. Hair analysis for aluminum monitoring in patients on long-term hemodialysis. Trace Elem Med. 1987b;4:72–74. [Google Scholar]
• Wisniewski HM, Kozlowski PB. Evidence for blood-brain barrier changes in senile dementia of the Alzheimer type (SDAT) Ann N Y Acad Sci. 1982;396:119–129. [PubMed] [Google Scholar]
• Woodson GC. An interesting case of osteomalacia due to antacid use associated with stainable bone aluminum in a patient with normal renal function. Bone. 1998;22:695–698. [PubMed] [Google Scholar]
• Woodworth CD, Mossman BT, Craighead JE. Comparative effects of fibrous and nonfibrous minerals on cells and liposomes. Environ Res. 1982;27:190–205. [PubMed] [Google Scholar]
• World Bureau of Metal Statistics. World bauxite production. World Met Stat. 1994;47:6. [Google Scholar]
• Wrobel K, Gonzalez EB, Wrobel K, Sanz-Medel A. Aluminum and silicon speciation in human serum by ion-exchange high-performance liquid chromatography-electrothermal atomic absorption spectrometry and gel electrophoresis. Analyst. 1995;120:809–815. [PubMed] [Google Scholar]
• Wu Y, Zhou Z, Xiong Y, Wang Y, Sun J. Distribution of aluminum of alunite in blood and brain of normal mice and mice with high permeability of blood-brain barrier. Zhongguo Zhongyao Zazhi. 1999;24:234–235. [Google Scholar]
• Wyatt JP, Riddell ACR. The morphology of bauxite-fume pneumoconiosis. Am J Pathol. 1949;25:447–465. [PMC free article] [PubMed] [Google Scholar]
• Xiao B, Dong Q, Li S, Li D, Zhan C. Aluminum and fluorine in blood and bone of rats fed on diet mixed with various contents of aluminum, fluoride or their mixture. Hua Xi Yi Ke Da Xue Xue Bao. 1992;23:185–189. [PubMed] [Google Scholar]
• Xie CX, Mattson MP, Lovell MA, Yokel RA. Intraneuronal aluminum potentiates iron-induced oxidative stress in cultured rat hippocampal neurons. Brain Res. 1996;743:271–277. [PubMed] [Google Scholar]
• Xu N, Majidi V, Markesbery WR, Ehmann WD. Brain aluminum in Alzheimer’s disease using an improved GFAAS method. Neurotoxicology. 1992c;13:735–743. [PubMed] [Google Scholar]
• Xu ZC, Tang JP, Xu ZX, Melethil S. Kinetics of aluminum in rats. IV: Blood and cerebrospinal fluid kinetics. Toxicol Lett. 1992b;63:7–12. [PubMed] [Google Scholar]
• Xu ZX, Pai SM, Melethil S. Kinetics of aluminum in rats. II: Dose-dependent urinary and biliary excretion. J Pharm Sci. 1991;80:946–951. [PubMed] [Google Scholar]
• Xu ZX, Tang JP, Badr M, Melethil S. Kinetics of aluminum in rats. III: Effect of route of administration. J Pharm Sci. 1992a;81:160–163. [PubMed] [Google Scholar]
• Yamamoto T, Watsuji T, Ishikawa M, Harina Y, Yabuki T. Zinc, copper, and aluminum contents of various human organs, especially of the male genital organs. Kobe Ika Daigaku Kiyo. 1959;16:185–190. [Google Scholar]
• Yamane Y, Ohtawa M. Possible mechanisms of suppressive action of aluminium chloride on lung carcinogenesis in mice induced by 4-nitro-quinoline 1-oxide: II. Effects of aluminium chloride on metabolism of 4-niroquinoline 1-oxide. Gann. 1979;70:147–152. [PubMed] [Google Scholar]
• Yamazaki K, Kajima T, Yoshida Y, Yuzuriha T, Wakabayashi T, Shigematsu T, Yamamoto H, Kawaguchi Y. Sodium ferrous citrate does not cause aluminum retention in rats with experimentally induced renal failure. J Bone Miner Metab. 1995;13:87–92. [Google Scholar]
• Yang SJ, Lee JE, Lee KH, Huh JW, Choi SY, Cho SW. Opposed regulation of aluminum-induced apoptosis by glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor in rat brains. Brain Res Mol Brain Res. 2004;127:146–149. [PubMed] [Google Scholar]
