Calcium disodium EDTA

374.26800

374.00100

200-529-9

DTXSID2036409|DTXSID20217976

Powder|White powder or flakes

29349990

167.00000

-7.41000

White, odourless crystalline granules or white to nearly white powder, slightly hygroscopic

>300

614.2ºC at 760 mmHg

325.2ºC

Insoluble in organic solvents

Edetate calcium disodium injection should be stored at controlled room temperature (15-30 °C).|Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. Store in a refrigerator.

Odorless

Faint saline taste

Between 6,5 and 7,5 (1 % solution)

Slightly hygroscopic. It acts as a chelating agent for heavy metals.

NONH for all modes of transport

2

R36/37/38

S26-S36

EV7700000

Xi

Stable. Incompatible with strong oxidizing agents.

P261-P305 + P351 + P338

H315-H319-H335

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Edetate calcium disodium has been reported to be physically incompatible with 10% dextrose, 10% invert sugar, 10% invert sugar in 0.9% sodium chloride, lactated Ringer's, Ringer's, and (1/6) M sodium lactate injections and with injectable preparations of amphotericin B and hydralazine hydrochloride.

The following substances may be safely used as diluents in color additive mixtures for food use exempt from certification, subject to the condition that each straight color in the mixture has been exempted from certification or, if not so exempted, is from a batch that has previously been certified and has not changed in composition since certification. If a specification for a particular diluent is not set forth in this part 73, the material shall be of a purity consistent with its intended use. Calcium disodium EDTA is included on this list. Restriction: May be used in aqueous solutions and aqueous dispersions as a preservative and sequestrant in color additive mixtures intended only for ingested use; the color additive mixture (solution or dispersion) may contain not more than 1% by weight of the diluent (calculated as anhydrous calcium disodium ethylenediaminetetraacetate)|The food additive calcium disodium EDTA (calcium disodium ethylene-diaminetetraacetate) may be safely used in designated foods for the purposes and in accordance with the conditions prescribed, as follows: (a) The additive contains a minimum of 99 percent by weight of either the dihydrate C10H12O8N2CaNa2.2H2O or the trihydrate C10H12O8N2CaNa2.3H2O, or any mixture of the two. (b) It is used or intended for use as follows: (1) Alone, in the following foods at not to exceed the levels prescribed, calculated as the anhydrous compound: [Table#4798]|The food additive calcium disodium EDTA (calcium disodium ethylene-diaminetetraacetate) may be safely used in designated foods for the purposes and in accordance with the conditions prescribed, as follows: (a) The additive contains a minimum of 99 percent by weight of either the dihydrate C10H12O8N2CaNa2.2H2O or the trihydrate C10H12O8N2CaNa2.3H2O, or any mixture of the two. (b) It is used or intended for use as follows: ... (2) With disodium EDTA (disodium ethylenediaminetetraacetate) in the following foods at not to exceed, in combination, the levels prescribed, calculated as anhydrous C10H12O8N2CaNa2: [Table#4799]

|Warning|H315 (91.84%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 242 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Danger|H318 (100%): Causes serious eye damage [Danger Serious eye damage/eye irritation]|P280, P305+P351+P338, and P310|Aggregated GHS information provided by 38 companies from 1 notifications to the ECHA C&L Inventory.

Engineering controls such as exhaust ventilation are recommended.|Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.|This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|/Wear/ chemically compatible gloves /and/ safety glasses or goggles. Protect exposed skin.

Zinc supplements (concurrent use may decrease the effectiveness of edetate calcium disodium and zinc supplements due to chelation; zinc supplement therapy should be withheld until edetate calcium disodium therapy is completed)|Edetate calcium disodium interferes with the action of zinc insulin preparations by chelating the zinc.|Concomitant administration of CaNa2EDTA and dimercaprol (BAL) increases the rate of lead mobilization from tissue depots and probably reduces the incidence of central nervous system toxicity when compared with the single use of CaNa2EDTA.|Steroids enhance the renal toxicity of edetate calcium disodium in animals.

LD50 Rat oral 10 g/kg|LD50 Rat ip 3.85 g/kg|LD50 Rat iv 3 g/kg|LD50 Mouse ip 4.5 g/kg|For more Non-Human Toxicity Values (Complete) data for DISODIUM CALCIUM EDTA (6 total), please visit the HSDB record page.

