61-73-4CN(C)c1ccc2nc3ccc(=[N+](C)C)cc-3sc2c1.[Cl-]CXKWCBBOMKCUKX-UHFFFAOYSA-MMethylene blue is an organic chloride salt having 3,7-bis(dimethylamino)phenothiazin-5-ium as the counterion. A commonly used dye that also exhibits antioxidant, antimalarial, antidepressant and cardioprotective properties. It has a role as an antioxidant, an antimicrobial agent, a physical tracer, an antidepressant, an EC 3.1.1.8 (cholinesterase) inhibitor, an antimalarial, an EC 1.4.3.4 (monoamine oxidase) inhibitor, an acid-base indicator, a fluorochrome, a neuroprotective agent, a histological dye, a cardioprotective agent and an EC 4.6.1.2 (guanylate cyclase) inhibitor. It contains a 3,7-bis(dimethylamino)phenothiazin-5-ium.
61-73-4、7220-79-3、97130-83-1DTXSID0023296CHEMBL405110、CHEMBL550495Dark green crystals or powder from chloroform-ethyl ether
Solutions have a deep blue color /Methylene blue zinc-free dye/
In water, 43,600 mg/L at 25 °C.
Soluble in water
Soluble in ethanol, chloroform; slightly soluble in pyridine; insoluble in ethyl ether
Soluble in glacial acetic acid and glycerol; insoluble in xylene and oleic acid, in ethanol 2%, and in acetone 0.5%.
Breast Feeding; Lactation; Milk, Human; Enzyme Inhibitors; Coloring Agents
FDA approved drugs -> Active ingredient
EMA approved medicines: Human medicine
EMA approved medicines: Human medicine
FDA approved drugs -> Active ingredient
Antidotes and other substances used in poisonings > Specific
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This chemical does not meet GHS hazard criteria for 8.1% (22 of 273) of reports.
Danger
H302 (91.6%): Harmful if swallowed [Warning Acute toxicity, oral]
P264, P264+P265, P270, P273, P280, P301+P317, P305+P354+P338, P317, P330, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 273 reports by companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Danger
Chemical: Phenothiazin-5-ium, 3,7-bis(dimethylamino)-, chloride (1:1)
Methylene blue: Does not have an individual approval but may be used under an appropriate group standard
Workers handling methylene blue are at risk for photoirritant contact dermatitis (PICD). [Marks, p. 201-3] Listed in table of Methemoglobinemia-inducing agents: industrial, environmental, and pharmaceutical; Antidote for symptomatic methemoglobinemia; At high doses, methylene blue causes methemoglobinemia, and it is not indicated in cases of G6PD deficiency. [Sullivan, p. 729, 731]
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including methylene blue, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Methylene blue is included in orally administered menstrual drug products.
V - Various
V - Various
QV - Various
QV - Various
V03AB17
* Main mechanism of action involves the inhibition of nitric oxide synthase and guanylate cyclase. * In Alzheimers Disease: a mechanistic study found that methylene blue oxidizes cysteine sulfhydryl groups on tau to keep tau monomeric. One preclinical treatment study in tauopathy mice reported anti-inflammatory or neuroprotective effects mediated by the Nrf2/antioxidant response element (ARE); another reported insoluble tau reduction and a learning and memory benefit when given early. * In Methemoglobinemia: Methylene Blue acts by reacting within RBC to form leukomethylene blue, which is a reducing agent of oxidized hemoglobin converting the ferric ion (fe+++) back to its oxygen-carrying ferrous state(fe++). * As antimalarial agent: Methylene Blue, a specific inhibitor of P.falciparum glutathione reductase has the potential to reverse CQ resistance and it prevents the polymerization of haem into haemozoin similar to 4-amino-quinoline antimalarials. * For ifosfamide induced neurotoxicity: Methylene blue functions as an alternate electron acceptor. It acts to reverse the NADH inhibition caused by gluconeogenesis in the liver while blocking the transformation of chloroethylamine into chloroacetaldehyde. In addition, it inhibits various amine oxidase activities, which also prevents the formation of chloroacetaldehyde. * Methylene blue is a reversible inhibitor of monoamine oxidase A.
