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Amphotericin B, Antibiotic for Culture Media Use Only

PubChem CID
156595875
Structure
Amphotericin B, Antibiotic for Culture Media Use Only_small.png
Molecular Formula
Synonyms
  • 1397-89-3
  • A-7680
  • Amphotericin B, Antibiotic for Culture Media Use Only
Molecular Weight
924.1 g/mol
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Dates
  • Create:
    2021-09-10
  • Modify:
    2025-01-18

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Amphotericin B, Antibiotic for Culture Media Use Only.png

1.2 3D Status

Conformer generation is disallowed since too many atoms, too many undefined stereo centers

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,33R,35S,36R,37S)-33-[(3S,4S,5R,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.05.07)

2.1.2 InChI

InChI=1S/C47H73NO17/c1-27-17-15-13-11-9-7-5-6-8-10-12-14-16-18-34(64-46-44(58)41(48)43(57)30(4)63-46)24-38-40(45(59)60)37(54)26-47(61,65-38)25-33(51)22-36(53)35(52)20-19-31(49)21-32(50)23-39(55)62-29(3)28(2)42(27)56/h5-18,27-38,40-44,46,49-54,56-58,61H,19-26,48H2,1-4H3,(H,59,60)/t27-,28-,29-,30+,31+,32+,33-,34-,35+,36+,37-,38-,40+,41-,42+,43-,44-,46?,47+/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.05.07)

2.1.3 InChIKey

APKFDSVGJQXUKY-ITPUTMHRSA-N
Computed by InChI 1.0.6 (PubChem release 2021.05.07)

2.1.4 SMILES

C[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@@H](C[C@H]2[C@@H]([C@H](C[C@](O2)(C[C@H](C[C@H]([C@@H](CC[C@H](C[C@H](CC(=O)O[C@H]([C@@H]([C@@H]1O)C)C)O)O)O)O)O)O)O)C(=O)O)OC3[C@H]([C@H]([C@H]([C@H](O3)C)O)N)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C47H73NO17
Computed by PubChem 2.1 (PubChem release 2021.05.07)

2.3 Other Identifiers

2.3.1 CAS

1397-89-3

2.3.2 European Community (EC) Number

2.4 Synonyms

2.4.1 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
924.1 g/mol
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
XLogP3-AA
Property Value
0
Reference
Computed by XLogP3 3.0 (PubChem release 2021.05.07)
Property Name
Hydrogen Bond Donor Count
Property Value
12
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Hydrogen Bond Acceptor Count
Property Value
18
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Rotatable Bond Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Exact Mass
Property Value
923.48784986 Da
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
Monoisotopic Mass
Property Value
923.48784986 Da
Reference
Computed by PubChem 2.1 (PubChem release 2021.05.07)
Property Name
Topological Polar Surface Area
Property Value
320 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Heavy Atom Count
Property Value
65
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
1670
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.05.07)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
18
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
1
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
7
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.05.07)

3.2 Experimental Properties

3.2.1 Color / Form

Deep yellow prisms or needles from n,n-dimethylformamide
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
YELLOW TO ORANGE POWDER
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1164

3.2.2 Odor

ODORLESS OR PRACTICALLY SO
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1164

3.2.3 Melting Point

170 °C (gradual decomposition)
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 69

3.2.4 Solubility

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
INSOL IN ANHYDROUS ALC, ETHER, BENZENE & TOLUENE; SLIGHTLY SOL IN METHANOL
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1164
Insol in water at pH 6-7; solubility in water at pH 2 or pH 11 about 0.1 mg/ml; water sol increased by sodium desoxycholate
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
In water, 750 mg/L at 25 °C
Yalkowsky, S.H., He, Yan., Handbook of Aqueous Solubility Data: An Extensive Compilation of Aqueous Solubility Data for Organic Compounds Extracted from the AQUASOL dATAbASE. CRC Press LLC, Boca Raton, FL. 2003., p. 1263

3.2.5 Stability / Shelf Life

Solids and solutions appear stable for long periods between pH 4 and 10 when stored at moderate temperature out of light and air.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
Drug is unstable under unfavorable conditions (eg, exposure to heat, light, low ph). Dry powder should be refrigerated and stored no more than 24 hr.
American Medical Association. AMA Drug Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991., p. 1485

