Fluoride is the anion F
−, the
reducedRedox describes all chemical reactions in which atoms have their oxidation number changed....
form of
fluorineFluorine is the chemical element with atomic number 9, represented by the symbol F. Fluorine forms a single bond with itself in elemental form, resulting in the diatomic F
2 molecule. F
2 is a supremely reactive, poisonous, pale, yellowish brown gas. Elemental fluorine is the...
. Both organic and inorganic compounds containing the
elementA chemical element is a pure chemical substance consisting of one type of atom distinguished by its atomic number, which is the number of protons in its nucleus. The term is also used to refer to a pure chemical substance composed of atoms with the same number of protons.Common examples of elements...
fluorine are sometimes called fluorides. Fluoride, like other
halideA halide is a binary compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound. Many salts are halides...
s, is a monovalent ion (−1 charge). Its compounds often have properties that are distinct relative to other halides. Structurally, and to some extent chemically, the fluoride ion resembles the
hydroxideIn chemistry, hydroxide is the name for the diatomic anion OH−, consisting of oxygen and hydrogen atoms, usually derived from the dissociation of a base. It is one of the simplest diatomic ions known....
ion. Fluorine-containing compounds range from potent toxins such as
sarinSarin, also known by its NATO designation of GB, is an extremely toxic substance whose sole application is as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...
to life-saving pharmaceuticals such as
efavirenzEfavirenz is a non-nucleoside reverse transcriptase inhibitor and is used as part of highly active antiretroviral therapy for the treatment of a human immunodeficiency virus type 1....
and from refractory materials such as
calcium fluorideCalcium fluoride is an insoluble ionic compound of calcium and fluorine. It occurs naturally as the mineral fluorite and as Blue John, and it is the source of most of the world's fluorine...
to the highly reactive
sulfur tetrafluorideSulfur tetrafluoride is the chemical compound with the formula SF
4. This species exists as a gas at standard conditions. It is a corrosive species that releases dangerous HF upon exposure to water or moisture...
. The range of fluorine-containing compounds is considerable as fluorine is capable of forming compounds with all the elements except helium and neon.
Compounds containing fluoride anions and in many cases those containing covalent bonds to fluorine are called fluorides.
Occurrence
Solutions of inorganic fluorides in water contain F
− and bifluoride HF
2−. Few inorganic fluorides are soluble in water without undergoing significant hydrolysis. Examples of inorganic fluorides include
hydrofluoric acidHydrofluoric acid is a solution of hydrogen fluoride in water. While it is extremely corrosive and difficult to handle, it is technically a weak acid...
(HF),
sodium fluorideSodium fluoride is the inorganic compound with the formula NaF. This colorless solid is a source of the fluoride ion in diverse applications. Sodium fluoride is less expensive and less hygroscopic than the related salt potassium fluoride....
(NaF), and
uranium hexafluorideUranium hexafluoride , referred to as "hex" in the nuclear industry, is a compound used in the uranium enrichment process that produces fuel for nuclear reactors and nuclear weapons. It forms solid grey crystals at standard temperature and pressure , is highly toxic, reacts violently with water...
(UF
6). In terms of its reactivity, fluoride differs significantly from
chlorideThe chloride ion is formed when the element chlorine picks up one electron to form an anion Cl
−...
and other halides, and is more strongly solvated due to its smaller radius/charge ratio. Its closest chemical relative is
hydroxideIn chemistry, hydroxide is the name for the diatomic anion OH−, consisting of oxygen and hydrogen atoms, usually derived from the dissociation of a base. It is one of the simplest diatomic ions known....
. The Si-F linkage is one of the strongest single bonds. In contrast, other silyl halides are easily hydrolyzed.
Natural occurrence
Many fluoride minerals are known, but paramount in commercial importance are
fluoriteFluorite is a halide mineral composed of calcium fluoride, CaF
2. It is an isometric mineral with a cubic habit, though octahedral and more complex isometric forms are not uncommon. Cubic crystals up to 20 cm across have been found at Dalnegorsk, Russia...
and
fluorapatiteFluorapatite, often with the alternate spelling of fluoroapatite, is a mineral with the formula Ca
53F . Fluorapatite is a hard crystalline solid. Although samples can have various color , the pure mineral is colorless as expected for a material lacking transition metals...