Since lead poisoning occurs in pediatric populations and adults but is frequently more severe in pediatric patients, edetate calcium disodium is used in patients of all ages. The intramuscular route is preferred by some for young pediatric patients. In cases where the intravenous route is necessary, avoid rapid infusion. Urine flow must be monitored throughout therapy; edetate calcium disodium therapy must be stopped if anuria or severe oliguria develops. At no time should the recommended daily dosage be exceeded.|The manufacturer states that the drug is contraindicated in patients with anuria and in those with active renal disease. Edetate calcium disodium also is contraindicated in patients with hepatitis.

According to the 2006 TSCA Inventory Update Reporting data, the number of persons reasonably likely to be exposed in the industrial manufacturing, processing, and use of disodium calcium EDTA is 100 to 999; the data may be greatly underestimated(1).|NIOSH (NOES Survey 1981-1983) has statistically estimated that 24,794 workers (14,315 of these were female) were potentially exposed to disodium calcium EDTA in the US(1).

Edetate calcium disodium is indicated 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. Chelation therapy should not replace effective measures to eliminate or reduce further exposure to lead. /Included in US product label/|The US Food and Drug Administration (FDA) states that the safety and effectiveness of edetate calcium disodium for use in removing heavy metals (eg, mercury) and toxins from the body, management of coronary artery disease, or other uses not described in the manufacturer's labeling have not been established.|VET: Chelating agent in lead poisoning.|/SRP: Former use/ EDTA lead-mobilization test has proved to be a sensitive indicator of excessive body stores of lead. This test was used to evaluate cumulative past lead absorption in 48 men diagnosed as having essential hypertension, a disease considered a possible complication of lead poisoning.|For more Therapeutic Uses (Complete) data for DISODIUM CALCIUM EDTA (8 total), please visit the HSDB record page.

/BOXED WARNING/ WARNINGS: Calcium Disodium Versenate is capable of producing toxic effects which can be fatal. Lead encephalopathy is relatively rare in adults, but occurs more often in pediatric patients in whom it may be incipient and thus overlooked. The mortality rate in pediatric patients has been high. Patients with lead encephalopathy and cerebral edema may experience a lethal increase in intracranial pressure following, intravenous infusion; the intramuscular route is preferred for these patients. In cases where the intravenous route is necessary, avoid rapid infusion. The dosage schedule should be followed and at no time should the recommended daily dose be exceeded.|Fatal medication errors have occurred that involve confusion between edetate calcium disodium (calcium EDTA) and edetate disodium (no longer commercially available in the US). Children and adults have mistakenly received edetate disodium instead of edetate calcium disodium; at least 5 deaths have occurred as a result of inadvertent administration of edetate disodium. Although both edetate calcium disodium and edetate disodium are heavy metal antagonists, the 2 drugs were originally approved by the US Food and Drug Administration (FDA) for different uses and have different effects; edetate disodium was formerly FDA approved for use in selected patients for the emergency treatment of hypercalcemia or for the control of ventricular arrhythmias associated with cardiac glycoside toxicity. Use of edetate disodium may result in a substantial, and sometimes fatal, decrease in serum calcium concentrations. In June 2008, FDA withdrew its prior approval for edetate disodium because of safety concerns following a review of the risk-benefit profile of the drug. FDA stated that it was not considering additional action regarding edetate calcium disodium at that time; most of the fatalities following administration of an EDTA drug have involved medication errors in which edetate disodium was administered instead of edetate calcium disodium. FDA has not received reports of any fatalities resulting from the administration of edetate calcium disodium that involve a medication error.|The manufacturer states that the drug is contraindicated in patients with anuria and in those with active renal disease. Edetate calcium disodium also is contraindicated in patients with hepatitis.|The principal and most serious toxic effect of edetate calcium disodium is renal tubular necrosis, which tends to occur when the daily dose is excessive and may result in fatal nephrosis. Edetate calcium disodium may produce the same signs of renal damage as lead poisoning, such as proteinuria and microscopic hematuria. Rarely, changes in distal renal tubules and glomeruli, glycosuria, presence of large renal epithelial cells in urinary sediment, increased urinary frequency, and urgency may occur. Hydropic degeneration of proximal renal tubular cells also may occur; however, recovery usually occurs following discontinuance of therapy.|For more Drug Warnings (Complete) data for DISODIUM CALCIUM EDTA (24 total), please visit the HSDB record page.

