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DSSTox_CID_2977

DSSTox_CID_2977

Synopsis, Chemistry

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Also known as: Edta, Ethylenediaminetetraacetic acid, 60-00-4, Edathamil, Versene, Endrate

Molecular Formula

C₁₀H₁₆N₂O₈

Molecular Weight

292.24 g/mol

InChI Key

KCXVZYZYPLLWCC-UHFFFAOYSA-N

FDA UNII

9G34HU7RV0

A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.

Edetic acid is a Lead Chelator and Anti-coagulant. The mechanism of action of edetic acid is as a Lead Chelating Activity and Calcium Chelating Activity. The physiologic effect of edetic acid is by means of Decreased Coagulation Factor Activity.

1 2D Structure

DSSTox_CID_2977

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

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

2.1.2 InChI

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)

2.1.3 InChI Key

KCXVZYZYPLLWCC-UHFFFAOYSA-N

2.1.4 Canonical SMILES

C(CN(CC(=O)O)CC(=O)O)N(CC(=O)O)CC(=O)O

2.2 Other Identifiers

2.2.1 UNII

9G34HU7RV0

2.3 Synonyms

2.3.1 MeSH Synonyms

1. Acid, Edetic

2. Acid, Ethylenediaminetetraacetic

3. Acid, Ethylenedinitrilotetraacetic

4. Calcitetracemate, Disodium

5. Calcium Disodium Edetate

6. Calcium Disodium Versenate

7. Calcium Tetacine

8. Chelaton 3

9. Chromium Edta

10. Copper Edta

11. Coprin

12. Dicobalt Edta

13. Dinitrilotetraacetate, Disodium Ethylene

14. Dinitrilotetraacetate, Ethylene

15. Disodium Calcitetracemate

16. Disodium Edta

17. Disodium Ethylene Dinitrilotetraacetate

18. Disodium Versenate, Calcium

19. Distannous Edta

20. Edathamil

21. Edetate Disodium Calcium

22. Edetate, Calcium Disodium

23. Edetates

24. Edetic Acid, Calcium Salt

25. Edetic Acid, Calcium, Sodium Salt

26. Edetic Acid, Chromium Salt

27. Edetic Acid, Dipotassium Salt

28. Edetic Acid, Disodium Salt

29. Edetic Acid, Disodium Salt, Dihydrate

30. Edetic Acid, Disodium, Magnesium Salt

31. Edetic Acid, Disodium, Monopotassium Salt

32. Edetic Acid, Magnesium Salt

33. Edetic Acid, Monopotassium Salt

34. Edetic Acid, Monosodium Salt

35. Edetic Acid, Potassium Salt

36. Edetic Acid, Sodium Salt

37. Edta

38. Edta, Chromium

39. Edta, Copper

40. Edta, Dicobalt

41. Edta, Disodium

42. Edta, Distannous

43. Edta, Gallium

44. Edta, Magnesium Disodium

45. Edta, Potassium

46. Edta, Stannous

47. Ethylene Dinitrilotetraacetate

48. Ethylene Dinitrilotetraacetate, Disodium

49. Ethylenediaminetetraacetic Acid

50. Ethylenedinitrilotetraacetic Acid

51. Gallium Edta

52. Magnesium Disodium Edta

53. N,n'-1,2-ethanediylbis(n-(carboxymethyl)glycine)

54. Potassium Edta

55. Stannous Edta

56. Tetacine, Calcium

57. Tetracemate

58. Versenate

59. Versenate, Calcium Disodium

60. Versene

2.3.2 Depositor-Supplied Synonyms

1. Edta

2. Ethylenediaminetetraacetic Acid

3. 60-00-4

4. Edathamil

5. Versene

6. Endrate

7. Havidote

8. Sequestrol

9. Titriplex

10. Edta Acid

11. Versene Acid

12. Cheelox

13. Sequestric Acid

14. Warkeelate Acid

15. Gluma Cleanser

16. Sequestrene Aa

17. Komplexon Ii

18. Quastal Special

