Ethylenediaminetetraacetic acid

Absorption

Poorly absorbed from the gastrointestinal tract. Well absorbed following intramuscular injection.

Toxicity

Inadvertent administration of 5 times the recommended dose, infused intravenously over a 24 hour period, to an asymptomatic 16 month old patient with a blood lead content of 56 mcg/dl did not cause any ill effects. Edetate calcium disodium can aggravate the symptoms of severe lead poisoning, therefore, most toxic effects (cerebral edema, renal tubular necrosis) appear to be associated with lead poisoning. Because of cerebral edema, a therapeutic dose may be lethal to an adult or a pediatric patient with lead encephalopathy. Higher dosage of edetate calcium disodium may produce a more severe zinc deficiency.

Description

Ethylenediaminetetraacetic Acid (EDTA) is a common polydentate ligand. In EDTA, the hydrogen atoms are easily removed in solution to produce anionic EDTA4-. In its anionic form Ethylenediaminetetraacetic Acid (EDTA) has six binding atoms, two nitrogen and four oxygen.
Ethylenediaminetetraacetic Acid (EDTA) binds to a metal ion at the six binding sites, wrapping itself around the metal ion, forming a very stable complex.the strong grasp of Ethylenediaminetetraacetic Acid (EDTA) on the metal ion is analogous to a crab or lobster clamping down on an object with its claw, hence the name chelation. Ethylenediaminetetraacetic Acid (EDTA) is such an effective chelating agent because it can deactivate a metal at up to six sites.

Chemical properties

white crystals or powder

Chemical properties

EDTA is a white, odorless, crystalline material or white powder

Chemical properties

Edetic acid occurs as a white crystalline powder.

Chemical properties

Ethylenediaminetetraacetic acid is a solid.

History

Ethylenediaminetetraacetic Acid (EDTA) was first synthesized in the early 1930s by the German chemist Ferdinand Münz working for I. G. Farben. Münz, who was looking for a substitute for citric acid to use with dye solutions in the textile industry, was the first to patent a process for Ethylenediaminetetraacetic Acid (EDTA) synthesis in Germany in 1935. Münz subsequently applied for United States patents in 1936 and 1937 (U.S. Patent Number 2130505); his method involved reacting monochloroacetic acid (C2H3ClO2) and ethylene diamine (C2H8N2). Concurrent with Münz’s work, Frederick C. Bersworth in the United States synthesized Ethylenediaminetetraacetic Acid (EDTA) using different methods that gave greater yields and made EDTA’s commercial production economically viable. Bersworth syntheses involved reacting formaldehyde, amines, and hydrogen cyanide. Bersworth and Münz obtained patents for Ethylenediaminetetraacetic Acid (EDTA) production in the 1940s (U.S. Patent Numbers 2407645 and 2461519).

The Uses of Ethylenediaminetetraacetic acid

EDTA, also known as editic acid, is a colorless crystalline substance widely used to chelate metal ions.
Ethylenediaminetetraacetic Acid (EDTA) is marketed in its salt forms such as sodium Ethylenediaminetetraacetic Acid (EDTA) or calcium EDTA. Ethylenediaminetetraacetic Acid (EDTA) hasindustrial and medical uses as a chelating agent. Much of its utility is related to the fact that metals and metal compounds are important catalysts in numerous reactions. By chelatingmetals, Ethylenediaminetetraacetic Acid (EDTA) prevents the metal from catalyzing reactions, thereby limiting degradation, oxidation,and other undesirable reactions.the major industries using Ethylenediaminetetraacetic Acid (EDTA) and other chelatingagents are paper and pulp, cleaning products, chemicals, agriculture, and water treatment.The paper and pulp industry is the major user of EDTA, where it is used to stabilize bleachesby sequestering metals that catalyze the degradation of bleaches. EDTA’s ability to stabilizebleaches also makes them useful in laundry detergents and various other cleaning products.In addition to improving bleaching effi ciency, Ethylenediaminetetraacetic Acid (EDTA) use in detergents and cleansers alsosoftens hard water by tying up divalent metal ions responsible for water hardness, primarilyCa2+ and Mg2+. Its softening ability helps Ethylenediaminetetraacetic Acid (EDTA) reduce scale formation and improves foamingproperties in cleaning formulations. Ethylenediaminetetraacetic Acid (EDTA) is applied in general water treatment to softenwater, helping to prevent scale and corrosion. Ethylenediaminetetraacetic Acid (EDTA) has low toxicity and is used in the foodand beverage industry. Foods naturally contain small traces of metals and small quantities areadded during food processing. Ethylenediaminetetraacetic Acid (EDTA) is used with foods to preserve color and preserve flavor,prevent odors, maintain nutrient content, and extend shelf life. When used in beverages,Ethylenediaminetetraacetic Acid (EDTA) preserves color and stabilizes other ingredients such as citric acid and benzoates. In thechemical industry, Ethylenediaminetetraacetic Acid (EDTA) is used to control metal catalytic processes during reactions. EDTAsalts are used in agriculture to provide metal micronutrients in fertilizers.