Substances that bind to and sequester CALCIUM ions. (See all compounds classified as Calcium Chelating Agents.)|Substances used in the processing or storage of foods or animal feed including ANTIOXIDANTS; FOOD PRESERVATIVES; FOOD COLORING AGENTS; FLAVORING AGENTS; ANTI-INFECTIVE AGENTS; EXCIPIENTS and other similarly used substances. Many of the same substances are used as PHARMACEUTIC AIDS. (See all compounds classified as Food Additives.)|Agents that prevent BLOOD CLOTTING. (See all compounds classified as Anticoagulants.)

Edetate calcium disodium is poorly absorbed from the gastrointestinal tract.|Edetate calcium disodium is well absorbed following IM or subcutaneous administration. When edetate calcium disodium is administered IV in the treatment of lead poisoning, urinary excretion of chelated lead begins within about 1 hour and peak excretion of chelated lead occurs within 24-48 hours. Colic caused by lead poisoning may disappear within 2 hours, muscular weakness and tremors disappear after 4-5 days, and coproporphyrinuria and stippled erythrocytes usually decrease within 4-9 days after therapy is initiated.|Edetate calcium disodium is distributed mainly into extracellular fluid. The drug does not penetrate erythrocytes...|Following parenteral administration, it is rapidly excreted by glomerular filtration in urine, either unchanged or as metal chelates. Following IV administration, 50% of a dose appears in urine within 1 hour and 95% within 24 hours. ... Changes in urine flow and/or pH do not affect the excretion rate of edetate calcium disodium, but impaired renal function with reduced glomerular filtration delays excretion of the drug and thus may increase its nephrotoxicity.|For more Absorption, Distribution and Excretion (Complete) data for DISODIUM CALCIUM EDTA (10 total), please visit the HSDB record page.

Edetate calcium disodium is not metabolized.

The plasma half-life of the drug has been reported to be 20-60 minutes following IV administration and 1.5 hours following IM administration.

The calcium in edetate calcium disodium can be displaced by divalent and trivalent metals, particularly lead, to form stable soluble complexes that can then be excreted in urine. Unlike edetate disodium (no longer commercially available in the US), edetate calcium disodium is saturated with calcium and therefore can be administered IV in relatively large quantities without causing any substantial changes in serum or total body calcium concentrations. Although 1 g of edetate calcium disodium theoretically sequesters 620 mg of lead, an average of only 3-5 mg of lead is excreted in urine following parenteral administration of 1 g of the drug to patients with symptoms of acute lead poisoning or with high concentrations of lead in soft tissues.|Parenteral administration of edetate calcium disodium chelates and greatly increases the urinary excretion of zinc and, to a much lesser extent, cadmium, manganese, iron, and copper. Excretion of uranium, plutonium, yttrium, and some other heavier radioactive isotopes can be increased to a limited extent by edetate calcium disodium chelation. Although mercury readily displaces calcium from edetate calcium disodium in vitro, patients with mercury poisoning do not respond to the drug.|The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron mobilized are not significant. Copper is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased.|The primary source of lead chelated by calcium disodium edetate is from bone; subsequently, soft-tissue lead is redistributed to bone when chelation is stopped. There is also some reduction in kidney lead levels following chelation therapy.|For more Mechanism of Action (Complete) data for DISODIUM CALCIUM EDTA (6 total), please visit the HSDB record page.

