Sodium Fluorescein

Orange-red powder

Yellow powder

Orange-brown powder

greater than or equal to 100 mg/mL at 68 °F (NTP, 1992)

Soluble in ethanol, glycerol, dilute acetone

Slightly soluble in alcohol

In water, 4.0X10+4 mg/L, temperature not specified

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Fluorescein, disodium salt is an orange-red to dark red powder. Water-soluble form of fluorescein. Odorless and almost tasteless. pH (5% solution) 7.8. May be sensitive to prolonged exposure to light and to heat.

Wet Solid

Orange-red hygroscopic solid; [Merck Index] Dark red powder; [Sigma-Aldrich MSDS]

This chemical does not meet GHS hazard criteria for 87.1% (263 of 302) of all reports.

Warning

H315 (10.6%): Causes skin irritation [Warning Skin corrosion/irritation]

P264, P264+P265, P280, P302+P352, P305+P351+P338, P321, P332+P317, P337+P317, and P362+P364 (click each P-code to see the statement)

Aggregated GHS information provided per 302 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one, 3',6'-dihydroxy-, disodium salt

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one, 3',6'-dihydroxy-, sodium salt (1:2) is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one, 3',6'-dihydroxy-, sodium salt (1:2) are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 18-05-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/17278

C.I. Acid Yellow 73: Non hazardous

SYMPTOMS: Symptoms of exposure to this compound include irritation of the eyes. It may also cause irritation of the skin. Excess inhalation of the dust can cause the onset of asthma. Other symptoms include nausea, urticaria, sneezing, bitter taste and dizziness. There is a low incidence of serious side effects including respiratory embarrassment, pulmonary edema, pharyngeal edema, cardiac arrest, myocardial infarction, shock, hypotension and death. Symptoms that may occur after intravenous injection include vomiting, syncope and urticaria. The skin and urine may be transiently colored.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl fluorescein sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

All batches of this color additive when used as a color additive for externally applied drugs shall meet the specifications, uses and restrictions, and labeling regulations contained in 21 CFR Part 74 and be certified in accordance with regulations in 21 CFR Part 80.

All batches of this color additive when used as a color additive in externally applied cosmetics shall meet the specifications, uses and restrictions, and labeling regulations contained in 21 CFR Part 74 and be certified in accordance with regulations in 21 CFR Part 80.

A batch of this straight color may be certified, in accordance with 21 CFR Part 82, for use in externally applied drugs and cosmetics, if such batch conforms to the requirements of 21 CFR 82.5 and to the specifications in 21 CFR Part 82.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials. This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity. As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Wear approved respiratory protection, chemically compatible gloves and protective clothing.

LC50; Species: Daphnia pulex (Water Flea) age <24 hr neonate; Conditions: freshwater, static, 25 °C, pH 7.4-7.8, hardness 80-100 mg/L CaCO3, alkalinity 60-70 mg/L CaCO3, conductivity 260-320 umhos/cm, dissolved oxygen >8.0 mg/L; Concentration: 337000 ug/L for 48 hr (95% confidence interval: 278000-403000 ug/L) /formulation/

LC50; Species: Oryzias latipes (Medaka); Conditions: freshwater, static, 25 °C; Concentration: 3000000 ug/L for 48 hr

LC50; Species: Psetta maxima (Left-Eyed Flounder) length 4 cm, weight 1.5 g; Conditions: saltwater, static, 14.0 °C, pH 8.1, salinity 36.0'%, dissolved oxygen 7.9 mg/L; Concentration: 997100 ug/L for 24 hr

LC50; Species: Psetta maxima (Left-Eyed Flounder) length 4 cm, weight 1.5 g; Conditions: saltwater, static, 14.0 °C, pH 8.1, salinity 36.0'%, dissolved oxygen 7.9 mg/L; Concentration: 997100 ug/L for 96 hr

TERRESTRIAL FATE: Based on a classification scheme(1), measured Koc values of 88.81 in a silty clay soil and 69.43 in a sediment(2), indicate that D&C Yellow No. 8 is expected to have high mobility in soil(SRC). Volatilization of D&C Yellow No. 8 from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.8X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(3). D&C Yellow No. 8 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). D&C Yellow No. 8, present at 100 mg/L, exhibited <25% elimination in 42 days using an activated sludge inoculum at 0.5 mg/L dry material in the modified static test suggesting the dye may be resistant to biodegradation(4).

