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Isosulfan Blue

PubChem CID
50108
Structure
Isosulfan Blue_small.png
Isosulfan Blue_3D_Structure.png
Molecular Formula
Synonyms
  • ISOSULFAN BLUE
  • 68238-36-8
  • Sulphan Blue
  • Isosulfan blue [USAN]
  • Sulfanblau
Molecular Weight
566.7 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-08-08
  • Modify:
    2025-01-18
Description
Isosulfan Blue is a synthetic visual lymphatic imaging agent. Injected into the periphery of the tumor site, isosulfan blue localizes to the lymphatic system and aids in the surgical identification of tumor sentinel nodes which stain blue. (NCI04)
ISOSULFAN BLUE is a small molecule drug with a maximum clinical trial phase of IV that was first approved in 1981 and has 1 investigational indication.
See also: isosulfan blue inner salt (has active moiety).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Isosulfan Blue.png

1.2 3D Conformer

3D Conformer of Parent

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

sodium;2-[[4-(diethylamino)phenyl]-(4-diethylazaniumylidenecyclohexa-2,5-dien-1-ylidene)methyl]benzene-1,4-disulfonate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C27H32N2O6S2.Na/c1-5-28(6-2)22-13-9-20(10-14-22)27(21-11-15-23(16-12-21)29(7-3)8-4)25-19-24(36(30,31)32)17-18-26(25)37(33,34)35;/h9-19H,5-8H2,1-4H3,(H-,30,31,32,33,34,35);/q;+1/p-1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

NLUFDZBOHMOBOE-UHFFFAOYSA-M
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CCN(CC)C1=CC=C(C=C1)C(=C2C=CC(=[N+](CC)CC)C=C2)C3=C(C=CC(=C3)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+]
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C27H31N2NaO6S2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

68238-36-8
748080-29-7

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEMBL ID

2.3.5 DrugBank ID

2.3.6 DSSTox Substance ID

2.3.7 KEGG ID

2.3.8 Metabolomics Workbench ID

2.3.9 NCI Thesaurus Code

2.3.10 RXCUI

2.3.11 Wikidata

2.3.12 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 4-(alpha-(p-(diethylamino)phenyl)-(2,5-disulfobenzylidene)-2,5-cyclohexadien-1-ylidene)diethylammonium hydroxide inner salt, sodium salt
  • iso-sulfan blue
  • iso-sulphan blue
  • isosulfan blue
  • Lymphazurin
  • lymphazurin blue

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
566.7 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
7
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
7
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
566.15212334 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
566.15212334 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
137 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
38
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
1040
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
2
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Color / Form

Blue-green liquid
Bioniche pharna; Material Safety Data Sheet. Isosulfan Blue Injection 1%. ID: BNP-22. 4/23/1020. Lake Forest, IL: Bioniche Pharma. Available from, as of Jan 10, 2013: https://www.bionichepharmausa.com/pdf/Bioniche_IsosulfanBlue_MSDS.PDF

3.2.2 Solubility

Dark bluish-green powder. Solubility in water, 30 mg/mL at 25 °C; solubility in ethylene glycol monomethyl ether 30 mg/mL; in ethanol 7 mg/mL. UV max 635 nm in water /Acid Blue 1/
Green FJ; p. 553 The Sigma-Aldrich Handbook of Stains, Dyes, and Indicators. Milwaukee, WI: Aldrich Chem Co. (1990)

3.3 Chemical Classes

3.3.1 Drugs

3.3.1.1 Human Drugs
Human drug -> Prescription; Discontinued; Active ingredient (ISOSULFAN BLUE)
Human drug -> Discontinued

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug Indication

Isosulfan Blue is a synthetic visual lymphatic imaging agent. Isosulfan blue upon subcutaneous administration, delineates the lymphatic vessels draining the region of injection. It is an adjunct to lymphography in: primary and secondary lymphedema of the extremities; chyluria, chylous ascites or chylothorax; lymph node involvement by primary or secondary neoplasm; lymph node response to therapeutic modalities.