19. Tetrine Acid

20. Metaquest A

21. Trilon Bw

22. Complexon Ii

23. Hamp-ene Acid

24. Titriplex Ii

25. Cheelox Bf Acid

26. Trilon Bs

27. Celon A

28. Chelest 3a

29. Questex 4h

30. Celon Ath

31. Chemcolox 340

32. (ethylenedinitrilo)tetraacetic Acid

33. Universne Acid

34. Vinkeil 100

35. Dissolvine E

36. Nullapon B Acid

37. Nullapon Bf Acid

38. Perma Kleer 50 Acid

39. Nervanaid B Acid

40. Clewat Taa

41. Edta (chelating Agent)

42. Versenate

43. Calcium Disodium Versenate

44. Acidum Edeticum

45. Edetate Disodium

46. Acide Edetique

47. Acido Edetico

48. Caswell No. 438

49. Disodium Edta

50. Chelaton 3

51. Icrf 185

52. Cheladrate

53. Seq 100

54. Edetate Calcium

55. Ethylenebisiminodiacetic Acid

56. Yd 30

57. Acide Edetique [inn-french]

58. Acido Edetico [inn-spanish]

59. Acidum Edeticum [inn-latin]

60. Ccris 946

61. Ethylenebis(iminodiacetic Acid)

62. Edetate

63. Ethylenediamine Tetraacetic Acid

64. Glycine, N,n'-1,2-ethanediylbis[n-(carboxymethyl)-

65. Hsdb 809

66. Acide Ethylenediaminetetracetique

67. Ethylenediaminetetraacetate

68. Ethylenediamine-n,n,n',n'-tetraacetic Acid

69. 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic Acid

70. Acetic Acid, (ethylenedinitrilo)tetra-

71. Epa Pesticide Chemical Code 039101

72. Edta Disodium

73. Disodium Edetate

74. Disodium Versene

75. Endrate Disodium

76. Kyselina Ethylendiamintetraoctova

77. Sodium Versenate

78. Edetic Acid Disodium Salt

79. Kyselina Ethylendiamintetraoctova [czech]

80. Acide Ethylenediaminetetracetique [french]

81. Metaquest B

82. Ethylene Diamine Tetraacetic Acid

83. Kiresuto B

84. Chelaplex Iii

85. Complexon Iii

86. Diso-tate

87. Titriplex Iii

88. 3,6-diazaoctanedioic Acid, 3,6-bis(carboxymethyl)-

89. Ai3-17181

90. Chelaton Iii

91. Glycine, N,n'-1,2-ethanediylbis(n-(carboxymethyl)-

92. Versene Na

93. Triplex Iii

94. Disodium Versenate

95. Edathamil Disodium

96. Trilon Bd

97. Versene Na2

98. Disodium Sequestrene

99. Disodium Tetracemate

100. Edta Disodium Salt

101. F 1 (complexon)

102. Mfcd00003541

103. Edta, Ion(4-)

104. Chembl858

105. Sequestrene Sodium 2

106. Acetic Acid, 2,2',2'',2'''-(1,2-ethanediyldinitrilo)tetrakis-

107. N,n'-1,2-ethanediylbis(n-(carboxymethyl)glycine)

108. {[-(bis-carboxymethyl-amino)-ethyl]-carboxymethyl-amino}-acetic Acid

109. Disodium Salt Of Edta

110. 9g34hu7rv0

111. Perma Kleer Di Crystals

112. Calcium Disodium Versenate (tn)

113. Disodium Edetate Dihydrate

114. Ethylene-diamine Tetraacetic Acid

115. 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic Acid

116. Chebi:42191

117. 2-({2-[bis(carboxymethyl)amino]ethyl}(carboxymethyl)amino)acetic Acid

118. 4-04-00-02449 (beilstein Handbook Reference)

119. N,n'-1,2-ethane Diylbis-(n-(carboxymethyl)glycine)

120. 470462-56-7

121. Edt

122. Ethylenediaminetetraacetic Acid Disodium Salt

123. Edetate Calcium Disodium (usp)

124. Sequestrene Na2

125. Trilon B

126. Ethylenedinitrilotetraacetic Acid

127. Selekton B2

128. Disodium Ethylenediaminetetraacetate

129. (ethylenedinitrilo)tetraacetic Acid, Ion(4-)

