Trypan blue

960.81

959.982422

200-786-7

I2ZWO3LS3M

3077

DTXSID4026268

C910

Bluish-grey powder|Dark greenish-brown powder.|Aqueous solution deep blue with violet tinge

32041400

404.26000

10.78520

Dark greenish-brown Powder

1.007 g/mL at 20 °C

>300 °C

H2O: 10 g/L (25 ºC)

Store at RT.

LD100 i.v. in rats: 300 mg/kg (Anderson)

Azo dyes can be explosive when suspended in air at specific concentrations. Slightly soluble in water.

Azo, Diazo, Azido, Hydrazine, and Azide Compounds

Explosive

TRYPAN BLUE is an azo compound. Azo, diazo, azido compounds can detonate. This applies in particular to organic azides that have been sensitized by the addition of metal salts or strong acids. Toxic gases are formed by mixing materials of this class with acids, aldehydes, amides, carbamates, cyanides, inorganic fluorides, halogenated organics, isocyanates, ketones, metals, nitrides, peroxides, phenols, epoxides, acyl halides, and strong oxidizing or reducing agents. Flammable gases are formed by mixing materials in this group with alkali metals. Explosive combination can occur with strong oxidizing agents, metal salts, peroxides, and sulfides. This chemical is incompatible with strong oxidizing agents and strong acids. (NTP, 1992)

2811

3

45-41-37/38-36/37/38-22

53-45-36/37/39-36-26

QJ6475000

T,Xi

Stable. Incompatible with strong oxidizing agents.

P201-P308 + P313

H350

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U236, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.|A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.|PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... Summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/|For more Disposal Methods (Complete) data for Trypan blue (7 total), please visit the HSDB record page.

Strong oxidizers

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

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Danger|H350 (98.91%): May cause cancer [Danger Carcinogenicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 183 companies from 10 notifications to the ECHA C&L Inventory.|H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]|Warning|H351: Suspected of causing cancer [Warning Carcinogenicity]

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. STORAGE PRECAUTIONS: You should store this material under ambient temperatures. (NTP, 1992)

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves. RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)|Safety glasses. Handle with gloves. Choose body protection according to the amount and concentration of the dangerous substance at the work place. Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

This chemical is a noncombustible solid. Use extinguisher appropriate for burning material ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors or shows any signs of deforming), withdraw immediately to a secure position ... The only respirators recommended for fire fighting are self-contained breathing apparatuses that have full facepieces and are operated in a pressure-demand or other positive-pressure mode.

Spill handling: evacuate persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after clean-up is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Contact your Department of Environmental Protection or your regional office of the federal EPA for specific recommendations.|PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... . Filter housing that is designed so that used filters can be transferred into plastic bags without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... . The plastic bag should be sealed immediately ... . The sealed bag should be labelled properly ... . Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bags, so that outer surface ... is not contaminated ... . The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

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.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|Wear protective gloves and clothing to prevent any reasonable probability of skin contact ... Wear dust-proof chemical goggles and face shield unless full facepiece respiratory protection is worn.|PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for Trypan blue (12 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

May cause eye irritation. May cause skin irritation. May cause respiratory tract irritation.

| 0 - Materials that, under emergency conditions, would offer no hazard beyond that of ordinary combustible materials.| 1 - Materials that must be preheated before ignition can occur. Materials require considerable preheating, under all ambient temperature conditions, before ignition and combustion can occur.| 0 - Materials that in themselves are normally stable, even under fire conditions.

