Maltol

126.11

126.11

112169

204-271-8

3A9RD92BS4

404458|2829

DTXSID0025523

Monoclinic prisms from chloroform, orthorhombic bypyramidal crystals + monoclinic prisms from 50% alcohol|White crystalline powder

29329995

46.5

0.09

Clear colorless Liquid

1.046 g/mL at 25 °C

161.5 °C

140-150 °C @ Press: 20 Torr

198 °F

n 20/D 1.541

H2O: 1.2 g/100 mL (25 ºC);methanol: 50 mg/mL, clear

Store below +30°C.

3.26X10-4 mm Hg at 25 deg C (extrapolated from reduced pressure boiling point)

The acute oral LD
50
in rats was reported to be 2.33 g/kg (1.57-3.09 g/kg) (Moreno, 1974). The acute oral 7-day LD
50
s in mice, rats and chicks were reported to be 848, 1440 and 3720 mg/kg, respectively (Gralla, Stebbins, Coleman & Delahunt, 1969). Acute oral LD
50
values were found to be 550 mg/kg in mice, 1620 mg/kg in rabbits and 1410 mg/kg in guinea-pigs (Dow Chemical Company, 1967). The acute sc LD
50
in mice was found to be 820 mg/kg.

25%

Fragrant, caramel-like odor

Taste characteristics at 200.00 ppm: Sweet, caramellic, cotton candy with fruity, jammy strawberry nuance

pH of 0.5% aqueous solution = 5.3

Henry's Law constant = 5.0X10-9 atm-cu m/mole at 25 °C (est)

pKa = 8.6

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

Volatile with steam|May be sensitive to prolonged exposure to light and air. Reacts with bases. May react with reducing agents.|Hydroxyl radical reaction rate constant = 5.0X10-11 cu cm/molec-sec at 25 °C (est)|Ozone reaction rate constant = 1.3X10-17 cu cm/molec-sec at 25 °C (est)

May be sensitive to prolonged exposure to light and air. Somewhat soluble in water at room temperature. Freely soluble in hot water [Merck]. Slightly soluble in cold water.

Ethers

MALTOL is weakly acidic. Reacts with bases. May react with reducing agents. Volatile with steam. (NTP, 1992)

UN 3334

3

22-38-36/37/38-41-20/22

37-37/39-26-36-36/37/39-36/37

UQ1050000

Xn,Xi

Maltol solutions may be stored in glass or plastic containers. The bulk material should be stored in a well-closed container, protected from light, in a cool, dry place.

Irritant

Stable under recommended storage conditions.

P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, P501

H302

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Contact a licensed professional waste disposal service to dispose of this material. Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents

Maltol is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

WHO/JEFCA; WHO Food Additives Series 56; Maltol and Related Substances (2006)[Available from, as of May 26, 2016: http://www.inchem.org/pages/jecfa.html]

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

|Warning|H302 (99.94%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 1939 companies from 18 notifications to the ECHA C&L Inventory.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, and P501

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing 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 protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)|Eye/face protection: Safety glasses with side-shields conforming to EN166. 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: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.|Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.|Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|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.|For more Preventive Measures (Complete) data for Maltol (6 total), please visit the HSDB record page.

A skin irritant.

Maltol was detected in the emissions from wood heaters at mean emissions rates of 20.8-69.2 mg/kg wood burned in the fine particles emitted and 3.03-18.8 mg/kg wood burned in the vapor emissions(1). Maltol has been identified in both tobacco smoke and tobacco substitute smoke and in tobacco collected from cigarettes(2).

IDENTIFICATION AND USE: Maltol is a white crystalline powder. It is used as a flavoring agent, to impart "freshly baked" odor and flavor to breads and cakes. It is also used as medication. HUMAN EXPOSURE AND TOXICITY: Maltol at concentrations ranging from 0.1 to 1.5 umol/mL induced sister chromatid exchanges in human lymphocytes. It was suggested that these results were due to an indirect action of maltol and not to its direct reactivity with DNA. ANIMAL STUDIES: Eight female mice were fed a diet containing maltol at a level of 0.5% (w/w) for 21 weeks, calculated to provide an average daily intake of 750 mg/kg bw. At termination, no differences in general health, behavior, body-weight gain or relative liver weights were reported. Gross and microscopic examination revealed no histological abnormalities in the livers of the treated mice when compared with the controls. A three-generation study of reproductive toxicity was conducted, in which groups of 20 male and 20 female rats were given diets containing maltol at concentrations resulting in 100, 200 or 400 mg/kg bw per day. On day 134, animals of the F1 generation showed signs of sialodacryodenitis due to a contagious virus. No deaths occurred, and the signs diminished within 10 days. Maltol had no effect on copulation rate, mating viability index, lactation, offspring sex ratio or 21-day pup survival index. Maltol at concentrations ranging from 0.1 to 1.5 umol/mL induced sister chromatid exchanges in Chinese hamster ovary cells. It was suggested that these results were due to an indirect action of maltol and not to its direct reactivity with DNA. Maltol was weakly mutagenic (two- to threefold increases in number of revertants) in Salmonella typhimurium TA100 at concentrations of 1-3 mg/plate either alone or with metabolic activation. Activity against TA98 was not detected. Maltol tested at concentrations of 0.1-10.0 mg/plate increased the number of revertants in strain TA97 at 1 mg/plate by about twofold. No increase found in the presence of an activation system, or in TA102 alone or with activation. In other studies with S. typhimurium, maltol was not consistently mutagenic when tested at concentrations up to 10,000 ug/plate alone or in the presence of an activation system.