130. Perma Kleer 50 Crystals Disodium Salt

131. Disodium (ethylenedinitrilo)tetraacetate

132. Disodium Ethylenediaminetetraacetic Acid

133. Sodium Ethylenediaminetetraacetate

134. Caedta

135. Cbc 50152966

136. Dr-16133

137. Ethylenediaminetetraacetate, Disodium Salt

138. Disodium Diacid Ethylenediaminetetraacetate

139. D'e.d.t.a. Disodique

140. Disodium (ethylenedinitrilo)tetraacetic Acid

141. 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate

142. Disodium Dihydrogen Ethylenediaminetetraacetate

143. Ethylenediaminetetraacetic Acid, Disodium Salt

144. Disodium Dihydrogen(ethylenedinitrilo)tetraacetate

145. 139-33-3

146. Nsc2760

147. N,n'-1,2-ethanediylbis[n-(carboxymethyl)glycine]

148. Ncgc00159485-02

149. 6381-92-6

150. Einecs 200-449-4

151. Brn 1716295

152. Unii-9g34hu7rv0

153. Disodium-edta

154. Edetic Acid [inn:ban:nf]

155. (ethylenedinitrilo)tetraacetic Acid, Disodium Salt

156. 2-[2-(bis(carboxymethyl)amino)ethyl-(carboxymethyl)amino]acetic Acid

157. Tricon Bw

158. ([2-(bis-carboxymethyl-amino)-ethyl]-carboxymethyl-amino)-acetic Acid

159. {[2-(bis-carboxymethyl-amino)-ethyl]-carboxymethyl-amino}-acetic Acid

160. Calcium Disodium Edetate (jan)

161. Techrun Do

162. Edta, Anhydrous

163. Zonon Ao

164. Edta, Free Acid

165. Edta, Free Base

166. Acetic Acid, (ethylenedinitrilo)tetra-, Disodium Salt

167. Versene Acid (tn)

168. Acroma Dh 700

169. Spectrum_001018

170. Edetic Acid (nf/inn)

171. Edta [vandf]

172. 53632-26-1

173. Spectrum2_000003

174. Spectrum3_000412

175. Spectrum4_000531

176. Spectrum5_000955

177. Edta [inci]

178. Edetic Acid [ban:inn]

179. Dsstox_cid_2977

180. Edetic Acid [ii]

181. Edetic Acid [inn]

182. Edta [mi]

183. Ec 200-449-4

184. Edetic Acid [hsdb]

185. Edta, Anhydrous Acs Grade

186. Dsstox_rid_76814

187. Dsstox_gsid_22977

188. Ethylenediaminetetracetic Acid

189. Bspbio_001964

190. Diaminoethanetetra-acetic Acid

191. Edetic Acid [mart.]

192. Ethylenediamineteraacetic Acid

193. Kbiogr_001161

194. Kbioss_001498

195. Ethylenediaminetetraacetic-acid

196. Mls001249457

197. Bidd:er0565

198. Divk1c_000777

199. Edetic Acid [usp-rs]

200. Edetic Acid [who-dd]

201. Ethylenediamine Tetracetic Acid

202. Spbio_000005

203. Ethylenediamine-tetraacetic Acid

204. Dtxsid6022977

205. Kbio1_000777

206. Kbio2_001498

207. Kbio2_004066

208. Kbio2_006634

209. Kbio3_001184

210. (ethylenedintrilo)tetraacetic Acid

211. Ethylen-ediamine Tetra-acetic Acid

212. Ninds_000777

213. Edetic Acid [ep Monograph]

214. Cs-b1827

215. Hy-y0682

216. Str08855

217. Tox21_202736

218. Bdbm50330325

219. S6350

220. Stk386291

221. Zinc19364242

222. Akos001574475

