Kojic acid

142.11

142.11

120895

207-922-4

6K23F1TT52

1942

DTXSID2040236

Prismatic needles from acetone, ethanol+ether or methanol+ethyl acetate|Crystals|Prisms, needles from acetone

29329995

66.8

-0.9

White to beige-brown Crystalline Powder

1.5±0.1 g/cm3

153.5 °C

401.7°C at 760 mmHg

179.9±22.2 °C

1.607

H2O: soluble

Refrigerator

3.21X10-6 mm Hg at 25 deg C (est)

Henry's Law constant = 2.39X10-7 atm-cu m/mol at 25 °C (est)

pKa = 7.66 (approx., at 25 °C)

121.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 6.44X10-11 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

3

40-68

22-24/25-36/37-36

UQ0875000

Xn

Stable. Combustible. Incompatible with strong oxidizing agents.

P201, P202, P281, P308+P313, P405, P501

H351

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

Kojic acid (5-hydroxy-2-hydroxymethyl-gamma-pyrone) is a bacterial metabolic product used intensively in the food industry. In the presence of visible light and molecular oxygen it was found to cause breakage of calf thymus DNA. Such degradation was considerably enhanced in the presence of the transition metal ions Fe(III), Fe(II) and Cu(II). The cleavage of DNA in the presence of Fe(III) did not appear to have any preferred site(s) or sequence(s) for strand scission. Kojic acid catalysed the reduction of transition metal which in the case of Cu(II) was found to play an essential role in the degradation of DNA. Kojic acid also reduced oxygen to superoxide and hydroxyl radicals were formed in the presence of metal ions. The involvement of these active oxygen species in the reaction was established by the inhibition of DNA breakage by superoxide dismutase, catalase, iodide, mannitol, formate and sodium azide.|... The anti-wrinkling activity of kojic acid /was evaluated/ by using hairless mice exposed to chronic solar-simulating ultraviolet (UV) irradiation as a model animal. At the end of a 20-week irradiation period, topical application of kojic acid before UV irradiation was observed to dramatically prevent: (1) the wrinkling, (2) hyperplasia of the epidermis, (3) fibrosis of the lower dermis, and (4) the increase of extracellular matrix components in the upper dermis. These findings indicate that kojic acid is a typical agent preventing wrinkling of the skin due to chronic photodamage.|The individual and combined effects of kojic acid and aflatoxin were studied in male broiler chicks (Peterson x Hubbard). The experiment had a two by two factorial arrangement of treatments with dietary treatments of 0 and 2,500 mg kojic acid/kg feed and 0 and 2.5 mg aflatoxin/kg feed. The broilers were obtained at 1 day of age and housed in electrically heated batteries with feed and water available for ad libitum intake until they reached 3 wk of age. The toxicity of kojic acid was characterized by significant (P less than .05) reductions in body weight, the relative weight of the bursa of Fabricius, serum cholesterol concentration, and serum alkaline phosphatase activity, and by significant (P less than .05) increases in the relative weight of the pancreas, proventriculus, and gizzard, and serum concentrations of uric acid and triglycerides. Aflatoxicosis was characterized by significant (P less than .05) reductions in body weight, serum concentrations of total protein, albumin, cholesterol, and inorganic phosphorus, serum glutamic oxalacetic transaminase activity, and mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Significant (P less than .05) increases in the relative weight of the liver, kidney, spleen, pancreas, proventriculus, and heart, and the serum pyruvic transaminase activity were also caused by aflatoxin alone. The only significant (P less than .05) interaction between kojic acid and aflatoxin, which can best be described as antagonistic, was seen through an increase in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. These data indicate that kojic acid is not an aflatoxin synergist at the levels used in the present study.

Kojic acid is a fungal metabolite commonly produced by many species of Aspergillus, Acetobacter, and Penicillium. ... Different Aspergillus species are known to produce variable amounts of kojic acid.|Kojic acid is an antibiotic substance produced in an aerobic process by a variety of microorganisms from a wide-range of carbon sources(1).