The major hazards encountered in the use and handling of trypan blue stem from its toxicologic properties. Exposure to this bluish-grey powder may occur from its manufacture, and use as a dye for textiles, leather, and paper; and as a stain in biological investigations. The International Agency for Research on Cancer (IARC) has designated trypan blue as a Group 2B carcinogen, meaning, "The agent is possibly carcinogenic to humans." Mechanical exhaust ventilation fitted with a high efficiency particulate arrestor (HEPA) should be used to minimize airborne levels of trypan blue. In activities and situations where over-exposure may occur, wear a protective suit and a carefully fitted respirator. If contact should occur, irrigate exposed eyes with copious amounts of tepid water for at least 15 minutes, and wash exposed skin thoroughly with soap and water. Smoking, eating, and drinking should be prohibited in trypan blue work areas, and cleanliness following the handling of this substance should be emphasized. Trypan blue should be kept in securely sealed containers.

U236; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

U236; As stipulated in 40 CFR 261.33, when trypan blue, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

The effect of L-glutamic acid on the embryolethal and teratogenic action of trypan blue was investigated in Wistar albino rats. L-glutamic acid was either incorporated into the diet, from gestation day 2 to day 20, or suspended in sesame oil and administered by gavage, from gestation day 6 to day 10. A teratogenic dose of trypan blue was injected at day 8 of pregnancy, either intraperitoneally (14 mg/kg maternal body weight) or subcutaneously (160 mg/kg). The amount of glutamic acid consumed, after the injection of trypan blue, ranged from 600 to 1,500 mg/rat/day. At day 20, the fetuses were examined. Glutamic acid failed consistently to protect the rat embryo against the lethal and teratogenic action of trypan blue. These results are in contrast to those obtained in mice. The administration of sesame oil alone was found to cause embryonic death but not malformations.

LD50 Rat oral 6200 mg/kg|LD50 Mouse sc 267 mg/kg|LD50 Mouse iv 328 mg/kg

/BIRDS and MAMMALS/ Ovaries of adult Japanese quails were exposed in vivo to ... trypan blue (TB) which binds to plasma albumin, the plasma precursor of the yolk protein alpha-livetin. ... Trypan blue alters vitellogenesis in the non-disc region of follicles in rapid growth in a reversible and dose-dependent way. Less yolk is produced over 24 hr and its morphology is different when compared to controls... . /It was proposed/ that the inhibitory action of TB on vitellogenesis can be explained by a defective receptor-ligand dissociation in endosomes.

There are no known natural sources of Trypan Blue(1).

Trypan Blue's production and use as a dye for dyeing of textiles, leather, paper(1), a discharge-print for cotton(2), a vital stain for most living cells, a stain for collagen and amyloid, in chlamydospore agar for fungi(3), and in off-line sample measurements of cell viability in fermentation processes(4) may result in its release to the environment through various waste streams(SRC). Trypan Blue's former use as a diagnostic agent for ocular diseases(5) and in the treatment of sleeping sickness(1) may have resulted in its release to the environment(SRC); as of 1975, it was no longer used in foods, drugs or cosmetics(1).

TERRESTRIAL FATE: Trypan Blue is considered soluble in the water(1) which suggests it may not adsorb to soil(SRC). However, adsorption to activated sludge may have been the main source of removal during a biodegradation screening test(2), indicating that this compound may adsorb to particulate matter under some environmental conditions(SRC). It is not expected to undergo volatilization from water surfaces(3,4) since it is an ionic compound(SRC). Trypan Blue was 75% removed from the aerobic activated sludge inoculum based on DOC and 87% removed based on color removal after 48 days, although the adsorption may have been the main process of removal(5). It degraded 90% after 7 days in anaerobic sludge, indicating Trypan Blue may biodegrade in anaerobic environments(6).|AQUATIC FATE: Trypan Blue is considered soluble in the water(1) which suggests it may not adsorb to aquatic soils and sediments(SRC). However, adsorption to activated sludge may have been the main source of removal during a biodegradation screening test(2), indicating that this compound may adsorb to particulate matter under some environmental conditions(SRC). It is not expected to undergo volatilization from water surfaces(3,4) since it is an ionic compound(SRC). It's solubility in water(1) suggests bioconcentration in aquatic organisms may be low(5). Trypan Blue was 75% removed from the aerobic activated sludge inoculum based on DOC and 87% based on color removal after 48 days, although the adsorption may have been the main process of removal(6). It degraded 90% after 7 days in anaerobic sludge, indicating Trypan Blue may biodegrade in anaerobic environments(7).|ATMOSPHERIC FATE: Trypan Blue is an ionic compound that will be essentially non-volatile in the environment(1,2). Therefore it is expected to exist solely in the particulate phase in the ambient atmosphere(SRC). Particulate-phase Trypan Blue may be removed from the air by wet or dry deposition(SRC). Trypan Blue absorbs light at 607 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