223. Glycine, (n,n'-1,2-ethanediylbis(n-(carboxymethyl)-, Labeled With Carbon-14

224. (ethane-1,2-diyldinitrilo)tetraacetate

225. Db00974

226. Cas-60-00-4

227. Idi1_000777

228. Ncgc00159485-03

229. Ncgc00159485-04

230. Ncgc00260284-01

231. 688-55-1

232. Ac-10615

233. Smr000058776

234. Sbi-0051360.p003

235. Db-084840

236. Ds-003836

237. B7197

238. E0084

239. Ethylenediaminetetraacetic Acid, 2na (edta)

240. Ethylenediaminetetraacetic Acid, Lr, >=98%

241. Ft-0626319

242. Ft-0668253

243. Ft-0668254

244. C00284

245. D00052

246. Ethylenediaminetetraacetic Acid, P.a., 98.0%

247. Ab00053468_03

248. Ethylenediaminetetraacetic Acid Solution, 0.02 N

249. Ethylenediaminetetraacetic Acid, >=98.0% (kt)

250. A832566

251. N,n'-1,2-ethanediylbis[n-(carboxymethyl)]glycine

252. Q408032

253. Sr-01000883946

254. Anticoagulant Ethylenediamine Tetraacetic Acid

255. Ethylenediaminetetraacetic Acid Sodium Salt Solution

256. Ethylenediaminetetraacetic Acid, Cell Culture Reagent

257. J-610078

258. Sr-01000883946-1

259. 37c3c5e7-d921-445f-82d6-febf1ae5aef5

260. Ethylenediaminetetraacetic Acid, Electrophoresis Grade

261. Z2688689169

262. Anticoagulant Ethylenediamine Tetraacetic Acid (edta)

263. Ethylenediaminetetraacetic Acid, Bioultra, >=99.0% (kt)

264. Ethylenediaminetetraacetic Acid, 0.5m Aq. Solution, Ph 8.0

265. Ethylenediaminetetraacetic Acid, 99.995% Trace Metals Basis

266. Ethylenediaminetetraacetic Acid, Saj Special Grade, >=99.0%

267. Ethylenediaminetetraacetic Acid, Vetec(tm) Reagent Grade, 98%

268. [{2-[bis(carboxymethyl)amino]ethyl}(carboxymethyl)amino]acetic Acid

269. 2,2',2'',2'''-(ethane-1,2-diylbis(azanetriyl))tetraacetic Acid

270. Edetic Acid, United States Pharmacopeia (usp) Reference Standard

271. Ethylenediaminetetraacetic Acid, Acs Reagent, 99.4-100.6%, Powder

272. Ethylenediaminetetraacetic Acid, Purified Grade, >=98.5%, Powder

273. 2,2'',2'''',2''''''-(ethane-1,2-diylbis(azanetriyl))tetraacetic Acid

274. Ethylenediaminetetraacetic Acid, 0.5m Aqueous Solution, Ph 8.0, Autoclaved

275. Ethylenediaminetetraacetic Acid, Bioultra, Anhydrous, >=99% (titration)

276. Glycine, N,n'-1, {2-ethanediylbis[n-(carboxymethyl)-,} Disodium Salt

277. {[2-(bis-carboxymethyl-amino)-ethyl]-carboxymethyl-amino}-acetic Acid(edta)

278. 2-[2-[bis(2-hydroxy-2-oxoethyl)amino]ethyl-(2-hydroxy-2-oxoethyl)amino]ethanoic Acid

279. Ethylenediaminetetraacetic Acid, Anhydrous, Free-flowing, Redi-dri(tm), >=98%

280. 124949-23-1

281. Ethylenediamine-n,n,n Inverted Exclamation Mark ,n Inverted Exclamation Mark -tetraacetic Acid-13c4 (

282. A-labels)

283. Ethylenediaminetetraacetic Acid Solution, 0.02% In Dpbs (0.5 Mm), Sterile-filtered, Bioreagent, Suitable For Cell Culture