. Fluoride is found naturally in low concentration in drinking water and foods. Water with underground sources is more likely to have higher levels of fluoride, whereas the concentration in seawater averages 1.3 parts per million (ppm). Fresh water supplies generally contain between 0.01-0.3 ppm, while the ocean contains between 1.2 and 1.5 ppm.
Applications
Fluorides are pervasive in modern technology.
Hydrofluoric acidHydrofluoric acid is a solution of hydrogen fluoride in water. While it is extremely corrosive and difficult to handle, it is technically a weak acid...
is the most important fluoride synthesized. It is principally used in the production of fluorocarbons and aluminium fluorides. Hydrofluoric acid has a variety of specialized applications, including its ability to dissolve glass.
Organic synthesis
Fluoride reagents are significant in
syntheticOrganic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
organic chemistryOrganic chemistry is a discipline within chemistry which involves the scientific study of the structure, properties, composition, reactions, and preparation of chemical compounds that contain carbon...
. Due to the affinity of
siliconSilicon is the most common metalloid. It is a chemical element, which has the symbol Si and atomic number 14. A tetravalent metalloid, silicon is less reactive than its chemical analog carbon...
for fluoride, and the ability of silicon to expand its coordination number,
silyl etherSilyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy group. The general structure is R1R2R3Si−O−R4 where R4 is an alkyl group or an aryl group. Silyl ethers are usually used as protecting...
protecting groupA protecting group or protective group is introduced into a molecule by chemical modification of a functional group in order to obtain chemoselectivity in a subsequent chemical reaction...
s can be easily removed by the fluoride sources such as
sodium fluorideSodium fluoride is the inorganic compound with the formula NaF. This colorless solid is a source of the fluoride ion in diverse applications. Sodium fluoride is less expensive and less hygroscopic than the related salt potassium fluoride....
and
tetra-n-butylammonium fluorideTetra-n-butylammonium fluoride or TBAF is a quaternary ammonium salt with the chemical formula 4N+F-...
(TBAF).
Enzyme inhibitors
In
biochemistryBiochemistry is the study of the chemical processes in living organisms. It deals with the structure and function of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules....
, fluoride salts are commonly used to
inhibitEnzyme inhibitors are molecules that bind to enzymes and decrease their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
the activity of phosphatases, such as
serineSerine is an organic compound with the formula HO
2CCHCH
2OH.-Occurrence:...
/
threonineThreonine is an α-amino acid with the chemical formula HO
2CCHCHCH
3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
phosphatases. It may do this by replacing the
nucleophilicIn chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases . All molecules or ions with a free pair of electrons can act as nucleophiles...
hydroxyl ion in these enzymes' active sites.
Beryllium fluorideBeryllium fluoride is the chemical compound with the formula BeF2. It is the binary beryllium compound with the greatest amount of ionic character , but even so it is not considered ionic by many chemists...
and
aluminium fluorideAluminium fluoride is the inorganic compound with the formula AlF
3. This colourless solid can be prepared synthetically but also occurs in nature...
are also used as phosphatase inhibitors, since these compounds are structural mimics of the
phosphateA phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
group and can act as analogues of the
transition stateThe transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate...
of the reaction.
Inorganic fluorides
Sulfur hexafluorideSulfur hexafluoride is an inorganic, colorless, odorless, non-toxic and non-flammable gas . has an octahedral geometry, consisting of six fluorine atoms attached to a central sulfur atom. It is a hypervalent molecule. Typical for a nonpolar gas, it is poorly soluble in water but soluble in...
is an inert, nontoxic insulator that is used in electrical transformers.
Uranium hexafluorideUranium hexafluoride , referred to as "hex" in the nuclear industry, is a compound used in the uranium enrichment process that produces fuel for nuclear reactors and nuclear weapons. It forms solid grey crystals at standard temperature and pressure , is highly toxic, reacts violently with water...
is used in the separation of isotopes of uranium between the
fissileIn nuclear physics and nuclear chemistry, nuclear fission is a nuclear reaction in which the nucleus of an atom splits into smaller parts, often producing free neutrons and lighter nuclei, which may eventually produce photons...
isotope
U-235U235 or U-235 may be:* German submarine U-235, a German U-boat of World War II* Uranium-235, an isotope of uraniumbang bang there goes the ship...
