2(5H)-Furanone

log Kow = -0.60

-0.60

-0.6

1.185 mg/L at 25 °C

1.183-1.187

Soluble in water

Soluble (in ethanol)

BP: 86-87 °C at 12 mm Hg

86.00 to 87.00 °C. @ 12.00 mm Hg

52-53 °C

4-5 °C

4.5 °C

Index of refraction: 1.469 at 20 °C/D

1.466-1.472

Liquid

Colourless to pale brown yellow clear liquid; Rich winey meat-like aroma

Warning

H302 (96.8%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 1476 reports by companies from 9 notifications to the ECHA C&L Inventory.

Warning

H315: Causes skin irritation [Warning Skin corrosion/irritation]

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

2(5H)-Furanone: Does not have an individual approval but may be used under an appropriate group standard

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.

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 °C. Light sensitive. Store under inert gas.

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.

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.

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.

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).

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.

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).

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.

/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/

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.

/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

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).

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).

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The effects of 2-buten-4-olide, an endogenous feeding suppressant, on the estrous cycle and LH secretion were studied to determine the influence of this compound on reproductive function. Estrous cycling female Wistar rats were treated ip with 2-buten-4-olide (0, 30 or 100 mg/kg/day) for 2 weeks. Treatment with 100 mg/kg/day delayed the estrous cycle. 2-Buten-4-olide increased the pituitary content of LH (1651.3 +/- 164.4 vs 927.7 +/- 65.1 ng/pituitary; p< 0.01), and decreased the serum LH level compared with the control level in diestrus (0.16 +/- 0.01 vs 0.26 +/- 0.03 ug/L; p < 0.05). However, it did not affect the GnRH content of the mediobasal hypothalamus. The direct effects of 2-buten-4-olide on the pituitary response to GnRH was examined by perifusing the pituitary. Medium containing 2-buten-4-olide (10(-4) mol/L) suppressed the pituitary response to GnRH (2 ug/L) (percent increase at 50 min after start of GnRH stimulation: 180 +/- 47 vs 406 +/- 66%; p < 0.05). These findings suggest that 2-buten-4-olide is involved in the regulation of pituitary gonadotropin secretion directly by suppressing the pituitary responsiveness to GnRH, and that 2-buten-4-olide may play an important role in starvation-induced anestrus.

/LABORATORY ANIMALS: Neurotoxicity/ An endogenous sugar acid, 2-buten-4-olide (2-B4O) has been reported to act as a potent suppressant of food intake in the central nervous system, and to activate serotonergic system in the brainstem. In the present study, involvement of serotonergic neurons in feeding suppression by 2-B4O was assessed. Adult male Wistar rats were injected intraperitoneally with 100 mg 2-B4O/kg 2 hr before transcardiac perfusion with phosphate-buffered 4% paraformaldehyde. Vibratome sections were prepared, and immunostained for Fos and/or a serotonin synthesizing enzyme, tryptophan hydroxylase (TpOH). Administration of 2-B4O induced Fos expression in specific regions of the brainstem, the ventrolateral medulla, nucleus of the solitary tract, lateral parabrachial nucleus, locus coeruleus and dorsal (DR) and median raphe nuclei (MnR). Double immunostaining for Fos and TpOH showed that subsets of TpOH-positive neurons express Fos-immunoreactivity in the DR and MnR. These results suggest that neurons in the above regions are influenced by endogenous 2-B4O under the anorexic condition, and that serotonergic neurons may mediate central actions of 2-B4O on the hypothalamic regulatory system for feeding.

/DEVELOPMENTAL NEUROTOXICITY/ The factors that control the satiety behavior and consequently the milk intake in neonates are complex. Mechanical stimulus of gastric filling and emptying are understood to be critical players, though not exclusive. Recently, sugar acid namely, 2-Buten-4-Olide (2-B4O) has been suggested as an endogenous satiety substance in studies conducted on adult rats and monkeys. However, the role of 2-B4O in neonate and suckling rat pups is not well elucidated and this study investigates the same. 2-B4O (50, 75 mg/kg, ip) was injected in rat pups on post-natal days (0-2, 4-6 and 12-14) and the mean difference in body weight at 0.5, 1.2 and 24 hr following treatment was recorded. A dose dependent effect on body weight that correlated with the age of the pups was recorded. In another set of experiment, 2-B4O was micro-infused bilaterally into lateral hypothalamus of 12-14 days old pups (1 uL of 10 ug/uL). Within 30min of microinfusion, 2-B4O initiated a significant reduction of body weight that lasted up to 24hr following treatment. The results of the present study implicate a critical role of 2-B4O as an endogenous feeding suppressant even in neonate and suckling rat pups.

/BEHAVIORAL STUDIES/ Rats were trained to discriminate cue tone stimuli (CTS) predicting reward (CTS+) [juice or intracranial self-stimulation (ICSS)], or aversion (CTS-) (mild electric shock or tail pinch). Unit activity in the lateal hypothalamus (LHA) and lateral preoptic-anterior hypothalamic area (lPOA-AHA) of the rat was recorded during CTS learning. The effects of local anesthesia of the amygdala (AM), ventral tegmental area (VTA) or LHA by procaine hydrochloride, and the effects of intraperitoneal or intravenous 2-buten-4-olide (2-B4O) on LHA neural activity and licking behavior were compared. LHA neurons differentiated between rewarding and aversive stimuli, and acquired corresponding discrimination of CTS+ and CTS-. In the lPOA-AHA, neurons responded similarly to CTS+, rewarding stimuli, CTS- and aversive stimuli. Procainization of the AM suppressed LHA neural responses to CTS1+ predicting juice, and stopped licking for juice. Procainization of the VTA suppressed LHA neural responses to CTS2+ predicting ICSS, and stopped licking for ICSS. LHA procainization suppressed both licking for juice and ICSS. Both intraperitoneal and intravenous 2-B4O stopped licking for juice and ICSS, but did not influence LHA responses to CTS1+ or CTS2+. The results suggest that dynamic interaction of AM-LHA-VTA are important for CTS+ learning, and 2-B4O acts directly on LHA neurons while maintaining afferent sensory inputs to the LHA.

For more Non-Human Toxicity Excerpts (Complete) data for 2(5H)-Furanone (16 total), please visit the HSDB record page.

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).

The sugar acids, 3,4-dihydroxybutanoic acid gamma-lactone, 2-buten-4-olide and 2,4,5-trihydroxy pentanoic acid gamma-lactone which were found in blood modulate feeding behavior of rats by modifying neuronal activity in the lateral hypothalamic area [LHA] and the ventromedial hypothalamic nucleus [VMH]. The former two act as satiety substances and the latter as a hunger substance. Detection of changes in the concentration of these sugar acids in the blood by glucoreceptor neurons in the VMH and glucose-sensitive neurons in the LHA is important in the regulation of feeding. A phasic increase in fibroblast growth factor [FGF] was found in the cerebrospinal fluid after feeding. Cerebroventricular application of acidic FGF suppresses food intake. Interleukin-1 beta and tumor necrosis factor which have a quite similar amino acid sequence as FGF also suppress feeding. The neuronal mechanism of satiety action of these polypeptides is the same as the sugar acids. The results indicate that these endogenous substances participate in the central regulation of feeding. Hierarchial organization of the endogenous chemical information processing system which is composed of the viscera, medulla, hypothalamus and the cortex is discussed.

Appetite Depressant, Immunosuppressive Agent

MEDICATION

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

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/