The mechanism of modulation of cyclic guanosine monophosphate accumulation by methylene blue, a putative inhibitor of soluble guanylate cyclase, was investigated in cultured rabbit pulmonary arterial smooth muscle cells. Control or methylene blue pretreated rabbit pulmonary arterial smooth muscle were stimulated with sodium nitroprusside, nitrosothiols or endothelium derived relaxing factor released basally from bovine pulmonary arterial endothelial cells, in short term cocultures. The putative endothelium-derived relaxing factor, S-nitroso-L-cysteine, a stab1e deaminated analog of S-nitroso-L-cysteine, S-nitroso-3-mercaptoproprionic acid and sodium nitroprusside produced concentration-dependent (1-100 uM) increase (1.5- to 12-fold) in rabbit pulmonary arterial smooth muscle cells cyclic guanosine monophospate levels. Methylene blue pretreatment inhibited S-nitroso-L-cysteine and sodium nitroprusside induced cyclic guanosine monophosphate accumulation by 51% to 100%, but S-nitroso-3-mercaptoproprionic acid mediated responses were not altered by methylene blue. The inhibition profile of methylene blue on nitrovasodilator induced cyclic guanosine monophosphate accumulation was quantitatively reproduced by extracellular generation of superoxide anion with xanthine (100 uM) and xanthine oxidase (5 mU). Similarly to methylene blue pretreatment, superoxide anion generation had no effects on base-line cyclic guanosine phosphate levels or cyclic guanosine phosphate responses elicited by S-nitroso-3-mercaptoproprionic acid. Furthermore, methylene blue induced a dose and time dependent generation of superoxide anion from rabbit pulmonary arterial smooth muscle cells, as evidenced from spectrophotometric determination of cytochrome c reduction. Inhibition of cyclic guanosine monophosphate accumulation in response to S-nitroso-L-cysteine and sodium nitroprusside by methylene blue was completely prevented by superoxide dismutase but not catalase. Selective pretreatment of endothelial cells with methylene blue before co-culture with untreated rabbit pulmonary arterial smooth muscle produced a reduction in rabbit pulmonary arterial smooth muscle cyclic guanosine monophosphate levels of a magnitude comparable with that seen in cocultures of methylene blue pretreated rabbit pulmonary arterial smooth muscle with untreated endothelial cells, and which was partially prevented by superoxide dismutase.
불러오는 중…
CHEBI:6872FCS -> FDA Cumulative Estimated Daily Intake (CEDI)
FCS -> FDA Inventory of Food Contact Substances Listed in 21 CFR
Methylene blue is a heterocyclic aromatic chemical compound with the molecular formula C16H18N3SCl. It has many uses in a range of different fields, such as biology and chemistry. At room temperature it appears as a solid, odorless, dark green powder, that yields a blue solution when dissolved in water. The hydrated form has 3 molecules of water per molecule of methylene blue. Methylene blue should not be confused with methyl blue, another histology stain, new methylene blue, nor with the methyl violets often used as pH indicators.
Residues of the following chemical substances are exempted from the requirement of a tolerance when used in accordance with good manufacturing practice as ingredients in an antimicrobial pesticide formulation, provided that the substance is applied on a semi-permanent or permanent food-contact surface (other than being applied on food packaging) with adequate draining before contact with food. (a) The following chemical substances when used as ingredients in an antimicrobial pesticide formulation may be applied to: Food-contact surfaces in public eating places, dairy-processing equipment, and food-processing equipment and utensils. Methylene blue is included on this list. Limit: When ready for use, the end-use concentration is not to exceed 0.4 ppm.
Residues of the following chemical substances are exempted from the requirement of a tolerance when used in accordance with good manufacturing practice as ingredients in an antimicrobial pesticide formulation, provided that the substance is applied on a semi-permanent or permanent food-contact surface (other than being applied on food packaging) with adequate draining before contact with food. ... (c) The following chemical substances when used as ingredients in an antimicrobial pesticide formulation may be applied to: Food-processing equipment and utensils. Methylene blue is included on this list. Limit: When ready for use, the end-use concentration is not to exceed 0.4 ppm.
Acute Tox. 4 (91.6%)
Acute Tox. 4 (100%)
Acute toxicity (Oral) - Category 4
Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.
Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non Combustible Liquids.
Commercially available methylene blue 10-mg/mL solution for IV use should be stored at 20-25 °C, but may be exposed to temperatures ranging from 15-30 °C.
ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Environmental precautions: No special environmental precautions required. Methods and materials for containment and cleaning up Keep in suitable, closed containers for disposal.
SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.
ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Environmental precautions: No special environmental precautions required.
Appropriate engineering controls: General industrial hygiene practice.
Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Residues of the following chemical substances are exempted from the requirement of a tolerance when used in accordance with good manufacturing practice as ingredients in an antimicrobial pesticide formulation, provided that the substance is applied on a semi-permanent or permanent food-contact surface (other than being applied on food packaging) with adequate draining before contact with food. (a) The following chemical substances when used as ingredients in an antimicrobial pesticide formulation may be applied to: Food-contact surfaces in public eating places, dairy-processing equipment, and food-processing equipment and utensils. Methylene blue is included on this list. Limit: When ready for use, the end-use concentration is not to exceed 0.4 ppm.