3.2.6 Optical Rotation

Specific optical rotation at 24 °C/D: +333 deg (acidic N,N-dimethylformamide); -33.6 deg (0.1 N methanolic hydrochloric acid)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98

3.2.7 Decomposition

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 272

3.3 Chemical Classes

3.3.1 Drugs

3.3.1.1 Human Drugs
Breast Feeding; Lactation; Antifungal Agents

4 Spectral Information

4.1 UV Spectra

Maximum absorption (methanol): 406, 382, 363, 345 nm.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Classes

Breast Feeding; Lactation; Antifungal Agents

7.2 Clinical Trials

7.2.1 EU Clinical Trials Register

7.3 Therapeutic Uses

Ambecides; Antibiotics, Antifungal; Antibiotics, Macrolide; Antiprotozoal Agents
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
MEDICATION: Antifungal; (VET): Antifungal
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
MEDICATION (VET): ... Blastomycosis, histoplasmosis.
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 18
Parenteral amphotericin B is used as a secondary agent in the treatment of paracoccidioidomycosis caused by Paracoccidioide brasillensis. /NOT included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 131
For more Therapeutic Uses (Complete) data for AMPHOTERICIN B (19 total), please visit the HSDB record page.

7.4 Drug Warnings

Rash (including maculopapular or vesiculobullous rash), purpura, pruritus, urticaria, sweating, exfoliative dermatitis, erythema multiforme, alopecia, dry skin, and skin discoloration or ulcer, have been reported in patients receiving amphotericin B.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 538
IV administration of conventional amphotericin B, amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal may cause erythema, pain, or inflammation at the injection site. Phlebitis or thrombophlebitis has been reported with conventional IV amphotericin B. The manufacturer of conventional IV amphotericin B and some clinicians suggest that the addition of 500-1000 units of heparin to the amphotericin B infusion, the use of a pediatric scalp-vein needle, or alternate-day therapy may decrease the incidence of thrombophlebitis. Extravasation of the drug causes local irritation.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 538
Conventional IV amphotericin B is associated with a high incidence of adverse effects, and most patients who receive the drug experience potentially severe adverse effects at some time during the course of therapy. Acute infusion reactions (e.g., fever, chills, headache, nausea, vomiting) and nephrotoxicity are the most frequent adverse reactions to conventional IV amphotericin B. Although clinical experience with amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, and amphotericin B liposomal is limited to date, these drugs appear to be better tolerated than conventional IV amphotericin B. As with conventional IV amphotericin B, the most frequent adverse reactions to amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal are acute infusion reactions; however, data accumulated to date indicate that lipid-based and liposomal formulations of amphotericin B may be associated with a lower overall incidence of adverse effects and a lower incidence of hematologic and renal toxicity than the conventional formulation of the drug.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 537
Acute infusion reactions consisting of fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea, and tachypnea may occur 1-3 hours after initiation of IV infusions of conventional amphotericin B, amphotericin B cholesteryl sulfate, amphotericin B lipid complex, or amphotericin B liposomal. These reactions are most severe and occur most frequently with initial doses and usually lessen with subsequent doses. Fever (with or without shaking chills) may occur as soon as 15-20 minutes after IV infusions of conventional amphotericin B are started. The majority of patients receiving conventional IV amphotericin B (50-90%) exhibit some degree of intolerance to initial doses of the drug, even when therapy is initiated with low doses. Although these reactions become less frequent following subsequent doses or administration of the drug on alternate days, they recur if conventional IV amphotericin B therapy is interrupted and then reinstituted.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 537
For more Drug Warnings (Complete) data for AMPHOTERICIN B (18 total), please visit the HSDB record page.

