2(5H)-Furanone

84.074

84.07

207-839-3

8KXK25H388

197009|51296

DTXSID7075422

2932209090

26.3

-0.6

Liquid

1.193 g/cm³ @ Temp: 20 °C

4.5 °C

86.5 °C

101 deg C (214 deg F) (Closed cup)

1.481

In water, 8.50X10+5 mg/L at 25 deg C (est)

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature: 2 - 8 deg C. Light sensitive. Store under inert gas.

0.981 mm Hg at 25 deg C (est)

Henry's Law constant = 9.74X10-6 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.22X10-11 cu cm/mol-sec at 25 °C (est)|Ozone radical reaction rate constant = 1.13X10-17 cu cm/mol-sec at 25 °C (est)

I; II; III

NONH for all modes of transport

3

R36/37/38

S26

LU3453000

Xi:Irritant;

Stable under recommended storage conditions.

P264, P270, P301+P312, P330, P501

H302

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

|Warning|H315: Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501

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: 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: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

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

Special hazards arising from the substance or mixture: Carbon oxides

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.|Control of environmental exposure: Do not let product enter drains.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapor or mist. Normal measures for preventive fire protection.|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.

IDENTIFICATION AND USE: 2(5H)-Furanone is an endogenous satiety substance which suppresses appetite and/or food intake. Experimental animal models show promise for therapeutic use of 2-furanone as medication for treatment of obesity and autoimmune diseases. HUMAN EXPOSURE AND TOXICITY: 2-furanone and 2-pyrone induce cellular DNA damage and the formation of topoisomerase I- and topoisomerase II-DNA complexes in cells. Both lactones were cytotoxic in human cell lines: in A549 lung cancer cells at lower concentrations than in MRC5 non-malignant lung fibroblasts. These results suggest possible anticancer and DNA-damaging activities for 2-furanone and 2-pyrone. ANIMAL TOXICITY STUDIES: To study the effect of 2-furanone on food intake, Wistar rats were subjected to various applications. Intraperitoneal administration in doses of 30 to 100 mg/kg decreased food intake dose-dependently, but drinking patterns and locomotor activity were not significantly affected. Administration of 2-furanone intragastrically, and intra-third cerebroventricularly also dose-dependently reduced food intake. In other studies effect on feeding behavior of Rhesus monkey was tested. The cannula was implanted in the third ventricle of three adult male Rhesus monkeys. Various doses of 2-furanone were administered intracerebroventricularly on different days five minutes prior to presentation of food. The effective dose for inducing significant satiety effect was 20.0 mg, while 10.6 mg induced a mild and 25.0 mg a severe effect. This study is suggestive of the presence of 2-furanone satiety mechanism in monkeys and rats. The intraperitoneal injection of 2-furanone (5 mg/kg) facilitated the spatial performance in mice. In addition, 2-furanone also suppresses the clinical symptoms of experimental allergic encephalomyelitis in Lewis rats [induced by immunization with a myelin basic protein (MBP)], a model for human multiple sclerosis. After immunization with MBP, the delayed-type hypersensitivity response to MBP is also reduced in 2-furanone-treated rats. These results indicate that 2-furanone is not only a powerful satiety substance, but also effective as a memory facilitation and a modulator of immune functions.

2-Deoxy-D-glucose (2-DG) administered intraperitoneally, dose-dependently increased the secretion of gastric acid, and the changes were comparable with those on the activity of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) in the stomach. Double-reciprocal plot analysis of the increased activity of CAT and AChE, induced by 2-DG, showed that the changes were due to the increase of Vmax, with no change in the Km-value for the substrates. The uptake of [(3)H]choline and subsequent synthesis of [(3)H]ACh was observed in the forestomach, corpus and antrum of the stomach and in the duodenum. 2-Deoxy-D-glucose significantly increased the uptake of [(3)H]choline and synthesis of [(3)H]ACh in every region of the stomach and in the duodenum, in a dose-dependent manner. The increase of secretion of gastric acid, induced by 2-DG paralleled that of uptake of [(3)H]choline and synthesis of [(3)H]ACh at an early stage. The conversion of [(3)H]choline taken up to [(3)H]ACh was negligibly influenced by 2-DG. Neither the content of ACh and choline, nor the turnover rate of ACh, were changed by administration of 2-DG. 2-Buten-4-olide (2-B4O), which inhibits the activity of the vagus nerve through the central nervous system, prevented 2-DG-induced uptake of [(3)H]choline and subsequent synthesis of [(3)H]ACh, as well as the increase in secretion of gastric acid. These results suggest that the uptake of [(3)H]choline and subsequent synthesis of [(3)H]ACh are closely related to the neuronal activity of the vagus nerve, and that cholinergic neuronal activity is dependent upon quantitative changes of metabolism of ACh in the gastroduodenum.