• Yase Y. The pathogenesis of amyotrophic lateral sclerosis. Lancet. 1972;2:292–296. [PubMed] [Google Scholar]
• Yase Y. The role of aluminum in CNS degeneration with interaction of calcium. Neurotoxicology. 1980;1:101–109. [Google Scholar]
• Yasui M, Yoshimasu F, Yase Y, Uebayashi Y. Wilson’s disease; increased aluminum in liver. Folia Psychiatr Neurol Jpn. 1979;33:547–552. [PubMed] [Google Scholar]
• Yasui MS, Kita SF, Yoshimasu F, Higashi Y, Yase Y, Uebayashi Y, Miyamoto K, Nagasaki Y, Miyoshi K, Hayashi S, Ogura Y. Accumulation of aluminum in central nervous system and other organs in a case of generalized amyloidosis. Nippon Naika Gakkai Zasshi. 1980;69:982–991. [PubMed] [Google Scholar]
• Yasui M, Yano I, Ota K, Oshima A. Calcium, phosphorus and aluminium concentrations in the central nervous system, liver and kidney of rabbits with experimental atherosclerosis: preventive effects of vinpocetine on the deposition of these elements. J Int Med Res. 1990a;18:142–152. [PubMed] [Google Scholar]
• Yasui M, Yano I, Yase Y, Ota K. Aluminum contents in soft tissues of mice fed low Ca-Mg, low Ca-Mg+ high aluminum, and low Ca-Mg+ high aluminum diets with administration of 1,25-(OH)2D3. Igaku no Ayumi. 1990b;153:601–602. [Google Scholar]
• Yasui M, Yase Y, Ota K, Garruto RM. Evaluation of magnesium, calcium and aluminum metabolism in rats and monkeys maintained on calcium-deficient diets. Neurotoxicology. 1991a;12:603–614. [PubMed] [Google Scholar]
• Yasui M, Yase Y, Ota K, Mukoyama M, Adachi K. High aluminum deposition in the central nervous system of patients with amyotrophic lateral sclerosis from the Kii Peninsula, Japan: two case reports. Neurotoxicology. 1991b;12:277–283. [PubMed] [Google Scholar]
• Yasui MS, Yase Y, Ota K, Garruto RM. Aluminum deposition in the central nervous system of patients with amyotrophic lateral sclerosis from the Kii peninsula of Japan. Neurotoxicology. 1991c;12:615–620. [PubMed] [Google Scholar]
• Yasui MS, Kihira T, Ota K. Calcium, magnesium and aluminum concentrations in Parkinson’s disease. Neurotoxicology. 1992;13:593–600. [PubMed] [Google Scholar]
• Yasui M, Ota K. Aluminum decreases the magnesium concentration of spinal cord and trabecular bone in rats fed a low calcium, high aluminum diet. J Neurol Sci. 1998;157:37–41. [PubMed] [Google Scholar]
• Ye Q, Ohsaki K, Ii K, Li DJ, Matsuoka H, Tenshin S, Yamamoto T. A subcutaneous tissue reaction in the early stage to a synthetic auditory ossicle (Bioceram) in rats. J Med Invest. 1998;44:173–177. [PubMed] [Google Scholar]
• Yokel RA. Hair as an indicator of excessive aluminum exposure. Clin Chem. 1982;28:662–665. [PubMed] [Google Scholar]
• Yokel RA. Persistent aluminum accumulation after prolonged systemic aluminum exposure. Biol Trace Elem Res. 1983;5:467–474. [PubMed] [Google Scholar]
• Yokel RA. Toxicity of aluminum exposure during lactation to the maternal and suckling rabbit. Toxicol Appl Pharmacol. 1984;75:35–43. [PubMed] [Google Scholar]
• Yokel RA. Toxicity of gestational aluminum exposure to the maternal rabbit and offspring. Toxicol Appl Pharmacol. 1985;79:121–133. [PubMed] [Google Scholar]
• Yokel RA. The toxicology of aluminum in the brain: a review. Neurotoxicology. 2000;21:813–828. [PubMed] [Google Scholar]
• Yokel RA. Aluminum toxicokinetics at the blood-brain barrier. In: Exley C, editor. Aluminium and Alzheimer’s Disease. New York: Elsevier; 2001. pp. 233–260. [Google Scholar]