The pyrones, 3-hydroxy-2-methyl-4-pyrone (maltol) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol) chelate iron with a high affinity and selectivity. The resulting 1:3 (metal-ligand) complexes, being neutral, are able to partition readily across cell membranes and thus may facilitate iron transport across the intestinal wall. Absorption of radioactive iron ((59)Fe) in the presence of these pyrones was investigated in male rats 1, 2, 4 and 6 hr after intraduodenal administration of a 7 micrograms dose and compared with that of (59)Fe given as the sulfate, gluconate, fumarate or complexed to EDTA. Total body absorption and distribution were calculated from the (59)Fe content of various tissue samples. With all the iron preparations used, blood levels of (59)Fe were highest 1 hr after injection whilst the (59)Fe content at the major site of deposition, i.e. the bone marrow, increased up to 6 hr. No (59)Fe was found in the urine. Total body absorption of (59)Fe was significantly higher from the pyrones than from the other four preparations. Over the dose range 0.7-700 micrograms, the proportion of (59)Fe absorbed from both iron maltol and iron sulphate decreased with increasing dose. Enhanced (59)Fe uptake from maltol was evident at 0.7-70 micrograms but not at 700 micrograms suggesting that use of these pyrones will not result in iron overload. Absorption of (59)Fe given into the stomach was slower in onset but was sustained longer presumably via a steady delivery of iron to the duodenum from the gastric reservoir.|Neurofilamentous tangles have been induced in cultured neurons from rat brain hemispheres by application of both aluminum and maltol. Quantitative evaluation revealed a significantly higher percentage of tangle containing neurons when using the aluminum-maltol mixture than after application of aluminum alone. Tangles were found to be consistently stained with monoclonal antibodies to neurofilament proteins but failed to react with polyclonal antibodies against microtubule-associated proteins 1, 2 and tau.|Aluminum (Al) has been observed to cause neurofilament protein accumulation in both experimental animals and cultured cells. Impairment of axonal transport is thought to be a mechanism of toxicity. Inhibition of the degradation of neurofilament proteins, however, resulting in accumulation of these proteins may be an alternative mechanism for Al toxicity. In the present study, the effect of calcium (Ca) on the proteolysis of the neurofilament triplet proteins by calcium-activated neutral proteases (CANP) was studied in the isolated sciatic nerve explants. The extent of the degradation was found to be dependent on the Ca concentration. The effect of Al chloride, -citrate and -maltol on the calcium-induced degradation was studied. No effect of any of the Al compounds was observed, suggesting that the metal may exert its neurotoxic effect via a mechanism other than impairment of neurofilament proteolysis. Maltol itself was found to enhance the effect of Ca on the degradation of neurofilament proteins, probably by facilitating the movement of Ca across the neuronal membrane.|Deposition of aluminum in the body is responsible for the development of dialysis-related diseases in patients with renal dysfunction and may play a role in the development of certain neurodegenerative disorders. Although citric acid is known to be a strong enhancer of gastrointestinal absorption of aluminum, its effect on aluminum distribution and accumulation is not yet clear. Maltol has been shown to increase the neurotoxicity of aluminum, but little is known about its effect on aluminum deposition in the body. To elucidate the role of citric acid and maltol in aluminum accumulation and toxicity, rats were loaded intraperitoneally during a 7-day period with different amounts of aluminum chloride in absence or presence of citric acid or maltol before analysis of aluminum in serum, brain, bone, and urine. Coadministration of citric acid led to relatively reduced serum levels, as compared with aluminum and aluminum-maltol treatment. This is explained by both tissue elimination and enhanced renal elimination. ... Maltol was shown to be a strong enhancer of aluminum accumulation in serum, brain, and bone. The rise of aluminum in these target tissues was dose dependent.|For more Interactions (Complete) data for Maltol (7 total), please visit the HSDB record page.

