HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Etidronisure
HEDP · ETIDRONIC ACID · DEQUEST 2010 · 1-HYDROXYETHYLIDENE-1,1-DIPHOSPHONIC ACID · HEDP2NA · 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID · ehdp · 1-diphosphonic acid
Identifikatoren & physikalische Daten
| CAS No. | 2809-21-4 |
|---|---|
| Summenformel | C2H8O7P2 |
| Durchschnittliche Molmasse | 206,03 g/mol |
| Monoisotopische Masse | 205,97452586 g/mol |
| SMILES | CC(O)(P(=O)(O)O)P(=O)(O)O |
| InChIKey | DBVJJBKOTRCVKF-UHFFFAOYSA-N |
| PubChem CID | 3305 |
| ChEMBL | CHEMBL871 |
| ChEBI | CHEBI:4907 |
| EC No. | 220-552-8 |
| DTXSID | DTXSID6023028 |
| Lokaler Name | Etidronisure |
Chemische & physikalische Eigenschaften
| XLogP | -3,7 |
|---|---|
| Polarare Oberfläche (TPSA) | 135 |
| H-Brücken-Donoren | 5 |
| H-Brücken-Akzeptoren | 7 |
| Frei drehbare Bindungen | 2 |
| Schwere Atome | 11 |
| Formalladung | 0 |
| Komplexität | 211 |
| Stoffklassen | Other Classes -> Organic Acids |
| Arzneimittel | PharmaceuticalsPharmaceuticals -> Listed in ZINC15 |
| Kosmetika | Cosmetic ingredients (Etidronic Acid) -> CIR (Cosmetic Ingredient Review)Chelating |
| Duftstoffe | Fragrance Ingredient (Phosphonic acid, (1-hydroxyethylidene)bis-) -> IFRA transparency List |
| LogP (Verteilungskoeffizient) | -3.8 |
| Lebensmittelzusatzstoffe | BOILER WATER ADDITIVE -> FDA Substance added to food |
| Löslichkeit | 1.15e+01 g/LMethanol (Slightly), Water (Slightly)Soluble in water. |
| Human Drugs | Breast FeedingLactationBisphosphonatesBone Density Conservation AgentsDiphosphonates |
| Schmelzpunkt | 198-199105 °C198~199℃ |
| Food Contact Substances | FCS -> FDA Cumulative Estimated Daily Intake (CEDI)FCS -> FDA Inventory of Food Contact Substances Listed in 21 CFR |
| Physical Description | CBIDry PowderLiquidWhite odorless powder[MSDSonline]Solid |
| Siedepunkt | 578.8±60.0 °C(Predicted) |
| Dichte | 1.45 (60% aq.) |
| Dampfdruck | 0Pa at 25℃ |
| Lagerbedingungen | Sealed in dry,Room Temperature |
| pKa (Säurekonstante) | 1.35, 2.87, 7.03, 11.3(at 25℃) |
| Aggregatzustand | Powder |
| Farbe | white |
| pH | pH (1.7→100, 25℃) : 1.3～1.8 |
| Merck | 14,3863 |
| BRN | 1789291 |
| Stabilität | Stable. Incompatible with strong oxidizing agents. |
| Kosmetik-Inhaltsstoffe Funktionen | CHELATING |
| InChI | 1S/C2H8O7P2/c1-2(3,10(4,5)6)11(7,8)9/h3H,1H3,(H2,4,5,6)(H2,7,8,9) |
| InChIKey | DBVJJBKOTRCVKF-UHFFFAOYSA-N |
| SMILES | CC(O)(P(O)(O)=O)P(O)(O)=O |
| LogP (Verteilungskoeffizient) | -3.5 |
| CAS Datenbank | 2809-21-4(CAS DataBase Reference) |
| EPA chemische Informationen | Etidronic acid (2809-21-4) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 1.6% (35 of 2257) of reports.DangerH290 (34.6%): May be corrosive to metals [Warning Corrosive to Metals]P234, P260, P264, P264+P265, P270, P273, P280, P301+P317, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P321, P330, P363, P390, P405, P406, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 2257 reports by companies from 33 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Chemical: Phosphonic acid, (1-hydroxyethylidene)bis-Phosphonic acid, P,P'-(1-hydroxyethylidene)bis- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Phosphonic acid, P,P'-(1-hydroxyethylidene)bis- 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)Status: Active Update: 15-11-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/16011Etidronic acid: Does not have an individual approval but may be used under an appropriate group standard |
| Weitere Sicherheitsinformationen | IMAP assessments - Etidronic acids: Human health tier II assessment |
