T3D0187 - Aluminum
| Record Information | |
|---|---|
| Version | 1.0 |
| Creation Date | 2009-03-06 18:58:14 UTC |
| Update Date | 2013-04-25 08:33:12 UTC |
| Accession Number | T3D0187 |
| Identification | |
| Common Name | Aluminum |
| Description | Aluminum is the most abundant metal in the earth’s crust. It is always found combined with other elements such as oxygen, silicon, and fluorine. Aluminium is extracted from aluminum-containing minerals such as bauxite ore. Small amounts of aluminum can be found dissolved in water. It is often mixed with small amounts of other metals to form aluminum alloys, which are stronger and harder. Aluminum compounds have many different uses, for example, as alums in water-treatment and alumina in abrasives and furnace linings. They are also found in consumer products such as antacids, astringents, buffered aspirin, food additives, cosmetics, and antiperspirants. Aluminum is used for beverage cans, pots and pans, airplanes, siding and roofing, and foil. (R1128, R1129) |
| Compound Type |
|
| Chemical Structure |
|
| Synonyms |
|
| Chemical Formula | Al |
| Average Molecular Weight | 26.9815386 |
| Monoisotopic Molecular Weight | 26.981538441 |
| Chemical IUPAC Name | aluminium(3+) |
| CAS Registry Number | 7429-90-5 |
| SMILES | [Al+3] |
| InChI Identifier | InChI=1S/Al/q+3 |
| InChI Key | InChIKey=REDXJYDRNCIFBQ-UHFFFAOYSA-N |
| Chemical Taxonomy | |
| Kingdom | Inorganic Compounds |
| Super Class | Homogeneous Metal Compounds |
| Class | Homogeneous Post-transition Metal Compounds |
| Sub Class | Not Available |
| Direct Parent | Homogeneous Post-transition Metal Compounds |
| Alternative Parents | Not Available |
| Molecular Framework | Acyclic Compounds |
| Substituents | Not Available |
| External Descriptors |
|
| External Links | |
| DrugBank ID | Not Available |
| PubChem Compound ID | 5359268 ![]() |
| KEGG ID | C06264 ![]() |
| UniProt ID | Not Available |
| OMIM ID | 103180
104300
105500
108730
155140
211900
601924 ![]() |
| ChEBI ID | 28984 ![]() |
| BioCyc ID | Not Available |
| CTD ID | D000535 ![]() |
| Stitch ID | Aluminum ![]() |
| PDB ID | Not Available |
| ACToR ID | 7939 |
| Wikipedia Link | http://en.wikipedia.org/wiki/Aluminum ![]() |
| Physical Properties | |
| Appearance | Silvery white metallic solid. |
| Melting Point | 660 C |
| Solubility | Not Available |
| Predicted LogP | 1.4499999999999997 |
| Toxicity Profile | |
| Route of Exposure | Oral (R1128) ; inhalation (R1128) |
| Mechanism of Action | The main targets of aluminum are the central nervous system and bones. Aluminum binds to dietary phosphorus and impairs gastrointestinal absorption of phosphorus. The decreased phosphate body burden results in osteomalacia and rickets. Aluminum's neurotoxicity is believed to involve different mechanisms. Changes in cytoskeletal protein functions as a result of altered phosphorylation, proteolysis, transport, and synthesis are believed to be one cause. Aluminum may induce neurobehavioral effects by affecting permeability of the blood-brain barrier, cholinergic activity, signal transduction pathways, lipid peroxidation, and impair neuronal glutamate nitric oxide-cyclic GMP pathway, as well as interfere with metabolism of essential trace elements because of similar coordination chemistries and consequent competitive interactions. Aluminum can also interact with estrogen receptors, increasing the expression of estrogen-related genes and contributing to the progression of breast cancer. Certain aluminum salts induce immune responses by activating inflammasomes. (R1128, R1130, R1132) |
| Metabolism | Aluminum is poorly absorbed following oral or inhalation exposure and is essentially not absorbed dermally. The bioavailability of aluminum is strongly influenced by the aluminum compound and the presence of dietary constituents which can complex with aluminum and enhance or inhibit its absorption. Aluminum binds to various ligands in the blood and distributes to every organ, with highest concentrations found in bone and lung tissues. In living organisms, aluminum is believed to exist in four different forms: as free ions, as low-molecular-weight complexes, as physically bound macromolecular complexes, and as covalently bound macromolecular complexes. Absorbed aluminum is excreted principally in the urine and, to a lesser extent, in the bile, while unabsorbed aluminum is excreted in the faeces. (R1128) |
| Toxicity Values | Not Available |
| Lethal Dose | Not Available |
| Carcinogenicity (IARC Classification) | Not Available |
| Uses/Sources | Aluminum is used for beverage cans, pots and pans, airplanes, siding and roofing, and foil. It is often mixed with small amounts of other metals to form aluminum alloys, which are stronger and harder. Aluminum compounds have many different uses, for example, as alums in water-treatment and alumina in abrasives and furnace linings. They are also found in consumer products such as antacids, astringents, buffered aspirin, food additives, cosmetics, and antiperspirants. (R1128, R1129) |
| Minimum Risk Level | Intermediate Oral: 1.0 mg/kg/day (R260) Chronic Oral: 1.0 mg/kg/day (R260) |
| Health Effects | Aluminum targets the nervous system and causes decreased nervous system performance and is associated with altered function of the blood-brain barrier. The accumulation of aluminum in the body may cause bone or brain diseases. High levels of aluminum have been linked to Alzheimer’s disease. A small percentage of people are allergic to aluminium and experience contact dermatitis, digestive disorders, vomiting or other symptoms upon contact or ingestion of products containing aluminium. (R1128, R1129) |
| Symptoms | Inhalating aluminum dust causes coughing and abnormal chest X-rays. A small percentage of people are allergic to aluminium and experience contact dermatitis, digestive disorders, vomiting or other symptoms upon contact or ingestion of products containing aluminium. (R1128, R1129) |
| Treatment | Not Available |
| References | |
| General References |
|
Targets
1. Phosphorus
Aluminum binds with dietary phosphorus and impairs gastrointestinal absorption of phosphorus. The decreased phosphate body burden results in osteomalacia (softening of the bones due to defective bone mineralization) and rickets. (R1128)UniProt ID: Phosphorus

References:
- R1128 — ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for aluminum. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
2. Estrogen receptor
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.
Aluminum can also interact with estrogen receptors, increasing the expression of estrogen-related genes and contributing to the progression of breast cancer. (R1130)UniProt ID: P03372

Gene: ESR1

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report

References:
- R1130 — Darbre PD: Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. J Appl Toxicol. 2006 May-Jun;26(3):191-7.
[16489580
]
3. NACHT, LRR and PYD domains-containing protein 3
May function as an inducer of apoptosis. Interacts selectively with ASC and this complex may function as an upstream activator of NF-kappa-B signaling. Inhibits TNF-alpha induced activation and nuclear translocation of RELA/NF-KB p65. Also inhibits transcriptional activity of RELA. Activates caspase-1 in response to a number of triggers including bacterial or viral infection which leads to processing and release of IL1B and IL18.
Certain aluminum salts induce immune responses by activating the NALP3 inflammasome, which in turn induces the production of interleukins. (R1132)UniProt ID: Q96P20

Gene: NLRP3

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report

References:
- R1132 — Aimanianda V, Haensler J, Lacroix-Desmazes S, Kaveri SV, Bayry J: Novel cellular and molecular mechanisms of induction of immune responses by aluminum adjuvants. Trends Pharmacol Sci. 2009 Jun;30(6):287-95. Epub 2009 May 11.
[19439372
]