LD50 Chicken oral 3720 mg/kg|LD50 Guinea pig oral 1410 mg/kg|LD50 Rabbit oral 1620 mg/kg|LD50 Mouse sc 820 mg/kg|For more Non-Human Toxicity Values (Complete) data for Maltol (6 total), please visit the HSDB record page.

Maltol is found in the bark of young larch trees (Larix decidua Mill.), in pine needles (Abies alba Mill., Pinaceae), in chickory, in wood tars and oils, and in roasted malt(1). Maltol is found in a variety of plants including clover, ginseng, licorice, pepper, paprika and raspberry(2).

Maltol's production and use as a flavoring agent to impart "freshly baked" odor and flavor to bread and cakes(1) and as a flavor enhancer in confections, cookies, ice cream, fruit juices, puddings, and beverages(2) may result in its release to the environment through various waste streams(SRC). Maltol has been detected in emissions from burning wood(3) and in tobacco smoke and substitute-tobacco smoke(4). Maltol has use as a flavor chemical in electronic cigarette fluids(5). Maltol is produced when cellulose or starch is heated(6).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that maltol is expected to have very high mobility in soil(SRC). Volatilization of maltol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.0X10-9 atm-cu m/mole(SRC), derived from its extrapolated vapor pressure, 3.26X10-4 mm Hg(2), and water solubility, 1.09X10+4 mg/L(3). Maltol is not expected to volatilize from dry soil surfaces(SRC) based upon its extrapolated vapor pressure(2); however, maltol does have a characteristic fragrant odor(4) even though it exists as a solid. Biodegradation data in soil were not available(SRC, 2016).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that maltol 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 5.0X10-9 atm-cu m/mole(SRC), derived from its extrapolated vapor pressure, 3.26X10-4 mm Hg(2), and water solubility, 1.09X10+4 mg/L(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of 0.09(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2016). Maltol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Maltol is an olefinic compound and olefins in surface waters exposed to sunlight react with photo-oxidants with a half-life on the order of 25 days(7).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), maltol, which has an extrapolated vapor pressure of 3.26X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase maltol 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 7.7 hours(SRC), calculated from its rate constant of 5.0X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Vapor-phase maltol is also degraded in the atmosphere by reaction with ozone(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(2). Maltol absorbs at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of maltol with photochemically-produced hydroxyl radicals has been estimated as 5.0X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 7.7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of maltol 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). Maltol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). The UV absorption spectrum of maltol in methanol solution shows weak absorption between 290-340 nm(3) and, therefore, maltol may be susceptible to direct photolysis by sunlight(SRC). It has been reported that maltol may be sensitive to prolonged exposure to light(4). Maltol is an olefinic compound and olefins in surface waters exposed to sunlight react with photo-oxidants (such as hydroxyl radicals, peroxy radicals and singlet oxygen) with a half-life on the order of 25 days(5).

An estimated BCF of 3 was calculated in fish for maltol(SRC), using a log Kow of 0.09(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).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of maltol can be estimated to be 1(SRC). According to a classification scheme(2), this estimated Koc value suggests that maltol is expected to have very high mobility in soil.

The Henry's Law constant for maltol is estimated as 5.0X10-9 atm-cu m/mole(SRC) derived from its extrapolated vapor pressure, 3.26X10-4 mm Hg(1), and water solubility, 1.09X10+4 mg/L(2). This Henry's Law constant indicates that maltol is expected to be essentially nonvolatile from water surfaces(3). A study measuring the volatility of flavor compounds from water found maltol to be highly non-volatile(4). Maltol's estimated Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Maltol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1); however, maltol does have a characteristic fragrant odor(5) even though it exists as a solid.

Maltol has been reportedly been found in wheat and rye bread, milk, butter, smoked pork, beer, cocoa, coffee, roasted barley, filberts, peanuts, soybean, beans, tamarind, licorice, sake, dried bonito, clam and cocoa butter(1). A maltol concentration of 490 ug/kg was detected in microwave-oven popcorn(2). Volatiles emitted from rice cakes from two commercial companies contained maltol levels of 29 and 60 ppb respectively(3). Maltol was identified at concentrations ranging from 35.5 to 209 ug/L in red wines aged in wooden barrels(4). Maltol was identified in volatiles from roasted chestnuts(5). The volatile compounds extracted from the red-skinned cultivar of rambutan, Jitlee (Nephelium lappaceum L.), a tropical fruit native to Southeast Asia, contained a maltol concentration of 53.79 ug/L in the juice(6).