Residues of the following chemical substances are exempted from the requirement of a tolerance when used in accordance with good manufacturing practice as ingredients in an antimicrobial pesticide formulation, provided that the substance is applied on a semi-permanent or permanent food-contact surface (other than being applied on food packaging) with adequate draining before contact with food. ... (c) The following chemical substances when used as ingredients in an antimicrobial pesticide formulation may be applied to: Food-processing equipment and utensils. Methylene blue is included on this list. Limit: When ready for use, the end-use concentration is not to exceed 0.4 ppm.
Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection: Handle with gloves.
Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection: Respiratory protection not required. For nuisance exposures use type OV/AG (US) or type ABEK (EU EN 14387) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Although the clinical importance is unclear, in vitro studies indicate that the antimalarial effects of methylene blue and artemisinin, artemether, or artesunate are synergistic and the antimalarial effects of methylene blue and mefloquine or quinine are additive against Plasmodium falciparum. Antagonism occurred when methylene blue was used with chloroquine or pyrimethamine in vitro.
Methylene Blue Injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Avoid concomitant use of Methylene blue injection with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors.
This is the first report of a fatal outcome from serotonin toxicity, precipitated by an interaction between methylene blue and venlafaxine. Methylene blue-associated serotonin toxicity has been described before but usually as mild toxicity. Its presentation after general anesthesia may be atypical and therefore more difficult to diagnose. However, the syndrome is completely preventable if serotonin re-uptake inhibiting agents are stopped beforehand.
Sodium azide (NaN(3)) is widely employed to quench singlet oxygen during photodynamic therapy (PDT), especially when PDT is used to kill bacteria in suspension. We observed that addition of NaN(3) (100 uM or 10 mM) to gram-positive Staphylococcus aureus and gram-negative Escherichia coli incubated with methylene blue (MB) and illuminated with red light gave significantly increased bacterial killing (1-3 logs), rather than the expected protection from killing. A different antibacterial photosensitizer, the conjugate between polyethylenimine and chlorin(e6) (PEI-ce6), showed reduced PDT killing (1-2 logs) after addition of 10 mM NaN(3). Azide (0.5 mM) potentiated bacterial killing by Fenton reagent (hydrogen peroxide and ferrous sulfate) by up to 3 logs, but protected against killing mediated by sodium hypochlorite and hydrogen peroxide (considered to be a chemical source of singlet oxygen). The intermediacy of N(3)() was confirmed by spin-trapping and electron spin resonance studies in both MB-photosensitized reactions and Fenton reagent with addition of NaN(3). We found that N(3)() was formed and bacteria were killed even in the absence of oxygen, suggesting the direct one-electron oxidation of azide anion by photoexcited MB. This observation suggests a possible mechanism to carry out oxygen-independent PDT.
For more Interactions (Complete) data for Methylene blue (9 total), please visit the HSDB record page.
LC50; Species: Penaeus californiensis (Shrimp) age 6 months, weight 2.54 g; Conditions: saltwater, static, 27 °C, salinity 24 ppt; Concentration: 100,000 ug/L for 1 hr
LC50; Species: Heteropneustes fossilis (Indian catfish) adult, weight 22.2 g, length 18.3 cm; Conditions: freshwater, renewal, 18-22 °C; Concentration: 188500 ug/L for 24 hr (95% confidence interval: 184260-192840 ug/L) /formulated product/
LC50; Species: Heteropneustes fossilis (Indian catfish) adult, weight 22.2 g, length 18.3 cm; Conditions: freshwater, renewal, 18-22 °C; Concentration: 181500 ug/L for 48 hr (95% confidence interval: 180240-182770 ug/L) /formulated product/
LC50; Species: Heteropneustes fossilis (Indian catfish) adult, weight 22.2 g, length 18.3 cm; Conditions: freshwater, renewal, 18-22 °C; Concentration: 172000 ug/L for 72 hr (95% confidence interval: 171660-172340 ug/L) /formulated product/
For more Ecotoxicity Values (Complete) data for Methylene blue (33 total), please visit the HSDB record page.
TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8000(SRC), determined from a structure estimation method(2), indicates that methylene blue is expected to be immobile in soil(SRC). The estimated pKa of methylene blue is 3.14(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Methylene blue is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.0X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). More than 90% of color removal efficiency was observed when using an anaerobic sludge reactor and a low methylene blue concentration(5), suggesting that biodegradation may occur in soil under specific conditions(SRC).