Trypan Blue is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Trypan Blue absorbs light at 607 nm(2) and therefore may be susceptible to direct photolysis by sunlight(SRC).

Trypan Blue is soluble in water(1) which suggests bioconcentration in aquatic organisms may be low(2).

Trypan Blue is considered soluble in the water(1) which suggests it may not adsorb to soils and sediments(SRC). However, in an activated sludge biodegradation screening test, a COD removal of 84% was attributed to sludge adsorption(2), indicating that this compound may adsorb to particulate matter under some environmental conditions(SRC).

Trypan Blue is an ionic compound(SRC). Therefore, it is not expected to undergo volatilization(1,2).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 813 workers (623 of these were female) were potentially exposed to Trypan Blue in the US(1). Occupational exposure to Trypan Blue may occur through inhalation of dust and dermal contact with this compound at workplaces where Trypan Blue is produced or used. Use data indicate that the general population may be exposed to Trypan Blue via dermal contact with this compound or other consumer products containing Trypan Blue(SRC).

A diazo-naphthalene sulfonate that is widely used as a stain.|A therapeutic agent in the treatment of sleeping sickness. /Former use/|MembraneBlue 0.15% is indicated for use as an aid in ophthalmic surgery by staining the epiretinal membranes during ophthalmic surgical vitrectomy procedures, facilitating removal of the tissue.|/Experimental Therapy/ Trypan blue can be used to stain the superior oblique tendon for easy identification and delineation of it at its insertion, making the current surgical technique less difficult.|For more Therapeutic Uses (Complete) data for Trypan blue (6 total), please visit the HSDB record page.

Adverse reactions reported following use of VisionBlue include discoloration of high water content hydrogen intraocular lenses (see Contraindications) and inadvertent staining of the posterior lens capsule and vitreous face. Staining of the posterior lens capsule or staining of the vitreous face is generally self limited, lasting up to one week.|It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when trypan blue is administered to a nursing woman.|VisionBlue is contraindicated when a non-hydrated (dry state), hydrophilic acrylic intraocular lens is planned to be inserted into the eye because the dye may be absorbed by the intraocular lens and stain theintraocular lens.|It is recommended that after injection all excess VisionBlue be immediately removed from the eye by thorough irrigation of the anterior chamber.|FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./

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.)

Trypan blue ... was observed in animals to pass from bloodstream through walls of vessels of iris & choroid, but not through walls of retinal vessels.|Following sc or ip injections into mice or rats, trypan blue is rapidly absorbed & widely distributed throughout the body. Max serum concentrations are ... within 2 hr; it appears bound to serum proteins with ... rapid excretion in urine & uptake by the reticulo-endothelial system.|Trypan blue never reaches the rat embryo, but accumulates in maternal reticuloendothelial system and in the placenta.|Experiments with ring-labelled radioactive trypan blue did not give evidence of any embryonic incorporation of the (14)C. The absence of teratogenic action after the initiation of chorio-allantoic placentation also indicated that yolk sac function was important in pathogenesis. The dye can be visualized in the cells of the visceral yolk sac.|For more Absorption, Distribution and Excretion (Complete) data for Trypan blue (6 total), please visit the HSDB record page.

