Tmic
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-03-06 18:58:17 UTC
Update Date2014-12-24 20:21:20 UTC
Accession NumberT3D0211
Identification
Common NameFluorine
ClassSmall Molecule
DescriptionFluorine (Latin: fluere, meaning to flow), is the chemical element with the symbol F and atomic number 9. It is a nonmetallic, diatomic gas that is a trace element and member of the halogen family. Pure fluorine (F2) is a corrosive, poisonous, pale yellowish brown gas that is a powerful oxidizing agent. It is the most reactive and electronegative of all the elements (4.0), and readily forms compounds with most other elements. Fluorine even combines with the noble gases, krypton, xenon, and radon. Even in dark, cool conditions, fluorine reacts explosively with hydrogen. It is so reactive that glass, metals, and even water, as well as other substances, burn with a bright flame in a jet of fluorine gas. It is far too reactive to be found in elemental form and has such an affinity for most elements, including silicon, that it can neither be prepared nor be kept in ordinary glass vessels. Instead, it must be kept in specialized quartz tubes lined with a very thin layer of fluorocarbons. In moist air it reacts with water to form also-dangerous hydrofluoric acid. Elemental fluorine is a powerful oxidizer which can cause organic material, combustibles, or other flammable materials to ignite. Both elemental fluorine and fluoride ions are highly toxic and must be handled with great care and any contact with skin and eyes should be strictly avoided. Physiologically, fluorine. exists as an ion in the body. When it is a free element, fluorine has a characteristic pungent odor that is detectable in concentrations as low as 20 nL/L. Fluorine is used in dentistry as flouride (Fluorides) to prevent dental caries. Sodium and stannous salts of fluorine are commonly used in dentifrices. Contact of exposed skin with HF (hydrofluoric acid) solutions posses one of the most extreme and insidious industrial threats-- one which is exacerbated by the fact that HF damages nerves in such a way as to make such burns initially painless. The HF molecule is capable of rapidly migrating through lipid layers of cells which would ordinarily stop an ionized acid, and the burns are typically deep. HF may react with calcium, permanently damaging the bone. More seriously, reaction with the body's calcium can cause cardiac arrhythmias, followed by cardiac arrest brought on by sudden chemical changes within the body. These cannot always be prevented with local or intravenous injection of calcium salts. HF spills over just 2.5% of the body's surface area, despite copious immediate washing, have been fatal If the patient survives, HF burns typically produce open wounds of an especially slow-healing nature. Fluorine in the form of fluorspar (also called fluorite) (calcium fluoride) was described in 1530 by Georgius Agricola for its use as a flux , which is a substance that is used to promote the fusion of metals or minerals. In 1670 Schwanhard found that glass was etched when it was exposed to fluorspar that was treated with acid. Karl Scheele and many later researchers, including Humphry Davy, Gay-Lussac, Antoine Lavoisier, and Louis Thenard all would experiment with hydrofluoric acid, easily obtained by treating calcium fluoride (fluorspar) with concentrated sulfuric acid.
Compound Type
  • Food Toxin
  • Halogen
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Metabolite
  • Natural Compound
  • Non-Metal
Chemical Structure
Thumb
Synonyms
Synonym
F(-1)
Fluoride
Fluorine anion
Fluorine(-1) anion
Chemical FormulaF
Average Molecular Mass18.999 g/mol
Monoisotopic Mass18.999 g/mol
CAS Registry Number7782-41-4
IUPAC Namefluoride
Traditional Namefluoride
SMILES[F-]
InChI IdentifierInChI=1S/FH/h1H/p-1
InChI KeyInChIKey=KRHYYFGTRYWZRS-UHFFFAOYSA-M
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as homogeneous halogens. These are inorganic non-metallic compounds in which the largest atom is a nobel gas.