7.5 Drug Tolerance

Resistance to amphotericin B has been produced in vitro by serial passage of fungi in the presence of increasing concentrations of the drug, and resistant strains of some fungi (eg, Candida) have been isolated from patients who received long-term therapy with conventional amphotericin B. Amphotericin B-resistant Candida are reported relatively infrequently; however, primary resistance to the drug occurs in some strains of C. lusitaniae and also occurs in C. guilliermondii.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541
While the clinical importance is unclear, fluconazole-resistant strains of C. albicans that were cross-resistant to amphotericin B have been isolated from a few immunocompromised individuals, including leukemia patients and patients with human immunodeficiency virus (HIV) infection. In addition, a few isolates of Cryptococcus neoformans resistant to fluconazole also have been resistant to amphotericin B.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541
Fungi resistant to conventional amphotericin B also may be resistant to amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, and amphotericin B liposomal.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541

8 Pharmacology and Biochemistry

8.1 Absorption, Distribution and Excretion

The pharmacokinetics of amphotericin B vary substantially depending on whether the drug is administered as conventional amphotericin B (formulated with sodium desoxycholate), amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal, and pharmacokinetic parameters reported for one amphotericin B formulation should not be used to predict the pharmacokinetics of any other amphotericin B formulation.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541
Amphotericin B is poorly absorbed from the GI tract and must be given parenterally to treat systemic fungal infections. In one study, immediately after completion of iv infusion of 30 mg of amphotericin B (administered over a period of several hours), average peak serum concentrations were about 1 ug/ml; when the dose was 50 mg, average peak serum concentrations were approximately 2 ug/ml. Immediately after infusion, no more than 10% of the amphotericin B dose can be accounted for in serum. Average minimum serum concentrations (recorded just prior to the next drug infusion) of approximately 0.4 ug/ml have been reported when doses of 30 mg were given daily or when doses of 60 mg were given every other day.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541
Information on the distribution of amphotericin B is limited, although distribution is apparently multicompartmental. The volume of distribution of the drug following administration of conventional amphotericin B has been reported to be 4 L/kg; the volume of distribution at steady state after administration of amphotericin B cholesteryl sulfate is reported to be 3.8-4.1 L/kg. Amphotericin B concentrations attained in inflamed pleura, peritoneum, synovium, and aqueous humor following IV administration of conventional amphotericin B reportedly are about 60% of concurrent plasma concentrations; the drug also is distributed into vitreous humor, pleural, pericardial, peritoneal, and synovial fluid. Amphotericin B reportedly crosses the placenta and low concentrations are attained in amniotic fluid.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541
Following IV administration of conventional amphotericin B, CSF concentrations of the drug are approximately 3% of concurrent serum concentrations. To achieve fungistatic CSF concentrations, the drug must usually be administered intrathecally. In patients with meningitis, intrathecal administration of 0.2-0.3 mg of conventional amphotericin B via a subcutaneous reservoir has produced peak CSF concentrations of 0.5-0.8 ug/mL; 24 hours after the dose, CSF concentrations were 0.11-0.29 ug/mL. Amphotericin B is removed from the CSF by arachnoid villi and appears to be stored in the extracellular compartment of the brain, which may act as a reservoir for the drug.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541
For more Absorption, Distribution and Excretion (Complete) data for AMPHOTERICIN B (14 total), please visit the HSDB record page.

8.2 Biological Half-Life

Amphotericin B cholesteryl sulfate complex has a distribution half-life of 3.5 minutes and an elimination half-life of 27.5-28.2 hours. /Amphotericin B cholesteryl sulfate complex/
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541
Following IV administration of conventional amphotericin B in patients whose renal function is normal prior to therapy, the initial plasma half-life is approximately 24 hours. After the first 24 hours, the rate at which amphotericin B is eliminated decreases and an elimination half-life of approximately 15 days has been reported.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 541
Elimination, half life: Neonates: Variable (range, 18 to 62.5 hours). Children: Variable (range, 5.5 to 40.3 hours). Adults: Approximately 24 hours. Terminal half life: Approximately 15 days. NOTE: There is large interindividual variation among neonates in the elimination of amphotericin B. Amphotericin B may persist in the circulation of neonates for up to 17 days after it has been discontinued.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 131
. The half life of elimination of amphotericin B from the lungs /of rats/ was 4.8 days according to serial sacrifices done after a single dose of 3.2 mg of aerosol doses of amphotericin B per kg.
Niki Y et al; Antimicrob Agents Chemother 34 (1): 29-32 (1990)