| Gefahrenübersicht | No human data, but not expected to increase risk of congenital abnormalities based on animal studies[REPROTOX] Safe to use as a sequestrant in food preparation[JECFA] Causes gastrointestinal bleeding in lethal-dose feeding studies of mice[RTECS] A corrosive substance that can cause injury to the skin, eyes, and respiratory tractInhalation may cause chemical pneumonitis[MSDSonline] |
| Special Reports | THE SYSTEMIC TOXICITY, SKIN TOLERANCE & ECOTOXICITY OF PRIMARY MATERIALS USED IN THE TREATMENT OF WATER, EG, ANTICORROSION PHOSPHONATES WAS STUDIED. HYDROXYETHANE DIPHOSPHONIC ACID HAD LOW TOXICITY & PRESENTED NO POTENTIAL HAZARD.[KASTNER W ET ALTOXICITY AND ECOTOXICITY OF WATER TREATMENT PRODUCTSL' EAU, L' INDUSTRIE, LES NUISANCES 72: 47 (1983)] |
| EPA Safer Chemical | Chemical: Etidronic acid |
| Hazard Classes and Categories | Met. Corr. 1 (34.6%)Acute toxicity - category 4Acute toxicity (Oral) - Category 4 |
| Protective Action Criteria (PAC) | 4.3 [mg/m3]48 [mg/m3]290 [mg/m3] |
| Unerwünschte Wirkungen | Dermatotoxin - Skin burns. |
| Expositionspfade | The amount of drug absorbed after an oral dose is approximately 3%. |
| Toxizitätsübersicht | Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.orgBisphosphonates, when attached to bone tissue, are absorbed by osteoclasts, the bone cells that breaks down bone tissue. Although the mechanism of action of non-nitrogenous bisphosphonates has not been fully elucidated, available data suggest that they bind strongly to hydroxyapatite crystals in the bone matrix, preferentially at the sites of increased bone turnover and inhibit the formation and dissolution of the crystals. Other actions may include direct inhibition of mature osteoclast function, promotion of osteoclast apoptosis, and interference with osteoblast-mediated osteoclast activation. Etidronic acid does not interfere with bone mineralization. In malignancy-related hypercalcemia, etidronic acid decreases serum calcium by inhibiting tumour-induced bone resorption and reducing calcium flow from the resorbing bone into the blood. Etidronic acid also reduces morbidity of osteolytic bone metastases by inhibiting tumour-induced bone resorption. Etidronic acid may promote osteoclast apoptosis by competing with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone. |
| Signs and Symptoms | Clinical experience with acute etidronic acid overdosage is extremely limited. Decreases in serum calcium following substantial overdosage may be expected in some patients. Signs and symptoms of hypocalcemia also may occur in some of these patients. Some patients may develop vomiting. In one event, an 18-year-old female who ingested an estimated single dose of 4800 to 6000 mg (67 to 100 mg/kg) of etidronate was reported to be mildly hypocalcemic (7 .5 2 mg/ dl) and experienced paresthesia of the fingers. |
| TSCA Test Submissions | In a perinatal and postnatal study, pregnant female Long-Evans rats (20/group, except 21/high-dose group) were orally exposed by gavage to (1-hydroxyethylidene)bis-phosphonic acid at dose levels of 16.51, 110.09, or 330.28 mg/kg/day (in one-half doses, twice daily in deionized water10 ml/kg/day) on gestation day (GD) 15 through the end of gestation and the period of lactation. Surviving animals were sacrificed on lactation day 21. Significant differences were observed between treated and control animals in the following: decreased implantations/dam (high-dose group), decreased live fetuses/total fetuses (low-dose group), increased pup survival (lactation days 0-4, high-dose group), increased pup body weight (high- and mid-dose groups), and decreased number of females (mid-dose group). No significant differences were observed between