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8000(SRC), determined from a structure estimation method(2), indicates that methylene blue is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 3.14(3) indicates methylene blue will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of 0.75(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). More than 90% of color removal efficiency was observed when using an anaerobic sludge reactor and a low methylene blue concentration(5), suggesting that biodegradation may occur in water under specific conditions(SRC).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), methylene blue, which has an estimated vapor pressure of 7.0X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase methylene blue is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 2 hrs(SRC), calculated from its rate constant of 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase methylene blue may be removed from the air by wet and dry deposition(SRC). The trihydrate of methylene blue has UV absorption maxima at 688 and 609 nm(3) which suggests that methylene blue may be susceptible to direct photolysis by sunlight(SRC).
Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect
Methylene blue is generally well-tolerated but carries several critical adverse effects and contraindications that clinicians must consider when treating methemoglobinemia or using it for off-label indications. The most commonly reported adverse reactions include headache, hypokalemia, diarrhea, hypomagnesemia, myoclonus, nausea, and seizure-like phenomena. Additional adverse effects include hemolytic anemia; cardiovascular effects, such as palpitations, tachycardia, and hypertension; gastrointestinal disturbances; and blue-green discoloration of urine, which is expected and benign.
IDENTIFICATION AND USE: Methylene blue is a solid. Water solutions are deep blue. It is used as a stain in bacteriology, as mixed indicator, a dye, a redox colorimetric agent, and a targeting agent for melanoma. It is also used as a medication to treat drug-induced methemoglobinemia. HUMAN STUDIES: Methemoglobinemia is usually treated with methylene blue. However, in patients with glucose-6-phosphate dehydrogenase deficiency, methylene blue can induce methemoglobinemia. Preclinical studies have shown that low-dose methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. The intracameral use of 1% methylene blue has a cytotoxic effect on the corneal endothelium and iris epithelium. Several cases of suspected serotonin syndrome have been reported in patients who received methylene blue in combination with serotonin active agents. Allergic hypersensitivity reaction to methylene blue-treated plasma transfusion has also been reported. A preterm infant had methemoglobulinemia and hemolytic anemia after enteral administration of methylene blue. There is epidemiologic evidence that methylene blue is a teratogen, and the drug can cause fetal harm if administered during pregnancy. Use of methylene blue in amniocentesis has been associated with atresia of the ileum and jejunum, ileal occlusion, and other adverse effects in neonates. Use of methylene blue during pregnancy has resulted in hemolytic anemia, hyperbilirubinemia, methemoglobinemia, respiratory distress, skin staining, and phototoxicity in neonates. ANIMAL STUDIES: Methylene blue treatment resulted in methemoglobin formation and oxidative damage to red blood cells, leading to a regenerative anemia and a variety of tissue and biochemical changes secondary to erythrocyte injury. An early change was a dose-related increase in methemoglobin, where the response of rats and mice was similar in magnitude. Mice appeared to be more sensitive than rats to the formation of Heinz bodies and the development of anemia that was characterized by a decrease in hemoglobin, hematocrit, and erythrocyte count. Splenomegaly was apparent in all treated mice and in the 100 mg/kg (males only) and 200 mg/kg rats at necropsy. Methylene blue was embryotoxic in the rat. Methylene blue caused the mice to deliver before gestation day 18 (term gestation). This response was observed in 45%, 50% and 83% of animals receiving methylene blue at 50, 60 or 85 mg/kg, respectively. Under cell-free conditions methylene blue induced DNA damage. It is characterized by a high number of base modifications sensitive to the repair endonuclease FPG protein (formamidopyrimidine-DNA glycosylase). Methylene blue was mutagenic in cultured mammalian cells. In contrast, results from the mouse micronucleus assay suggest that the genotoxicity is not expressed in vivo. The greatest concerns with methylene blue therapy in veterinary use are the development of Heinz body anemia or other red cell morphological changes, methemoglobinemia, and decreased red cell life spans. Cats tent to be very sensitive to these effects and some consider it contraindicated in feline patients, but dogs and horses can also develop hematologic adverse effects at relatively low dosages. ECOTOXICITY STUDIES: Methylene blue had a teratogenic effect in angelfish.
/AQUATIC SPECIES/ Failure to inflate the swim bladder is regarded a major obstacle in the rearing of many fish species. A study of swim bladder non-inflation (SBN) in angelfish, Pterophyllum scalare. A normal developing primordial swim bladder was first discernable at the end of the first day post-hatch (p.h.) as a cluster of epithelial cells with a central lumen, surrounded by presumably mesenchymal cells. Initial inflation occurred on the fourth day p.h. Prior to inflation the swim bladder epithelium consisted of an outer squamous and inner columnar layer. Cells of the inner layer were filled at their basal region with an amorphous material, which disappeared upon inflation. A pneumatic duct was absent, and larvae presented no need to reach the water surface for inflation, suggesting that angelfish are pure physoclists. A model for the role of the amorphous material in normal initial inflation is proposed. Abnormal swim bladders were apparent from the fourth day p.h., and methylene blue (MB) at a concentration of 5 ppm significantly increased the prevalence of SBN. Histologically, abnormal swim bladders in larvae hatched in 5 ppm MB could not be distinguished from those in fish raised under routine conditions (0.5 ppm MB). ...MB may have a teratogenic effect in angelfish.