The Uses of Ethylenediaminetetraacetic acid

antispasmodic

The Uses of Ethylenediaminetetraacetic acid

Ethylenediamine-N,N,N’N’tetraacetic Acid (EDTA) is a powerful chelating agent; EDTA forms stable complexes with most metal ions. EDTA is used in treatment of lead and heavy metal poisoning of farm a nimals.

The Uses of Ethylenediaminetetraacetic acid

EDTA is helps boost a formulation’s preservative system and is also a chelating agent.

The Uses of Ethylenediaminetetraacetic acid

Ethylenediaminetetraacetate (EDTA) is a sequestrant and chelating agent that functions in water but not in fats and oils. It is used to control the reaction of trace metals with some organic and inorganic components to prevent deterioration of color, texture, and development of precipitates, as well as to prevent oxidation which results in rancidity. The reactive sites of the metal ions are blocked, which prevents their normal reactions. The most common interfering metal ions in food products are iron and copper. It can be used in combination with the antioxidants bht and propyl gallate. It is used in margarine, mayonnaise, and spreads to prevent the vegetable oil from going rancid. It is used in canned corn prior to retorting to prevent discoloration caused by trace quantities of copper, iron, and chromium. It also inhibits copper-catalyzed oxidation of ascorbic acid. It occurs as disodium calcium and disodium dihydrogen . Its use is approved in specified foods, with an average usage level being in the range of 100–300 ppm.

Background

A chelating agent, employed in pharmaceutical manufacturing and as a food additive, effectively sequesters various polyvalent cations. This versatile compound plays a crucial role in pharmaceutical processes, ensuring product stability and quality. Additionally, its application as a food additive underscores its significance in food preservation and enhancement, where it acts as a sequestrant, binding undesirable metal ions and preventing their adverse effects on food quality and shelf life.

Indications

For the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults.

Definition

An organic chelating agent.

Production Methods

Edetic acid may be prepared by the condensation of ethylenediamine with sodium monochloroacetate in the presence of sodium carbonate. An aqueous solution of the reactants is heated to about 90°C for 10 hours, then cooled, and hydrochloric acid is added to precipitate the edetic acid.
Edetic acid may also be prepared by the reaction of ethylenediamine with hydrogen cyanide and formaldehyde with subsequent hydrolysis of the tetranitrile, or under alkaline conditions with continuous extraction of ammonia.

Definition

A compound with the formula (HOOCCH₂)2N(CH₂)2N(CH₂COOH)₂ It is used in forming chelates of transition metals.

brand name

Versene Acid (Dow Chemical).

General Description

Ethylenediamine tetraacetic acid is a colorless crystalline solid. Ethylenediaminetetraacetic acid is slightly soluble in water. The primary hazard is the threat to the environment. Immediate steps should be taken to limit its spread to the environment. Ethylenediaminetetraacetic acid is used in chemical analysis, to make detergents and cleaning compounds, and for many other uses.

Air & Water Reactions

Slightly soluble in water.

Reactivity Profile

Behaves as a weak organic acid. Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt. Carboxylic acids with six or fewer carbon atoms are freely or moderately soluble in water; those with more than six carbons are slightly soluble in water. Soluble carboxylic acid dissociate to an extent in water to yield hydrogen ions. The pH of solutions of carboxylic acids is therefore less than 7.0. Many insoluble carboxylic acids react rapidly with aqueous solutions containing a chemical base and dissolve as the neutralization generates a soluble salt. Carboxylic acids in aqueous solution and liquid or molten carboxylic acids can react with active metals to form gaseous hydrogen and a metal salt. Such reactions occur in principle for solid carboxylic acids as well, but are slow if the solid acid remains dry. Even "insoluble" carboxylic acids may absorb enough water from the air and dissolve sufficiently in Ethylenediaminetetraacetic acid to corrode or dissolve iron, steel, and aluminum parts and containers. Carboxylic acids, like other acids, react with cyanide salts to generate gaseous hydrogen cyanide. The reaction is slower for dry, solid carboxylic acids. Insoluble carboxylic acids react with solutions of cyanides to cause the release of gaseous hydrogen cyanide. Flammable and/or toxic gases and heat are generated by the reaction of carboxylic acids with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Their reaction with carbonates and bicarbonates generates a harmless gas (carbon dioxide) but still heat. Like other organic compounds, carboxylic acids can be oxidized by strong oxidizing agents and reduced by strong reducing agents. These reactions generate heat. A wide variety of products is possible. Like other acids, carboxylic acids may initiate polymerization reactions; like other acids, they often catalyze (increase the rate of) chemical reactions