/Trypan blue/ is reduced in vitro by a rat liver enzyme to ortho-tolidine & 2,8-diamino-1-naphthol-3,6-disulfonic acid.|Six azo dyes, including trypan blue, were reduced, N-acetylated, and N-conjugated. No N,N'-diacetylated metabolites were detected in rat urine.|Azo dyes based on beta-diketone coupling components exist preferentially as the tautomeric hydrazones. A series of hydrazone dyes based on benzidine and benzidine congeners ... was prepared. The hydrazone dyes were resistant to enzymatic reduction by FMN supplemented hamster liver post-mitochondrial supernatant (S-9); under identical conditions, azo dyes such as trypan blue were rapidly reduced.|Metabolism experiments were conducted with rats dosed with 9 azo dyes based on dimethyl-, dimethoxy-, or dichlorobenzidine to determine whether the free amine congeners, their monoacetyl or diacetyl metabolites, or alkaline hydrolyzable conjugates were excreted in the urine. 2-mg doses were administered and urine samples were collected at intervals up to 96 hr. Peak levels of metabolites were excreted either 0-12 or 12-24 hr after administration and, in 7 of 9 instances, no metabolites persisted in the urine after 48 hr. Minimum detectable levels of all metabolites were 12 ppb or less. All 9 dyes were converted to measurable levels of their benzidine-congener-based metabolites in rats.|The ability of rat liver microsomes from phenobarbitone pretreated animals to reduce the azo groups of amaranth, sunset yellow, congo red, trypan blue, chloramine sky blue FF and direct black 38 was measured in vitro. The dyes amaranth and sunset yellow acted as positive controls. Of the dyes derived from (the carcinogen) benzidine or its congeners, only direct black 38 was reduced to an appreciable extent; the rate of reduction was 10% of that for amaranth. The dyes were tested for mutagenicity in the Salmonella/microsome assay, the only active compound being direct black 38. Mutagenicity of this dye may be due in part to the mutagen 1,2,4-triaminobenzene. Mutagenic activity and azo-reduction of direct black 38 was independent of the presence of oxygen. Mammalian liver may play only a minor or negligible role in the azo-reduction of dyes derived from benzidine or its congeners.

A dose of 50 mg per kg /of trypan blue/ appears to be the optimum teratogenic dose. A characteristic observation with trypan blue is that with treatment after the 9th day of gestation defects are rare. This fact has supported other evidence that the mechanism of action was dependent on disruption of yolk sac nutrition. ... Studies have produced evidence indicating a possible action of trypan blue on a nutritive function of the visceral yolk sac. The failure of the trypan blue to act directly upon the embryo is generally held ... .|The absence of teratogenic action after the initiation of chorio-allantoic placentation also indicated that yolk sac function was important in pathogenesis. The dye can be visualized in the cells of the visceral yolk sac. ... . The protein-trypan blue complex is concentrated in lysosomes. Through disruption of the enzymatic digestive process in the yolk sac lysosome, trypan blue may interfere with normal embryonic nutritive processes.

... Substances identified in various samples /are/ 8-amino-2-[4'-(3,3' -dimethyl-biphenylazo)]-1-naphthol-3,6-disulfonic acid; and 8-amino-2-[4'-(3,3' -dimethyl-4-hydroxybiphenylazo)]-1-napthol-3,6-disulfonic acid; and 8-amino-2 -[4'-(3,3'-dimethyl-4-aminobiphenylazo)]-1-napthol-3,6-disulfonic acid ... and in addition ... can contain varying amt of its starting materials, including ortho-tolidine ... and inorganic salts.