/AQUATIC SPECIES/ The acute and 7-day subchronic toxicity of methylene blue were determined for fathead minnow larvae using U.S. Environmental Protection Agency methods. The 96-hr lethal concentration (LC50) was 45 and 15 mg/L at 20 and 25 °C, respectively. The 7-day chronic value for survival under laboratory light and low light was the same (2.1 mg/L). However, under laboratory light, larval growth was impaired at lower concentrations (chronic value = 0.6 mg/L) than under low light (chronic value = 2.1 mg/L). To assess prior methylene blue treatment on larval sensitivity, embryos, larvae <24 hr old, and embryos followed by larvae were treated with 3 mg/L methylene blue. Cadmium LC50 values were similar between methylene blue-treated and untreated control groups. When larvae treated with methylene blue as embryos were subchronically exposed to an effluent, survival was similar to that of the untreated group. However, dry weight of the treated larvae was significantly lower. Differences in dry weight between treated and untreated groups were reduced as the age of the larvae at test initiation increased. Treatment of incubating embryos using 3 mg/L methylene blue does not appear to affect larvae sensitivity to cadmium but may affect the growth of larvae used in subchronic testing.
/OTHER TOXICITY INFORMATION/ Methylene blue, a heterocyclic aromatic chemical compound used to treat fish diseases in the ornamental fish aquaculture industry, is believed to impair nitrification as a side effect. However, very little is known about the toxicity of methylene blue to nitrifying micro-organisms. Here, /is reported/ the susceptibility of six bacterial and one archaeal ammonia-oxidizing micro-organisms to methylene blue within the range of 10 ppb to 10 ppm. Remarkably high susceptibility was observed in the archaeal species Nitrosopumilus maritimus compared to the bacterial species. Ammonia oxidation by Nitrosopumilus maritimus was inhibited 65% by 10 ppb of methylene blue. Of the bacterial species examined, Nitrosococcus oceani was the most resistant to methylene blue toxicity. For similar inhibition of Nitrosococcus oceani (75% inhibition), one thousand times more methylene blue (10 ppm) was needed. The examination of single cell viability on Nitrosomonas marina demonstrated that methylene blue is lethal to the cells rather than reducing their single cell ammonia oxidation activity. The level of susceptibility to methylene blue was related to the cell volume, intracytoplasmic membrane arrangement and the evolutionary lineage of nitrifying micro-organisms. Our findings are relevant for effectively using methylene blue in various aquaculture settings by helping minimize its impact on nitrifiers during the treatment of fish diseases. In the future, resistant nitrifiers such as Nitrosococcus oceani may be purposely added to aquaculture systems to maintain nitrification activity during treatments with methylene blue. The susceptibility of six bacterial and one archaeal nitrifying micro-organisms to methylene blue was tested. Remarkably high susceptibility was observed in the archaeal species compared to the bacterial species. The level of resistance to methylene blue was related to the cell volume, cytomembrane system and the taxonomic position of the nitrifying micro-organisms. This may be significant in the design and management of engineered nitrification systems and the stability of the nitrification process in various ecosystems if these systems are exposed to harmful chemicals or toxins.
The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for methylene blue trihydrate is available. /Methylene blue trihydrate/[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]
EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of February 4, 2019: http://actor.epa.gov/dashboard/]
Aqueous waste effluents are generated at manufacturing sites where azine and thioazine dyes (such as methylene blue) are produced(1). Losses of dyes (in general) to wastewater effluents during manufacture have been estimated to be 1-2%(2). For the organic dye industry in general, it has been estimated that as much as 10% of the dye is lost to wastewater effluents during dyeing operations(2,3).
Using a structure estimation method based on molecular connectivity indices(1), the Koc of methylene blue can be estimated to be 8000(SRC). According to a classification scheme(2), this estimated Koc value suggests that methylene blue is expected to be immobile in soil. The estimated pKa of methylene blue is 3.14(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
Laboratory adsorption studies determined that methylene blue was strongly adsorbed to soil organic matter, sodium montmorillonite, and sodium kaolinite(1); desorption studies using three different extraction methods found that only 2% of adsorbed methylene blue was extractable(2).
RURAL/REMOTE: Mean concentrations of 103 and 887 ng/cu methylene blue active substances (MBAS) in PM10 coastal aerosols from the northwest Mediterranean basin. Values correspond to samples from the remote Porquerolles Island-Var, France and more populated site of San Rossore National Park - Tuscany, Italy, respectively(1).