• Yokel RA. Aluminum chelation principles and recent advances. Coord Chem Rev. 2002;228:97–113. [Google Scholar]
• Yokel RA, Florence RL. Aluminum bioavailability from the approved food additive leavening agent acidic sodium aluminum phosphate, incorporated into a baked good, is lower than from water. Toxicology. 2006;227:86–93. [PubMed] [Google Scholar]
• Yokel RA, McNamara PJ. Aluminum bioavailability and disposition in adult and immature rabbits. Toxicol Appl Pharmacol. 1985;77:344–352. [PubMed] [Google Scholar]
• Yokel RA, McNamara PJ. Influence of renal impairment, chemical form, and serum protein binding on intravenous and oral aluminum kinetics in the rabbit. Toxicol Appl Pharmacol. 1988;95:32–43. [PubMed] [Google Scholar]
• Yokel RA, McNamara PJ. Elevated aluminium persists in serum and tissues of rabbits after a six-hour infusion. Toxicol Appl Pharmacol. 1989;99:133–138. [PubMed] [Google Scholar]
• Yokel RA, McNamara PJ. The influence of dietary calcium reduction on aluminum absorption and kinetics in the rabbit. Biol Trace Elem Res. 19891990;23:109–117. [PubMed] [Google Scholar]
• Yokel RA, McNamara PJ. Aluminum toxicokinetics: an updated minireview. Pharmacol Toxicol. 2001;88:159–167. [PubMed] [Google Scholar]
• Yokel RA, Datta AK, Jackson EG. Evaluation of potential aluminum chelators in vitro by aluminum solubilization ability, aluminum mobilization from transferrin and the octanol/aqueous distribution of the chelators and their complexes with aluminum. J Pharmacol Exp Ther. 1991a;257:100–106. [PubMed] [Google Scholar]
• Yokel RA, Lidums V, McNamara PJ, Ungerstedt U. Aluminum distribution into brain and liver of rats and rabbits following intravenous aluminum lactate or citrate: A microdialysis study. Toxicol Appl Pharmacol. 1991b;107:153–163. [PubMed] [Google Scholar]
• Yokel RA, Ackrill P, Burgess E, Day JP, Domingo JL, Flaten TP, Savory J. Prevention and treatment of aluminum toxicity including chelation therapy: status and research needs. J Toxicol Environ Health. 1996a;48:667–683. [PubMed] [Google Scholar]
• Yokel RA, Meurer KA, Skinner TL, Fredenburg AM. The 3-hydroxypyridin-4-ones more effectively chelate aluminum in a rabbit model of aluminum intoxication than does desferrioxamine. Drug Metab Dispos. 1996b;24:105–111. [PubMed] [Google Scholar]
• Yokel RA, Rhineheimer SS, Sharma P, Elmore D, McNamara PJ. Entry, half-life, and desferrioxamine-accelerated clearance of brain aluminum after a single (26)Al exposure. Toxicol Sci. 2001a;64:77–82. [PubMed] [Google Scholar]
• Yokel RA, Rhineheimer SS, Brauer RD, Sharma P, Elmore D, McNamara PJ. Aluminum bioavailability from drinking water is very low and is not appreciably influenced by stomach contents or water hardness. Toxicology. 2001b;161:93–101. [PubMed] [Google Scholar]
• Yokel RA, Wilson M, Harris WR, Halestrap AP. Aluminum citrate uptake by immortalized brain endothelial cells: implications for its blood-brain barrier transport. Brain Res. 2002;930:101–110. [PubMed] [Google Scholar]
• Yokel RA, Urbas AA, Lodder RA, Selegue JP, Florence RL. 26Al containing acidic and basic sodium aluminum phosphate preparation and use in studies of oral aluminum bioavailability from foods utilizing 26Al as an aluminum tracer. Nucl Instr Meth Phys Res B. 2005;229:471–478. [Google Scholar]
• Yoshida H, Yoshimasu F. Alzheimer’s disease and trace elements. Nippon Rinsho. 1996;54:111–116. [PubMed] [Google Scholar]