TERRESTRIAL FATE: A field study was conducted to identify critical parameters governing the mobility and fate of pesticides in soil/aquifer systems. The test field as located in Juelich, Krauthausen, Germany, characterized as a loamy 20-20% clay; the underlying aquifer consists of fluvial sands and gravel. Only 0.18% of the injected uranine mass could be recovered after 365 days. A mean plume velocity of 0.089 m/day was calculated(1).

AQUATIC FATE: Based on a classification scheme(1), measured Koc values of 88.81 in a silty clay soil and 69.43 in a sediment(2), indicate that D&C Yellow No. 8 is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.8X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 75(SRC), from an estimated log Kow of -0.67(4) and a regression-derived equation(4), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). D&C Yellow No. 8, present at 100 mg/L, exhibited <25% elimination in 42 days using an activated sludge inoculum at 0.5 mg/L dry material in the modified static test suggesting the dye may be resistant to biodegradation(6).

AQUATIC FATE: Sure-Dye formulation was accidentally spilled on the staging area of the Kaiku agricultural landing strip on Kauai Island, HI, October 18, 1996. The formulation was comprised of phloxine B and uranine; spill amounts of 1.2 and 0.54 kg, respectively. The concentration of uranine in a puddle immediately following the spill was approximately 500 ppm; levels decreased to 3 ppb 26 days after the spill. None was detected in the Halenanahu Reservoir, 100 feet away. No uranine was detected in sediment samples from the puddle(1). /Uranine/

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), D&C Yellow No. 8, which has an estimated vapor pressure of 1.6X10-17 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 D&C Yellow No. 8 may be removed from the air by wet or dry deposition(SRC). D&C Yellow No. 8 absorbs light at wavelengths of 493 nm(3), and therefore may be susceptible to direct photolysis by sunlight(SRC).

/AQUATIC SPECIES/ The toxicity of two xanthene dyes, fluorescein sodium salt and phloxine B, to Daphnia pulex was assessed using acute and chronic level toxicological endpoints. The 48-hr LC50 (95% FL) of fluorescein and phloxine B to D. pulex neonates was 337 (278-403) mg/L and 0.423 (0.376-0.477) mg/L, respectively. Statistical comparison of the lethal concentration regressions showed no significant difference between the slopes of the two curves. Acute exposure to combinations of these two dyes together resulted in a synergistic increase in mortality compared to exposure to each dye separately. Following 10-day chronic exposure under static conditions, fluorescein caused a concentration-dependent decline in the mean number of offspring produced by D. pulex. In contrast, chronic exposure to phloxine B did not appear to result in significant sublethal effects with respect to the reproductive potential of exposed organisms.

A Koc of 88.81 in Lihue silty clay (pH 7.0; 18.6 % iron; 7640 ug/g Ca; 1632 ug/g Mg; 3.10% organic carbon) was been reported for uranine(1). According to a classification scheme(2), this Koc value suggests that uranine is expected to have high mobility in soil. The octanol-isotonic salt solution partition coefficient is 0.72 at 25 °C. Sorption experiments indicate that uranine tends to stay in the aqueous phase at low concentration. A Koc of 69.43 has been measured in sediment (pH 8.0; 18.7 % iron; 2398 ug/g Ca; 109 ug/g Mg; 3.94% organic carbon)(1). Freundlich sorption coefficients in Rur gravel and Rhine gravel of 0.76 and 0.42, respectively, have been reported using a uranine concentration in the range of 2-500 ug/L(3). /Uranine/

/SIGNS AND SYMPTOMS/Eye, skin, ... and/or respiratory tract irritation.

/SIGNS AND SYMPTOMS/ ... Side effects or adverse events reported in the literature were related to intravenous bolus injection. Transient nausea and vomiting may occur. Other adverse events such as vasovagal reaction, cardiac or respiratory effects and anaphylaxis are extremely rare but may be fatal. Intradermal injection may cause mild itch or pain; systemic adverse event was reported. Epicutaneous labeling is associated with no reported problem. A typical local dose is several magnitudes of order smaller than a typical intravenous dose. ...