/PLANTS/ Exposure of seeds to aerosol smoke or crude smoke extracts stimulates the germination of a number of fire-dependent and fire-independent plant species. /The authors/ now report the identity of a germination-promoting compound present in plant- and cellulose-derived smoke. The structure of this compound, deduced from spectroscopic analysis and confirmed by synthesis, was shown to be that of the butenolide 3-methyl-2H-furo[2,3-c]pyran-2-one (1). Here /the authors/ show that 1 promotes germination of a number of plant species at a level similar to that observed with plant-derived smoke water. /Butenolides/

2(5H)-Furanone's production and use as an appetite depressant(1) 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 6(SRC), determined from a structure estimation method(2), indicates that 2(5H)-furanone is expected to have very high mobility in soil(SRC). Volatilization of 2(5H)-furanone from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.7X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 2(5H)-Furanone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.98 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 6(SRC), determined from a structure estimation method(2), indicates that 2(5H)-furanone is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 9.7X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 3.6 and 29 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of -0.6(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 2(5H)-Furanone is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2(5H)-furanone, which has an estimated vapor pressure of 0.98 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 2(5H)-furanone 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 29 hours(SRC), calculated from its rate constant of 1.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 2(5H)-Furanone also degrades in the atmosphere by reaction with ozone(SRC); the half-life for this reaction is estimated to be 13 hours(SRC), calculated from its reported rate constant of 2.2X10-17 cu cm/molecule-sec(4). 2(5H)-Furanone contains chromophores that absorb at wavelengths >290 nm(5) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of 2(5H)-furanone with photochemically-produced hydroxyl radicals has been estimated as 1.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 29 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of 2(5H)-furanone with ozone has been reported as 2.2X10-17 cu cm/molecule-sec at 25 °C(2). This corresponds to an atmospheric half-life of about 13 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(3). 2(5H)-Furanone may undergo hydrolysis in the environment based on very slow hydrolysis of butyrolactone, a similar 5-member cyclic structure(4). 2(5H)-Furanone contains chromophores that absorb at wavelengths >290 nm(5) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for 2(5H)-furanone(SRC), using a log Kow of -0.6(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 2(5H)-furanone can be estimated to be 6(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2(5H)-furanone is expected to have very high mobility in soil.

The Henry's Law constant for 2(5H)-furanone is estimated as 9.7X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 2(5H)-furanone is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 3.6 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 29 days(SRC). 2(5H)-Furanone's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 2(5H)-Furanone is not expected to volatilize from dry soil surfaces(SRC) based upon a an estimated vapor pressure of 0.98 mm Hg(SRC), determined from a fragment constant method(3).

2(5H)-Furanone was detected as a volatile component of roasted filberts(1).

Occupational exposure to 2(5H)-furanone may occur through inhalation and dermal contact with this compound at workplaces where 2(5H)-furanone is produced or used. Use data indicate exposure via medical administration of this compound as an appetite depressant or immuno suppressant. Limited monitoring data indicate that the general population may be exposed to 2(5H)-furanone via ingestion of some foods. (SRC)