and the non-fissile isotope
U-238U238 or U-238 may be:* German submarine U-238, a German World War II U-Boat * Uranium-238, the most common isotope of uranium...
in preparation of
nuclear reactorA nuclear reactor is a device in which nuclear chain reactions are initiated, controlled, and sustained at a steady rate.The most significant use of nuclear reactors is as an energy source for the generation of electrical power and for the power in some ships...
fuelNuclear fuel is any material that can be consumed to derive nuclear energy, by analogy to chemical fuel that is burned to derive energy. By far the most common type of nuclear fuel is heavy fissile elements that can be made to undergo nuclear fission chain reactions in a nuclear fission reactor;...
and atomic bombs. The
volatility of fluoridesFluoride volatility is jargon that describes the volatility of fluorides, which is relevant to the separation of radionuclides. The volatility of fluorides is the basis of technologies used in the processing and reprocessing of nuclear fuel, both of the conventional fuel rods used in today's LWRs...
of uranium and other elements may also be used for nuclear fuel reprocessing.
Fluoropolymers
Fluoropolymers such as polytetrafluoroethylene, Teflon, are used as chemically inert and biocompatible materials for a variety of applications, including as
surgical implantsIn medicine, a prosthesis is an artificial extension that replaces a missing body part. It is part of the field of biomechatronics, the science of fusing mechanical devices with human muscle, skeleton, and nervous systems to assist or enhance motor control lost by trauma, disease, or defect...
such as coronary bypass grafts, and a replacement for
soft tissueIn medicine, the term soft tissue refers to tissues that connect, support, or surround other structures and organs of the body.Soft tissue includes tendons, ligaments, fascia, fibrous tissues, fat, and synovial membranes , and muscles, nerves and blood vessels .It is sometimes defined by what it is...
in cosmetic and
reconstructive surgeryReconstructive surgery is, in its broadest sense, the use of surgery to restore the form and function of the body.Although plastic surgery and plastic surgeons are involved in many aspects of reconstructive surgery, there are other branches of surgery that also perform reconstructive procedures...
. These compounds are also commonly used as
non-stick surfaceA non-stick surface is a surface engineered to reduce the ability of other materials to stick to it. A non-stick coating may be applied to a substrate to produce such a surface.-Teflon:...
s in
cookware and bakewareCookware and bakeware are types of food preparation containers commonly found in the kitchen. Cookware comprises cooking vessels, such as saucepans and frying pans, intended for use on a stove or range cooktop. Bakeware comprises cooking vessels intended for use inside an oven...
, and the fluoropolymer fabric
Gore-TexGore-Tex is a waterproof/breathable fabric, and a registered trademark of W.L. Gore & Associates. It was co-invented by Wilbert L. Gore , Rowena Taylor, and Gore's son, Robert W. Gore. Robert Gore was granted on April 27, 1976, for a porous form of polytetrafluoroethylene with a micro-structure...
used in breathable garments for outdoor use.
Cavity prevention
Fluoride-containing compounds are used in topical and systemic
fluoride therapyFluoride therapy is the delivery of fluoride to the teeth topically or systemically in order to prevent tooth decay which results in cavities. Most commonly, fluoride is applied topically to the teeth using gels, varnishes, toothpaste/dentifrices or mouth rinse. Systemic delivery involves...
for preventing
tooth decayDental caries, also known as tooth decay or cavity, is a disease wherein bacterial processes damage hard tooth structure . These tissues progressively break down, producing dental cavities . Two groups of bacteria are responsible for initiating caries: Streptococcus mutans and Lactobacilli...
. They are used for
water fluoridationWater fluoridation is the controlled addition of fluoride to a public water supply to reduce tooth decay. Fluoridated water has fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding fluoride...
and in many products associated with
oral hygieneTeeth cleaning is the removal of dental plaque from teeth, to prevent cavities , gingivitis, and periodontitis. It is part of a complete program of oral hygiene.-Brushing:...
. Originally,
sodium fluorideSodium fluoride is the inorganic compound with the formula NaF. This colorless solid is a source of the fluoride ion in diverse applications. Sodium fluoride is less expensive and less hygroscopic than the related salt potassium fluoride....
was used to fluoridate water; however, hexafluorosilicic acid (H
2SiF
6) and its salt sodium hexafluorosilicate (Na
2SiF
6) are more commonly used additives, especially in the United States. The fluoridation of water is known to prevent tooth decay and is considered by the U.S.