Occupational exposure to maltol may occur through inhalation and dermal contact with this compound at workplaces where maltol is produced or used. Monitoring and use data indicate that the general population may be exposed to maltol via inhalation of air in the vicinity of burning wood or tobacco smoke, ingestion of food and beverages, and dermal contact with consumer products containing maltol. (SRC)

/EXPL THER/ /The objective of the study was/ to evaluate the neuroprotective and neurite outgrowth effects of maltol, a natural aroma compound, on retinal ganglion cells (RGCs) under oxidative stress in vitro. Mouse primary RGCs were isolated using immunopanning-magnetic separation and exposed to H2O2 in the presence of maltol. The cell viability and apoptosis were determined by using adenosine 5'-triphosphate (ATP) assay and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), respectively. Neurite outgrowth was assessed by immunofluorescence for alpha-tubulin. The activation of nuclear factor-kappaB (NF-kappaB) was also evaluated using immunofluorescence. When the RGCs were exposed to 20 uM of H2O2 for 16 hr, their viability dropped to 40.3 +/- 3.4%. However, the maltol treatment restored the cells in a dose-dependent manner. The viability recovered to 73.9 +/- 5.1% with 10 uM of maltol and even reached 175.1 +/- 11.3% with 2 mM of maltol, as measured by ATP assay. This oxidative stress significantly increased the number of TUNEL-positive RGCs, but the maltol drastically reduced the proportion of those apoptotic cells. The oxidative stress hampered the neurite outgrowth of the RGCs, whereas maltol restored their ability to sprout neurites. Regarding NF-kappaB, the active form of phosphorylated NF-kappaB (pNF-kappaB) increased the oxidative stress level but the maltol treatment again reduced it to an unstressful level. Our data revealed that maltol attenuated the oxidative stress-induced injury in the primary mouse RGCs. Its neuroprotective and neurite outgrowth effects seemed to be related to NF-kappaB signaling. Maltol has potential as a new neuroprotective therapeutic agent for oxidative stress-related ocular diseases, including glaucoma.

Groups of two beagle dogs of each sex were given a single intravenous injection of 10 mg/kg bw maltol, and urine samples were collected for 72 hr. An average of 58.5% of the administered dose was excreted as a mixture of sulfate and glucuronic acid conjugates of maltol. About 98% of the total urinary excretion of conjugates occurred within the first 24 hr, males and females excreting an average of 42% and 73% of the administered dose, respectively.

Maltol and derivatives contain a gamma-pyrone ring system. Gamma-pyrones are relatively basic, and the behavior as a base is partly due to the aromatic character and relative stability of the conjugate acid. As the gamma-pyrone ring also contains a 3-hydroxy substituent, it is expected that maltol and its derivatives will be readily conjugated with glucuronic acid or sulfate. In addition, maltol may form a complex with metal ions (e.g. Fe++), like phenols.

Maltol (3-hydroxy-2-methyl-4-pyrone) produced reactive oxygen species as a complex with transition metals. Maltol/iron complex inactivated aconitase the most sensitive enzyme to oxidative stress. The inactivation of aconitase was iron-dependent, and prevented by TEMPOL, a scavenger of reactive oxygen species, suggesting that the maltol/iron-mediated generation of superoxide anion is responsible for the inactivation of aconitase. Addition of maltol effectively enhanced the ascorbate/copper-mediated formation of 8-hydroxy-2'-deoxyguanosine in DNA. Oxidation of ascorbic acid by CuSO(4) was effectively stimulated by addition of maltol, and the enhanced oxidation rate was markedly inhibited by the addition of catalase and superoxide dismutase. These results suggest that maltol can stimulate the copper reduction coupled with the oxidation of ascorbate, resulting in the production of superoxide radical which in turn converts to hydrogen peroxide and hydroxyl radical. Cytotoxic effect of maltol can be explained by its prooxidant properties: maltol/transition metal complex generates reactive oxygen species causing the inactivation of aconitase and the production of hydroxyl radical causing the formation of DNA base adduct.|... We examined the ability of maltol to induce the cytochrome P450 1a1 (Cyp1a1), an enzyme known to play an important role in the chemical activation of xenobiotics to carcinogenic derivatives. Our results showed that treatment of Hepa 1c1c7 cells with maltol significantly induced Cyp1a1 at mRNA, protein, and activity levels in a concentration-dependent manner. The RNA synthesis inhibitor, actinomycin D, completely blocked the Cyp1a1 mRNA induction by maltol, indicating a requirement of de novo RNA synthesis through transcriptional activation. In addition, maltol induced aryl hydrocarbon receptor (AhR)-dependent luciferase reporter gene expression in stably transfected H1L1.1c2 cells, suggesting an AhR-dependent mechanism. This is the first demonstration that the food flavoring agent, maltol, can directly induce Cyp1a1 gene expression in an AhR-dependent manner and represents a novel mechanism by which maltol promotes carcinogenicity and toxicity.|Maltol has antioxidant properties, presumably through its ability to complex metal ions such as Fe++ and to promote the formation of reduced glutathione (GSH). Maltol at a concentration of 130 umol/L inhibited iron-mediated lipid peroxidation and increased scavenging of reactive oxygen species by enhancing the supply of NADPH required for regeneration of GSH. Maltol inhibited the formation of thiobarbituric acid-reactive substances when incubated with rat liver microsomes in the presence of Fe++ and ascorbate. Maltol at concentrations of 130-140 umol/L also effectively inhibited the inactivation of NADP-isocitrate dehydrogenase, the principal NADPH-generating enzyme, by Fe++. Maltol significantly increased the oxidation of Fe++, while dimethylpyrone had no effect. The latter results suggest that the 3-hydroxy substituent in maltol is necessary to promote Fe++ oxidation.

