Absorption, Distribution and Excretion
Poorly absorbed via the gastrointestinal tract. Goodly absorbed after intramuscular injection. Primarily excreted via the kidneys, approximately 50% is excreted within 1 hour, and over 95% within 24 hours. This compound undergoes minimal metabolism. The study method for (14C-EDTA) was similar to that for (14C-diethylenetriaminepentaacetic acid (DTPA). Four patients received 10 to 15 mg of (14C-DTPA, 14C activity of 15 to 20 pCi) intravenously. Two patients received oral administration of either 3 mg (14C-EDTA, 14C activity of 5 to 10 pCi) or 50 mg (14C-EDTA, 14C activity of 75 to 100 pCi). The urinary excretion pattern of (14C-EDTA) was similar to that of (14C-DTPA. Following intravenous administration of (14C-DTPA), the kidneys were the primary route of excretion. After 24 hours, 90% to 100% of (14C-DTPA) was excreted. The dose was excreted in the urine. 95% to 100% of the dose was excreted in the feces within 2 to 5 days after oral administration of (14)C-DTPA. The urinary excretion rate was less than 8% in all 7 patients who received oral (14)C-DTPA. Similar results were obtained with (14)C-EDTA, although (14)C-EDTA was administered orally to two patients. Furthermore, no (14)C activity was detected in blood samples collected 1 hour to 3 days after oral administration of (14)C-DTPA. Similar results were obtained with (14)C-EDTA. /Investigatos/ found that increasing EDTA concentration increased its binding to albumin per milligram. This binding was enhanced as pH increased from 5.1 to 8.2, and the β-globulin component bound more EDTA than other plasma proteins. /Investigators/ reported that (51)Cr-EDTA could passively cross the canine gastrointestinal epithelium. Researchers used a concentration of 9.0 mM... 0.5 mL of the chelate was used to treat the demuscularized stomach, ileum, and colon. The flux of the chelate was highest in the ileum, followed by the colon, and lowest in the stomach. No net accumulation of the probe was observed. Furthermore, blocking neurons with tetrodotoxin did not affect the transport of the chelate in the ileum. The researchers hypothesized that (51)Cr-EDTA is transported from the intestinal lumen via a bypass pathway. The researchers instilled a solution containing 5 MBq (51)Cr-EDTA (dissolved in 14 mL of isotonic saline) into the nasal cavities of 6 smokers and 12 nonsmokers and exposed them for 15 minutes. Urine was collected 24 hours after instillation. The median recovery of the chelate in the urine of smokers was 0.07 mL, and the median recovery of the chelate in the urine of nonsmokers was 0.16 mL. After repeated instillation with the addition of 0.6% sodium sulfosuccinate to the solution, the median recovery in the 6 nonsmokers increased to 1.13 mL. mL. Researchers concluded that nasal airway absorption was not increased in smokers compared to non-smokers. Researchers also administered 5 MBq of (51)Cr-EDTA and 0.6% sodium sulfosuccinate (dissolved in 2.0 mL of physiological saline) to four subjects to determine the gastrointestinal absorption of EDTA. The average amount of chelates recovered in urine was equivalent to 1.4% of the administered dose. For more data on absorption, distribution and excretion (complete) of EDTA (11 items in total), please visit the HSDB record page. After intravenous administration, the chelates formed were excreted in urine, with 50% excreted within 1 hour and more than 95% excreted within 24 hours. Disodium EDTA…is poorly absorbed in the gastrointestinal tract and has fewer adverse reactions when used as an excipient in pharmaceutical preparations. Twenty male Sprague-Dawley rats were divided into four groups of five. Group 1 rats were injected intraperitoneally with (14)Cr-EDTA. Disodium EDTA was applied to the skin of rats in Group 2 after hair removal, and to rats in Group 3 after hair removal and skin abrasion treatment (ablation every 2 or 3 cm). Group 4 was the control group. The specific activity of (14)C disodium EDTA was 21.6 mCi/mM, and it was dissolved in physiological saline to prepare a solution with a concentration of 50 pCi/mL. Rats in the intraperitoneal injection group were injected with 0.5 mL of this solution, i.e., 25 pCi of (14)C disodium EDTA. Animals that received the compound through skin application had 25 pCi of (14)C disodium EDTA applied to their skin. Disodium EDTA ointment (components: modulan, mineral oil, petrolatum, cetyl alcohol, in a ratio of 35:21:25:12) was applied to an area of 50 square centimeters onto a thin polyethylene film. The film was fixed to the torso of each animal with tape. Rats wore collars around their necks. All animals were decapitated 24 hours after treatment. 24 hours after intraperitoneal injection of (14)C disodium EDTA, the drug distribution in each tissue (per 100 mg wet weight) was as follows: liver 577±13, small intestine 631±25, large intestine 696±19, kidney 1964±220. 24 hours after application to normal skin, the drug distribution in each tissue was as follows: liver 6±4, small intestine 99±22, large intestine 107±24, kidney 29±12. 24 hours after application to broken skin... After hours, the drug distribution in various tissues was as follows: liver 139±34, small intestine 214±76, large intestine 309±115, kidney 222±30.
/Researchers/reported that rats fed 0.5% (14)C disodium ethylenediaminetetraacetate, 1.0% and 5.0% disodium ethylenediaminetetraacetate for 12 weeks excreted 82.2% and 44.5% of the ingested dose in urine and feces, respectively. And 45.4%. Feces contained 99.4%, 98.2%, and 97.5% of the excrement, respectively, and urine contained 0.6%, 1.8%, and 2.5% of the excrement (corresponding to the respective doses).
For more complete data on the absorption, distribution, and excretion of disodium ethylenediaminetetraacetate (7 types), please visit the HSDB record page.