treated and control animals in the following: pregnancy rate, length of gestation period, number of litters delivered, maternal weight gain, mortality, physical observations, or necropsy observations, numbers of pups/dam, live or dead fetuses/litter, live fetuses/implantation, pup sex ratios, and gross pup necropsy observations.Teratogenicity was evaluated in pregnant Long-Evans rats (20/group) orally exposed by gavage to (1-hydroxyethylidene) bis-phosphonic acid at dose levels of 0, 16.51, 110.09 or 330.28 mg/kg/day (in deionized water solutions, 10 ml/kg/day, one-half doses given twice daily) on gestation days (GD) 6-15. All surviving rats were sacrificed on GD 20. Significant differences were observed between treated and control animals with respect to a decreased incidence of soft tissue abnormalities (low-dose group). No significant differences were observed between treated and control animals in the following: maternal mortality, body weight, body weight change, pregnancy rate, physical observations, numbers of corpora lutea, implantations, live fetuses, resorptions, implantation frequency, necropsy observations, percent viable or resorbed fetuses, fetal weight, crown-rump length, sex ratio, ossification variations, and skeletal malformations. |
| Human Toxicity Excerpts | IV ADMIN OF 5 MG 1-HYDROXYETHYLIDENE DIPHOSPHONATE (HEDP) DAILY TO YOUNG MALES FOR 5 DAYS DID NOT ALTER THE BLOOD & URINARY LEVELS OF CALCIUM & PHOSPHATE, & OTHER BIOCHEMICAL PARAMETERS. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)etidronic acidDidronel®BisphosphonatesNot Applicableno-DILI-concern |
| Non-Human Toxicity Excerpts | ETHANEHYDROXY DIPHOSPHONATE (EHDP) WAS ADMIN SC TO ADULT BEAGLE DOGS FOR 1-2 YR AT VARIOUS DOSE LEVELS TO DETERMINE ITS SKELETAL EFFECTS WHEN GIVEN CHRONICALLY. AT LOW DOSES (0.1 & 0.5 MG/KG/DAY), EHDP CAUSED A TIME-&-DOSE DEPENDENT REDN IN PERCENTAGE OF BONE SURFACE WITH ACTIVE MINERALIZATION, A REDN IN MINERALIZATION RATES, REDN IN RESORPTION SPACE, BUT NO CHANGES IN OSTEOID SEAM WIDTHS. EHDP CAN HAVE PROFOUND EFFECTS ON BONE REMODELING IN THE DOG, BUT THESE EFFECTS ARE DOSE-&-TIME-DEPENDENT & APPEAR TO BE REVERSIBLE.THE ENERGY CHARGE OF THE ADENYLATE POOL & ATP & INORG PHOSPHATE CONTENT WERE NOT CHANGED BY TREATMENT OF CULTURED CALVARIA CELLS WITH ETHANE-1-HYDROXY-1,1-DIPHOSPHONATE.FETAL MOUSE CALVARIA WERE CULTURED FOR 48 HR IN PRESENCE OF ETHANE-1-HYDROXY-1,1-DIPHOSPHONATE (EHDP) AFTER WHICH ACTIVITY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE, 6-PHOSPHOGLUCONATE DEHYDROGENASE, HEXOKINASE, LACTATE DEHYDROGENASE, ACONITASE, & ISOCITRATE DEHYDROGENASE WAS DETERMINED. EHDP HAD NO EFFECT ON ANY OF THE ENZYMES STUDIED.ETHANE-1-HYDROXY-1,1-DIPHOSPHONATE ADMIN TO IMMATURE RATS INHIBITED MINERALIZATION AS EVIDENCED BY WIDENED TIBIAL EPIPHYSEAL PLATES AND DECREASED BONE ASH TO DRY WT RATIOS.For more Non-Human Toxicity Excerpts (Complete) data for 1-HYDROXY-1,1-DIPHOSPHONOETHANE (7 total), please visit the HSDB record page. |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| F | 10 |
| Wassergefährdungsklasse (WGK) | 2 |
| TSCA-Inventar-Status | TSCA listed |
| UN-Transportnummer | UN 3265 |
| Zollcode | 29319090 |
| RTECS-Nr. | SZ8562100 |
| R-Sätze (R) | 37/38-41-22 |
| Toxizität | LD50 oral in mouse: 1800mg/kg |
| Gefahrensymbole | Xi,Xn |
| Sicherheitshinweise (S) | 26-39 |
| Gefahrenklasse | 8Eye Dam. 1Met. Corr. 1 |
| Verpackungsgruppe | II |
| Lagerklasse | 8A - Combustible corrosive hazardous materials |
| Gefahrstoffdaten | 2809-21-4(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
Etidronate (Didronel) is a human protein tyrosine phosphatase inhibitor with IC50 of 0.2 μM.