8.3 Mechanism of Action

Amphotericin B usually is fungistatic in action at concentrations obtained clinically, but may be fungicidal in high concentrations or against very susceptible organisms. Amphotericin B exerts its antifungal activity principally by binding to sterols (e.g., ergosterol) in the fungal cell membrane. As a result of this binding, the cell membrane is no longer able to function as a selective barrier and leakage of intracellular contents occurs. Cell death occurs in part as a result of permeability changes, but other mechanisms also may contribute to the in vivo antifungal effects of amphotericin B against some fungi. Amphotericin B is not active in vitro against organisms that do not contain sterols in their cell membranes (eg, bacteria).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 540
Binding to sterols in mammalian cells (such as certain kidney cells and erythrocytes) may account for some of the toxicities reported with conventional amphotericin B therapy. At usual therapeutic concentrations of amphotericin B, the drug does not appear to hemolyze mature erythrocytes, and the anemia seen with conventional IV amphotericin B therapy may result from the action of the drug on actively metabolizing and dividing erythropoietic cells.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 540
...Nephrotoxicity associated with conventional IV amphotericin B appears to involve several mechanisms, including a direct vasoconstrictive effect on renal arterioles that reduces glomerular and renal tubular blood flow and a lytic action on cholesterol-rich lysosomal membranes of renal tubular cells. ...
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 537

9 Use and Manufacturing

9.1 Uses

MEDICATION
MEDICATION (VET)
Amphotericin B is an antifungal antibiotic produced from a strain of Streptomyces nodosus.
Physicians Desk Reference. 59th ed. Thomson PDR. Montvale, NJ 2005., p. 1228
THERAP CAT: Antifungal
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
Very high concentrations of amphotericin B increase the permeability of the sarcolemmal membrane, and electrophysiologists use the drug to create perforated patch-clamp models.
Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 621

Use (kg; approx.) in Germany (2009): >1000

Use (kg) in USA (2002): 73

Use (kg) in France (2004): 18179

Consumption (g per capita; approx.) in Germany (2009): 0.0122

Consumption (g per capita) in the USA (2002): 0.000258

Consumption (g per capita) in France (2004): 0.301

Excretion rate: 1

Calculated removal (%): 75.1

9.2 Methods of Manufacturing

Dutcher et al., US patent 2,908,611 (1959 to Olin Mathieson)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
Fermentation of Streptomyces nodosus cultures
SRI

9.3 Formulations / Preparations

U.S. Department of Health, Education & Welfare, Public Health Service. Center for Disease Control, National Institute for Occupational Safety & Health. Registry of Toxic Effects of Chemical Substances. 1977 edition. Washington, D. C.: U.S. Government Printing Office, 1977., p. 92
Amphotericin B is ... formulated for iv infusion by complexing it with the bile salt deoxycholate ... /and/ marketed as a lyophilized powder (FUNGIZONE) containing 50 mg of amphotericin B, 41 mg of deoxycholate, and a small amount of sodium phosphate buffer. The amphotericin B-deoxycholate complex (DOC) forms a colloid in water ... N-acyl and O-acyl derivatives of amphotericin B form water-soluble salts, but none is available commercially.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1297
... /Three/ lipid formulations for iv infusion /are available/. Amphotericin B colloidal dispersion (ABCD, AMPHOTEC, AMPHOCIL) ... /contains/ roughly equimolar amounts of amphotericin B and cholesteryl sulfate ... /In/ a unilamellar vesicle formulation ... (AMBISOME) ... amphotericin B (50 mg) is combined with 350 mg of lipid in an approximately 10% molar ratio. The lipid contains hydrogenated soy lecithin (phosphatidylcholine), cholesterol, and distearoylphosphatidylglycerol in a 10:5:4 molar ratio. The drug is supplied as a lyophilized powder, which is reconstituted with sterile water for injection and then the dose diluted with 5% dextrose solution ... The third lipid formulation is amphotericin B lipid complex (ABLC, ABELCET). This preparation of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 mixture with approximately 35 mol% amphotericin B forms ribbon-like sheets ...
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1297
The amphotericin B-deoxycholate complex (DOC) has been mixed with a 20% lipid emulsion (INTRALIPID) ...
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1298
For more Formulations/Preparations (Complete) data for AMPHOTERICIN B (10 total), please visit the HSDB record page.