6.2 FDA Approved Drugs

6.3 FDA Orange Book

6.4 FDA National Drug Code Directory

6.5 Drug Labels

Drug and label
Active ingredient and drug

6.6 Clinical Trials

6.6.1 ClinicalTrials.gov

6.7 Therapeutic Uses

Isosulfan blue injection 1% upon subcutaneous administration, delineates lymphatic vessels draining the region of injection. It is an adjunct to lymphography in: primary and secondary lymphedema of the extremities; chyluria, chylous ascites or chylothorax; lymph node involvement by primary or secondary neoplasm; and lymph node response to therapeutic modalities. /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff

6.8 Drug Warnings

Isosulfan blue injection 1% is contraindicated in those individuals with known hypersensitivity to triphenylmethane or related compounds.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff
Life-threatening anaphylactic reactions (respiratory distress, shock, angioedema) have occurred after isosulfan blue injection 1% administration. Reactions are more likely to occur in patients with a history of bronchial asthma, allergies, drug reactions or previous reactions to triphenylmethane dyes. Monitor patients closely for at least 60 minutes after administration of isosulfan blue injection 1%. Trained personnel should be available to administer emergency care including resuscitation.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff
Isosulfan blue injection 1% interferes with measurements of oxygen saturation in peripheral blood by pulse oximetry and can cause falsely low readings. The interference effect is maximal at 30 minutes and minimal generally by four hours after administration. Arterial blood gas analysis may be needed to verify decreased arterial partial pressure of oxygen.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff
Isosulfan blue injection 1% may also cause falsely elevated readings of methemoglobin by arterial blood gas analyzer. Therefore, co-oximetry may be needed to verify methemoglobin level.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff
For more Drug Warnings (Complete) data for Isosulfan blue (10 total), please visit the HSDB record page.

7 Pharmacology and Biochemistry

7.1 Pharmacodynamics

Following subcutaneous administration, Lymphazurin 1% binds to serum proteins and is picked up by the lymphatic vessels. Thus, the lymphatic vessels are delineated by the blue dye.

7.2 MeSH Pharmacological Classification

Coloring Agents
Chemicals and substances that impart color including soluble dyes and insoluble pigments. They are used in INKS; PAINTS; and as INDICATORS AND REAGENTS. (See all compounds classified as Coloring Agents.)

7.3 Absorption, Distribution and Excretion

Absorption
Intradermal and parenchymal injections of vital blue dyes, such as isosulfan blue, can lead to systemic absorption through lymphatic channels and vascular beds near tumor sites.
Route of Elimination
Excreted unchanged in the urine
Volume of Distribution
Not available
Clearance
Up to 10% of the subcutaneously administered dose of isosulfan blue 1% is excreted in 24 hours in human.
Following subcutaneous administration, isosulfan blue injection 1% binds to serum proteins and is picked up by the lymphatic vessels. Thus, the lymphatic vessels are delineated by the blue dye.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff
It is not known whether this drug is excreted in human milk.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff
Up to 10% of the subcutaneously administered dose of isosulfan blue injection 1% is excreted unchanged in the urine in 24 hours in humans.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff

7.4 Biological Half-Life

Slow release of the dye from the subcutaneous tissue or the lymphatic tissue and the half-life of the dye in the body of several hours.

7.5 Mechanism of Action

Isosulfan Blue is injected into the periphery of the tumor site, it localizes to the lymphatic system and aids in the surgical identification of tumor sentinel nodes which stain blue.

8 Use and Manufacturing

8.1 Uses

Coloring medicinal products; dyeing and printing wool, silk.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1542
MEDICATION

8.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

8.2 Methods of Manufacturing

Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1273

8.3 Formulations / Preparations

Isosulfan blue injection 1% is supplied as a 5 mL single use vial, 1% aqueous solution in a phosphate buffer prepared by appropriate manufacturing to be sterile and pyrogen-free.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff

9 Safety and Hazards

9.1 Hazards Identification

9.1.1 GHS Classification

Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (100%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

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

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

9.1.2 Hazard Classes and Categories

Skin Irrit. 2 (100%)

Eye Irrit. 2 (100%)

STOT SE 3 (100%)

9.2 Accidental Release Measures

9.2.1 Disposal Methods

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.

