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Record Information
Version2.0
Creation Date2009-03-06 18:58:14 UTC
Update Date2014-12-24 20:21:18 UTC
Accession NumberT3D0187
Identification
Common NameAluminum
ClassSmall Molecule
DescriptionAluminium is a soft, lightweight metal with appearance ranging from silvery to dull gray, depending on the surface roughness. Data indicate that aluminum contaminates much of the raw material used to manufacture solutions used for intravenous nutritional support of hospitalized and ambulatory patients, and that pharmaceutical manufacturers have only recently obtained the technology necessary to detect aluminum contamination of their products. As a result, aluminum bypassed normal barriers and entered the blood, accumulating in tissues such as bone, liver and the central nervous system with toxic consequences. Now that the FDA has finally issued a rule governing aluminum contamination in these solutions, manufacturers will need to develop methods to minimize such contamination; scientists should also realize that when data they obtain indicate a serious problem in the manufacturing sector they should be sure that the problem is properly addressed. Physiologically, this metal/element. exists as an ion in the body. (3).
Compound Type
  • Aluminum Compound
  • Cosmetic Toxin
  • Drug
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Metabolite
  • Metal
  • Natural Compound
Chemical Structure
Thumb
Synonyms
Synonym
13Al
Al
Aluminium
Aluminium(3+)
Aluminium(3+) ion
Aluminium(III) cation
Aluminum(3+)
Aluminum(3+) ion
Aluminum(III) cation
Metallic Aluminum
Chemical FormulaAl
Average Molecular Mass26.982 g/mol
Monoisotopic Mass26.982 g/mol
CAS Registry Number7429-90-5
IUPAC Namealumane
Traditional Namealumane
SMILES[Al]
InChI IdentifierInChI=1S/Al
InChI KeyInChIKey=XAGFODPZIPBFFR-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as homogeneous post-transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a post-transition metal atom.
KingdomInorganic compounds
Super ClassHomogeneous metal compounds
ClassHomogeneous post-transition metal compounds
Sub ClassNot Available
Direct ParentHomogeneous post-transition metal compounds
Alternative ParentsNot Available
Substituents
  • Homogeneous post-transition metal
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceSilvery white metallic solid.
Experimental Properties
PropertyValue
Melting Point2.375 g*Cm -3
Boiling Point2327°C (4220.6°F)
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP1.45ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m3·mol-1ChemAxon
Polarizability1.78 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-9000000000-9378da25f3a524cf38e8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-9000000000-9378da25f3a524cf38e8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-9378da25f3a524cf38e8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-9000000000-71051ebfdb9ee6a6ce2dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9000000000-71051ebfdb9ee6a6ce2dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9000000000-71051ebfdb9ee6a6ce2dView in MoNA
Toxicity Profile
Route of ExposureOral (24) ; inhalation (24)
Mechanism of ToxicityThe 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. It has been suggested that aluminum's interaction with estrogen receptors increases the expression of estrogen-related genes and thereby contributes to the progression of breast cancer (1), but studies have not been able to establish a clear link between aluminum and increased risk of breast cancer (22). Certain aluminum salts induce immune responses by activating inflammasomes. (24, 1, 2) Aluminum Acetate is an astringent. An astrignent is a chemical that tends to shrink or constrict body tissues, usually locally after topical medicinal application. The shrinkage or constriction is through osmotic flow of water (or other fluids) away from the area where the astringent was applied. Astringent medicines cause shrinkage of mucous membranes or exposed tissues and are often used internally to check discharge of blood serum or mucous secretions. This can happen with a sore throat, hemorrhages, diarrhea, or with peptic ulcers. Externally applied astringents, which cause mild coagulation of skin proteins, dry, harden, and protect the skin. Acne sufferers are often advised to use astringents if they have oily skin. Astringents also help heal stretch marks and other scars. Mild astringent solutions are used in the relief of such minor skin irritations as those resulting from superficial cuts, allergies, insect bites, or fungal infections such as athlete's foot.
MetabolismAluminum 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. (24)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC. IARC classified aluminum production as carcinogenic to humans (Group 1), but did not implicate aluminum itself as a human carcinogen. (26) A link between use of aluminum-containing antiperspirants and increased risk of breast cancer has been proposed (1), but studies have not been able to establish a clear link (22).