KingdomInorganic compounds
Super ClassHomogeneous non-metal compounds
ClassHomogeneous halogens
Sub ClassNot Available
Direct ParentHomogeneous halogens
Alternative ParentsNot Available
Substituents
  • Homogeneous halogen
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cell surface
  • Cytoplasm
  • Extracellular
  • Plasma Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Kidney
  • Liver
  • Teeth
Pathways
NameSMPDB LinkKEGG Link
Dna replicationNot Availablemap03030
Tryptophan MetabolismSMP00063 map00380
ApoptosisNot Availablemap04210
Cell cycleNot Availablemap04110
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateGas
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point-219.61°C
Boiling PointNot Available
Solubility0.00169 mg/mL at 25°C
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.15ChemAxon
pKa (Strongest Acidic)3.17ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0.87 m³·mol⁻¹ChemAxon
Polarizability0.44 ųChemAxon
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, Positivesplash10-00di-9000000000-15e49aa98d47f1ff8145View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-9000000000-15e49aa98d47f1ff8145View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-9000000000-15e49aa98d47f1ff8145View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-9000000000-0ca435743791c1006c74View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-9000000000-0ca435743791c1006c74View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-9000000000-0ca435743791c1006c74View in MoNA
Toxicity Profile
Route of ExposureOral (8) ; inhalation (8) ; dermal (8)
Mechanism of ToxicityFluoride ions are incorporated into bone by substituting for hydroxyl groups in the carbonate-apatite structure to produce hydroxyfluorapatite, thus altering the mineral structure of the bone. Alteration in mineralization increases hardness and bone mass, but also decreases mechanical strength. A portion of the circulating inorganic fluoride acts as an enzyme inhibitor because it forms metalfluoride-phosphate complexes that interfere with the activity of those enzymes requiring a metal ion cofactor. In addition, fluoride may interact directly with the enzyme or the substrate. It is a general inhibitor of the energy production system of the cell. Fluorine may bind calcium and decrease its concentration. This is thought to indirectly inhibit amelogeninase activity, resulting in altered crystal growth and subsequently causing dental fluorosis. (8)
MetabolismFluorides may be absorbed following inhalation, oral, or dermal exposure. Once in the body, the fluoride ion is transported in the blood and accumulates in the bones and teeth. Fluoride is believed to replace the hydroxyl ion (OH-) and possibly the bicarbonate ion (HCO3-) associated with hydroxyapatite—a mineral phase during formation of bone. The resultant material is hydroxyfluorapatite. Once absorbed, a portion of the fluoride is deposited in the skeleton, and most of the remainder is excreted in the urine, with smaller amounts in feces, and sweat, and saliva. (8)
Toxicity ValuesNot Available
Lethal Dose25 ppm over 5 minutes for an adult human. (7)
Carcinogenicity (IARC Classification)Inorganic fluorides used in drinking-water are not classifiable as to their carcinogenicity to humans (Group 3). (11)
Uses/SourcesFluoride compounds are used in making steel, chemicals, ceramics, lubricants, dyes, plastics, and pesticides. Fluorides are often added to drinking water supplies and to a variety of dental products, including toothpaste and mouth rinses, to prevent dental cavities. (8)
Minimum Risk LevelAcute Inhalation: 0.01 ppm (6)
Health EffectsExposure to high levels of fluoride can result in denser bones. However, if exposure is high enough, these bones may be more fragile and brittle and there may be a greater risk of fracture. Chronic exposure may also cause dental fluorosis, which alters the appearance of children's teeth during tooth development. (8, 10)
SymptomsFluorine is very irritating to the skin, eyes, and respiratory tract. Symptoms of fluoride exposure include abdominal pain, diarrhea, dysphagia, hypersalivation, mucosal injury, nausea, vomiting. Electrolyte abnormalities including hyperkalemia, hypocalcemia, hypoglycemia, and hypomagnesemia may occur. Neurological symptoms include headache, muscle weakness, hyperactive reflexes, muscular spasms, paresthesia seizures, tetanic contractions, and tremors. In severe cases, multiorgan failure will occur. Death typically results from cardiac arrest, shock, widening of QRS, and various arrhythmias occur. (8, 10)
TreatmentOral exposure to fluoride compounds should be treated by giving milk, calcium carbonate, or milk of magnesia to slow absorption. Eye or skin contact should be treated by removing any contaminated clothing and flushing with water. (10)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00662
PubChem Compound ID28179
ChEMBL IDCHEMBL1232767
ChemSpider ID26214
KEGG IDC00742
UniProt IDNot Available
OMIM ID173395177400
ChEBI ID17051
BioCyc IDNot Available
CTD IDD005461
Stitch IDFluorine
PDB IDF
ACToR ID6447
Wikipedia LinkFluorine
References
Synthesis ReferenceLi, Rong. Electrolytic cell for manufacturing fluorine at intermediate temperature. Shiyong Xinxing Zhuanli Shuomingshu (2007), 13pp. CODEN: CNXXAR CN 2895439 Y 20070502 CAN 147:310009 AN 2007:902560
MSDSLink
General References
  1. Schaafsma A, de Vries PJ, Saris WH: Delay of natural bone loss by higher intakes of specific minerals and vitamins. Crit Rev Food Sci Nutr. 2001 May;41(4):225-49. [11401244 ]
  2. Taylor A: Detection and monitoring of disorders of essential trace elements. Ann Clin Biochem. 1996 Nov;33 ( Pt 6):486-510. [8937580 ]
  3. Schneider E, Bolo NR, Frederick B, Wilkinson S, Hirashima F, Nassar L, Lyoo IK, Koch P, Jones S, Hwang J, Sung Y, Villafuerte RA, Maier G, Hsu R, Hashoian R, Renshaw PF: Magnetic resonance spectroscopy for measuring the biodistribution and in situ in vivo pharmacokinetics of fluorinated compounds: validation using an investigation of liver and heart disposition of tecastemizole. J Clin Pharm Ther. 2006 Jun;31(3):261-73. [16789992 ]