ACUTE/CHRONIC HAZARDS: This chemical may cause irritation and may be absorbed through the skin. It is a positive animal carcinogen. When heated to decomposition this compound emits very toxic fumes of nitrogen oxides, sulfur oxides, carbon monoxide and carbon dioxide. (NTP, 1992)|Carcinogens

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Naphthalene and Related Compounds/|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 necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. 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. Administer activated charcoal ... . /Naphthalene and Related Compounds/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Start IV administration of 0.9% saline (NS) or lactated Ringer's (LR). Adequate hydration must be maintained to prevent renal failure secondary to myoglobinuria unless signs of cerebral or pulmonary edema are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Naphthalene and related compounds/

/HUMAN EXPOSURE STUDIES/ Trypan blue ... Tested by injection of 0.2 ml of 1% soln subconjunctivally in patients caused no injury. A small drop at the same concn applied to the surface of the eye in patients caused practically no irritation, & though it stained superficial tissues, especially degenerating epithelial cells & mucous, it caused no damage.|/SIGNS AND SYMPTOMS/ Short term exposure: Inhalation: no symptoms reported. Skin: may stain skin. Eyes: application of 0.2 mL (0.007 oz) of a 1% solution caused no eye irritation. Ingestion: moderately toxic. Probable lethal dose between 1 oz and 1 pound for a 150 pound person. Long term exposure: A potential occupational carcinogen, mutagen, and teratogen. Has been shown to cause birth defects, cancer, and liver injury in laboratory animals.|/ALTERNATIVE and IN VITRO TESTS/ Three in vitro experiments were performed. (1) cultured human corneal fibroblasts /were exposed/ to trypan blue (0.0001% to 0.1%) in Eagle modified minimum essential medium (EMEM) or phosphate-buffered saline (PBS) for 15 minutes to 24 hours. Cytotoxicity was evaluated by Mosmann's colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MMT) assay. (2) human corneas /were exposed/ in EMEM for 24 hours to trypan blue (0.001% to 0.1%). Fellow donor corneas served as controls. Endothelial survival was evaluated morphologically and by cell density assessment. (3) the endothelial viability of human donor corneas /was morphologically compared/ after exposure to 0.1% trypan blue for 5 to 30 minutes with control corneas. RESULTS: In experiment 1, trypan blue in EMEM was not significantly toxic at concentrations of 0.005% or lower. Higher concentrations were toxic only after exposure to trypan blue for at least 6 hours. In PBS, significant toxicity was found after exposure to 0.1% trypan blue for 30 minutes or longer. Lower concentrations were toxic after longer exposures. In experiment 2, exposure to 0.01% and 0.1% trypan blue for 24 hours resulted in significant loss in cell density. At lower concentrations, the endothelium was affected only morphologically. In experiment 3, endothelial morphology changed in control corneas and after exposure to 0.1% trypan blue for as little as 5 minutes. After 30-minute exposure, morphologic deterioration was more pronounced. CONCLUSIONS: Trypan blue was toxic in vitro to corneal endothelium and corneal fibroblasts at higher concentrations and notably longer exposure times. Toxicity was less in EMEM than in PBS. Clinical Relevance: At commonly used concentrations, both during cataract surgery and in the cornea bank, trypan blue is safe for corneal cells. At higher concentrations or longer exposures, however, caution is warranted.|/ALTERNATIVE and IN VITRO TESTS/ ... Three concentrations (0.06 mg/mL, 0.6 mg/mL, and 4 mg/mL) of trypan blue were applied to human ARPE19 cells for 1 minute. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RPE cells were sampled daily for 6 consecutive days to assess the effects of trypan blue on cell viability. The effects of trypan blue on the expression of apoptosis related and cell cycle arrest gene expressions including c-fos, c-jun, p53, and p21 were performed using reverse transcription-polymerase chain reaction and immunostaining. RESULTS: The MTT assay showed a concentration dependent suppression effect of trypan blue on cell viability, with higher reduction in the 0.6 mg/ml and 4 mg/mL trypan blue treated groups. No significant change in the expression of c-fos and c-jun was found with all three concentrations of trypan blue. An increase in p53 expression was found in the 4 mg/mL trypan blue treated group at 10-30 minutes after trypan blue application. Immunostaining showed a mild, albeit insignificant, increase of p53 expression in the RPE cells. No significant increase in p21 expression was observed in the 0.06 mg/mL trypan blue treated group but there were significant increases in p21 expression in both the 0.6 mg/mL (p = 0.032) and the 4 mg/mL (p = 0.025) treated groups. CONCLUSIONS: Trypan blue may lead to toxicity on cultured RPE cells as indicated by the reduction in cell viability and changes in the expression of apoptosis related and cell cycle arrest genes at higher concentrations. The application of 0.06 mg/mL trypan blue for 1 minute appeared to have no significant effect on cultured RPE.|/ALTERNATIVE and IN VITRO TESTS/ Indocyanine green, infracyanine green, and trypan blue are frequently used as aids to visualize structures removed during vitreoretinal surgery. But they may have toxic effects on the retina. ... The acute and chronic toxicities of these stains on cultured human retinal pigmented epithelial (RPE) cells /were compared/ using clinically relevant concentrations and an identical experimental setup for each agent. METHODS: Monolayers of RPE cells were incubated with various concentrations of indocyanine green, infracyanine green (each at 0.005%, 0.05%, and 0.5%) or trypan blue (0.05%, 0.06%, 0.1%, 0.15%, and 0.5%) for 5 min (acute exposure) or 6 days (chronic exposure). Using the propidium iodide assay, acute cytotoxicity was monitored at 15-min intervals for up to 3 hr. Chronic cytotoxicity was assessed by monitoring cell calcein esterase activity, cell proliferation, and cell morphology (viability) after 6 days of exposure. RESULTS: Indocyanine and infracyanine green induced acute and chronic toxicities at a concentration above 0.05%. Trypan blue evoked no acute toxicity, but it was chronically cytotoxic at all tested concentrations. CONCLUSIONS: Despite thorough rinsing after application, significant amounts of the not sufficiently water soluble indocyanine and infracyanine green are retained after surgery by the eye. Trypan blue, being more water-soluble than ICG, is probably retained to the least degree. This circumstance is fortunate given that trypan blue exhibits a chronic cytotoxicity comparable to ICG at all clinically relevant concentrations. During vitrectomy, surgeons should aim to expose retinal tissue to only low concentrations of these stains and for as short a period as possible.