Uses/SourcesAluminum 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. (24, 25)
Minimum Risk LevelIntermediate Oral: 1.0 mg/kg/day (23) Chronic Oral: 1.0 mg/kg/day (23)
Health EffectsAluminum 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. (24, 25)
SymptomsInhalating 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. (24, 25)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01370
HMDB IDHMDB01247
PubChem Compound ID5359268
ChEMBL IDNot Available
ChemSpider ID4514248
KEGG IDC06264
UniProt IDNot Available
OMIM ID103180 , 104300 , 105500 , 108730 , 155140 , 211900 , 601924
ChEBI ID28984
BioCyc IDNot Available
CTD IDD000535
Stitch IDAluminum
PDB IDAL
ACToR ID7939
Wikipedia LinkAluminium
References
Synthesis Reference

Bela Czegledi, Mihaly Csovari, Miklos Erdelyi, Lajos Streker, Istvan Toth, Katalin Szabo nee Mogyorosi, Szilard Riederauer, Geza Szentgyorgyi, “Process for producing alumina and ferric oxide from aluminium carriers with high iron and silicon content.” U.S. Patent US4366129, issued 1876.

MSDSLink
General References
  1. 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 ]
  2. 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. doi: 10.1016/j.tips.2009.03.005. Epub 2009 May 11. [19439372 ]
  3. Klein GL: Aluminum: new recognition of an old problem. Curr Opin Pharmacol. 2005 Dec;5(6):637-40. Epub 2005 Sep 28. [16198633 ]
  4. Strunecka A, Strunecky O, Patocka J: Fluoride plus aluminum: useful tools in laboratory investigations, but messengers of false information. Physiol Res. 2002;51(6):557-64. [12511178 ]
  5. Elmore AR: Final report on the safety assessment of aluminum silicate, calcium silicate, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, sodium magnesium 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 1:37-102. [12851164 ]
  6. Savory J, Herman MM, Ghribi O: Intracellular mechanisms underlying aluminum-induced apoptosis in rabbit brain. J Inorg Biochem. 2003 Sep 15;97(1):151-4. [14507471 ]
  7. Arnold CJ, Miller GG, Zello GA: Parenteral nutrition-associated cholestasis in neonates: the role of aluminum. Nutr Rev. 2003 Sep;61(9):306-10. [14552065 ]
  8. Zatta P, Lucchini R, van Rensburg SJ, Taylor A: The role of metals in neurodegenerative processes: aluminum, manganese, and zinc. Brain Res Bull. 2003 Nov 15;62(1):15-28. [14596888 ]
  9. Gherardi RK, Authier FJ: Aluminum inclusion macrophagic myofasciitis: a recently identified condition. Immunol Allergy Clin North Am. 2003 Nov;23(4):699-712. [14753387 ]
  10. Becaria A, Campbell A, Bondy SC: Aluminum as a toxicant. Toxicol Ind Health. 2002 Aug;18(7):309-20. [15068131 ]
  11. Kawahara M: Effects of aluminum on the nervous system and its possible link with neurodegenerative diseases. J Alzheimers Dis. 2005 Nov;8(2):171-82; discussion 209-15. [16308486 ]
  12. Aremu DA, Meshitsuka S: Some aspects of astroglial functions and aluminum implications for neurodegeneration. Brain Res Rev. 2006 Aug 30;52(1):193-200. Epub 2006 Mar 10. [16529821 ]
  13. Perl DP, Moalem S: Aluminum and Alzheimer's disease, a personal perspective after 25 years. J Alzheimers Dis. 2006;9(3 Suppl):291-300. [17004365 ]
  14. Savory J, Herman MM, Ghribi O: Mechanisms of aluminum-induced neurodegeneration in animals: Implications for Alzheimer's disease. J Alzheimers Dis. 2006 Nov;10(2-3):135-44. [17119283 ]
  15. Campbell A: The role of aluminum and copper on neuroinflammation and Alzheimer's disease. J Alzheimers Dis. 2006 Nov;10(2-3):165-72. [17119285 ]
  16. Miu AC, Benga O: Aluminum and Alzheimer's disease: a new look. J Alzheimers Dis. 2006 Nov;10(2-3):179-201. [17119287 ]
  17. Yokel RA: Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration. J Alzheimers Dis. 2006 Nov;10(2-3):223-53. [17119290 ]
  18. Domingo JL: Aluminum and other metals in Alzheimer's disease: a review of potential therapy with chelating agents. J Alzheimers Dis. 2006 Nov;10(2-3):331-41. [17119296 ]
  19. Riggs K, Keller M, Humphreys TR: Ablative laser resurfacing: high-energy pulsed carbon dioxide and erbium:yttrium-aluminum-garnet. Clin Dermatol. 2007 Sep-Oct;25(5):462-73. [17870524 ]
  20. Hem SL, Hogenesch H: Relationship between physical and chemical properties of aluminum-containing adjuvants and immunopotentiation. Expert Rev Vaccines. 2007 Oct;6(5):685-98. [17931150 ]
  21. Nokleby H: Neurological adverse events of immunization: experience with an aluminum adjuvanted meningococcal B outer membrane vesicle vaccine. Expert Rev Vaccines. 2007 Oct;6(5):863-9. [17931164 ]