/CASE REPORTS/ The case of a 35-yr-old man with hypertension and diabetes mellitus who underwent fluorescein angiography (FAG) to evaluate diabetic retinopathy and developed a psoriasiform drug eruption several days after receiving fluorescein sodium during FAG is presented. Concomitant therapy included insulin and cilazapril. Initially, cilazapril was suspected as the cause of the psoriasiform eruption. However, a drug-induced lymphocyte stimulation test (DLST) and patch testing with cilazapril were both negative. Topical application of steroid ointments was effective, and the eruption resolved within 7 days. The eruption recurred after fluorescein sodium was readministered for a second FAG examination the following month. Patch testing with fluorescein sodium was negative, but a DLST was positive for this agent. Two months after the psoriasiform eruption resolved, a similar eruption recurred on the trunk in the absence of FAG and had the histological features of psoriasis. The patient was rechallenged with an intravenous injection of 2.5 mL of fluorescein sodium. Three days after the injection, a similar psoriatic eruption occurred.

/CASE REPORTS/ A serious cutaneous adverse effect associated with parenteral diagnostic injection of sodium fluorescein, 16.7 mg/kg, in a sick neonate at 2 days of age, with hyperbilirubinemia and necrotizing enterocolitis, was reported. After the appearance of skin lesions, phototherapy was discontinued and the lesions were treated with local application of silver sulfadiazine cream and sterile dressings. The skin lesions resolved completely over the ensuing 21 days.

For more Human Toxicity Excerpts (Complete) data for D&C Yellow No. 8 (11 total), please visit the HSDB record page.

D&C Yellow No. 8's production and use as a dye(1) may result in its release to the environment through various waste streams(SRC). D&C Yellow No. 8's use as a tracer for underground streams and effluent discharges(2) releases the compound directly to the environment(SRC).

Drug Induced Liver Injury Rank (DILIrank 2.0)

Fluorescein sodium

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

An estimated BCF of 75 was calculated in fish for D&C Yellow No. 8(SRC), using an estimated log Kow of -0.67(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

The Henry's Law constant for D&C Yellow No. 8 is estimated as 2.8X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that D&C Yellow No. 8 is expected to be essentially nonvolatile from water surfaces(2). D&C Yellow No. 8's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected occur(SRC). D&C Yellow No. 8 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-17 mm Hg(SRC), determined from a fragment constant method(1).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl fluorescein sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

All batches of this color additive when used as a color additive for externally applied drugs shall meet the specifications, uses and restrictions, and labeling regulations contained in 21 CFR Part 74 and be certified in accordance with regulations in 21 CFR Part 80.

All batches of this color additive when used as a color additive in externally applied cosmetics shall meet the specifications, uses and restrictions, and labeling regulations contained in 21 CFR Part 74 and be certified in accordance with regulations in 21 CFR Part 80.

A batch of this straight color may be certified, in accordance with 21 CFR Part 82, for use in externally applied drugs and cosmetics, if such batch conforms to the requirements of 21 CFR 82.5 and to the specifications in 21 CFR Part 82.

Fluorescein sodium responds to electromagnetic radiation and light between the wavelengths of 465 to 490 nm and fluoresces, i.e., emits light at wavelengths of 520 to 530 nm. Thus, the hydrocarbon is excited by blue light and emits light that appears yellowish green. Following intravenous injection of fluorescein sodium in an aqueous solution, the unbound fraction of the fluorescein can be excited with a blue light flash from a fundus camera as it circulates through the ocular vasculature, and the yellowish green fluorescence of the dye is captured by the camera. In the fundus, the fluorescence of the dye demarcates the retinal and/or choroidal vasculature under observation, distinguishing it from adjacent areas/structures.

... The pharmacokinetics of fluorescein and fluorescein glucuronide /were studied/ for 38 hr in the plasma of five normal subjects given 14 mg/kg of sodium fluorescein intravenously. ... The terminal half-lives of fluorescein and fluorescein glucuronide in the plasma ultrafiltrate were 23.5 and 264 min, respectively, ... .

