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Record Information
Version2.0
Creation Date2009-03-06 18:58:18 UTC
Update Date2014-12-24 20:21:20 UTC
Accession NumberT3D0214
Identification
Common NameSilver
ClassSmall Molecule
DescriptionSilver is widely distributed in the earth's crust and is found in soil, fresh and sea water, and the air. It is readily absorbed into the human body with food and drink and through inhalation, but the low levels of silver commonly present in the bloodstream (< 2.3 b.mu g/L) and in key tissues like liver and kidney have not been associated with any disease or disability. Silver is not an acknowledged trace element in the human body and fulfills no physiological or biochemical role in any tissue even though it interacts with several essential elements including zinc and calcium. Physiologically, it exists as an ion in the body. Silver has a long history in the treatment of human diseases, including epilepsy, neonatal eye disease, venereal diseases, and wound infections. It has been employed in water purification and is currently used to safeguard hospital hot water systems against Legionella infections. Principle routes of human exposure to silver nowadays are through its widespread use as an antimicrobial agent in wound care products and medical devices, including in-dwelling catheters, bone cements, cardiac valves and prostheses, orthopedic pins, and dental devices. In each case, the antimicrobial properties of silver are dependent upon release of biologically active silver ion (Ag*) from metallic silver (including nanocrystalline forms), silver nitrate, silver sulfadiazine, and other silver compounds incorporated in the various devices, and its lethal effect on pathogenic organisms. Experience has shown that a large proportion of the silver ion released from medical devices not required for antimicrobial action is disseminated into tissue fluids and exudates, where it combines with albumins and macroglobulins. These silver-protein complexes are absorbed into the systemic circulation to be deposited in key soft tissues, including the skin, liver, kidney, spleen, lungs, and brain. As a xenobiotic material, silver must be presumed to present a health risk to exposed persons under some circumstances. Unlike the well-documented neurotoxic metals including lead and mercury, silver does not appear to be a cumulative poison and is eliminated from the body through the urine and feces. Excretion of silver by these routes may be a measure of mean daily intake, but since this view is based largely on the clinical use of silver nitrate and silver sulfadiazine used in burn wound therapy, its true relevance in the metabolism of silver used in the wider context of medical devices is questionable. Argyria is the most widely publicized clinical condition associated with silver accumulation in blood and soft tissues. It commonly occurs in individuals exposed to high levels of silver occupationally (metallurgy, photography, and mining industries), or consuming or inhaling silver hygiene products (including colloidal silver products) for long periods. Silver is absorbed into the body and deposited in the perivascular regions of the skin and other soft tissues as black granules of silver sulfide or silver selenide. The resulting slate grey discoloration of the skin occasionally associated with melanogenic changes, is semipermanent and cosmetically undesirable but is not known to be life-threatening. (5).
Compound Type
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Metabolite
  • Metal
  • Natural Compound
  • Pollutant
  • Silver Compound
Chemical Structure
Thumb
Synonyms
Synonym
Ag
Ag(1+)
Ag+
Argentum
Silver cation
Silver ion (1+)
Silver metal
Silver(0)
Silver(1+)
Silver(1+) ion
Silver(I) cation
Chemical FormulaAg
Average Molecular Mass107.868 g/mol
Monoisotopic Mass106.905 g/mol
CAS Registry Number7440-22-4
IUPAC Namesilver(1+) ion
Traditional Namesilver(1+) ion
SMILES[Ag+]
InChI IdentifierInChI=1S/Ag/q+1
InChI KeyInChIKey=FOIXSVOLVBLSDH-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom.
KingdomInorganic compounds
Super ClassHomogeneous metal compounds
ClassHomogeneous transition metal compounds
Sub ClassNot Available
Direct ParentHomogeneous transition metal compounds
Alternative ParentsNot Available
Substituents
  • Homogeneous 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
AppearanceWhite metallic solid.