/HUMAN EXPOSURE STUDIES/ OBJECTIVE: Preclinical studies have shown that low-dose methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. The authors report on the first controlled experiment to examine the memory-enhancing effects of posttraining methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. METHOD: Adult participants displaying marked claustrophobic fear were randomly assigned to double-blind administration of 260 mg of methylene blue (N=23) or administration of placebo (N=19) immediately following six 5-minute extinction trials in an enclosed chamber. Retesting occurred 1 month later to assess fear renewal as indexed by peak fear during exposure to a nontraining chamber, with the prediction that the effects of methylene blue would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive-enhancing effects of methylene blue independent of its effects on fear attenuation. RESULTS: Consistent with predictions, participants displaying low end fear posttraining showed significantly less fear at the 1-month follow-up if they received methylene blue posttraining compared with placebo. In contrast, participants displaying moderate to high levels of posttraining fear tended to fare worse at the follow-up if they received methylene blue posttraining. Methylene blue's enhancement of contextual memory was unrelated to initial or posttraining claustrophobic fear. CONCLUSIONS: Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session but may have a deleterious effect on extinction when administered after an unsuccessful exposure session.
/HUMAN EXPOSURE STUDIES/ Renal blood flow (RBF) and arterial blood pressure (BP) were monitored in 12 patients undergoing nephrolithotomy in the lateral flexed position. All patients were preoxygenated and were anesthetized with sodium thiopental, N2O, O2, and fentanyl. Maintenance relaxation was obtained with pancuronium bromide. Arterial pressure was monitored by percutaneous arterial catheter. Following exposure of the kidney and renal pedicle, an electromagnetic flow probe was attached to the renal artery and baseline flows recorded. Following baseline measurements, 20 mL of 1 percent methylene blue was given intravenously. All patients studied showed an immediate rise in BP, and 11/12 showed a simultaneous decrease in RBF. The average fall in RBF was 35 percent at one minute. Both parameters returned to normal values on the average in 177 seconds. The decreased RBF appeared to be part of a generalized vasoconstrition caused either by sympathetic reflexes or by the direct action of methylene blue.
/SIGNS AND SYMPTOMS/ Large IV doses of methylene blue may produce nausea, vomiting, abdominal pain, precordial pain, dizziness, headache, profuse sweating, dyspnea, hypertension, and mental confusion. Urinary tract irritation may occur. High IV dosage or high local concentrations of methylene blue may cause formation of methemoglobin and cyanosis.
Methylene blue's production and use as a paper dye, in silk dyeing and microscopy stain, chemical intermediate, medicinal agent, and cosmetic dye(1,2) and photosensitizer(3) may result in its release to the environment through various waste streams(SRC). Methylene blue is a cationic dye(4). The compound is used as an antidote to methemglobinemia(5). Methylene Blue-curcumin is used in the treatment of Alzheimer's disease(2).
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including methylene blue, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Methylene blue is included in orally administered menstrual drug products.
Residues of the following chemical substances are exempted from the requirement of a tolerance when used in accordance with good manufacturing practice as ingredients in an antimicrobial pesticide formulation, provided that the substance is applied on a semi-permanent or permanent food-contact surface (other than being applied on food packaging) with adequate draining before contact with food. (a) The following chemical substances when used as ingredients in an antimicrobial pesticide formulation may be applied to: Food-contact surfaces in public eating places, dairy-processing equipment, and food-processing equipment and utensils. Methylene blue is included on this list. Limit: When ready for use, the end-use concentration is not to exceed 0.4 ppm.
Residues of the following chemical substances are exempted from the requirement of a tolerance when used in accordance with good manufacturing practice as ingredients in an antimicrobial pesticide formulation, provided that the substance is applied on a semi-permanent or permanent food-contact surface (other than being applied on food packaging) with adequate draining before contact with food. ... (c) The following chemical substances when used as ingredients in an antimicrobial pesticide formulation may be applied to: Food-processing equipment and utensils. Methylene blue is included on this list. Limit: When ready for use, the end-use concentration is not to exceed 0.4 ppm.
5–6.5 hours (after IV dose).
Following IV administration, the estimated half-life of methylene blue is 5-6.5 hours.
... The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after IV and oral administration of 100 mg methylene blue with and without mesna. The distribution of methylene blue in different tissues was measured in rats after intraduodenal and IV application. The time course of methylene blue in whole blood after IV administration showed a multiphasic time course with an estimated terminal half-life of 5.25 hr. ...
Following distribution into tissues, rapidly reduced to leukomethylene blue (leucomethylthioninium chloride). Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals.