Fluorescein is metabolized to fluorescein monoglucuronide. After IV administration of fluorescein sodium (14 mg/kg) to 7 healthy subjects, approximately 80% of fluorescein in plasma was converted to glucuronide conjugate after a period of 1 hour post dose.

FLUORESCEIN SODIUM

Dyes [MoA]; Diagnostic Dye [EPC]

Substances used to allow enhanced visualization of tissues.

Chemicals that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.

Uranine is rapidly absorbed in the lungs and in the respiratory tract, and is affected by the presence of surfactants. It is not metabolized in the lung. Inhaled uranine is excreted in the urine.

Within 7 to 14 seconds after IV administration into the antecubital vein, fluorescein usually appears in the central retinal artery of the eye. Within a few minutes of IV administration of fluorescein sodium, a yellowish discoloration of the skin occurs, which begins to fade 6 to 12 hours after dosing. Various estimates of volume of distribution indicate that fluorescein distributes into interstitial space (0.5 L/kg).

Fluorescein sodium has been demonstrated to be excreted in human milk.

Fluorescein and its metabolite are mainly eliminated via renal excretion. After IV administration, the urine remains slightly fluorescent for 24 to 36 hours. A renal clearance of 1.75 mL/min/kg and a hepatic clearance (due to conjugation) of 1.50 mL/min/kg have been estimated. The systemic clearance of fluorescein was essentially complete by 48 to 72 hours after administration of 500 mg fluorescein.

For more Absorption, Distribution and Excretion (Complete) data for D&C Yellow No. 8 (7 total), please visit the HSDB record page.

Used in analysis of subterranean waters, as a reagent (protein label, immunohistological stain, and immunofluorescent label), diagnostic aid (corneal abrasions), and for ophthalmic angiography and contact lens fitting; [Merck Index] Used as a marker for sea rescues, for dyeing silk and wool, to make fluorescent laminates, and in commercial antifreezes; [HSDB] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]

Textiles (Printing, Dyeing, or Finishing) [Category: Industry]

Highly purified product is used in solution as a diagnostic aid for evaluating corneal trauma and for treating intraocular inflammation.

Because of its intense fluorescence and /non-/biodegradability, it is in great demand for tracing the course of underground streams and of factory effluents and sewage sources that contaminate underground water supplies.

As a marker for sea-rescue operations

Dyeing silk and wool yellow

2023: 35,700 lb

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#7954]

Grades: Technical, USP (as sodium fluorescein)

Trade names: C.I. Acid Yellow 73; Fluor-I-strip A.T.; Ful-Glo; 12417 Yellow; 11824 Yellow

Fluorescite (fluorescein injection, USP) 10% contains fluorescein sodium (equivalent to fluorescein 10% w/v).

Ak-Fluor (fluorescein injection, USP) 10% is 100 mg/mL in a 5 mL single vial and Ak-Fluor (fluorescein injection, USP) 25% is 250 mg/mL in a 2 mL single dose vial

Spiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one, 3',6'-dihydroxy-, sodium salt (1:2): ACTIVE

The name D&C Yellow No. 8 can be used only when applied to batches of color that have been certified according to the United States certification regulations. The CFTA Adopted Name for non-certified batches of this color is Acid Yellow 73 Sodium Salt.

Color additives were initially regulated in the United States under the U.S. Department of Agriculture's (USDA) Bureau of Chemistry. In 1906, the Food and Drugs Act was passed by Congress, which prohibited the use of poisonous or deleterious colors in confectionery and the coloring or staining of food to conceal damage or inferiority. In 1927, responsibility of the Food and Drugs Act was transferred to FDA. Increasing government oversight, the Federal Food, Drug, and Cosmetic Act (FFDCA) was passed in 1938 and established the three following categories for colors: FD&C: colors used in foods, drugs and cosmetics; D&C: colors used in drugs and cosmetics when in contact with mucous membranes or ingested; and Ext. D&C: colors used in products applied externally.

Serves to ascertain source of springs, connections between streams and sea, determining approximate volume of water delivered by a spring, detecting source of contamination of drinking water, infiltration of soil with waste waters of factories. /Fluorescein disodium/

Incompatibility: ... not compatible with effective preservatives such as benzalkonium chloride or substances known to be effective against Pseudomonas aeruginosa, such as polymyxin B sulfate.