9.4 Consumption Patterns

ESSENTIALLY 100% AS AN ANTIBIOTIC
SRI

9.5 U.S. Production

(1977) PROBABLY GREATER THAN 9.08X10+5 GRAMS
SRI
(1979) PROBABLY GREATER THAN 9.08X10+5 GRAMS
SRI

9.6 General Manufacturing Information

Polyene antibiotic produced by Streptomycetes nodosus M4575 obtained from soil of the Orinoco river region of Venezuela.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
Commercially available as a deoxycholate complex.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 69
Amphotericin B was found in the mycelium of Streptomyces nodosus M-4575 by Gold et al. of the Squibb Institute of Medical Research in 1956. It is produced with another polyene macrolide antibiotic, amphotericin A, and separated by solvent extraction.
Ullmann's Encyclopedia of Industrial Chemistry. 6th ed.Vol 1: Federal Republic of Germany: Wiley-VCH Verlag GmbH & Co. 2003 to Present, p. 411

10 Identification

10.1 Analytic Laboratory Methods

A SYNTHETIC AGAR CULTURE MEDIUM WAS DEVELOPED; TURBIDIMETRIC ADJUSTMENT OF CELL SUSPENSIONS RESULTED IN STANDARD REPRODUCIBLE INOCULA, WHICH GAVE SHARP, CLEAR ZONES IN INHIBITION WHEN APPLIED BY AN AGAR OVERLAY METHOD.
SAUBOLLE MA, HOEPRICH PD; ANTIMICROB AGENTS CHEMOTHER 14 (4): 517-30 (1978)
Analyte: amphotericin B; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p164 (2006)
Analyte: amphotericin B; matrix: chemical purity; procedure: cylinder-plate method or turbidimetric method with comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p164 (2006)
Analyte: amphotericin B; matrix: pharmaceutical preparation (cream; injection solution; lotion; ointment); procedure: cylinder-plate method or turbidimetric method with comparison to standards (chemical purity)
U.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p164 (2006)
For more Analytic Laboratory Methods (Complete) data for AMPHOTERICIN B (10 total), please visit the HSDB record page.

10.2 Clinical Laboratory Methods

SIMPLE MICRO AGAR DIFFUSION METHOD FOR DETERMINATION OF ANTIBIOTIC CONCN IN BLOOD & OTHER BODY FLUIDS.
GEORGOPOULOS A; ZENTRALBL BAKTERIOL, PARASITENKD, ENFEKTIONSKR HYG, ABT 1: ORIG, REIHE A, 242 (3): 387-93 (1978)
Analyte: amphotericin B; matrix: cerebral spinal fluid; procedure: high-performance liquid chromatography with ultraviolet detection at 410 nm; limit of detection: 0.5 ng/mL
Liu H et al; J Pharm Biomed Anal 13: 1395-1400 (1995). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000., p.424
Analyte: amphotericin B; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 382 nm; limit of detection: 0.2 ng
Betto R et al; J Liq Chromatogr Rel Technol 20: 1857-1866 (1997). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000., p.424
Analyte: amphotericin B; matrix: blood (whole); procedure: high-performance liquid chromatography with ultraviolet detection at 405 nm; limit of quantitation: 75 ng/mL
Adedoyin A et al; Antimicrob Agents Chemother 41: 2201-2208 (1997). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000., p.425
For more Clinical Laboratory Methods (Complete) data for AMPHOTERICIN B (15 total), please visit the HSDB record page.

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H315 (97.4%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (96.1%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (97.4%): 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

Aggregated GHS information provided per 152 reports by companies from 23 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Skin Irrit. 2 (97.4%)

Eye Irrit. 2 (96.1%)

STOT SE 3 (97.4%)