Appetite Depressant, Immunosuppressive Agent|EXPL THER 2-Buten-4-olide (2-B4O) is an endogenous substance which suppresses appetite and/or food intake. /The authors/ studied its effect on type II collagen-induced arthritis (CIA) in Lewis rats, an animal model for human rheumatoid arthritis. Bovine type II collagen with incomplete Freund's adjuvant was injected intradermally into Lewis rats to induce CIA. 2-B4O (50 or 100 mg/kg) significantly inhibited the expression of the clinical symptoms when administered i.p. daily from day 1 to 21 after immunization. Furthermore, administration of 2-B4O daily from day 15 to 21 significantly reduced the severity of symptoms in established CIA. In addition, the progression of soft tissue swelling and articular bone erosions were suppressed by daily administration of 2-B4O. 2-B4O also significantly suppressed the delayed-type hypersensitivity (DTH) response to type II collagen at doses of 50 and 100 mg/kg. Finally 2-B4O significantly inhibited the formation of anti-type II collagen antibody at a dose of 100 mg/kg, but not at 50 mg/kg. These results suggest that 2-B4O has the strong inhibitory effects and therapeutic usefulness effects on CIA through the suppression of immune responses to type II collagen.|EXPL THER Starvation is well known to induce immune suppression. Moreover, the concentration of 2-B4O, an endogenous sugar acid, is elevated in the circulation during starvation. To determine if these events are related, the influence of 2-B4O on experimental allergic encephalomyelitis (EAE) in Lewis rats, a model of human multiple sclerosis (MS), was studied. EAE, characterized by paralysis of hind legs, was induced by immunization with residues 68 to 84 (MB 68-84) of the guinea pig myelin basic protein (MBP) in complete adjuvant H37Ra. Interestingly, the daily administration of 2-B4O intraperitoneally from the day of MB 68-84 immunization (day 0) to day 20 dramatically suppressed the clinical severity of EAE. The daily administration of 2-B4O intraperitoneally from day 0 to day 7 also markedly reduced the clinical symptoms of EAE. In fact, passively induced EAE, using Con A activated spleen cells from rats immunized with MB 68-84 in H37Ra, was also inhibited by daily administration of 2-B4O. Histological examination confirmed clinical findings and revealed that mononuclear cell infiltration into the central nervous system was significantly inhibited by 2-B4O. To clarify the mechanism(s) responsible for suppression of EAE, the effects of 2-B4O on the immune responses to MB 68-84 were examined. When rats were treated daily with 2-B4O for 15 days after immunization with MB 68-84 in H37Ra, the delayed-type hypersensitivity (DTH) response to MB 68-84 was significantly reduced in 2-B4O treated rats as compared with saline treated rats. The proliferative response to MB 68-84 of spleen cells from 2-B4O treated rats was also significantly lower than that of saline treated rats. /This/ data demonstrate that 2-B4O has the potential to suppress autoimmune responses in both inductive and effector phases. 2-B4O may have significant potential to treat autoimmune diseases|EXPL THER Evidence suggests that endogenous sugar acids 3,4-dihydroxybutanoic acid (2-deoxytetronic acid, 2-DTA) and 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA) may participate in the regulation of feeding. To study the effect of 2-buten-4-olide, a 2-DTA synthetic derivative, on food intake, male Wistar rats were subjected to various applications. Intraperitoneal administration of 2-buten-4-olide in doses of 30 to 100 mg/kg, decreased food intake dose-dependently by reducing meal frequency, meal size and eating rate, and prolonging meal duration, latency to eat the first meal after injection and post-prandial intermeal intervals. Drinking patterns and locomotor activity were not significantly affected. Administration of 2-buten-4-olide intragastrically in doses of 50 to 300 mg/kg, and intra-third cerebroventricularly in doses of 1.2 to 5.0 mumol/rat, dose-dependently reduced food intake. This and previous evidence suggest that: 2-DTA and its derivatives that share its bioactive components suppress food intake in the rat; They might represent a new category of potential therapeutic agents for hyperphagia and obesity.|EXPL THER The involvement of a feeding-related endogenous sugar acid, 2-buten-4-olide (2-B40) on central regulation of gastric acid secretion and its antiulcer effects on several gastric and duodenal experimental ulcer models were investigated in rats. Spontaneous gastric acid secretion was not affected by 2-B40 at doses below 10 mg/kg. The peripheral secretagogue-stimulated gastric secretions were significantly increased by pretreatment with 2-B40. Gastric acid secretion induced by 2-deoxy-D-glucose (2-DG) was significantly suppressed by pretreatment with 2-B40 at doses between 0.1 and 100 mg/kg. Gastric and duodenal ulcerations induced by cold stress plus indomethacin, restraint and water immersion stress, pylorus ligation on cysteamine were also inhibited by pretreatment with 2-B40. The results suggest that antiulcer effects of 2-B40 are due to suppression of gastric acid secretion via reduction of activity of the vagus nerve and gastric-related hypothalamic neurons. Thus, 2-B40 may be useful for treatment of gastroduodenal ulcer.

Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. (See all compounds classified as Immunosuppressive Agents.)|Agents that are used to suppress appetite. (See all compounds classified as Appetite Depressants.)

/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/

/GENOTOXICITY/ The alpha, beta-unsaturated lactones 2-furanone and 2-pyrone are part of the chemical structure of a variety of naturally occurring compounds (e.g., cardenolides, bufadienolides, acetogenins, coumarins, and food-flavoring furanones), some of which have shown anticancer activity and/or DNA damaging effects. Here /investigators/ report that 2-furanone and 2-pyrone induce cellular DNA damage (assessed by the comet assay and the gamma-H2AX focus assay) and the formation of topoisomerase I- and topoisomerase II-DNA complexes in cells (visualized and quantified in situ by the TARDIS assay). Cells mutated in BRCA2 (deficient in homologous recombination repair) were significantly hypersensitive to the cytotoxic activity of 2-pyrone, therefore suggesting that BRCA2 plays an important role in the repair of DNA damage induced by this lactone. Both lactones were cytotoxic in A549 lung cancer cells at lower concentrations than in MRC5 non-malignant lung fibroblasts. The possible involvement of 2-furanone and 2-pyrone in the anticancer and DNA-damaging activities of compounds containing these lactones is discussed

2-B4O

Smoke plays an intriguing role in promoting the germination of seeds of many species following a fire. Recently, a bicyclic compound containing a condensed butenolide moiety, 3-methyl-2H-furo[2,3-c]pyran-2-one, was reported as a potent germination promoter from plant-derived smoke. In this study, a related butenolide, 3,4,5-trimethylfuran-2(5H)-one (2), which inhibits germination and significantly reduces the effect of 3-methyl-2H-furo[2,3-c]pyran-2-one when applied simultaneously, was also isolated from plant-derived smoke. The interaction of these compounds with opposing actions on seed germination may have important ecological implications in a post-fire environment and could be useful molecules for understanding the events involved in breaking seed dormancy and promoting seed germination. /Butenolide moiety/

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