エデト酸カルシウムナトリウム水和物

Cosmetic ingredients (Calcium Disodium EDTA) -> CIR (Cosmetic Ingredient Review)

Chelating

Foods, Drugs -> FDA Regulatory Status of Color Additives

ANTIOXIDANT, COLOR OR COLORING ADJUNCT, FLAVOR ENHANCER, FUMIGANT, SEQUESTRANT -> FDA Substance added to food

Powder

White powder or flakes

Powder. Solubility in water: at 20 °C a 0.1M solution can be prepared (pH approx 7). Pratically insoluble in organic solvents /Tetrahydrate/

Insoluble in organic solvents

Soluble in water

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antidotes and other substances used in poisonings > Specific

This chemical does not meet GHS hazard criteria for 81.1% (210 of 259) of all reports.

Warning

H315 (17.4%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 259 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Calciate(2-), [[N,N′-1,2-ethanediylbis[N-[(carboxy-.kappa.O)methyl]glycinato-.kappa.N,.kappa.O]](4-)]-, sodium (1:2), (OC-6-21)-

Regulation (EC) No 1831/2003 (amended)

Calciate(2-), [[N,N'-1,2-ethanediylbis[N-[(carboxy-.kappa.O)methyl]glycinato-.kappa.N,.kappa.O]](4-)]-, sodium (1:2), (OC-6-21)- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Calciate(2-), [[N,N'-1,2-ethanediylbis[N-[(carboxy-.kappa.O)methyl]glycinato-.kappa.N,.kappa.O]](4-)]-, sodium (1:2), (OC-6-21)- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

REACH registered substance: Sodium calcium edetate (EC: 200-529-9)

Calcium disodium EDTA: Does not have an individual approval but may be used under an appropriate group standard

Accidental administration of five times the normal dose, infused over 24 hours, caused no adverse effects to a 16 month old child being treated for lead poisoning; Repeated large doses cause degeneration of the proximal tubular cells of the kidneys; See possible adverse effects to patient when used as an intravenous drug; [HSDB] An irritant; [MSDSonline] See Edetic acid.

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#4796]

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#4797]

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.

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.

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.

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.

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.

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.

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.

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.

/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.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Edetate calcium disodium

Ambiguous-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Acute Exposure/ /Investigators/ administered Calcium Disodium EDTA ip in single doses of 1.0 or 2.5 g/kg. Control animals received a corresponding volume of 0.9% saline ip. The kidneys were removed 2 or 24 hours after injection. Microscopic lesions included vacuolization of predominantly the tubular part of the outer cortex of the kidney, fine vacuolization focally located 2 hours after administration of 1.0 g/kg Calcium Disodium EDTA, and changes in the proximal cells of the affected nephron. Vacuolization became more diffuse throughout the proximal convoluted tubule cells and the vacuoles were much larger 24 hours after administration of 1.0 g/kg Calcium Disodium EDTA. The same lesions were observed with the higher dose of Calcium Disodium EDTA; however, sometimes severe cell damage, characterized by the disruption of the brush border and the presence of free nuclei in the tubular lumens, was noted at 24 hours.

/LABORATORY ANIMALS: Acute Exposure/ Iv infusion of CaEDTA in time- and dose-response studies on intestines of rats 6.0 mmoles/kg/24 hr caused shortening of villi, reduced height of epithelium, degeneration of brush border and decreased mitotic index.

/LABORATORY ANIMALS: Acute Exposure/ Investigators/ injected intrastromally varying concentrations of a 0.1 mL solution of Calcium Disodium EDTA into the central cornea of 10 rabbit globes. The animals were sedated with chloropromazine and anesthetized with topical proparacaine. The eyes were examined daily and scored on a scale of 0 to 4+. A 0.2-M solution of Calcium Disodium EDTA caused very mild persistent central haze and edema. This same solution of Calcium Disodium EDTA produced a 0.2 score for opacity and edema on day 2 and 0.3 and 0.2 scores for opacity and edema, respectively, on day 10.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ When 10 rabbits were injected iv with 20 mg/kg Calcium Disodium EDTA on alternate days for 6 months, only slight changes occurred in the blood and blood-forming organs. Erythrocytes with basophilic stippling were observed in the peripheral blood, and the erythroblastic tissue of five of the treated rabbits had lesions of stimulation and impaired maturation. The amount of hemoglobin and the erythrocyte count were not significantly affected, despite slight initial decreases. The reticulocyte count increased slightly as did the amount of serum iron. The amount of copper in whole blood and serum phosphatase activity both were decreased significantly. Other parameters were not affected by treatment with Calcium Disodium EDTA.

For more Non-Human Toxicity Excerpts (Complete) data for DISODIUM CALCIUM EDTA (14 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).

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/

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.

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#4796]

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#4797]

Edetate calcium disodium is a polyvalent ion chelator used to remove lead from the body after lead poisoning. It has a wide therapeutic index, as overdoses must be well in excess of the therapeutic dose to show symptoms. It has a long duration of action, as doses are given at least a day apart. Patients should be counselled regarding the risk of increased intracranial pressure with intravenous infusions.

Edetate calcium disodium distributes into tissues, such as the kidney and bone, where it chelates lead ions. The lead ions are then eliminated in the normal urinary excretion of edetate. Lead in certain tissues such as the liver and bone, redistribute to other tissues after edetate calcium disodium treatment, but lead levels do not decrease to levels seen in unexposed patients.

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.

The half life of edetate calcium disodium is 20-60 minutes.

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.

Edetate calcium disodium is almost completely unmetabolized _in vivo_.

Edetate calcium disodium is not metabolized.

EDETATE CALCIUM DISODIUM

Lead Chelating Activity [MoA]; Decreased Coagulation Factor Activity [PE]; Calcium Chelating Activity [MoA]; Anti-coagulant [EPC]; Lead Chelator [EPC]

Calcium edetate disodium's Cmax and AUC are dependant on renal function. 5% of an oral dose is absorbed from the gastrointestinal tract.

Edetate calcium disodium is 95% eliminated in the urine within 24 hours. An oral dose in rats was 88.32% recovered in the feces and 10.30% recovered in the urine.

The volume of distribution of edetate calcium disodium is 0.19±0.10L/kg.

The mean clearance of edetate in 1 month olds is 54.6mL/min/1.73m². 2-17 year olds have a mean clearance of 113.9±24.4mL/min/1.73m².

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.

CIR ingredient: Calcium Disodium EDTA

Used as an antidote in metal poisoning, a sequestering agent in foods, an in vitro anticoagulant of blood, and an antigushing agent in beer; Also used in drugs, cosmetics, and other chemicals to sequester trace minerals and prevent oxidation and discoloration; [HSDB]

MEDICATION

Used in pharmaceutical formulations as a chelating agent in concentrations between 0.01-0.1% w/v. Usually edentate calcium disodium is used in pharmaceutical formulations in preference to edentate or sodium edentate to prevent calcium depletion occurring in the body.

Calcium Disodium EDTA is a preservative, sequestrant, flavoring agent, and color retention agent.

... Antigushing agent in fermented malt beverages.

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 additives

Fragrance Ingredients

Food Additives -> PRESERVATIVE; SEQUESTRANT -> JECFA Functional Classes

Food Additives -> PRESERVATIVE; SEQUESTRANT -> JECFA Functional Classes

Cosmetics -> Chelating

Wholesale and Retail Trade

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.