284. Ethylenediaminetetraacetic Acid Solution, Bioultra, For Molecular Biology, Ph 8.0, ~0.5 M In H2o

285. Ethylenediaminetetraacetic Acid, Anhydrous, Crystalline, Bioreagent, Suitable For Cell Culture

286. Ethylenediaminetetraacetic Acid, Anhydrous, Free-flowing, Powder, Redi-dri(tm), Acs Reagent, 99.4-100.6%

2.4 Create Date

2004-09-16

3 Chemical and Physical Properties

Molecular Formula	C₁₀H₁₆N₂O₈
Molecular Weight	292.24 g/mol
XLogP3	-5.9
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	11
Exact Mass	292.09066547 g/mol
Monoisotopic Mass	292.09066547 g/mol
Topological Polar Surface Area	156 Å²
Heavy Atom Count	20
Formal Charge	0
Complexity	316
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug Information

1 of 1
Drug Name	CALCIUM DISODIUM VERSENATE
Active Ingredient	EDETATE CALCIUM DISODIUM
Company	MEDICIS (Application Number: N008922)

4.2 Therapeutic Uses

Anticoagulants; Antidotes; Chelating Agents

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)

EDTA has been used to treat alkali, particularly lime, burns of the cornea.

Cosmetic Ingredient Expert Review Panel; Final Report on the Safety Assessment of EDTA, Calcium, Disodium EDTA, Diammonium EDTA, Dipotassium EDTA, Disodium EDTA, TEA-EDTA, Tetrasodium EDTA, Tripotassium EDTA, Trisodium EDTA, HEDTA, and Trisodium HEDTA. International Journal of Toxicology 21 (S2): 95-142 (2002)

(51)Cr-EDTA has been used since 1966 as a radiotracer for the assessment of glomerular filtration rate.

Chelation therapy using EDTA has been used since 1955 to treat atherosclerotic cardiovascular disease, but its efficacy has been disputed in recent years. /Former use/

For more Therapeutic Uses (Complete) data for ETHYLENEDIAMINE TETRAACETIC ACID (8 total), please visit the HSDB record page.

Anticoagulants; Chelating Agents; Food Additives

National Library of Medicine's Medical Subject Headings online file (MeSH, 2009)

Endrate (Edetate Disodium Injection, USP) is indicated in selected patients for the emergency treatment of hypercalcemia and for the control of ventricular arrhythmias associated with digitalis toxicity. /Included in US product label/

US Natl Inst Health; DailyMed. Current Medication Information for Endrate (edetate disodium, anhydrous) injection, solution (May 2006). Available from, as of February 16, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=290c3e9c-c0c6-440a-1a9c-46e3e2b07a77

Disodium edentate is also used therapeutically as an anticoagulant as it will chelate calcium and prevent the coagulation of blood in vitro. Concentrations of 0.1% w/v are used in small volumes for hematological testing and 0.3% w/v in transfusions.

Rowe, R.C., Sheskey, P.J., Quinn, M.E.; (Eds.), Handbook of Pharmaceutical Excipients 6th edition Pharmaceutical Press, London, England 2009, p. 243

Disodium EDTA is used occasionally to terminate the effects of injected calcium, to antagonize digitalis toxicity, or to suppress tachyarrhythmias. /Former/

Cosmetic Ingredient Expert Review Panel; Final Final Report on the Safety Assessment of EDTA, Calcium, Disodium EDTA, Diammonium EDTA, Dipotassium EDTA, Disodium EDTA, TEA-EDTA, Tetrasodium EDTA, Tripotassium EDTA, Trisodium EDTA, HEDTA, and Trisodium HEDTA. International Journal of Toxicology 21 (S2): 95-142 (2002)

For more Therapeutic Uses (Complete) data for Disodium EDTA (8 total), please visit the HSDB record page.

4.3 Drug Warning

... direct contact with EDTA may cause dermal sensitization (eczema) or allergic conjunctivitis.

Gesellschaft Deutscher Chemiker (GDCh) - Advisory Committee on Existing Chemicals of Environmental Relevance (BUA); S. Hirzel Verlag, P.O. Box 10 10 61, 70009 Stuttgart, Germany, 1997. xxi, 223p. Bibl.ref.

/BOXED WARNING/ The use of this drug in any particular patient is recommended only when the severity of the clinical condition justifies the aggressive measures associated with this type of therapy.

Clinical studies of edetate disodium did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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.

American Society of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011

Edetate Disodium Injection is contraindicated in anuric patients. It is not indicated for the treatment of generalized arteriosclerosis associated with advancing age.