  4. Thie JA, Smith GT, Hubner KF: 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography sensitivity to serum glucose: a survey and diagnostic applications. Mol Imaging Biol. 2005 Sep-Oct;7(5):361-8. [16228119 ]
  5. McGoron AJ, Mao X, Georgiou MF, Kuluz JW: Computer phantom study of brain PET glucose metabolism imaging using a rotating SPECT/PET camera. Comput Biol Med. 2005 Jul;35(6):511-31. [15780862 ]
  6. 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]
  7. HSDB: Hazardous Substances Data Bank. National Library of Medicine (2001). [Link]
  8. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for fluorides, hydrogen fluoride, and fluorine. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  9. Wikipedia. Fluorine. Last Updated 27 June 2009. [Link]
  10. Wikipedia. Fluoride poisoning. Last Updated 19 May 2009. [Link]
  11. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>300000 uMNot AvailableBindingDB 26978
References
  1. Innocenti A, Zimmerman S, Ferry JG, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the methanoarchaeon Methanobacterium thermoautotrophicum (Cab) with anions. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4563-7. [15357993 ]
  2. Innocenti A, Lehtonen JM, Parkkila S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of the newly isolated murine isozyme XIII with anions. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5435-9. [15454240 ]
  3. Innocenti A, Firnges MA, Antel J, Wurl M, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5769-73. [15501038 ]
  4. Innocenti A, Hilvo M, Parkkila S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: the membrane-associated isoform XV is highly inhibited by inorganic anions. Bioorg Med Chem Lett. 2009 Feb 15;19(4):1155-8. doi: 10.1016/j.bmcl.2008.12.082. Epub 2008 Dec 25. [19128966 ]
  5. Bertucci A, Innocenti A, Scozzafava A, Tambutte S, Zoccola D, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies with anions and sulfonamides of a new cytosolic enzyme from the scleractinian coral Stylophora pistillata. Bioorg Med Chem Lett. 2011 Jan 15;21(2):710-4. doi: 10.1016/j.bmcl.2010.11.124. Epub 2010 Dec 4. [21208801 ]
  6. Luca VD, Vullo D, Scozzafava A, Carginale V, Rossi M, Supuran CT, Capasso C: An alpha-carbonic anhydrase from the thermophilic bacterium Sulphurihydrogenibium azorense is the fastest enzyme known for the CO2 hydration reaction. Bioorg Med Chem. 2013 Mar 15;21(6):1465-9. doi: 10.1016/j.bmc.2012.09.047. Epub 2012 Sep 29. [23078755 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>300000 uMNot AvailableBindingDB 26978
References
  1. Innocenti A, Zimmerman S, Ferry JG, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of the beta-class enzyme from the methanoarchaeon Methanobacterium thermoautotrophicum (Cab) with anions. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4563-7. [15357993 ]
  2. Innocenti A, Lehtonen JM, Parkkila S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of the newly isolated murine isozyme XIII with anions. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5435-9. [15454240 ]
  3. Innocenti A, Firnges MA, Antel J, Wurl M, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5769-73. [15501038 ]
  4. Innocenti A, Hilvo M, Parkkila S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: the membrane-associated isoform XV is highly inhibited by inorganic anions. Bioorg Med Chem Lett. 2009 Feb 15;19(4):1155-8. doi: 10.1016/j.bmcl.2008.12.082. Epub 2008 Dec 25. [19128966 ]
  5. Bertucci A, Innocenti A, Scozzafava A, Tambutte S, Zoccola D, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies with anions and sulfonamides of a new cytosolic enzyme from the scleractinian coral Stylophora pistillata. Bioorg Med Chem Lett. 2011 Jan 15;21(2):710-4. doi: 10.1016/j.bmcl.2010.11.124. Epub 2010 Dec 4. [21208801 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular Weight:
35032.075 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory70 uMNot AvailableBindingDB 26978
References
  1. Innocenti A, Firnges MA, Antel J, Wurl M, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5769-73. [15501038 ]
  2. Innocenti A, Hilvo M, Parkkila S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: the membrane-associated isoform XV is highly inhibited by inorganic anions. Bioorg Med Chem Lett. 2009 Feb 15;19(4):1155-8. doi: 10.1016/j.bmcl.2008.12.082. Epub 2008 Dec 25. [19128966 ]
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2003). Toxicological profile for fluorides, hydrogen fluoride, and fluorine. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Its role in saliva is unknown.
Gene Name:
CA6
Uniprot ID:
P23280
Molecular Weight:
35366.615 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory600 uMNot AvailableBindingDB 26978
References
  1. Bertucci A, Innocenti A, Scozzafava A, Tambutte S, Zoccola D, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies with anions and sulfonamides of a new cytosolic enzyme from the scleractinian coral Stylophora pistillata. Bioorg Med Chem Lett. 2011 Jan 15;21(2):710-4. doi: 10.1016/j.bmcl.2010.11.124. Epub 2010 Dec 4. [21208801 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA7
Uniprot ID:
P43166
Molecular Weight:
29658.235 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1240 uMNot AvailableBindingDB 26978
References
  1. Vullo D, Ruusuvuori E, Kaila K, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the cytosolic human isozyme VII with anions. Bioorg Med Chem Lett. 2006 Jun 15;16(12):3139-43. Epub 2006 Apr 18. [16621537 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.
Gene Name:
CA9
Uniprot ID:
Q16790
Molecular Weight:
49697.36 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory48000 uMNot AvailableBindingDB 26978
References
  1. Innocenti A, Firnges MA, Antel J, Wurl M, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5769-73. [15501038 ]