Kojic acid's production and use as a flavoring agent, food additive(1), chemical intermediate and antimicrobial(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 11(SRC), determined from a log Kow of -0.64(2) and a regression-derived equation(3), indicates that kojic acid is expected to have very high mobility in soil(SRC). Volatilization of kojic acid from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.4X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Kojic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-6 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2008).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 11(SRC), determined from a log Kow of -0.64(2) and a regression-derived equation(3), indicates that kojic acid 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 2.4X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2008).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), kojic acid, which has an estimated vapor pressure of 3.2X10-6 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 kojic acid 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 6 hours(SRC), calculated from its rate constant of 6.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Vapor-phase kojic acid is degraded in the atmosphere by reaction with ozone radicals(SRC); the half-life for this reaction in air is estimated to be 21 hours(SRC), calculated from its rate constant of 1.3X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase kojic acid may be removed from the air by wet or dry deposition(SRC). Kojic acid contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of kojic acid with photochemically-produced hydroxyl radicals has been estimated as 6.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of kojic acid with ozone has been estimated as 1.3X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 21 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Kojic acid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Kojic acid contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for kojic acid(SRC), using a log Kow of -0.64(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of kojic acid is estimated as 11(SRC), using a log Kow of -0.64(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that kojic acid is expected to have very high mobility in soil.

The Henry's Law constant for kojic acid is estimated as 2.4X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that kojic acid is expected to be essentially nonvolatile from moist soil surfaces(2). Kojic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-6 mm Hg(SRC), determined from a fragment constant method(3).

Kojic acid is a fungal metabolite commonly produced by many species of Aspergillus, Acetobacter, and Penicillium. The Aspergillus flavus group has traditionally been used in the production of a number of foods, including miso (soybean paste), shoyu (soy sauce), and sake.... Because kojic acid is often produced during the fermentation of historically used dietary staples, it has a long history of consumption.

Occupational exposure to kojic acid may occur through inhalation and dermal contact with this compound at workplaces where kojic acid is produced or used. Use data indicate that the general population may be exposed to kojic acid via ingestion of food. (SRC)

Depigmenting agent /for skin lightening/|Melasma is a chronic and recurrent disorder. It has been underdiagnosed and undertreated due to lack of effective therapies and the perception that it is merely a cosmetic nuisance. Hydroquinone, corticosteroids, licorice extracts and kojic acid have been used as monotherapy to treat melasma. However, the present standard of care in melasma therapy is combination therapy. To date, the most effective treatment is a triple-combination agent that contains hydroquinone 4%, tretinoin 0.05% and fluocinolone acetonide 0.01%...|... Combination regimens, including frequent applications of superficial- and medium-depth chemical peels, appear to be particularly effective and well tolerated in dark-skinned patients with melanosis. Post-inflammatory hyperpigmentation is the result of excess pigment deposition following an inflammatory skin disorder. Topical tretinoin, hydroquinone, azelaic acid, kojic acid, and glycolic acid peels have been employed with variable degrees of success...|Facial and neck pigmentations are ... common in middle-aged women, and are related to endogenous (hormones) and exogenous factors (such as use of cosmetics and perfumes, and exposure to sun radiation). Melasma (chloasma) is the most common cause of facial pigmentation, but there are many other forms such as Riehl's melanosis, poikiloderma of Civatte, erythrose peribuccale pigmentaire of Brocq, erythromelanosis follicularis of the face and neck, linea fusca, and cosmetic hyperpigmentations. Treatment of melasma and other facial pigmentations has always been challenging and discouraging.... Several hypopigmenting agents have been used with differing results. Topical hydroquinone 2 to 4% alone or in combination with tretinoin 0.05 to 0.1% is an established treatment. Topical azelaic acid 15 to 20% can be as efficacious as hydroquinone, but is less of an irritant. Tretinoin is especially useful in treating hyperpigmentation of photoaged skin. Kojic acid, alone or in combination with glycolic acid or hydroquinone, has shown good results, due to its inhibitory action on tyrosinase. Chemical peels are useful to treat melasma: trichloroacetic acid, Jessner's solution, Unna's paste, alpha-hydroxy acid preparations, kojic acid, and salicyclic acid, alone or in various combinations have shown good results. In contrast, laser therapies have not produced completely satisfactory results, because they can induce hyperpigmentation and recurrences can occur. New laser approaches could be successful at clearing facial hyperpigmentation in the future.|For more Therapeutic Uses (Complete) data for KOJIC ACID (7 total), please visit the HSDB record page.

Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. (See all compounds classified as Antioxidants.)

The structure of kojic acid indicates a relatively simple route of metabolism much like dietary hexoses.

The mechanism of action of kojic acid is well defined and it has been shown to act as a competitive and reversible inhibitor of animal and plant polyphenol oxidases, xanthine oxidase, and D- and some L-amino acid oxidases.|The activation of NF-kappaB induced by kojic acid, an inhibitor of tyrosinase for biosynthesis of melanin in melanocytes, was investigated in human transfectant HaCaT and SCC-13 cells. These two keratinocyte cell lines transfected with pNF-kappaB-SEAP-NPT plasmid were used to determine the activation of NF-kappaB. Transfectant cells release the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the NF-kappaB activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selective marker of geneticin resistance. NF-kappaB activation was measured in the SEAP reporter gene assay using a fluorescence detection method. Kojic acid showed the inhibition of cellular NF-kappaB activity in both human keratinocyte transfectants. It could also downregulate the ultraviolet ray (UVR)-induced activation of NF-kappaB expression in transfectant HaCaT cells. Moreover, the inhibitory activity of kojic acid in transfectant HaCaT cells was found to be more potent than known antioxidants, e.g., vitamin C and N-acetyl-L-cysteine. These results indicate that kojic acid is a potential inhibitor of NF-kappaB activation in human keratinocytes, and suggest the hypothesis that NF-kappaB activation may be involved in kojic acid induced anti-melanogenic effect.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ALTERNATIVE and IN VITRO TESTS/ To discover safe and effective topical skin-lightening agents ... alkyl esters of the natural product gentisic acid (GA) ... , four putative tyrosinase inhibitors, /were evaluated/ utilizing mammalian melanocyte cell cultures and cell-free extracts. Desirable characteristics include the ability to inhibit melanogenesis in cells (IC50 less than 100 ug/mL) without cytotoxicity, preferably due to tyrosinase inhibition. Of the six esters synthesized, the smaller esters (e.g. methyl and ethyl) were more effective enzyme inhibitors (IC50 approximately 11 and 20 ug/mL, respectively). For comparison, hydroquinone (HQ), a commercial skin "bleaching" agent, was a less effective enzyme inhibitor (IC50 approximately 72 ug/mL), and was highly cytotoxic to melanocytes in vitro at concentrations substantially lower than the IC50 for enzymatic inhibition. Kojic acid was a potent inhibitor of the mammalian enzyme (IC50 approximately 6 ug/mL), but did not reduce pigmentation in cells. Both arbutin and magnesium ascorbyl phosphate were ineffective in the cell-free and cell-based assays... .

5-((3-aminopropyl)phosphinooxy)-2-(hydroxymethyl)-4H-pyran-4-one

Kojic acid is a fungal metabolite commonly produced by many species of Aspergillus, Acetobacter, and Penicillium. The Aspergillus flavus group has traditionally been used in the production of a number of foods, including miso (soybean paste), shoyu (soy sauce), and sake.... Because kojic acid is often produced during the fermentation of historically used dietary staples, it has a long history of consumption. Various types of compounds, such as glucose, sucrose, acetate, ethanol, arabinose, and xylose, have been used as carbon sources for kojic acid production. Different Aspergillus species are known to produce variable amounts of kojic acid.

Cosmetics -> Antioxidant