For more Drug Warnings (Complete) data for Disodium EDTA (22 total), please visit the HSDB record page.

4.4 Drug Indication

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.

5 Pharmacology and Biochemistry

5.1 Pharmacology

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.

5.2 MeSH Pharmacological Classification

Calcium Chelating Agents

Substances that bind to and sequester CALCIUM ions. (See all compounds classified as Calcium Chelating Agents.)

Food Additives

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.)

Anticoagulants

Agents that prevent BLOOD CLOTTING. (See all compounds classified as Anticoagulants.)

5.3 FDA Pharmacological Classification

5.3.1 Active Moiety

EDETIC ACID

5.3.2 FDA UNII

9G34HU7RV0

5.3.3 Pharmacological Classes

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

5.4 Absorption, Distribution and Excretion

Absorption

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

Route of Elimination

It is excreted primarily by the kidney, with about 50% excreted in one hour and over 95% within 24 hours.2 Almost none of the compound is metabolized.

Studies with (14)C-EDTA were performed in a similar manner to studies with (14)C-Diethylenetriamine Pentaacetic Acid (DTPA). (14)C-DTFA, 10 to 15mg with a (14)C activity of 15 to 20 pCi, was administered IV to 4 patients. Oral doses of (14)C-EDTA, either 3 mg with a 14C activity of 5 to 10 pCi or 50 mg (14)C-EDTA with a (14)C activity of 75 to 100 pCi, were administered to two patients. The urinary excretion pattern for (14)C-EDTA was similar to that of (14)C-DTPA. The kidneys were the major route of excretion for (14)C-DTPA after IV injection. At the end of 24 hours, 90% to 100% of the dose of (14)C-DTPA was excreted in the urine. Oral doses of (14)C-DTPA passed through the intestine and 95% to 100% of the dose was recovered in the stool within 2 to 5 days. The urinary excretion was < 8% in the seven patients who received (14)C-DTPA orally. Results for (14)C-EDTA were similar, although it was administered orally to two patients. Additionally, blood samples taken from 1 hour to 3 days after oral administration of (14)C-DTPA did not have any (14)C activity. Similar results were obtained for (14)C-EDTA.

/Investigatos/ found that increasing concentrations of EDTA increases its binding per milligram of albumin. This binding action increases as the pH values increase from 5.1 to 8.2 and the beta-globulin fraction binds more EDTA than other plasma proteins.

/Investigators/ reported that (51)Cr-EDTA moved passively across the epithelium of the gastrointestinal (GI) tract of dogs. The investigators treated muscle-stripped segments of the stomach, ileum, and colon with 0.5 mL of the chelate at a concentration of 9.0 mM. The rate of flux of the chelate was greatest in the ileum, less in the colon, and least in the stomach. No net accumulation of the probe was observed. In addition, the movement of the chelate across the ileum was not affected by neuronal blockade with tetrodotoxin. The investigators suggested that (51)Cr-EDTA moved from the gut lumen via a shunt pathway.

/Investigators/ instilled a solution containing 5 MBq (51)Cr-EDTA (in 14 mL of isotonic saline) in the nasal cavity of 6 smokers and 12 nonsmokers, and maintained the exposure for 15 minutes. Urine was collected for 24 hours after instillation. The median recovered amount of the chelate in smokers was 0.07 mL, and the median amount in nonsmokers was 0.16 mL. After instillation was repeated with the addition of 0.6% dioctylsodium sulfosuccinate to the solution, the median amount recovered for six nonsmokers increased to 1.13 mL. The investigators concluded that nasal airway absorption was not increased in smokers compared to nonsmokers. The investigators also administered 5 MBq (51)Cr-EDTA and 0.6% dioctylsodium sulfosuccinate in 2.0 mL saline to four separate subjects to determine the GI absorption of EDTA. The mean amount of the chelate recovered in the urine corresponded to 1.4% of the dose.

For more Absorption, Distribution and Excretion (Complete) data for ETHYLENEDIAMINE TETRAACETIC ACID (11 total), please visit the HSDB record page.