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Metabolism/Metabolites
This compound undergoes almost no metabolism.
It has been reported that disodium ethylenediaminetetraacetate is mainly excreted unchanged.
This compound undergoes almost no metabolism.

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Biological Half-Life
The half-life of disodium ethylenediaminetetraacetate is 20 to 60 minutes.
...After intravenous injection of disodium ethylenediaminetetraacetate, approximately 50% is excreted within 1 hour, and 90% within 7 hours. After intravenous injection, the chelates formed are excreted in the urine, with 50% excreted within 1 hour and over 95% within 24 hours.

Toxicity Summary
The pharmacological action of calcium edetate sodium is due to its chelation with divalent and trivalent metals. Any metal capable of displacing calcium ions from the molecule can form stable chelates with calcium edetate sodium; lead, zinc, cadmium, manganese, iron, and mercury all possess this property. Manganese and iron are metabolized in negligible amounts. Copper is not mobilized, while mercury cannot participate in chelation because it is too tightly bound to its ligands in the body or stored in inaccessible body cavities. Intravenous injection of calcium edetate sodium does not increase calcium excretion, but zinc excretion increases significantly. Toxicity Data
In a 16-month-old, asymptomatic patient with a blood lead level of 56 mcg/dl, intravenous infusion of calcium edetate sodium at five times the recommended dose over 24 hours was administered without any adverse reactions. Sodium calcium edetate can exacerbate the symptoms of severe lead poisoning; therefore, most toxic reactions (cerebral edema, renal tubular necrosis) appear to be related to lead poisoning. Even therapeutic doses can be fatal to adults or children with lead encephalopathy due to cerebral edema. Higher doses of calcium sodium EDTA may lead to more severe zinc deficiency.
Interactions
Total myocardial calcium levels were very high in rats treated with doxorubicin. EDTA treatment reduced calcium levels almost to normal; however, the histological changes in the heart induced by doxorubicin were not prevented.
This study evaluated the effect of EDTA (ethylenediaminetetraacetic acid) on the antibacterial activity of 10% sodium sulfacetamide solution by bactericidal rate and minimum inhibitory concentration (MIC). Regardless of the preservative, EDTA increased the bactericidal rate against Pseudomonas spp., Serratia spp., and Candida spp., but did not increase the MIC.
...Increased drug absorption...occurred...in the presence of ethylenediaminetetraacetic acid (EDTA). Following oral administration (100-500 mg/kg in rats), chelating agents enhanced the absorption of lipid-insoluble substances such as heparin, sulfonyl polysaccharides, mannitol, inulin, decylamine, sulfanilic acid, and phenol red, substances that are typically difficult to absorb from the gastrointestinal tract. The diversity of the chemical structures of these compounds suggests that the chelating agents act non-specifically and do not affect the physical or chemical state of the compounds in the intestine… There is direct evidence that EDTA's mechanism of action is through increasing the permeability of the intestinal epithelium… EDTA may alter permeability by widening the intercellular spaces of epithelial cells through enlargement of membrane pores or removal of calcium ions. We investigated the effects of EDTA on the contractile response of hamster cremasteric arterioles and rat aortic strips to epinephrine (EPI) or norepinephrine (NOR). In the presence of EDTA, lower concentrations of EPI or NOR induced similar contractile responses. Individual responses were maintained in the presence of EDTA; however, the responses rapidly declined in the absence of EDTA. Clearly, oxidation of EPI and NOR reduces apparent vascular reactivity, while EDTA can prevent or delay this reduction. More complete data on interactions with ethylenediaminetetraacetic acid (EDTA) (out of 8) can be found on the HSDB record page. Researchers reported that disodium EDTA (10 mg/mL) increased the intestinal absorption of neutral, basic, and acidic compounds in male Sprague-Dawley rats. This chelator increased the absorption of (14)C-mannitol and (14)C-inulin from <2% to 7%–1%, (14)CN-methyldecylamine from 2%–3% to 11%–15%, and sulfamethoxam from 11%–14% to 26%–32%. Plasma concentrations of the drugs were increased five to six times compared to the control group.
When 1% (w/v; 24 mM) disodium EDTA was used in combination with 1% (w/v) reduced glutathione, it increased the absorption of acetazolamide in the small intestine of male Charles River rats. Intestinal absorption increased by 1.5 to 2 times; however, treatment with EDTA and glutathione did not affect gastric absorption. Researchers believe that disodium EDTA alters the water permeability of intestinal epithelial cells by chelating magnesium and calcium ions, thereby causing epithelial cell separation.