11.2 Accidental Release Measures

11.2.1 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

11.3 Handling and Storage

11.3.1 Storage Conditions

Conventional amphotericin B powder for injection should be stored at 2-8 °C. Reconstituted colloidal dispersions of conventional amphotericin B should be protected from light and are stable for 24 hours at room temperature or 1 week when refrigerated at 2-8 °C. Although the manufacturers state that reconstituted dispersions or IV infusions of amphotericin B should be protected from light during administration, potency is unaffected if the infusion is exposed to light for less than 8-24 hours.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 542
Commercially available lyophilized amphotericin B cholesteryl sulfate complex should be stored at 15-30 °C. Following reconstitution with sterile water for injection, the colloidal dispersion should be refrigerated at 2-8 °C and used within 24 hours; reconstituted amphotericin B cholesteryl sulfate complex should not be frozen. Reconstituted amphotericin B cholesteryl sulfate complex that has been further diluted in 5% dextrose injection should be stored at 2-8 °C and used within 24 hours; any partially used vials of the drug should be discarded.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 542
Do not reconstitute with saline or add saline to the reconstituted concentration, or mix with other drugs. The use of any solution other than those recommended, or the presence of a bacteriostatic agent in the solution, may cause precipitation of am B isome.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 620

11.4 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Amphotericin B
New Zealand EPA Inventory of Chemical Status
Amphotericin B: Does not have an individual approval but may be used under an appropriate group standard

11.4.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl amphotericin, 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 25, 2006: https://www.fda.gov/cder/ob/

11.5 Other Safety Information

11.5.1 Special Reports

Benson JM, Nahata MC; Clinical Use of Systemic Antifungal Agents. Clin Pharm 7 (Jun): 424-38 (1988). The chemistry, pharmacology, mechanism of action, pharmacokinetics, clinical uses, adverse effects, and drug interactions of amphotericin B are reviewed.
Branch RA; Prevention of Amphotericin B Induced Renal Impairment: Review on the Use of Sodium Supplementation. Arch Intern Med 148 (Nov): 2389-94 (1988). The incidence and mechanism of kidney failure attributed to amphotericin B (Fungizone), guidelines for reducing the risk of renal impairment when the drug is used, and the potential use of sodium, either as sodium chloride or ticarcillin disodium, to reduce the risk of nephrotoxicity are discussed.
Gallis HA et al; Amphotericin B: 30 Years of Clinical Experience. Rev Infect Dis12 (2): 308-29 (1990). This paper discusses the clinical uses of amphotericin B, including its application in AIDS related fungal infections, in neutropenic cancer patients who are persistently febrile, and in infections of the central nervous system, lung, peritoneum, genitourinary system, eye, and skin. The paper also reviews the drug's adverse reactions, with a discussion of administration techniques that may reduce these reactions, and its spectrum of activity, pharmacokinetics, and dosage and administration.
Georgiev VS; Treatment and Developmental Therapeutics in Aspergillosis. 1. Amphotericin B and its Derivatives. Respiration 59 (5): 291-302 (1992). The clinical efficacy of amphotericin B, its toxicities and various routes of applications, are discussed. Different combinations of amphotericin B with other drugs have also been reviewed, along with the anti-Aspergillus activity of various other antibiotics and some ester derivatives of amphotericin B.
For more Special Reports (Complete) data for AMPHOTERICIN B (12 total), please visit the HSDB record page.

12 Toxicity

12.1 Toxicological Information

12.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Although no information exists on the milk excretion of amphotericin B, it is highly protein bound, has a large molecular weight, is virtually unabsorbed orally and has been use directly in the mouths of infants; therefore, most reviewers consider it acceptable to use in nursing mothers.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

12.1.2 Interactions

Since nephrotoxic effects may be additive, the concurrent or sequential use of amphotericin B and other drugs with similar toxic potentials (eg, aminoglycosides, capreomycin, colistill, cisplatin, cyclosporine, methoxyflurane, pentamidine, polymyxin B, vancomycin) should be avoided, if possible.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 539
Corticosteroids reportedly may enhance the potassium depletion caused by amphotericin B and should not be used concomitantly unless necessary to control adverse reactions to amphotericin B.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 540
Antineoplastic agents (eg, mechlorethamine) may enhance the potential for renal toxicity, bronchospasm, and hypotension in patients receiving amphotericin B and such concomitant therapy should be used only with great caution.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 540
In a randomized, double-blind study that evaluated use of conventional IV amphotericin B and amphotericin B cholesteryl sulfate complex in febrile neutropenic patients with normal baseline serum creatinine concentrations, the incidence of renal toxicity (defined as a doubling or an increase of 1 mg/dL or more from baseline serum creatinine or a 50% or greater decrease from baseline in calculated creatinine clearance) was 31% in adults and pediatric patients who received amphotericin B cholesteryl sulfate complex concomitantly with cyclosporine or tacrolimus compared with 68% in those who received conventional amphotericin B concomitantly with these agents. In adults and pediatric patients who did not receive cyclosporine or tacrolimus therapy, the incidence of renal toxicity was 8% in those who received amphotericin B cholesteryl sulfate complex and 35% in those who received conventional amphotericin B.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 539
For more Interactions (Complete) data for AMPHOTERICIN B (15 total), please visit the HSDB record page.