Agricultural Uses

EDTA is short for ethylenediamhetetraacetic acid, an amino polycarboxylic acid. It is a tetraprotic acid and is represented as H4Y with four carboxyl groups and two nitrogen atoms acting as ligand sites. Thus the compound is a hexadentate ligand. Ligands include ions such as Cl-, NO_2^-and CN- or neutral molecules like NH₃ and H₂O, which possess a lone pair of electrons that can be shared with a metal cation in coordinate covalent bonds.
The water solubility of EDTA is very low and, therefore, its di-sodium salt Na₂H₂Y.2H₂O is commonly used in titrations. The Y^4- forms very stable, one-to-one complexes with practically every metal ion in the Periodic Table. The reactions are carried out in a neutral or alkaline medium as the complex decomposes in acidic medium.
(and hence deterioration) of the food product, (d) to increase the storage life of whole blood by removing free calcium ions (Ca²⁺) to inhibit clotting, and (e) for extracting trace elements, especially copper. EDTA metal complexes, such as NaFeEDTA, MnEDTA, ZnEDTA and CuEDTA are used as fertilizers and foliar sprays.

Pharmaceutical Applications

Edetic acid and edetate salts are used in pharmaceutical formulations, cosmetics, and foods as chelating agents. They form stable water-soluble complexes (chelates) with alkaline earth and heavy metal ions. The chelated form has few of the properties of the free ion, and for this reason chelating agents are often described as ‘removing’ ions from solution; this process is also called sequestering. The stability of the metal–edetate complex depends on the metal ion involved and also on the pH. The calcium chelate is relatively weak and will preferentially chelate heavy metals, such as iron, copper, and lead, with the release of calcium ions. For this reason, edetate calcium disodium is used therapeutically in cases of lead poisoning.
Edetic acid and edetates are primarily used as antioxidant synergists, sequestering trace amounts of metal ions, particularly copper, iron, and manganese, that might otherwise catalyze autoxidation reactions. Edetic acid and edetates may be used alone or in combination with true antioxidants, the usual concentration employed being in the range 0.005–0.1% w/v. Edetates have been used to stabilize ascorbic acid; corticosteroids; epinephrine; folic acid; formaldehyde; gums and resins; hyaluronidase; hydrogen peroxide; oxytetracycline; penicillin; salicylic acid, and unsaturated fatty acids. Essential oils may be washed with a 2% w/v solution of edetate to remove trace metal impurities.
Edetic acid and edetates possess some antimicrobial activity but are most frequently used in combination with other antimicrobial preservatives owing to their synergistic effects. Many solutions used for the cleaning, storage, and wetting of contact lenses contain disodium edetate. Typically, edetic acid and edetates are used in concentrations of 0.01–0.1% w/v as antimicrobial preservative synergists.
Edetic acid and disodium edetate may also be used as water softeners since they will chelate the calcium and magnesium ions present in hard water; edetate calcium disodium is not effective. Many cosmetic and toiletry products, e.g. soaps, contain edetic acid as a water softener.

Biological Activity

Chelating agent; sequesters di- and trivalent metal ions.

Biochem/physiol Actions

Ethylenediaminetetraacetic acid (EDTA) is an anticoagulant, majorly used in preventing clotting of blood samples. EDTA may trigger aggregation of platelets resulting in pseudothrombocytopenia. EDTA along with tetracycline imparts serves as root conditioning agent and provides relief in gum infection. EDTA-tetracycline therapy decreases coronary artery calcium levels in atherosclerosis. Calcium Disodium EDTA administration is effective in slowing down the progression of chronic kidney disease.

Pharmacokinetics

Edetate calcium is a heavy metal chelating agent. The calcium in edetate calcium can be displaced by divalent or trivalent metals to form a stable water soluble complex that can be excreted in the urine. In theory, 1 g of edetate calcium can theoretically bind 620 mg of lead, but in reality only about 5 mg per gram is actually excreted into the urine in lead poisoned patients. In addition to chelating lead, edetate calcium also chelates and eliminates zinc from the body. Edetate calcium also binds cadmium, copper, iron and manganese, but to a much lesser extent than either lead or zinc. Edetate calcium is relatively ineffective for use in treating mercury, gold or arsenic poisoning.