Centers for Disease Control and PreventionThe Centers for Disease Control and Prevention is a United States federal agency under the Department of Health and Human Services based in Atlanta, Georgia. It works to protect public health and safety by providing information to enhance health decisions, and it promotes health through...
as "one of 10 great public health achievements of the 20th century". In some countries where large, centralized water systems are uncommon, fluoride is delivered to the populace by fluoridating table salt. Fluoridation of water is not without critics, however (see
Opposition to water fluoridation).
Biomedical applications
Positron emission tomographyPositron emission tomography is a nuclear medicine imaging technique which produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
is commonly carried out using fluoride-containing pharmaceuticals such as
fluorodeoxyglucoseFludeoxyglucose or Fluorodeoxyglucose is a glucose analog. Its full chemical name is 2-fluoro-2-deoxy-D-glucose, commonly abbreviated to FDG....
, which is labelled with the radioactive isotope
fluorine-18Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....
that emits
positronThe positron or antielectron is the antiparticle or the antimatter counterpart of the electron. The positron has an electric charge of +1, a spin of , and the same mass as an electron. When a low-energy positron collides with a low-energy electron, annihilation occurs, resulting in the production...
s when it decays into
18O.
Numerous drugs contain fluorine including
antipsychoticAntipsychotics are a group of psychoactive drugs commonly but not exclusively used to treat psychosis, which is typified by schizophrenia, but can also be present in severe bipolar disorder, as well as many other conditions. Over time a wide range of antipsychotics have been developed...
s such as
fluphenazineFluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder...
, HIV protease inhibitors such as
tipranavirTipranavir, or tipranavir disodium, is a nonpeptidic protease inhibitor manufactured by Boehringer-Ingelheim under the trade name Aptivus...
,
antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
s such as
ofloxacinOfloxacin is a fluoroquinolone antibiotic considered to be a second-generation fluoroquinolone. Floxin had been discontinued by the manufacturer, in the United States, effective June 18, 2009, though generic equivalents continue to be available.The fluoroquinolone class of chemotherapeutic agents...
and
trovafloxacinTrovafloxacin is a broad spectrum antibiotic that inhibits the uncoiling of supercoiled DNA in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It was withdrawn from the market due to the risk of hepatotoxicity...
, and anesthetics such as
halothaneHalothane vapour is an inhalational general anaesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anaesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine...
. Fluorine is incorporated in the drug structures to reduce
drug metabolismDrug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
, as the strong C-F bond resists deactivation in the liver by
cytochrome P450 oxidaseCytochrome P450 is a very large and diverse superfamily of hemoproteins found in all domains of life. Cytochromes P450 use a plethora of both exogenous and endogenous compounds as substrates in enzymatic reactions...
s.
Toxicology
Fluoride-containing compounds are so diverse that it is not possible to generalize on their
toxicityToxicity is the degree to which a substance is able to damage an exposed organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
, which depends on their reactivity and structure, and in the case of salts, their solubility and ability to release fluoride ions.
Soluble fluoride salts, of which
NaFThe acronym NAF can mean:* National Abortion Federation* National Academy Foundation - an education non profit organization.* National Academy Foundation School - a public high school located in Baltimore, Maryland....
is the most common, are mildly toxic but have resulted in both accidental and suicidal deaths from
acute poisoningAcute toxicity describes the adverse effects of a substance which result either from a single exposure or from multiple exposures in a short space of time...
. While the minimum fatal dose in humans is not known, a case of a fatal poisoning of an adult with 4 grams of NaF is documented.
Sodium fluorosilicateSodium fluorosilicate is a compound with formula Na2SiF6.-External links:*...
For Na
2SiF
6, the 50% lethal dose (
LD50In toxicology, the median lethal dose, LD50 , LC50 or LCt50 of a toxic substance or radiation is the dose required to kill half the members of a tested population...
) orally in rats is 0.125 g/kg, corresponding to 12.5 for a 100 kg adult.
. The fatal period ranges from 5 min to 12 hours. The mechanism of toxicity involves the combination of the fluoride anion with the calcium ions in the blood to form insoluble calcium fluorideCalcium fluoride is an insoluble ionic compound of calcium and fluorine. It occurs naturally as the mineral fluorite and as Blue John, and it is the source of most of the world's fluorine...