12.1.3 Antidote and Emergency Treatment

In the event of overdosage with any amphotericin B formulation, therapy with the drug should be discontinued and the patient's clinical status (eg, cardiorespiratory, renal, and liver function, hematologic status, serum electrolytes) monitored. Supportive therapy should be administered as required. ... The patient's condition should be stabilized, including correction of electrolyte abnormalities, prior to reinstituting amphotericin B therapy.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 540
Exchange transfusion may be useful in neonates and infants and should be considered after large iv exposures. In adults, extracorporeal elimination is not expected to be useful because of the drug's low water solubility and high blood-protein binding.
Goldfrank, L.R. (ed). Goldfrank's Toxicologic Emergencies. 7th Edition McGraw-Hill New York, New York 2002., p. 698
/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
If severe respiratory distress, anaphylaxis, or an anaphylactoid reaction occurs in a patient receiving amphotericin B, the drug should be discontinued immediately and the patient given appropriate therapy (eg, epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 538

12.1.4 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ Acute overdosage of conventional amphotericin B may result in cardiorespiratory arrest. Adverse cardiovascular effects, including hypotension, bradycardia, and cardiac arrest, have been reported in several pediatric patients who inadvertently received overdosage of conventional amphotericin B.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 540
/SIGNS AND SYMPTOMS/ Four /of 13/ infants had minimal elimination for /amphotericin B/ between doses, a finding that correlates with rises in serum creatinine (greater than 0.4 mg/dL, 40 umol/L) and blood urea nitrogen (greater than 10 mg/dL, 3.6 mmol/L).
Baley JE et al; J Pediatr 116 (5): 791-7 (1990)
/SIGNS AND SYMPTOMS/ Various adverse cardiopulmonary effects, including hypotension, tachypnea, cardiac failure, cardiac arrest, cardiomyopathy, shock, pulmonary edema, hypersensitivity pneumonitis, arrhythmias (including ventricular fibrillation), dyspnea, and hypertension, have been reported in individuals receiving conventional IV amphotericin B.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 538
/SIGNS AND SYMPTOMS/ If severe respiratory distress, anaphylaxis, or an anaphylactoid reaction occurs in a patient receiving amphotericin B, the drug should be discontinued immediately and the patient given appropriate therapy (eg, epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 538
For more Human Toxicity Excerpts (Complete) data for AMPHOTERICIN B (10 total), please visit the HSDB record page.