9.3 Handling and Storage

9.3.1 Storage Conditions

Isosulfan blue injection 1% upon subcutaneous administration, delineates lymphatic vessels draining the region of injection. It is an adjunct to lymphography in: primary and secondary lymphedema of the extremities; chyluria, chylous ascites or chylothorax; lymph node involvement by primary or secondary neoplasm; and lymph node response to therapeutic modalities. /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff

9.4 Stability and Reactivity

9.4.1 Hazardous Reactivities and Incompatibilities

The admixture of isosulfan blue injection 1% (with local anesthetics (i.e. lidocaine)) in the same syringe results in an immediate precipitation of 4 - 9% drug complex. Use a separate syringe to administer a local anesthetic.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff

9.5 Regulatory Information

New Zealand EPA Inventory of Chemical Status
Ethanaminium, N-4-4-(diethylamino)phenyl(2,5-disulfophenyl)methylene-2,5-cyclohexadien-1-ylidene-N-ethyl-, inner salt, sodium salt: 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.

9.5.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including isosulfan blue, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of July 5, 2012: https://www.fda.gov/cder/ob/

10 Toxicity

10.1 Toxicological Information

10.1.1 Antidote and Emergency Treatment

/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/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/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/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/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/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

10.1.2 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ Certain vital dyes are known to cause pulse oximetry (Spo2) desaturation. The authors studied the effect of isosulfan blue (IB) on Spo2. Thirty-three women, aged 34-81 yr, who were undergoing surgery for breast cancer were studied. IB, 5 mL (50 mg), was injected intraparenchymally around the tumor area by the surgeon. A pulse oximeter was used to continuously record Spo2 values up to 130 min after IB injection. Friedman repeated-measures analysis of ranks was used to analyze the baseline Spo2 and values at 5, 10, 20, 30, 40, 50, and 60 min. Spo2 values were significantly different from baseline values at 5, 10, 20, 30, 40, 50, and 60 min (p < 0.05). In a typical patient, a maximum Spo2 decrease of 3% can be anticipated 25 min after injection of IB. After peritumoral administration of IB, 50 mg, a significant interference with Spo2 will occur.
Vokach-Brodsky L et al; Anesthesiology 93 (4): 1002-3 (2000)
/HUMAN EXPOSURE STUDIES/ Two female patients with breast cancer were evaluated ... after suspected intraoperative anaphylactic episodes during sentinel lymph node biopsies in which they had received isosulfan blue 1% for the purpose of visualization of the lymph vessels. In the first case, the patient suffered hypotension and hypoxia requiring intubation. In the second case, the patient suffered prolonged hypotension. Both patients recovered without sequelae. The patients were /examined/ and skin tests were performed to isosulfan blue in addition to other agents the patients had received during anesthesia. In both cases, the patients demonstrated positive skin tests to isosulfan blue. Neither patient had positive skin tests to any other agent used for skin testing. Isosulfan blue skin tests were performed in nine control subjects and all skin tests in the control subjects were negative. Isosulfan blue may be a cause of anaphylactic reactions and this seems to be an immunoglobulin E-mediated event as confirmed by positive skin tests.
Laurie SA et al; Ann Allergy Asthma Immunol 88(1):64-6 (2002)
/SIGNS AND SYMPTOMS/ Life-threatening anaphylactic reactions (respiratory distress, shock, angioedema) have occurred after isosulfan blue injection 1% administration. Reactions are more likely to occur in patients with a history of bronchial asthma, allergies, drug reactions or previous reactions to triphenylmethane dyes. Monitor patients closely for at least 60 minutes after administration of isosulfan blue injection 1%. Trained personnel should be available to administer emergency care including resuscitation.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff
/CASE REPORTS/ Hypersensitivity Reactions: Case series report an overall incidence of hypersensitivity reactions in approximately 2% of patients. Life-threatening anaphylactic reactions have occurred. Manifestations include respiratory distress, shock, angioedema, urticaria, pruritus. A death has been reported following administration of a similar compound employed to estimate the depth of a severe burn. Reactions are more likely to occur in patients with a personal or family history of bronchial asthma, significant allergies, drug reactions or previous reactions to triphenylmethane dyes.
US Natl Inst Health; DailyMed. Current Medication Information for ISOSULFAN BLUE injection, solution (August 2010). Available from, as of June 8, 2012: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1878964e-5220-48c8-a872-dcadbc451aff
For more Human Toxicity Excerpts (Complete) data for Isosulfan blue (8 total), please visit the HSDB record page.