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. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital. 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. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. 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. (NTP, 1992)

/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 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 TKO. Use 0.9% saline (NS) or lactated Ringer's (LR) 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 (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/GENOTOXICITY/ Maltol at concentrations ranging from 0.1 to 1.5 umol/mL induced sister chromatid exchanges in ... human lymphocytes. /It was/ suggested that these results were due to an indirect action of maltol and not to its direct reactivity with DNA.|/ALTERNATIVE and IN VITRO TESTS/ Maltol (3-hydroxy-2-methyl-4-pyrone), a product of carbohydrate degradation, is known to enhance aluminum-induced neurofibrillary degeneration in neuronal systems, but few toxicological studies have been conducted. We report maltol toxicity in neuroblastoma cell lines of mouse (Neuro 2a) and human (IMR 32) origin, and in primary murine fetal hippocampal neuronal cultures. As determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2 -(4-sulfophenyl)-2H-tetrazolium, inner salt] conversion, maltol exhibited a dose-dependent toxicity on the viability of both neuroblastoma cell lines, but the toxicity was more pronounced in Neuro 2a cells. Maltol was also toxic in a dose-dependent manner in primary murine fetal hippocampal neurons at micromolar concentrations. Electrophoresis of DNA extracted from maltol-intoxicated cells showed a laddering pattern, suggestive of apoptotic cell death. In the maltol-exposed hippocampal neuronal cultures, fragmented DNA ends were visualized in situ in morphologically condensed nuclei by terminal deoxynucleotidyl transferase with digoxigenin-labelled UTP and subsequent immunohistochemistry. Collectively, our findings suggest that the toxic effect of maltol is mediated through apoptosis. ...|/ALTERNATIVE and IN VITRO TESTS/ Hydroxyketone chelators, deferiprone (HK1), maltol (HK3) and their related compounds (HK2, 4-8), were characterized for their cytotoxic profiles against oral human normal and tumor cells. ... The cytotoxic activity of ... /maltol/ was significantly increased by FeCl3. ... /Maltol/ did not induce DNA fragmentation in HL-60 cells, regardless of the presence or absence of FeCl3. In HSC-2 cells, ... /maltol/ did not induce DNA fragmentation in the presence or absence of FeCl3. ... /maltol/ did not activate the caspase 3, 8 and 9 in HL-60 cells, but activated the caspase 3 only slightly in the presence of FeCl3. ... /Maltol/ also activated the caspase 3, 8 and 9 in HSC-2 cells, but to a lesser extent. The present study suggested that the antitumor activity of hydroxyketones may be modified by Fe3+ concentration.

3-hydroxy-2-methyl-4-pyrone

Grade: FCC /Food Chemicals Codex/

4H-Pyran-4-one, 3-hydroxy-2-methyl-: ACTIVE

Food additives -> Flavoring Agents|Flavouring Agent -> FLAVOURING_AGENT; -> JECFA Functional ClassesFood Additives -> FLAVOUR_ENHANCER; -> JECFA Functional ClassesFood Additives -> STABILIZER; -> JECFA Functional Classes|Flavoring Agents -> JECFA Flavorings Index

Flavoring Agents|Flavouring Agent -> FLAVOURING_AGENT; Food Additives -> FLAVOUR_ENHANCER; Food Additives -> STABILIZER;