HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Diatrizoate
diatrizoate · amidotrizoate · AMIDOTRIZOIC ACID · Diatrizoic · diat · odiston · urotrast · NSC-61815
Identifikatoren & physikalische Daten
| CAS No. | 117-96-4 |
|---|---|
| Summenformel | C11H9I3N2O4 |
| Durchschnittliche Molmasse | 613,91 g/mol |
| Monoisotopische Masse | 613,76965077 g/mol |
| SMILES | CC(=O)Nc1c(I)c(NC(C)=O)c(I)c(C(=O)O)c1I |
| InChIKey | YVPYQUNUQOZFHG-UHFFFAOYSA-N |
| PubChem CID | 2140 |
| ChEMBL | CHEMBL1201220 |
| ChEBI | CHEBI:53691 |
| EC No. | 204-223-6 |
| DTXSID | DTXSID0044521 |
Chemische & physikalische Eigenschaften
| XLogP | 1,8 |
|---|---|
| Polarare Oberfläche (TPSA) | 95,5 |
| H-Brücken-Donoren | 3 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 3 |
| Schwere Atome | 20 |
| Formalladung | 0 |
| Komplexität | 390 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Used in Switzerland |
| SpringerMaterials Properties | Nuclear quadrupole resonance spectroscopy |
| LogP (Verteilungskoeffizient) | 3.3-1.05 |
| Color/Form | WHITE POWDERCrystals from dilute dimethylformideCrystals from ethanol (aqueous) |
| Löslichkeit | VERY SLIGHTLY SOL IN WATER, ALCOHOLSOL IN DIMETHYLFORMAMIDE, ALKALI HYDROXIDE SOLUTIONSIn water, 5.0X10+5 mg/L at 25 °C1.07e-01 g/LSoluble in Methanol.500g/L(25 ºC) |
| Human Drugs | Breast FeedingLactationMilk, HumanContrast MediaDiagnostic AgentsDiagnostic agents > Radiocontrast media |
| Decomposition | When heated to decomposition it emits very toxic fumes of /oxides of nitrogen and iodine/. |
| Schmelzpunkt | >250> 300 °C>300°C |
| Physical Description | Solid |
| Stability/Shelf Life | Preparations containing diatrizoate sodium should be protected from strong light. |
| Collision Cross Section | 179.4 Ų [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID0044521]176.3 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]175.26 Ų [M+H]+ |
| Other Experimental Properties | Rhombic needles. Slightly sweet tastemelting point 189-193 °C (decomposition)solubility in water at 20 °C: 89 g/100 mL /Meglumine diatrizoate/pH between 6.0 & 7.6 /Diatrizoate Meglumine/SOLN OF DIATRIZOATE SODIUM ARE CONSIDERABLY LESS VISCOUS THAN THOSE PREPD FROM DIATRIZOATE MEGLUMINE /SODIUM DIATRIZOATE/ |
| Siedepunkt | 614.1±55.0 °C(Predicted) |
| Dichte | 2.4079 (estimate) |
| Dampfdruck | 0Pa at 20℃ |
| Lagerbedingungen | Keep in dark place,Inert atmosphere,Room temperature |
| pKa (Säurekonstante) | 0.92±0.10(Predicted) |
| Aggregatzustand | Solid |
| Farbe | White to Off-White |
| Merck | 14,2992 |
| Henry-Konstante | 3.5×1012 mol/(m3Pa) at 25℃, Zhang et al. (2010) |
| Stabilität | Light Sensitive |
| Hauptanwendungen | diagnostic assay manufacturinghematologyhistology |
| InChI | InChI=1S/C11H9I3N2O4/c1-3(17)15-9-6(12)5(11(19)20)7(13)10(8(9)14)16-4(2)18/h1-2H3,(H,15,17)(H,16,18)(H,19,20) |
| InChIKey | YVPYQUNUQOZFHG-UHFFFAOYSA-N |
| SMILES | C(O)(=O)C1=C(I)C(NC(C)=O)=C(I)C(NC(C)=O)=C1I |
| LogP (Verteilungskoeffizient) | 3.3 at 20℃ |
| EPA chemische Informationen | Benzoic acid, 3,5-bis(acetylamino)-2,4,6-triiodo- (117-96-4) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 10% (1 of 10) of reports.DangerH317 (90%): May cause an allergic skin reaction [Warning Sensitization, Skin]P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 10 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Chemical: Benzoic acid, 3,5-bis(acetylamino)-2,4,6-triiodo-Status: Active Update: 03-12-2019 https://echa.europa.eu/registration-dossier/-/registered-dossier/11883Diatrizoic acid: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right. |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl diatrizoate meglumine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Diatrizoate meglumine/The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl diatrizoate sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Diatrizoate sodium/The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Diatrizoate meglumine is included on this list. /Diatrizoate meglumine/The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Diatrizoate sodium is included on this list. /Diatrizoate sodium/For more FDA Requirements (Complete) data for DIATRIZOATE (6 total), please visit the HSDB record page. |
| Hazard Classes and Categories | Skin Sens. 1 (90%) |
| Skin, Eye, and Respiratory Irritations | Adverse effects of intravascular ... diatrizoate sodium include nasal and conjunctival symptoms (e.g., rhinitis, lacrimation, sneezing). |
| Lagerbedingungen | Protect from light. Store at 20-25 °C (68-77 °F)avoid excessive heat. |
| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. |
| Wechselwirkungen | Neurologic effects, including paraplegia, of diatrizoates may increase during aortography when diatrizoates are administered after hypertensive agents used to increase contrastthis increase is due to contraction of vessels in the splanchic circulation, which forces more of the contrast material into the vessels leading to the spine and spinal cord.Incidence of delayed (more than 1 hour after administration) reactions (eg. hypersensitivity, fever, skin rash, flu-like symptoms, joint pain, flushing, pruritus, emesis, hypotension, dizziness) to intravenous contrast media may be increased in patients who have received interleukin-2some symptoms may resemble a "recall" reaction to interleukin-2supportive medical treatment may be necessary if symptoms are significantthere is some evidence that incidence is reduced if contrast media administration is delayed until 6 weeks after interleukin-2 administration.Concurrent use /of chymopapain/ with diatrizoates may increase the risk of toxicity, especially if either agent enters the subarachnoid spaceit is strongly recommended that diskography not be performed as part of the chemonucleolysis procedure.Concurrent intravascular administration of diatrizoates with beta-adrenergic blocking agents may increase the risk of moderate to severe anaphylactoid reactionalso, hypotensive effects may be exacerbateddiscontinuation of the beta-adrenergic blocking agent may be advisable before administration of contrast media in patients with other risk factors.For more Interactions (Complete) data for DIATRIZOATE (9 total), please visit the HSDB record page. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that diatrizoate is expected to have very high mobility in soil(SRC). The estimated pKa of diatrizoate is 1.13(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Diatrizoate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.6X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Iodinated X-ray contrast agents are considered nondegradable by microorganisms(6).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that diatrizoate is not expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 1.13(3) indicates diatrizoate will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water or moist soil surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of 1.37(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Iodinated X-ray contrast agents are considered nondegradable by microorganisms(7).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diatrizoate, which has an estimated vapor pressure of 3.8X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase diatrizoate may be removed from the air by wet or dry deposition(SRC). Diatrizoate does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| Milk Concentrations | Although problems in humans have not been documented, since diatrizoates are distributed unchanged into breast milk, temporary discontinuation of breast-feeding is recommended for at least 24 hours following administration. |
| Effluent Concentrations | Diatrizoate was found in outflow from a municipal sewage treatment plant in Germany monitored from 1996-1998the average concentration was 0.08 ug/L with a maximum of 8.7 ug/L reportedthe 90th percentile concentration was 1.5 ug/L, and 22 of 25 samples were above the detection limit of 0.010 ug/L(1). The compound was detected at a concentration of 4 ug/L in surface water treatment employing bank filtration(2). Diatrizoate was detected at a concentration range of approximately 210 to 1.0X10+6 ng/L in an industrial waste water of the Netherlands in 2002. Total riverine discharge was estimated at 8.989 tons/yr in 2002(3). The average concentration of diatrizoate in six sewage treatment works in the United Kingdom sampled in 2001 was 42.1 ng/Ldetection limit = 24.0 ng/L(4). |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of diatrizoate can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that diatrizoate is expected to have very high mobility in soil. Iodinated diagnostic contrast agents such as diatrizoate leach readily into groundwater(3). The estimated pKa of diatrizoate is 1.13(4), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Anaphylactic reactions: Anaphylactic reactions, including fatalities, have been reported with the use of Gastrografin. Patients at increased risk include those with a history of a previous reaction to a contrast medium, patients with a known sensitivity to iodine, and patients with a known clinical hypersensitivity (bronchial asthma, hay fever, and food allergies). Medical personnel trained in the treatment of anaphylactic reactions and the necessary drugs and medical equipment should always be readily available when Gastrografin is used./SIGNS AND SYMPTOMS/ Neurologic effects, including paraplegia, of diatrizoates may increase during aortography when diatrizoates are administered after hypertensive agents used to increase contrastthis increase is due to contraction of vessels in the splanchic circulation, which forces more of the contrast material into the vessels leading to the spine and spinal cord./SIGNS AND SYMPTOMS/ Other adverse effects of intravascular diatrizoate meglumine and diatrizoate sodium include nasal and conjunctival symptoms (e.g., rhinitis, lacrimation, sneezing), urticaria, pruritus, rash, angioedema, edema, weakness, pallor, cramps, sweating, severe retching and choking, and metallic taste. Neutropenia, erythrocyte sludging and agglutination, crenation, and transient changes in coagulation may occurrarely disseminated intravascular coagulation resulting in death has been reported. Infrequently, immediate or delayed chills can occur, sometimes with fever. Salivary gland swelling may occur a few hours to 4 days after administration of the medium and persist several days./SIGNS AND SYMPTOMS/ Arteriography of arterial trunks providing blood supply to spinal-artery branches or selective spinal arteriography can cause mild to severe muscle spasmsevere neurologic reactions including permanent paralysis, paraplegia, and quadriplegia have occasionally been reportedFor more Human Toxicity Excerpts (Complete) data for DIATRIZOATE (18 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Diatrizoate's production and use as a diagnostic contrast agent(1) may result in its release to the environment through various waste streams(SRC). |