Methylene blue can be reduced to a colorless form, leukomethylene blue; together, these compounds form a reversible oxidation-reduction system. In low concentrations, methylene blue accelerates conversion of methemoglobin to hemoglobin. In patients with methemoglobinemia, methylene blue is reduced to leukomethylene blue by methemoglobin reductases in erythrocytes; leukomethylene blue then reduces methemoglobin to hemoglobin. In high concentrations, methylene blue oxidizes the ferrous iron of reduced hemoglobin to the ferric state, thereby changing hemoglobin to methemoglobin.
Following distribution into tissues, methylene blue is rapidly reduced to leukomethylene blue (leucomethylthioninium chloride). Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals.
METHYLENE BLUE
Oxidation-Reduction Activity [MoA]; Oxidation-Reduction Agent [EPC]
Excreted in urine and bile. About 75% of an oral dose excreted in urine, primarily as stabilized colorless leukomethylene blue.
10 mg/kg (in rats).
3.0 ± 0.7 L/min.
... The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after IV and oral administration of 100 mg methylene blue with and without mesna. The distribution of methylene blue in different tissues was measured in rats after intraduodenal and IV application. The time course of methylene blue in whole blood after IV administration showed a multiphasic time course with an estimated terminal half-life of 5.25 hr. Following oral administration, the area under the concentration-time curve was much lower (9 nmol/min/mL vs 137 nmol/min/mL). Co-administration of mesna, which could influence distribution by ion-pairing, did not alter the pharmacokinetics. The urinary excretion of methylene blue and its leukoform was only moderately higher after IV administration (18% vs 28% dose). Intraduodenal administration to rats resulted in higher concentrations in intestinal wall and liver but lower concentrations in whole blood and brain than IV methylene blue. Differences in organ distribution of methylene blue are mainly responsible for the different pharmacokinetics after oral and IV administration. ...
Methylene blue is well absorbed from the GI tract, and peak plasma concentrations occur approximately 1-2 hours after an oral dose. ... Following distribution into tissues, methylene blue is rapidly reduced to leukomethylene blue (leucomethylthioninium chloride). Metabolism to leucomethylene blue may be less efficient in neonates than in older individuals. Methylene blue is excreted in urine and bile. About 75% of an oral dose of methylene blue is excreted in urine, mostly as stabilized colorless leukomethylene blue. On exposure to air, the urine turns green or blue, due to the presence of the oxidation product methylene azure (methylene blue sulfone). Some unchanged drug is also excreted in urine.
BACKGROUND: Although blue dye is routinely used for lymphatic mapping, it is not used for lymphatic mapping in pregnancy-associated breast cancer, because of concern of fetal risk. METHODS: To investigate the safety of blue dye for lymphatic mapping in pregnant women, the pharmacokinetics of methylene blue dye were examined in 10 nonpregnant women, and the results were extrapolated to estimate maximal fetal exposure to the dye. RESULTS: Plasma and urine measurements indicated that the dye quickly distributed from the breast injection site to the circulation, with 32% of the total dose excreted in urine within 48 hours. Combined with existing data on organ distribution of methylene blue, the estimated maximal dose to the fetus is 0.25 mg (5% of the administered dose), likely further reduced by other physiologic factors related to pregnancy. CONCLUSIONS: The analysis suggests that methylene blue dye can be used for lymphatic mapping in pregnancy-associated breast cancer with minimal fetal risk.
Used as a stain in bacteriology, a chemical reagent, an antimethemoglobinemic drug, a polymerization inhibitor, and a temporary hair colorant; also used as a paper, textile, and leather dye; [HSDB] Azine dye; [Kirk-Othmer]
Pulp and Paper Processing [Category: Industry]
For methylene blue (USEPA/OPP Pesticide Code: 039505) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./
Stain in bacteriology; reagent for several chemicals; as mixed indicator; as redox colorimetric agent. Targeting agent for melanoma.
Dyeing cotton and wool, biological and bacteriological stains, reagent in oxidation-reduction titrations in volumetric analysis, indicator
Methylene blue is mainly used to dye paper and office supplies, but also to tone up silk colors. ... as a stain in microscopy, as a hydrogen acceptor in enzymatic dehydrogenations, as a redox indicator in iodometry and titanometry, and as a cosmetic dye.
Methylene blue ... is obtained by oxidation of 4-aminodimethylaniline in the presence of sodium thiosulfate to give the quinonediiminothiosulfonic acid, reaction with dimethylaniline, oxidation to the indamine, and cyclization to give the thiazine. The dye is commercially available as the hydrochloride and as the zinc chloride double salt.
By treating a solution of N,N-dimethyl-p-phenylenediamine and N,N,-dimethylaniline hydrochlorides with H2S and FeCl3 or another suitable oxidizing agent.