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Non-human toxicity values
Rat intraperitoneal LD50: 512.9 mg/kg EDTA (1.38 mM/kg)
Mouse intraperitoneal LD50: 250 mg/kg
Rat intraperitoneal LD50: 397 mg/kg
Mouse oral LD50: 30 mg/kg
Mouse oral LD50: 400 mg/kg
Rat oral LD50: 3.7 g/kg
Rabbit intravenous LD50: 47 mg/kg
Rabbit oral LD50: 2300 mg/kg
For more complete (8 values) non-human toxicity data for disodium ethylenediaminetetraacetate (EDTA disodium), please visit the HSDB record page.

[1]. Artifact-inducing enrichment of ethylenediaminetetraacetic acid and ethyleneglycoltetraacetic acid on anion exchange resins. Anal Biochem. 2011 May 1;412(1):34-9.

[2]. The role of ethylenediamine tetraacetic acid (EDTA) as in vitro anticoagulant for diagnostic purposes. Clin Chem Lab Med. 2007;45(5):565-76.

[3]. Chelation therapy in the treatment of cardiovascular diseases. J Clin Lipidol. 2016 Jan-Feb;10(1):58-62.

[4]. The effect of ethylenediaminetetra-acetic acid on the cell walls of some gram-negative bacteria. J Gen Microbiol. 1965 Jun;39(3):385-99.

[5]. Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory activities in experimental liver fibrosis. Redox Rep. 2011;16(2):62-70.

[6]. Remediation of heavy metals contaminated silty clay loam soil by column extraction with ethylenediaminetetraacetic acid and nitrilo triacetic acid. Journal of Environmental Engineering, 2017, 143(8): 04017026.

[7]. Ethylenediaminetetraacetic acid (EDTA) enhances cAMP production in human TDAG8-expressing cells. Biochem Biophys Res Commun. 2022 Oct 20;626:15-20.

Therapeutic Uses
Anticoagulant; Antidote; Chelating agent Ethylenediaminetetraacetic acid (EDTA) has been used to treat alkali (especially lime) corneal burns. Since 1966, (51)Cr-EDTA has been used as a radiotracer to assess glomerular filtration rate. Chelating therapy with EDTA has been used to treat atherosclerotic cardiovascular disease since 1955, but its efficacy has been controversial in recent years. /Previous Uses/ For more complete data on the therapeutic uses of EDTA (8 items in total), please visit the HSDB record page. Anticoagulant; Chelating agent; Food additive Endartate (edetate disodium injection, USP) is indicated for the treatment of emergency hypercalcemia in specific patients and for the control of ventricular arrhythmias associated with digitalis poisoning. /US Product Label Includes/
Disodium edetate can also be used as an anticoagulant because it chelates calcium ions, thereby preventing blood clotting in vitro. A concentration of 0.1% w/v is used for low-dose hematologic tests, and a concentration of 0.3% w/v is used for transfusions.
Disodium edetate is sometimes used to terminate the effects of injected calcium, antagonize digitalis toxicity, or inhibit tachyarrhythmias. /Previous/
For more complete data on the therapeutic uses of disodium edetate (of 8 types), please visit the HSDB record page.