After intravenous administration, the chelate formed is excreted in the urine with 50% appearing in 1 hour and over 95% in 24 hours.

Disodium edentate ... /is/ poorly absorbed from the gastrointestinal tract and /is/ associated with few adverse effects when used as an excipient in pharmaceutical preparations.

Rowe, R.C., Sheskey, P.J., Quinn, M.E.; (Eds.), Handbook of Pharmaceutical Excipients 6th edition Pharmaceutical Press, London, England 2009, p. 243

Twenty male Sprague-Dawley rats were divided into four groups of five animals each. Rats in group 1 received ip injections of (14)C Disodium EDTA, group 2 received this compound on depilated skin, rats in group 3 received this compound on depilated and abraded skin (abraded every 2 or 3 cm over treated area), and group 4 was the control group. The specific activity of the (14)C Disodium EDTA was 21.6 mCi/mM and it was dissolved in saline to yield a final solution of 50 pCi/mL. Animals that received ip injections got 0.5 mL of this solution, or 25 pCi of (14)C Disodium EDTA. Animals that had the compound applied to the skin received 25 pCi of (14)C Disodium EDTA in the form of an ointment (modulan, mineral oil, petrolatum, cetyl alcohol 35:21 :25:12) spread over an area of 50 sq cm spread over a sheet of thin polyethylene. This sheet was taped to the trunk of each animal. A collar was fixed around the neck of the rats. All animals were decapitated 24 hours after treatment. The tissue distribution (per 100 mg wet organ weight) of (14)C Disodium EDTA 24 hours after ip administration was as follows: liver 577+/- 13, small intestine 631 +/- 25, large intestine 696 +/- 19, and kidney 1964 +/- 220. Twenty-four hours after application on normal skin the tissue distribution was as follows: liver 6 +/- 4, small intestine 99 +/- 22, large intestine 107 +/- 24, and kidneys 29 +/- 12. Twenty-four hours after application on abraded skin the tissue distribution was as follows: liver 139 +/- 34, small intestine 214 +/- 76, large intestine 309 +/- 115, and kidneys 222 +/- 30.

/Investigators/ reported that rats fed 0.5%, 1.0%, and 5.0% Disodium EDTA for 12 weeks excreted 82.2%, 44.5%, and 45.4%, respectively, of the ingested dose in the urine and feces. The feces contained 99.4%, 98.2%, and 97.5% of the excreted material and the urine contained 0.6%, 1.8%, and 2.5% of the material for the respective doses.

For more Absorption, Distribution and Excretion (Complete) data for Disodium EDTA (7 total), please visit the HSDB record page.

5.5 Metabolism/Metabolites

Almost none of the compound is metabolized.

EDTA is reportedly eliminated essentially unchanged.

Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V7 769

5.6 Biological Half-Life

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

... About 50% of EDTA admin iv is excreted within 1 hr and 90% within 7 hr. ...

International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 443

After intravenous administration, the chelate formed is excreted in the urine with 50% appearing in 1 hour and over 95% in 24 hours.

5.7 Mechanism of Action

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 metabolized 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.

Effects on rat liver glucocorticoid receptor in vitro was studied. At 4 C, 10 mmole EDTA had a stablizing effect on unbound hepatic glucocorticoid receptors. Apparently, endogenous metal ions are involved in the processes of glucocorticoid-receptor complex stabilization and transformation.

PMID:6411997 Hubbard J et al; J STEROID BIOCHEM 19 (2): 1163-7 (1983)

Edetate disodium injection forms chelates with the cations of calcium and many divalent and trivalent metals. Because of its affinity for calcium, edetate disodium will produce a lowering of the serum calcium level during intravenous infusion. Slow infusion over a protracted period may cause mobilization of extracirculatory calcium stores. Edetate disodium exerts a negative inotropic effect upon the heart.

US Natl Inst Health; DailyMed. Current Medication Information for Endrate (edetate disodium, anhydrous) injection, solution (May 2006).

Edetate disodium likewise forms chelates with other polyvalent metals and produces increases in urinary excretion of magnesium, zinc and other trace elements. It does not form a chelate with potassium but may reduce the serum level and increase urinary loss of potassium.