Experimental Properties
PropertyValue
Melting Point960.5°C
Boiling Point2212°C (4013.6°F)
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP-0.73ChemAxon
Physiological Charge1ChemAxon
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, Positivesplash10-0a4i-0900000000-3126e0d9c9c0db35ef52View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0900000000-3126e0d9c9c0db35ef52View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-0900000000-3126e0d9c9c0db35ef52View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-411976aa2a4fb62a6313View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-411976aa2a4fb62a6313View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-0900000000-411976aa2a4fb62a6313View in MoNA
Toxicity Profile
Route of ExposureOral (7) ; inhalation (7) ; dermal (7)
Mechanism of ToxicityMetallic silver is oxidized and may deposit in the tissues, causing arygria. The silver ion is known to inhibit glutathione peroxidase and NA+,K+-ATPase activity, respectively disrupting selenium-catalyzed sulfhydryl oxidation-reduction reactions and intracellular ion concentrations. Silver nanoparticles are believed to disrupt the mitochondrial respiratory chain, causing oxidative stress, reduced ATP synthesis, and DNA damage. (7, 1, 2, 3, 4)
MetabolismSilver and its compounds can be absorbed via inhalation, orally and dermally. It distributes throughout the body, particularily to the liver. Insoluble silver salts are transformed into soluble silver sulfide albuminates, bind to amino or carboxyl groups in RNA, DNA, and proteins, or are reduced to metallic silver by ascorbic acid or catecholamines. Metallic silver is oxidized and may deposit in the tissues, causing arygria. Silver is eliminated primarily in the faeces. (7)
Toxicity ValuesLD50: 100 mg/kg (Oral, Mouse) (6)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesMost silver is produced as a by-product of copper, gold, lead, and zinc refining. Silver is a precious metal used to make ornaments, jewelry, silverware, and currency coins. It is also used in electrical equipment, mirrors, dental fillings, and brazing alloys and solders. Silver compounds are used in photographic film and as antibacterial agents. (7, 8)
Minimum Risk LevelNot Available
Health EffectsSilver itself is not toxic to humans, but most silver salts are. In large doses, silver and compounds containing it can be absorbed into the circulatory system and become deposited in various body tissues, leading to argyria, which results in a blue-grayish pigmentation of the skin, eyes, and mucous membranes. Argyria is rare, and although, so far as known, this condition does not otherwise harm a person's health, it is disfiguring and usually permanent. Mild forms of argyria are sometimes mistaken for cyanosis. (8)
SymptomsExposure to high levels of silver for a long period of time may result in a condition called arygria, a blue-gray discoloration of the skin and other body tissues. Argyria is a permanent effect but does not appear to be harmful to health. Exposure to high levels of silver in the air has resulted in breathing problems, lung and throat irritation, and stomach pains. Skin contact with silver can cause mild allergic reactions such as rash, swelling, and inflammation in some people. (7)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB02659
PubChem Compound ID104755
ChEMBL IDNot Available
ChemSpider ID94565
KEGG IDC06710
UniProt IDNot Available
OMIM ID155550 , 180860 , 224410 , 270685 , 312780
ChEBI ID49468
BioCyc IDAG%2b
CTD IDD012834
Stitch IDSilver
PDB IDAG
ACToR ID6532
Wikipedia LinkSilver
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
  2. AshaRani PV, Low Kah Mun G, Hande MP, Valiyaveettil S: Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano. 2009 Feb 24;3(2):279-90. doi: 10.1021/nn800596w. [19236062 ]
  3. Kim S, Choi JE, Choi J, Chung KH, Park K, Yi J, Ryu DY: Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicol In Vitro. 2009 Sep;23(6):1076-84. doi: 10.1016/j.tiv.2009.06.001. Epub 2009 Jun 7. [19508889 ]
  4. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
  5. Lansdown AB: Critical observations on the neurotoxicity of silver. Crit Rev Toxicol. 2007 Mar;37(3):237-50. [17453933 ]
  6. Lewis RJ (2000). Sax's Dangerous Properties of Industrial Materials. 10th ed. New York, NY: Van Nostrand Reinhold Company.
  7. ATSDR - Agency for Toxic Substances and Disease Registry (1990). Toxicological profile for silver. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  8. Wikipedia. Silver. Last updated Dec 2014. [Link]
  9. International Programme on Chemical Safety (IPCS) INCHEM (1977). WHO Food Additive Series No. 12: Silver. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Superoxide dismutase copper chaperone activity
Specific Function:
May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells.