| Environmental Biodegradation | AEROBIC: Iodinated X-ray contrast agents are considered nondegradable by microorganisms(1,2). However when incubated with 1mM diatrizoate at 30 °C for 32 days, the fungus Trametes versicolor, has been shown to partially diiodinate C-14 ring-labeled diatrizoate, liberating traces of 14-CO2(1). The three main metabolites identified were 3,5-di(acetamido)-2,6-diiodobenzoic acid, 3,5-di(acetamido)-2,4-diiodobenzoic acid, and 3,5-di(acetamido)-2-iodobenzoic acid(1). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)diatrizoateDILI NegativeIntravenousDOI:10.1016/j.drudis.2019.09.022 |
| Environmental Bioconcentration | An estimated BCF of 3 was calculated in fish for diatrizoate(SRC), using an estimated log Kow of 1.37(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). |
| Volatilization from Water/Soil | The estimated pKa of diatrizoate is 1.13(1), indicating that this compound will primarily exist as an anion in the aqueous environment and anions do not volatilize from water or moist soil surfaces. Diatrizoate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.6X10-15 mm Hg(SRC), determined from a fragment constant method(2). |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Acute Exposure/ Hemodynamic changes and contrast nephropathy are well known complications of contrast media injection. However, the mechanisms of toxicity leading to these complications remain unclear. /It was/ hypothesized that contrast media toxicity would manifest as a change in antioxidant enzyme activity, thus leading to tissue damage.This study investigated the effects of injection of ionic high-osmolar diatrizoate, ionic low-osmolar ioxaglate, and nonionic low-osmolar iopromide on the activities of two antioxidant enzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), in the heart and kidney tissue of normal male Wistar rats (n = 51) and streptozotocin (STZ)-induced diabetic rats (n = 54). Activities of GPX and SOD were assayed spectrophotometrically. Renal GPX activities were significantly decreased in both normal (458.3 +/- 64.6 to 385.5 +/- 63.4 mU/mg, p = 0.005) and diabetic rats (669.0 +/- 98.1 vs. 564.0 +/- 153.3 mU/mg, p = 0.035) at 1 hour after diatrizoate injection. Renal SOD activities were not affected after contrast injection. Ioxaglate and iopromide injection did not cause any change in renal antioxidant enzyme activity. In contrast to kidney tissue, there was no significant change in GPX and SOD activities in heart tissue at 1 hour after injection of different contrast media. Intravenous injection of ionic high-osmolar diatrizoate reduced renal GPX activity during the first hour in both normal and STZ-induced diabetic rats. Heart tissue was not prone to antioxidant enzyme activity changes after intravenous contrast media injection. GPX activity reduction can be an important mechanism of nephrotoxicity after contrast media injection./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The biological effects of iodinated contrast media were examined by using spermatogenesis in mouse testis as the experimental model. Spermhead survival and abnormality assays were used as the biological end points. Diatrizoate meglumine/diatrizoate sodium and iopamidol were administered intravenously at equal rates and concentrations. Testicular uptake and clearance of these contrast agents were examined by high-performance liquid chromatography techniques. Appropriate mannitol solutions were employed as osmolality controls. Intravenous administration of the contrast agent or its respective mannitol control resulted in approximately a 30% decrease in spermhead count. A dose-related experiment with mannitol demonstrated that the spermhead count decreased rapidly until 600 mOsm/kg was reached, beyond which this decrease was minimal. Clearance of both contrast media was complete in approximately 4 hours. No significant increase in the induction of spermhead abnormalities was observed. Osmotic substances, such as iodinated contrast agents, affect the process of spermatogenesis./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ No teratogenic effects attributable to diatrizoate meglumine or diatrizoate sodium have been observed in teratology studies performed in animals./LABORATORY ANIMALS: Neurotoxicity/ The neurotoxicity of Iohexol was evaluated and compared with the neurotoxicity of sodium diatrizoate. Direct neurotoxicity was evaluated with in vitro rat hippocampal slices, and angiographic neurotoxicity was studied in a cat's spinal cord following thoracic aortography. Sodium diatrizoate caused early excitatory changes in electrical activity and later inhibition in the experiments with the rat brain slices while the cat's spinal cord experiments showed an increase in the ventral root reflexes.For more Non-Human Toxicity Excerpts (Complete) data for DIATRIZOATE (8 total), please visit the HSDB record page. |
| Wassergefährdungsklasse (WGK) | 3 |
| Zollcode | 2924.29.7790 |
| RTECS-Nr. | DG5950000 |
| Toxizität | LD50 intravenous in mouse: 8900mg/kg |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 117-96-4(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
Diatrizoic acid is a gradient reagent used for blood cell separation and diagnostic aid (radiopaque medium). Diatrizoic acid may be used as an alternative to barium sulfate for medical imaging of the gastrointestinal tract, such as upper gastrointestinal series and small bowel series.