, resulting in hypocalcemia; calcium is indispensable for the function of the nervous system, and the condition can be fatal. Treatment may involve oral administration of dilute calcium hydroxideCalcium hydroxide, traditionally called slaked lime, hydrated lime, slack lime, or pickling lime, is a chemical compound with the chemical formula Ca2. It is a colourless crystal or white powder, and is obtained when calcium oxide is mixed, or "slaked" with water...
or calcium chlorideCalcium chloride, CaCl2, is a common salt. It behaves as a typical ionic halide, and is solid at room temperature. It has several common applications such as brine for refrigeration plants, ice and dust control on roads, and in concrete...
to prevent further absorption, and injection of calcium gluconateCalcium gluconate is a mineral supplement. It is the form of calcium most widely used in the treatment of hypocalcemia. Calcium gluconate contains 9.3% calcium. It is also used to counteract an overdose of magnesium sulfate, often administered to pregnant women experiencing premature labor to slow...
to increase the calcium levels in the blood. Hydrogen fluorideHydrogen fluoride is a chemical compound with the formula HF. It is the principal industrial source of fluorine, often in the aqueous form as hydrofluoric acid, and thus is the precursor to many important compounds including pharmaceuticals and polymers . HF is widely used in the petrochemical...
is more dangerous than salts such as NaF because it is corrosive and volatile, and can result in fatal exposure through inhalation or upon contact with the skin; calcium gluconate gel is the usual antidote.
A few organofluorine compounds are extremely toxic, such as organophosphateAn organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...
s like sarinSarin, also known by its NATO designation of GB, is an extremely toxic substance whose sole application is as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...
and diisopropylfluorophosphateDiisopropyl fluorophosphate is an oily, colorless liquid with the chemical formula C
6H
14FO
3P. It is used in medicine and as an organophosphorous insecticide...
that react with the cholinesterase enzymeIn biochemistry, cholinesterase is an enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.-Types:...
at neuromuscular junctionA neuromuscular junction is the synapse or junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
s and thus block the transmission of nerve impulses to the muscles. Here, a reactive fluorine-phosphorus bond in the inhibitor is the site of nucleophilic attack by a serineSerine is an organic compound with the formula HO
2CCHCH
2OH.-Occurrence:...
residue in the enzyme's active site, causing the loss of a F− ion and alkylationAlkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...
and inactivation of the enzyme.
While PTFE itself is chemically inert and non-toxic, it begins to deteriorate near or above 500 °F (260 °C), and decompose completely at temperatures above 660 °F (350 °C). These degradation products can be lethal to birdBirds are winged, bipedal, endothermic , vertebrate animals that lay eggs. There are around 10,000 living species, making them the most numerous tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Birds range in size from the Bee Hummingbird to the ...
s, and can cause flu-like symptoms in humans. In comparison, cooking fats, oils, and butter will begin to scorch and smoke at about 392 °F (200 °C), and meat is usually fried between 400–450 °F (200–230 °C), but empty cookware can exceed this temperature if left unattended on a hot burner.
A 1959 study, (conducted before the U.S. Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
approved the material for use in food processing equipment) showed that the toxicity of fumes given off by the coated pan on dry heating was less than that of fumes given off by ordinary cooking oils.
See also
- Dental fluorosis
Dental fluorosis is a health condition caused by a child receiving too much fluoride during tooth development. The critical period of exposure is between 1 and 4 years old; children over age 8 are not at risk. In its mild form, which is the most common, fluorosis appears as tiny white streaks or...
- Fluoride therapy
Fluoride therapy is the delivery of fluoride to the teeth topically or systemically in order to prevent tooth decay which results in cavities. Most commonly, fluoride is applied topically to the teeth using gels, varnishes, toothpaste/dentifrices or mouth rinse. Systemic delivery involves...
- Fluoride poisoning
In high concentrations, soluble fluoride salts are toxic and skin or eye contact with high concentrations of many fluoride salts is dangerous. Referring to a common salt of fluoride, NaF, the lethal dose for most adult humans is estimated at 1–10 grams...
- Water fluoridation
Water fluoridation is the controlled addition of fluoride to a public water supply to reduce tooth decay. Fluoridated water has fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding fluoride...
- Halide
A halide is a binary compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound. Many salts are halides...
- PTFE