By oxidation of p-aminodimethylaniline with ferric chloride in the presence of hydrogen sulfide. The dye is the zinc chloride double salt of the chloride.
N,N-Dimethyl-p-phenylene diamine ... reacts with sodium thiosulfate ... to form the thiosulfonic acid which condenses with N,N-dimethylaniline ... in the presence of sodium dichromate ... to the indamine, then with copper sulfate ... and sodium dichromate to methylene blue.
Provided technically as the zinc double chloride; used medically in a zinc free form.
Parenteral: Injection, for IV use, 10 mg/mL (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Grade: USP, technical.
Information on 1 consumer products that contain Methylene blue in the following categories is provided:
Information on 2 consumer products that contain Methylene blue in the following categories is provided:
Phenothiazin-5-ium, 3,7-bis(dimethylamino)-, chloride (1:1): ACTIVE
C16H18N3SCl.3H2O (medicinal); (C16H18N3SCl)2.ZnCl2H20 (dye)
Methylene blue has also been described as a "photosensitizer" which means that it can absorb light and transfer the absorbed energy to another compound.
Methylene blue was first isolated in 1876. Its use covers many areas, including as an antiseptic, disinfectant, and cyanide-antidote. Methylene blue is also an antimicrobial agent in plastic materials such as food packaging wraps, surgical drapes, face masks, and other film materials. Light exposure of the dye dispersed in plastic generates reactive singlet oxygen, which is the active antimicrobial species. Methylene blue is approved for topical, intravenous, and oral administration. Its cellular adsorption selectivity, subcellular localization, reduction to leuko-dye by mitochondria, and photoreaction with DNA have been of interest for decades. Recent applications of this technology to HIV phototherapy have reviewed previous methylene blue literature .
Thiazine dyes are generally of minor importance in the textile field due to what is presently considered as inferior fastness
개요메틸렌 블루(Methylene blue)는 헤테로 고리 방향족 화합물이다. 상온에서 짙푸른 녹색을 띄며, 산화 시 푸른색, 환원 시 무색을 띄는 특징이 있다. 이 특성 때문에 산화 환원의 지표로 사용된다. 수화물은 파란색이며, 메틸렌 블루 1분자당 물 분자가 3분자 결합한 형태로 존재한다.100~110도에서 분해되며 동물 세포의 염색에도 널리 사용한다. 독일의 과학자 하인리히 카로에 의해 1876년 처음으로 합성되었다.
용도메틸렌 블루는 비뇨기 진통제로 널리 사용되며 그 외에도 다양한 용도로 사용된다.
용도Methylene Blue, 1% w/v aqueous solution is used as a dye in different staining procedures viz. Wright's stain and Jenner's stain. It also serves as an indicator and medicine. Further, it is used to examine RNA and DNA under the microscope or in a gel. It is widely used as a redox indicator in analytical chemistry. It is also used in the sulfide analysis.
일반 설명Methylene blue, also known as methylthioninium chloride, is a photoactive phenothiazine dye. It is a small molecular weight dye, which is effective against Gram positive and Gram negative bacteria.
정의ChEBI: An organic chloride salt having 3,7-bis(dimethylamino)phenothiazin-5-ium as the counterion. A commonly used dye that also exhibits antioxidant, antimalarial, antidepressant and cardioprotective properties.
Methylene blue demonstrates clear dose-dependent toxicity thresholds. At single doses of 3 mg/kg or more, hypotension, wheezing, and reduced oxygenation have been reported. Cumulative doses of 7 mg/kg or more can cause significant toxicity, including nausea, vomiting, precordial pain, dyspnea, tachypnea, chest tightness, tachycardia, apprehension, tremor, mydriasis, abdominal pain, dizziness, paresthesia, headache, confusion, and mild methemoglobinemia (up to 7%), with effects lasting 2 to 12 hours. Severe overdosage (single dose of 20 mg/kg or more) has caused severe intravascular hemolysis, hyperbilirubinemia, and death.
/CASE REPORTS/ We report the case of a 70-year-old female patient who developed corneal edema and iris discoloration following the inadvertent use of 1% methylene blue instead of 0.025% trypan blue to stain the anterior capsule during cataract phacoemulsification surgery. Copious irrigation was performed upon realization of incorrect dye use. Corneal edema and iris discoloration developed during the early postoperative period and persisted at 24-months follow-up. However, keratoplasty was not required. The intracameral use of 1% methylene blue has a cytotoxic effect on the corneal endothelium and iris epithelium. Copious irrigation for at least 30 min using an anterior chamber maintainer may improve outcomes.
For more Human Toxicity Excerpts (Complete) data for Methylene blue (31 total), please visit the HSDB record page.