• Yoshida H, Yoshimsu F, Chen KM. The study on trace elements in brains of dementia patients. Wakayama Igaku. 1993;44:529–539. [Google Scholar]
• Yoshida S. Application of PIXE in medical study: environmental minerals and neurodegenerative disorders. Int J PIXE. 1999;9:245–257. [Google Scholar]
• Yoshida S, Gershwin ME, Keen CL, Donald JM, Golub MS. The influence of aluminum on resistance to Listeria monocytogenes in Swiss-Webster mice. Int Arch Allergy Appl Immunol. 1989;89:404–409. [PubMed] [Google Scholar]
• Yoshida S, Wakayama I, Kihira T, Sasajima K, Yoshida K. Environmental minerals in Kii amyotrophic lateral scerosis in Japan: a PIXE analysis featuring aluminum. Int J PIXE. 1997;6:543–554. [Google Scholar]
• Yoshimasu F, Uebayashi Y, Yase Y, Iwata S, Sasajima K. Studies on amyotrophic lateral sclerosis by neutron activation analysis. Folia Psychiatr Neurol Jpn. 1976;30:49–55. [PubMed] [Google Scholar]
• Yoshimasu F, Yasui M, Yase Y, Iwata S, Gajdusek DC, Gibbs CJ, Jr, Chen KM. Studies on amyotrophic lateral sclerosis by neutron activation analysis --- 2. Comparative study of analytical results on Guam PD, Japanese ALS and Alzheimer’s disease cases. Folia Psychiatr Neurol Jpn. 1980;34:75–82. [PubMed] [Google Scholar]
• Yoshimasu F, Yasui M, Yoshida H, Yoshida S, Uebayashi Y, Yase Y, Gajdusek DC, Chen KM. Aluminum in Alzheimer’s disease in Japan and parkinsonism-dementia in Guam. In 13th world congress of neurology. J Neurol. 1985;232(Suppl):61. [Google Scholar]
• Ysart G, Miller P, Croasdale M, Crews H, Robb P, Baxter M, de L’Argy C, Harrison N. 1997 UK Total Diet Study--dietary exposures to aluminium, arsenic, cadmium, chromium, copper, lead, mercury, nickel, selenium, tin and zinc. Food Addit Contam. 2000;17:775–786. [PubMed] [Google Scholar]
• Yu B, Tsen HY. Lactobacillus cells in the rabbit digestive tract and the factors affecting their distribution. J Appl Bacteriol. 1993;75:269–275. [PubMed] [Google Scholar]
• Yuan B, Klein MH, Contiguglia RS, Mishell JL, Seligman PA, Miller NL, Molitoris BA, Alfrey AC, Shapiro JI. The role of aluminum in the pathogenesis of anemia in an outpatient hemodialysis population. Ren Fail. 1989;11:91–96. [PubMed] [Google Scholar]
• Yumoto S, Nagai H, Imamura M, Matsuzaki H, Hayashi K, Masuda A, Kumazawa H, Ohashi H, Kobayashi K. 26Al uptake and accumulation in the rat brain. Nuc Inst Meth Phys Res B. 1997;123:279–282. [Google Scholar]
• Yumoto S, Nagai H, Matsuzaki H, Kobayashi T, Tada W, Ohki Y, Kakimi S, Kobayashi K. Transplacental passage of 26Al from pregnant rats to fetuses and 26Al transfer through maternal milk to suckling rats. Nuc Inst Meth Phys Res B. 2000;172:925–929. [Google Scholar]
• Yumoto S, Nagai H, Matsuzaki H, Matsumura H, Tada W, Nagatsuma E, Kobayashi K. Aluminium incorporation into the brain of rat fetuses and sucklings. Brain Res Bull. 2001;55:229–234. [PubMed] [Google Scholar]
• Yumoto S, Nagai H, Kobayashi K, Tamate A, Kakimi S, Matsuzaki H. 26Al incorporation into the brain of suckling rats through maternal milk. J Inorg Biochem. 2003;97:155–160. [PubMed] [Google Scholar]
• Zafar TA, Weaver CM, Martin BR, Flarend R, Elmore D. Aluminum (26AI) metabolism in rats. Proc Soc Exp Biol Med. 1997;216:81–85. [PubMed] [Google Scholar]
• Zafar TA, Teegarden D, Ashendel C, Dunn MA, Weaver CM. Aluminium negatively impacts calcium utilization and bone in calcium-deficient rats. Nutr Res. 2004;24:234–259. [Google Scholar]
• Zaman K, Zaman W, Siddique H. Hematological and enzymatic results of aluminum intoxication in rats. Comp Biochem Physiol C. 1993;105:73–76. [PubMed] [Google Scholar]