Nephrotoxicity (e.g., acute tubular necrosis, proteinuria, and hematuria) may be minimized by adequate hydration, establishment of adequate urine flow, avoidance of excessive doses, and limitation of continuous administration to 5 or fewer days. Laboratory assessment of renal function should be performed daily during treatment for severe intoxication and after the second and fifth days in other cases.|Cerebral edema should be treated with repeated doses of mannitol. Steroids enhance the renal toxicity of edetate calcium disodium in animals and, therefore, are no longer recommended. Zinc levels must be monitored. Good urinary output must be maintained because diuresis will enhance drug elimination. It is not known if edetate calcium disodium is dialyzable.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ /Investigators/ patch-tested 50 subjects with 0.01% to 10% aqueous Calcium Disodium EDTA (pH 4.6 to 4.8). The test group included both normal volunteers and patients with assorted dermatoses. The test sites were covered with occlusive patches for 48 hours and were examined 30 minutes, 24 hours, and 48 hours after patch removal. One normal volunteer and two patients had positive reactions, and were subsequently tested with 0.1% to 1% EDTA in petrolatum. For the two patients, second challenge was performed "several weeks" after the acute dermatitis subsided. Two of the three subjects also cross-reacted with 0.01% to 10% aqueous ethylenediamine and/or ophthalmic drops containing 0.01% to 0.1% EDTA. ... The investigators concluded that Calcium Disodium EDTA was a weak sensitizer.|/HUMAN EXPOSURE STUDIES/ When eight hypercholesterolemic patients were treated with Disodium Calcium EDTA for 10 days, marked increases were observed in the renal excretion of zinc (10-fold) and lesser increases were observed for cadmium, manganese, lead, and vanadium. The patients were treated with 1.0 to 4.0 g of the chelating agent dissolved in 500 mL of 5% glucose in water. The untreated control group consisted of 24 normal subjects, who each provided a 24-hour sample. Day-to-day variations and the effects of pH changes and dilution were determined using an additional subject. The urinary excretions of titanium, chromium, tin, molybdenum, silver, and nickel were not changed. In addition, the average decrease in plasma cholesterol concentration was 96 mg/100 mL.|/HUMAN EXPOSURE STUDIES/ Ethylene diamine tetraacetate calcium disodium salt (EDTA Ca Na2), 1 g dissolved in 250 mL of 5% w/v glucose solution, was infused intravenously over 1 hr into 10 healthy subjects (eight males and two females). Urines were collected over 24 hr, the day before and on the day of the EDTA Ca Na2 infusion test. The elements Al, B, Ba, Cu, Fe, Mn, Si, Sr, Zn, Na, K, Ca, Mg, S and P were measured by inductively coupled plasma optical emission spectrometry. Pb was measured by inductively coupled plasma mass spectrometry. The EDTA Ca Na2 infusion increased the 24 hr elimination of Al from 9.8 ug to 58 ug, of Fe from 66 to 121 ug, of Mn from 2.9 to 16.5 ug, of Pb from 9.8 to 56 ug and of Zn from 623 to 8847 ug. The ratio of the increase of urinary elimination induced by EDTA Ca Na2 was about 2 for Fe, 5 for Al, Pb and Mn, and 15 for Zn.|/SIGNS AND SYMPTOMS/ 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.|For more Human Toxicity Excerpts (Complete) data for DISODIUM CALCIUM EDTA (9 total), please visit the HSDB record page.

Acid, Edetic

Calcium Disodium Versenate injection, 5 mL ampul containing 200 mg of edetate calcium disodium per mL (1 g per ampul), in boxes containing 6 ampuls.|The food- and pharmaceutical-grade chemical is a mixture of the dihydrate and trihydrate of Calcium Disodium EDTA (predominantly the dihydrate), and contains not less than 97.0% and not more than 100.2% of C10H12CaN2Na2O8, calculated on the anhydrous basis.|Grades: USP, FCC

Food, beverage, and tobacco product manufacturing|Calciate(2-), [[N,N'-1,2-ethanediylbis[N-[(carboxy-.kappa.O)methyl]glycinato-.kappa.N,.kappa.O]](4-)]-, sodium (1:2), (OC-6-21)-: ACTIVE|Ethylenediaminetetraacetic acid (edta), its sodium salt (... Na2edta), and closely related compounds chelate many divalent and trivalent metals.|... Edetate calcium disodium (CaNa2edta) can be used for treatment of poisoning by metals that have higher affinity for the chelating agent than does Ca2+.|The calcium disodium salt is a mixture of di- and trihydrate disodium calcium EDTA.|Sequestering agents: 1 g complexes 215 mg CaCO3. Usually added to pharmaceuticals in form of calcium disodium salt to prevent calcium-depleting action in the body.

Anion-exchange column chromatography of EDTA, DTPA, and the DTPA complexes of calcium and plutonium.|Analyte: disodium calcium EDTA; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: disodium calcium EDTA; matrix: chemical identification; procedure: visual reaction (white precipitate) with methyl red, ammonium hydroxide, hydrochloric acid, and ammonium oxalate (Calcium test)|Analyte: disodium calcium EDTA; matrix: chemical identification; procedure: visual reaction (intense yellow color in nonluminous flame) with potassium carbonate and potassium pyroantimonate (Sodium test)|For more Analytic Laboratory Methods (Complete) data for DISODIUM CALCIUM EDTA (10 total), please visit the HSDB record page.

Food additives|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Cosmetics -> Chelating

Food Additives -> PRESERVATIVE; SEQUESTRANT;