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Drug Warning
…Direct contact with edetate may cause skin allergies (eczema) or allergic conjunctivitis.
/Black Box Warning/ This drug is recommended for specific patients only if the clinical severity is sufficient to support aggressive measures related to this type of treatment.
Clinical studies of disodium edetate did not include a sufficient number of patients aged 65 years and older, therefore it is impossible to determine whether there are differences in response between them and younger subjects. Other reported clinical experiences have not found differences in response between elderly and younger patients. Generally, dosage selection should be cautious in elderly patients due to their higher incidence of impaired liver, kidney, or cardiac function, and the presence of other medical conditions or ongoing medication treatments. Fatal medication errors have occurred due to confusion between calcium edetate (EDTA calcium) and disodium edetate (currently discontinued in the US). Children and adults have been mistreated with disodium edetate instead of calcium edetate; at least five deaths were attributed to the misuse of disodium edetate. Although both calcium edetate and disodium edetate are heavy metal antagonists, they were initially approved by the US Food and Drug Administration (FDA) for different purposes and have different mechanisms of action; disodium edetate was approved by the FDA for the emergency treatment of hypercalcemia or the control of ventricular arrhythmias associated with cardiac glycoside poisoning in specific patients. Use of disodium edetate can lead to a significant decrease in serum calcium levels, sometimes fatal. In June 2008, after reviewing the risk-benefit ratio of the drug, the FDA revoked its previous approval of disodium edetate due to safety concerns. The FDA stated at the time that it was not considering further action on calcium disodium edetate; most deaths from disodium edetate were related to medication errors, specifically the misuse of disodium edetate instead of calcium disodium edetate. The FDA has not received any reports of deaths due to the use of calcium disodium edetate. Disodium edetate injection is contraindicated in patients with anuria. This product is not indicated for the treatment of age-related systemic arteriosclerosis. For more complete data on drug warnings for disodium ethylenediaminetetraacetate (EDTA) (22 in total), please visit the HSDB record page. Pharmacodynamics: Disodium ethylenediaminetetraacetate is a heavy metal chelator. The calcium in disodium ethylenediaminetetraacetate can be replaced by divalent or trivalent metals to form a stable, water-soluble complex that can be excreted in urine. Theoretically, 1 gram of disodium EDTA can bind 620 milligrams of lead, but in reality, only about 5 milligrams of lead per gram of disodium EDTA are excreted in the urine of lead-poisoned patients. Besides chelating lead, disodium EDTA can also chelate zinc and excrete it from the body. Disodium EDTA can also bind cadmium, copper, iron, and manganese, but its binding capacity is much lower than that of lead and zinc. Calcium edetate is relatively less effective in treating mercury, gold, or arsenic poisoning.

C10H16N2O8

292.2426

292.09

60-00-4

Ethylenediaminetetraacetic acid trisodium salt;150-38-9;Ethylenediaminetetraacetic acid sodium hydrate;10378-23-1;Ethylenediaminetetraacetic acid disodium dihydrate;6381-92-6;Ethylenediaminetetraacetic acid tetrasodium;64-02-8;EDTA-d12;203806-08-0;Ethylenediaminetetraacetic acid-d16;203805-96-3

6049

White to off-white solid powder

1.6±0.1 g/cm3

614.2±55.0 °C at 760 mmHg

250 °C (dec.)(lit.)

325.2±31.5 °C

0.0±3.8 mmHg at 25°C

1.580

-0.43

4

10

11

20

316

0

KCXVZYZYPLLWCC-UHFFFAOYSA-N

InChI=1S/C10H16N2O8/c13-7(14)3-11(4-8(15)16)1-2-12(5-9(17)18)6-10(19)20/h1-6H2,(H,13,14)(H,15,16)(H,17,18)(H,19,20)

2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

0.1 M NaOH : ~6.67 mg/mL (~22.82 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)