Gene Name:
ATP7A
Uniprot ID:
Q04656
Molecular Weight:
163372.275 Da
References
  1. Cobine PA, George GN, Winzor DJ, Harrison MD, Mogahaddas S, Dameron CT: Stoichiometry of complex formation between Copper(I) and the N-terminal domain of the Menkes protein. Biochemistry. 2000 Jun 13;39(23):6857-63. [10841766 ]
  2. Barry AN, Otoikhian A, Bhatt S, Shinde U, Tsivkovskii R, Blackburn NJ, Lutsenko S: The lumenal loop Met672-Pro707 of copper-transporting ATPase ATP7A binds metals and facilitates copper release from the intramembrane sites. J Biol Chem. 2011 Jul 29;286(30):26585-94. doi: 10.1074/jbc.M111.229039. Epub 2011 Jun 6. [21646353 ]
General Function:
Glutathione peroxidase activity
Specific Function:
Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-like protective system against peroxide damage in sperm membrane lipids.
Gene Name:
GPX5
Uniprot ID:
O75715
Molecular Weight:
25202.14 Da
References
  1. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
General Function:
Sh3 domain binding
Specific Function:
Protects the hemoglobin in erythrocytes from oxidative breakdown.
Gene Name:
GPX1
Uniprot ID:
P07203
Molecular Weight:
22087.94 Da
References
  1. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
General Function:
Glutathione peroxidase activity
Specific Function:
Could play a major role in protecting mammals from the toxicity of ingested organic hydroperoxides. Tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide but not phosphatidycholine hydroperoxide, can act as acceptors.
Gene Name:
GPX2
Uniprot ID:
P18283
Molecular Weight:
21953.835 Da
References
  1. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
General Function:
Transcription factor binding
Specific Function:
Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione.
Gene Name:
GPX3
Uniprot ID:
P22352
Molecular Weight:
25552.185 Da
References
  1. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
General Function:
Glutathione peroxidase activity
Specific Function:
Not Available
Gene Name:
GPX6
Uniprot ID:
P59796
Molecular Weight:
24970.46 Da
References
  1. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
General Function:
Peroxidase activity
Specific Function:
It protects esophageal epithelia from hydrogen peroxide-induced oxidative stress. It suppresses acidic bile acid-induced reactive oxigen species (ROS) and protects against oxidative DNA damage and double-strand breaks.
Gene Name:
GPX7
Uniprot ID:
Q96SL4
Molecular Weight:
20995.88 Da
References
  1. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
General Function:
Phospholipid-hydroperoxide glutathione peroxidase activity
Specific Function:
Protects cells against membrane lipid peroxidation and cell death. Required for normal sperm development and male fertility. Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development. Protects from radiation and oxidative damage.
Gene Name:
GPX4
Uniprot ID:
P36969
Molecular Weight:
22174.52 Da
References
  1. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
General Function:
Peroxidase activity
Specific Function:
Not Available
Gene Name:
GPX8
Uniprot ID:
Q8TED1
Molecular Weight:
23880.83 Da
References
  1. Dillard CJ, Tappel AL: Mercury, silver, and gold inhibition of selenium-accelerated cysteine oxidation. J Inorg Biochem. 1986 Sep;28(1):13-20. [3760861 ]
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. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
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, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A2
Uniprot ID:
P50993
Molecular Weight:
112264.385 Da
References
  1. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
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:
ATP1A3
Uniprot ID:
P13637
Molecular Weight:
111747.51 Da
References
  1. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
General Function:
Sodium:potassium-exchanging atpase activity
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. Plays a role in sperm motility.
Gene Name:
ATP1A4
Uniprot ID:
Q13733
Molecular Weight:
114165.44 Da
References
  1. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.Involved in cell adhesion and establishing epithelial cell polarity.
Gene Name:
ATP1B1
Uniprot ID:
P05026
Molecular Weight:
35061.07 Da
References
  1. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
Gene Name:
ATP1B2
Uniprot ID:
P14415
Molecular Weight:
33366.925 Da
References
  1. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
General Function:
Sodium:potassium-exchanging atpase activity
Specific Function:
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.
Gene Name:
ATP1B3
Uniprot ID:
P54709
Molecular Weight:
31512.34 Da
References
  1. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
General Function:
Transporter activity
Specific Function:
May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
Gene Name:
FXYD2
Uniprot ID:
P54710
Molecular Weight:
7283.265 Da
References
  1. Bianchini A, Playle RC, Wood CM, Walsh PJ: Mechanism of acute silver toxicity in marine invertebrates. Aquat Toxicol. 2005 Mar 25;72(1-2):67-82. Epub 2004 Dec 29. [15748748 ]
18. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da