12.1.5 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ On the corneas of rabbits even 0.0025% /of amphotericin B/ disrupts the epithelial cells, and 1% causes extensive damage to these cells and markedly delays healing of epithelial defects. When more than 5 mg are injected subconjunctivally, a severe local reaction results with permanent yellow discoloration of the conjunctiva and formation of raised nodules that are slow in resolving. Injected into the anterior chamber in rabbits, 0.5 mg severely damaged the corneal endothelium, but 25 ug or 50 ug did not. When injected into the vitreous body in rabbits, some investigators report 5 to 10 ug to be non toxic, while others have reported inflammation, cataract and retinal detachment and necrosis from as little as 1 or 2 ug.[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96]
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The embryotoxic action of amphotericin B and its methyl derivative was compared in rats after their iv and intraamniotic administration. The concn of amphotericin B and its methyl derivative in the amniotic cavity on days 13, 14 and 15 of pregnancy were 1.5 and 36 ug/mL, respectively. When administered iv during the preimplantation period the antibiotics had no embryotoxic action. Iv administration of amphotericin B in a dose of 500 ug/kg and its derivative in a dose of 2000 ug/kg during organ genesis induced a decrease in the craniocaudal size. In a dose of 3000 ug/kg administered iv the methyl derivative of amphotericin B induced an increase in postimplantation death rates. Administration of amphotericin B to the amniotic cavity had no damaging action. Administration of the methyl derivative on day 15 of pregnancy led to anomalous development of the lower extremities and slower ossification. The threshold doses by the embryotoxic action for iv administration are 500 ug/kg for amphotericin B and 2000 ug/kg for the methyl derivative. Administration of the antibiotics to the amniotic cavity revealed potential teratogenic properties of the amphotericin B methyl derivative.[Moguchenok EA; Antibiot Khimioter 37 (3): 25-8 (1992)]
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Studies in male and female rats using amphotericin B lipid complex at doses up to 0.32 times the usual human dose (based on body surface area) indicate that the drug does not affect fertility. When liposomal amphotericin was administered to rats in 10- or 15-mg/kg doses (equivalent to human doses of 1.6 or 2.4 mg/kg based on body surface area), there was evidence of an abnormal estrous cycle (prolonged diestrus) and decreased number of corpora lutea in female rats receiving the higher dosage but no effect on fertility or days to copulation; there were no effects on male reproductive function.[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 539]
/LABORATORY ANIMALS: Neurotoxicity/ The intracisternal administration of amphotericin B and its mono-methyl ester derivative, via direct intraventricular injection (0.01 to 5 mg/ml, 6 ul) in adult female Wistar rats, revealed that amphotericin B was significantly more toxic than amphotericin B mono-methyl ester, as measured by wt loss, lethargy, death, and central nervous system histopathology. Light and electron microscopy confirmed a greater neurotoxicity for amphotericin B, manifested as edema and modest gliosis extending along and beyond the injection tract. Neuronal degeneration and myelin damage were present in amphotericin B treated (1 mg/mL) animals but were present only modestly in animals treated with amphotericin B mono methyl ester at a fivefold greater concn. Iv administration of amphotericin B to adult female Wistar rats as five daily doses of 5 mg/kg of body wt resulted in significant wt loss and some deaths. Histopathologic examination of the brains, spinal cords, and sural nerves of surviving animals revealed neurotoxicity manifested by neuronal degeneration, gliosis, and myelin edema. In sharp contrast, similar treatment with amphotericin B mono methyl ester at a 10 fold greater dose resulted in neither death nor significant neurotoxicity. The administration of five daily doses of a mixture of amphotericin B mono methyl ester-amphotericin B (9:1; wt/wt) at 50 mg/kg of body wt resulted in neurotoxicity. These results indicate that amphotericin B exhibits significantly greater in vivo neurotoxicity than amphotericin B mono methyl ester.[Reuhl KR et al; Antimicrob Agents Chemother 37 (3): 419-28 (1993)]
For more Non-Human Toxicity Excerpts (Complete) data for AMPHOTERICIN B (6 total), please visit the HSDB record page.

12.1.6 Non-Human Toxicity Values

LD50 Mouse iv 4 mg/kg
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98
LD50 Mouse ip 88 mg/kg
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 98

13 Literature

13.1 Consolidated References

13.2 Chemical Co-Occurrences in Literature

13.3 Chemical-Disease Co-Occurrences in Literature

14 Classification

14.1 CAMEO Chemicals

14.2 UN GHS Classification

15 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
  2. European Chemicals Agency (ECHA)
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    https://echa.europa.eu/web/guest/legal-notice
  3. Hazardous Substances Data Bank (HSDB)
  4. New Zealand Environmental Protection Authority (EPA)
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    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  5. Drugs and Lactation Database (LactMed)
  6. EU Clinical Trials Register
  7. NORMAN Suspect List Exchange
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    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    AMPHOTERICIN B
  8. PubChem
  9. GHS Classification (UNECE)
  10. CAMEO Chemicals
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    CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data.
    https://cameochemicals.noaa.gov/help/reference/terms_and_conditions.htm?d_f=false
    CAMEO Chemical Reactivity Classification
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CONTENTS