  22. Willhite CC, Karyakina NA, Yokel RA, Yenugadhati N, Wisniewski TM, Arnold IM, Momoli F, Krewski D: Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts. Crit Rev Toxicol. 2014 Oct;44 Suppl 4:1-80. doi: 10.3109/10408444.2014.934439. [25233067 ]
  23. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  24. 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]
  25. Wikipedia. Aluminium. Last Updated 16 June 2009. [Link]
  26. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Transferrin receptor binding
Specific Function:
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
Gene Name:
TF
Uniprot ID:
P02787
Molecular Weight:
77063.195 Da
References
  1. Nolte E, Beck E, Winklhofer C, Steinhausen C: Compartmental model for aluminium biokinetics. Hum Exp Toxicol. 2001 Feb;20(2):111-7. [11327511 ]
  2. Nagaoka MH, Maitani T: Binding affinity of aluminium to human serum transferrin and effects of carbohydrate chain modification as studied by HPLC/high-resolution ICP-MS--speciation of aluminium in human serum. J Inorg Biochem. 2005 Sep;99(9):1887-94. [16139893 ]
  3. Mizutani K, Mikami B, Aibara S, Hirose M: Structure of aluminium-bound ovotransferrin at 2.15 Angstroms resolution. Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1636-42. Epub 2005 Nov 19. [16301797 ]
  4. Beardmore J, Rugg G, Exley C: A systems biology approach to the blood-aluminium problem: the application and testing of a computational model. J Inorg Biochem. 2007 Sep;101(9):1187-91. Epub 2007 Jun 12. [17629565 ]
  5. Hemadi M, Miquel G, Kahn PH, El Hage Chahine JM: Aluminum exchange between citrate and human serum transferrin and interaction with transferrin receptor 1. Biochemistry. 2003 Mar 18;42(10):3120-30. [12627980 ]
  6. 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. 1996 May 6;719(1-2):72-7. [8782865 ]
General Function:
Steroid hormone binding
Specific Function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A1
Uniprot ID:
P05023
Molecular Weight:
112895.01 Da
References
  1. Menz RI, Walker JE, Leslie AG: Structure of bovine mitochondrial F(1)-ATPase with nucleotide bound to all three catalytic sites: implications for the mechanism of rotary catalysis. Cell. 2001 Aug 10;106(3):331-41. [11509182 ]
  2. Silva VS, Goncalves PP: The inhibitory effect of aluminium on the (Na+/K+)ATPase activity of rat brain cortex synaptosomes. J Inorg Biochem. 2003 Sep 15;97(1):143-50. [14507470 ]
  3. Amador FC, Santos MS, Oliveira CR: Lipid peroxidation and aluminium effects on the cholinergic system in nerve terminals. Neurotox Res. 2001 Jul;3(3):223-33. [15111247 ]
  4. 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 May;78(5):276-82. [15254985 ]
  5. Kohila T, Tahti H: Effects of aluminium and lead on ATPase activity of knockout +/- mouse cerebral synaptosomes in vitro. Altern Lab Anim. 2004 Oct;32(4):361-7. [15651920 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Zinc ion binding
Specific Function:
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. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
References
  1. 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 ]
General Function:
Serine-type endopeptidase activity
Specific Function:
Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
Gene Name:
KLK1
Uniprot ID:
P06870
Molecular Weight:
28889.425 Da
References
  1. De Sousa MO, Santoro MM, De Souza Figueiredo AF: The effect of cations on the amidase activity of human tissue kallikrein: 1-linear competitive inhibition by sodium, potassium, calcium and magnesium. 2-linear mixed inhibition by aluminium. J Enzyme Inhib Med Chem. 2004 Aug;19(4):317-25. [15558947 ]
General Function:
Transcription factor binding
Specific Function:
As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitement of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP3 inflammasome is also required for HMGB1 secretion (PubMed:22801494). The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, beta-amyloid fibers, environmental or industrial particles and nanoparticles, etc. However, it is unclear what constitutes the direct NLRP3 activator. Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (By similarity). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity).
Gene Name:
NLRP3
Uniprot ID:
Q96P20
Molecular Weight:
118171.375 Da
References
  1. 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. doi: 10.1016/j.tips.2009.03.005. Epub 2009 May 11. [19439372 ]
References
  1. 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]