10.1.3 Protein Binding

1% binds to serum proteins

10.2 Ecological Information

10.2.1 Environmental Fate / Exposure Summary

Isosulfan Blue's production and use as a diagnostic contrast agent may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.9X10-36 mm Hg at 25 °C indicates Isosulfan Blue will exist solely in the particulate phase in the atmosphere. Particulate-phase Isosulfan Blue will be removed from the atmosphere by wet or dry deposition. Sulfan Blue, which is strucrually similar to Isosulfan Blue, absorbs light at 635 nm. Therefore, by analogy, Isosulfan Blue may be susceptible to direct photolysis by sunlight. If released to soil, Isosulfan Blue is expected to be immobile based upon an estimated Koc of 5.5X10+6. However, by analogy to Sulfan Blue which is an anionic dye, Isosulfan Blue may 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. Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Isosulfan Blue may not volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data in soil or water were not available. If released into water, Isosulfan Blue is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Isosulfan Blue is expected to exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis may be an important environmental fate process since this compound contains functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to Isosulfan Blue may occur through inhalation and dermal contact with this compound at workplaces where Isosulfan Blue is produced or used. Exposure to Isosulfan Blue among the general population may be limited to those administered the drug, a diagnostic contrast agent. (SRC)

10.2.2 Artificial Pollution Sources

Isosulfan Blue's production and use as a diagnostic contrast agent(1) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 14th ed., Whitehouse Station, NJ; Merck and Co., Inc., p 1542 (2006)

10.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 5.5X10+6(SRC), determined from a structure estimation method(2), indicates that Isosulfan Blue is expected to be immobile in soil(SRC). However, structurally similar Sulfan Blue is an anionic dye(3). Therefore, by analogy, Isosulfan Blue may 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. Isosulfan Blue is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-36 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2012).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(3) Green FJ; p. 553 The Sigma-Aldrich Handbook of Stains, Dyes, and Indicators. Milwaukee, WI: Aldrich Chem Co. (1990)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 5.5X10+6(SRC), determined from a structure estimation method(2), indicates that Isosulfan Blue is expected to adsorb to suspended solids and sediment(SRC). Structurally similar Sulfan Blue is an anionic dye(3); thus, analogous Isosulfan Blue is expected to exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of -2.34(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2012).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(3) Green FJ; p. 553 The Sigma-Aldrich Handbook of Stains, Dyes, and Indicators. Milwaukee, WI: Aldrich Chem Co. (1990)
(4) Franke C et al; Chemosphere 29: 1501-14 (1994)
(5) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
(6) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2010. Available from, as of Jun 12, 2012: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), Isosulfan Blue, which has an estimated vapor pressure of 1.9X10-36 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 Isosulfan Blue may be removed from the air by wet or dry deposition(SRC). Structurally similar Sulfan Blue absorbs light at 635 nm(3); therefore, by analogy, Isosulfan Blue may be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Green FJ; p. 553 The Sigma-Aldrich Handbook of Stains, Dyes, and Indicators. Milwaukee, WI: Aldrich Chem Co. (1990)

10.2.4 Environmental Abiotic Degradation

Isosulfan Blue may undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(1). Analogous Sulfan Blue absorbs light at 635 nm(2); therefore, Isosulfan Blue may be susceptible to direct photolysis by sunlight(SRC).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)
(2) Green FJ; p. 553 The Sigma-Aldrich Handbook of Stains, Dyes, and Indicators. Milwaukee, WI: Aldrich Chem Co. (1990)