• Zapatero MD, Garcia de Jalon A, Pascual F, Calvo ML, Escanero J, Marro A. Serum aluminum levels in Alzheimer’s disease and other senile dementias. Biol Trace Elem Res. 1995;47:235–240. [PubMed] [Google Scholar]
• Zatta P, Bordin C, Favarato M. The inhibition of trypsin and alpha-chymotrypsin proteolytic activity by aluminum(III) Arch Biochem Biophys. 1993;303:407–411. [PubMed] [Google Scholar]
• Zatta P, Zambenedetti P, Toffoletti A, Corvaja C, Corain B. Aluminum(III) induces alterations on the physical state of the erythrocytic membrane: an ESR evaluation. J Inorg Biochem. 1997;65:109–114. [PubMed] [Google Scholar]
• Zatta P, Zambenedetti P, Reusche E, Stellmacher F, Cester A, Albanese P, Meneghel G, Nordio M. A fatal case of aluminium encephalopathy in a patient with severe chronic renal failure not on dialysis. Nephrol Dial Transplant. 2004;19:2929–2931. [PubMed] [Google Scholar]
• Zecca L, Pietra R, Goj C, Mecacci C, Radice D, Sabbioni E. Iron and other metals in neuromelanin, substantia nigra, and putamen of human brain. J Neurochem. 1994;62:1097–1101. [PubMed] [Google Scholar]
• Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W. Salmonella mutagenicity tests. III. Results from the testing of 255 chemicals. Environ Mol Mutagen. 1987;9:1–109. [PubMed] [Google Scholar]
• Zhang ZJ, Qian YH, Hu HT, Yang J, Yang GD. The herbal medicine Dipsacus asper wall extract reduces the cognitive deficits and overexpression of beta-amyloid protein induced by aluminum exposure. Life Sci. 2003;73:2443–2454. [PubMed] [Google Scholar]
• Zhang B, Nie A, Bai W, Meng Z. Effects of aluminum chloride on sodium current, transient outward potassium current and delayed rectifier potassium current in acutely isolated rat hippocampal CA1 neurons. Food Chem Toxicol. 2004;42:1453–1462. [PubMed] [Google Scholar]
• Zhao HX, Mold MD, Stenhouse EA, Bird SC, Wright DE, Demaine AG, Millward BA. Drinking water composition and childhood-onset Type 1 diabetes mellitus in Devon and Cornwall, England. Diabet Med. 2001;18:709–717. [PubMed] [Google Scholar]
• Zhou Y, Yokel RA. The chemical species of aluminum influences its paracellular flux across and uptake into Caco-2 cells, a model of gastrointestinal absorption. Toxicol Sci. 2005;87:15–26. [PubMed] [Google Scholar]
• Zhu Y, Hattori R, Fujimori E, Umemura T, Haraguchi H. Multielemental determination of trace metals in river water (certified reference material JSAC 0301-1) by high efficiency nebulization ICP-MS after 100-fold preconcentration with a chelating resin-packed minicolumn. Anal Sci. 2005;21:199–203. [PubMed] [Google Scholar]
• Zook E, Lehmann J. Total diet study: Content of ten minerals - aluminum, calcium, phosphorus, sodium, potassium, boron, copper, iron, manganese and magnesium. J Assoc Off Agr Chem. 1965;48:850–855. [Google Scholar]
• Zumkley H, Spieker C, Kisters K, Zidek W, Fromme HG, Losse H, van Husen N, Bertram HP. Aluminum concentrations in gastric mucous membrane in renal insufficiency. Trace Subst Environ Health. 1984a;18:40–46. [Google Scholar]
• Zumkley H, Schmidt PF, Bertram HP, Lison AE, Winterberg B, Spieker K, Losse H, Barckhaus R. Aluminum concentration of bone cells in dialysis osteomalacia. Trace Elem Med. 1984b;1:103–106. [Google Scholar]
• Zumkley H, Bertram HP, Brandt M, Rodig M, Spieker C. Magnesium, aluminum and lead in various brain areas. Trace Subst Environ Health. 1986;20:29–35. [Google Scholar]