Safety Profile

Poison by intraperitoneal route. Experimental teratogenic and reproductive effects. Mutation data reported. A general-purpose chelaung and complexing agent. When heated to decomposition it emits toxic fumes of NOx.

Safety

Edetic acid and edetates are widely used in topical, oral, and parenteral pharmaceutical formulations. They are also extensively used in cosmetics and food products.
Edetic acid is generally regarded as an essentially nontoxic and nonirritant material, although it has been associated with doserelated bronchoconstriction when used as a preservative in nebulizer solutions. It has therefore been recommended that nebulizer solutions for bronchodilation should not contain edetic acid.
Edetates, particularly disodium edetate and edetate calcium disodium, are used in a greater number and variety of pharmaceutical formulations than the free acid.
Disodium edetate, trisodium edetate, and edetic acid readily chelate calcium and can, in large doses, cause calcium depletion (hypocalcemia) if used over an extended period or if administered too rapidly by intravenous infusion. If used in preparations for the mouth, they can also leach calcium from the teeth. In contrast, edetate calcium disodium does not chelate calcium. Edetate calcium disodium is nephrotoxic and should be used with caution in patients with renal impairment.
The WHO has set an estimated acceptable daily intake for disodium edetate in foodstuffs at up to 2.5 mg/kg body-weight.
LD50 (mouse, IP): 0.25 g/kg
LD50 (rat, IP): 0.397 g/kg

Potential Exposure

EDTA is a white, odorless, crystalline material or white powder

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith soap and water. Seek medical attention immediately. Ifthis chemical has been inhaled, remove from exposure,begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR ifheart action has stopped. Transfer promptly to a medicalfacility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit.

Environmental Fate

EDTA can be very persistent in water, including wastewatertreatment plants. EDTA is often found in the receiving waters of many industrial areas, thus being classified as one of the major organic pollutants discharged in waters. The available ecotoxicity data for EDTA indicate that these compounds are slow to degrade under typical environmental conditions but are not expected to bioconcentrate. EDTA compounds range from practically nontoxic to moderately toxic on an acute basis, depending on the salt. Algae and invertebrates are among the most sensitive species based on predictive modeling for acute and chronic endpoints for EDTA, depending on the compound. EDTA and its salts also do not appear to be very toxic for terrestrial wild mammals, and adverse effects from reasonably expected agricultural uses are not expected.

Metabolism

Almost none of the compound is metabolized.

storage

Although edetic acid is fairly stable in the solid state, edetate salts are more stable than the free acid, which decarboxylates if heated above 150°C. Disodium edetate dihydrate loses water of crystallization when heated to 120°C. Edetate calcium disodium is slightly hygroscopic and should be protected from moisture.
Aqueous solutions of edetic acid or edetate salts may be sterilized by autoclaving, and should be stored in an alkali-free container.
Edetic acid and edetates should be stored in well-closed containers in a cool, dry place.

Shipping

UN3082 Environmentally hazardous substances, liquid, n.o.s., Hazard class: 9; Labels: 9-Miscellaneous hazardous material, Technical Name Required

Purification Methods

Dissolve EDTA in aqueous KOH or ammonium hydroxide, and precipitate it twice with dilute HCl or HNO3. Boil it twice with distilled water to remove mineral acid, then recrystallise it from water or dimethylformamide. Dry it at 110o. It also recrystallises from boiling 1N HCl; wash the crystals with distilled H2O and dry them in vacuo. [Ma & Ray Biochemistry 19 751 1980, Beilstein 4 IV 2449.]

Toxicity evaluation

The principal toxicity of EDTA relates to the metal chelate, especially in lead poisoning. Lead may be released from the chelate in the kidneys, and then the lead may affect the tubules and glomeruli of the kidneys.

Incompatibilities

Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, copper, copper alloys, and nickel

Incompatibilities

Edetic acid and edetates are incompatible with strong oxidizing agents, strong bases, and polyvalent metal ions such as copper, nickel, and copper alloy.
Edetic acid and disodium edetate behave as weak acids, displacing carbon dioxide from carbonates and reacting with metals to form hydrogen.
Other incompatibilities include the inactivation of certain types of insulin due to the chelation of zinc, and the chelation of trace metals in total parenteral nutrition (TPN) solutions following the addition of TPN additives stabilized with disodium edetate. Calcium disodium edetate has also been reported to be incompatible with amphotericin and with hydralazine hydrochloride in infusion fluids.

Regulatory Status

Included in the FDA Inactive Ingredients Database (oral, otic, rectal, and topical preparations; submucosal injection preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.