10.2.5 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for Isosulfan Blue(SRC), using an estimated log Kow of -2.34(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).
(1) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2010. Available from, as of Jun 12, 2012: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

10.2.6 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of Isosulfan Blue can be estimated to be 5.5X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that Isosulfan Blue is expected to be immobile in soil. Analogous Sulfan Blue is an anionic dye(3). Therefore, by analogy, Isosulfan Blue may 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).
(1) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) Green FJ; p. 553 The Sigma-Aldrich Handbook of Stains, Dyes, and Indicators. Milwaukee, WI: Aldrich Chem Co. (1990)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

10.2.7 Volatilization from Water / Soil

Structurally similar Sulfan Blue is an anionic dye(1). Therefore, by analogy, Isosulfan Blue will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. Isosulfan Blue is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-36 mm Hg(SRC), determined from a fragment constant method(3).
(1) Green FJ; p. 553 The Sigma-Aldrich Handbook of Stains, Dyes, and Indicators. Milwaukee, WI: Aldrich Chem Co. (1990)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

10.2.8 Environmental Water Concentrations

While data specific to Isosulfan Blue were not located(SRC, 2012), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).
(1) Heberer T; Tox Lett 131: 5-17 (2002)
(2) Koplin DW et al; Environ Sci Toxicol 36: 1202-211 (2002)

10.2.9 Probable Routes of Human Exposure

Occupational exposure to Isosulfan Blue may occur through inhalation and dermal contact with this compound at workplaces where Isosulfan Blue is produced or used. Exposure to Isosulfan Blue among the general population may be limited to those administered the drug, a diagnostic contrast agent. (SRC)

11 Associated Disorders and Diseases

12 Literature

12.1 Consolidated References

12.2 NLM Curated PubMed Citations

12.3 Springer Nature References

12.4 Chemical Co-Occurrences in Literature

12.5 Chemical-Gene Co-Occurrences in Literature

12.6 Chemical-Disease Co-Occurrences in Literature

13 Patents

13.1 Depositor-Supplied Patent Identifiers

13.2 WIPO PATENTSCOPE

13.3 Chemical Co-Occurrences in Patents

13.4 Chemical-Disease Co-Occurrences in Patents

13.5 Chemical-Gene Co-Occurrences in Patents

14 Interactions and Pathways

14.1 Drug-Drug Interactions

15 Biological Test Results

15.1 BioAssay Results

16 Classification

16.1 MeSH Tree

16.2 NCI Thesaurus Tree

16.3 ChemIDplus

16.4 UN GHS Classification

16.5 NORMAN Suspect List Exchange Classification

16.6 EPA DSSTox Classification

16.7 MolGenie Organic Chemistry Ontology

17 Information Sources

  1. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    sodium;2-[[4-(diethylamino)phenyl]-(4-diethylazaniumylidenecyclohexa-2,5-dien-1-ylidene)methyl]benzene-1,4-disulfonate
    https://echa.europa.eu/substance-information/-/substanceinfo/100.248.842
    sodium;2-[[4-(diethylamino)phenyl]-(4-diethylazaniumylidenecyclohexa-2,5-dien-1-ylidene)methyl]benzene-1,4-disulfonate (EC: 814-985-7)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/256418
  6. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. Hazardous Substances Data Bank (HSDB)
  8. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
    Ethanaminium, N-4-4-(diethylamino)phenyl(2,5-disulfophenyl)methylene-2,5-cyclohexadien-1-ylidene-N-ethyl-, inner salt, sodium salt
    https://www.epa.govt.nz/industry-areas/hazardous-substances/guidance-for-importers-and-manufacturers/hazardous-substances-databases/
  9. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  10. DailyMed
  11. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  12. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  13. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  14. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  15. Metabolomics Workbench
  16. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  17. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  18. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  19. Therapeutic Target Database (TTD)
  20. Springer Nature
  21. Wikidata
    isosulfan blue, sodium salt
    https://www.wikidata.org/wiki/Q22075850
  22. Wikipedia
  23. PubChem
  24. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  25. GHS Classification (UNECE)
  26. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  27. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  28. PATENTSCOPE (WIPO)
  29. NCBI
CONTENTS