Blue, Diamine

Each mL of VisionBlue 0.06% contains: 0.6 mg trypan blue; 1.9 mg sodium mono-hydrogen orthophosphate (Na2HPO4.2H2O); 0.3 mg sodium di-hydrogen orthophosphate (NaH2PO4.2H2O); 8.2 mg sodium chloride (NaCl); and water for injection.|Each mL of MembraneBlue 0.15% contains: 1.5 mg trypan blue; 1.9 mg sodium mono-hydrogen orthophosphate (Na2HPO4.2H2O); 0.3 mg sodium di-hydrogen orthophosphate (NaH2PO4.2H2O); 8.2 mg sodium chloride (NaCl); and water for injection.|HPLC analysis reveals that the product of commerce has a total dye content of approximately 25%. Of this, Trypan Blue constitutes 30-40%, or a net Trypan Blue content of approximately 7-10%. A laboratory grade of the dye, with a net Trypan Blue content in excess of 80%, is available.

2,7-Naphthalenedisulfonic acid, 3,3'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(2,1-diazenediyl)]bis[5-amino-4-hydroxy-, sodium salt (1:4): ACTIVE|USA producton of Trypan Blue was first reported in 1921.|According to USA industry sources, Trypan Blue is not used in foods, drugs or cosmetics. ... its composition varies ... to meet customer shade and intensity requirement.|Trypan Blue, like other polysulfonic acids, is difficult to purify and commercial product is often mixture; thus, some of biological effects described as being caused by Trypan Blue may have been produced by impurities.

PROCEDURE DESCRIBED FOR RESIDUES IN FECES ASSAYS BASED ON REDUCTION OF THE DYES WITH TIN CHLORIDE FOLLOWED BY GAS CHROMATOGRAPHY OF THE RELEASED FREE AMINE. PURITIES RANGED FROM 26.4-83.4%.

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