2,3-Pentanedione

Yellow liquid

Yellow to yellow-green liquid

In water, 6.67X10+4 at 15 °C

Miscible with ethanol, diethyl ether, and acetone

66.7 mg/mL at 15 °C

insoluble in glycerol and water; miscible with alcohol, propylene glycol, fixed oils

1 ml in 3 ml 50% alcohol (in ethanol)

19 °C (66 °F) - open cup

66 °F

109.9 °C

108 °C

230-234 °F

Danger

H225 (98.6%): Highly Flammable liquid and vapor [Danger Flammable liquids]

P210, P233, P240, P241, P242, P243, P260, P261, P264+P265, P272, P280, P302+P352, P303+P361+P353, P305+P354+P338, P317, P319, P321, P333+P317, P362+P364, P370+P378, P403+P235, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 1656 reports by companies from 37 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H225: Highly Flammable liquid and vapor [Danger Flammable liquids]

Chemical: 2,3-Pentanedione

Regulation (EC) No 1831/2003 (amended)

2,3-Pentanedione is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 2,3-Pentanedione are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

REACH registered substance: Pentane-2,3-dione (EC: 209-984-8)

2,3-Pentanedione: Does not have an individual approval but may be used under an appropriate group standard

A moderate skin irritant; [RTECS] Safe when used as a flavoring agent in food; [JECFA] Due to structural similarities with diacetyl, there are concerns that occupational exposure may lead to a decline in pulmonary function; Airway epithelial damage demonstrated in rats is similar to that caused by diacetyl; [Reference #1] Danger of skin sensitization; [MAK] A skin and strong eye irritant; [Alfa Aesar MSDS] See Environmental characterization of a coffee processing workplace with obliterative bronchiolitis in former workers. [PMID 27105025] See Diacetyl. See 2,4-Pentanedione.

2,3-Pentanedione 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.

Flam. Liq. 2 (98.6%)

Flammable liquids - Category 2

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical, or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Use water spray to cool unopened containers.

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. Storage class (TRGS 510): Flammable liquids.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment, and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist, or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.

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: Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting as this material is highly flammable. 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.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment, and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist, or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapor or mist. Use explosion-proof equipment. Keep away from sources of ignition - No smoking. Take measures to prevent the build up of electrostatic charge.

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.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

<9.3 ppb [as an 8-hr TWA]

31 ppb [15 minutes]

Eye/face protection: Face shield and safety glasses. 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. Flame retardant antistatic protective 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).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that 2,3-pentanedione is expected to have very high mobility in soil(SRC). Volatilization of 2,3-pentanedione from moist soil surfaces may be an important fate process(SRC) given its Henry's Law constant estimated as 3.95X10-5 atm-cu m/mole(2) based upon its vapor pressure, 20 mm Hg(3), and water solubility, 6.67X10+4 mg/L(2). 2,3-Pentanedione is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 20 mm Hg at 20 °C(3). Biodegradation data in soil were not available(SRC, 2016). In a Warburg Repirometry test 2,3- pentanedione was toxic to the microogansims(4).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that 2,3-pentanedione is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces may be expected(3) based upon an estimated Henry's Law constant of 3.95X10-5 atm-cu m/mole(2), derived from its vapor pressure, 20 mm Hg(4), and water solubility, 6.67X10+4 mg/L(2). Using this Henry's Law constant and an estimation method(2), volatilization half-lives for a model river and model lake are 16 hours and 11 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of -0.85(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2016). In a Warburg Repirometry test 2,3-pentanedione was toxic to the microogansims(6).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2,3-pentanedione, which has a vapor pressure of 20 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 2,3-pentanedione 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 12 days(SRC), calculated from its rate constant of 1.33X10-12 cu cm/molecule-sec at 25 °C(3). 2,3-Pentanedione contains chromophores that absorb at wavelengths >290(4) and, therefore, is expected to be susceptible to direct photolysis by sunlight(SRC). The half-life for the direct photolysis of 2,3-pentanedione is 3 hours(5).

2,3-Pentanedione has been detected, not quantified in peach, wheat bread, cocoa, coffee, black tea, roasted filbert, roasted peanut, roasted almonds, pecans, soybean, malt, peated malt, chayote, peas, cooked potato, tomato, boiled egg, cooked chicken and fat, cooked beef and pork, beer, cognac, sweet corn, okra, mate and soursop(1). 2,3-Pentanedione has been identified, but not quantified, in pork liver(1), chicken, beef, and pork meat volatiles(2) and cooked beef(3).

2,3-Pentanedione has been reported as a coffee aroma constituent at concentrations ranging between 9.0 nmol - 0.9 mmol (1). 2,3-Pentanedione has been reported as a volatile compound of cooked sweet corn products with concentrations of 5 ppb in canned cream and canned kernel corn, and <2 ppb in frozen kernel and fresh kernel corn(2). 2,3-Pentanedione has been reported as a volatile compound of microwave popped corn kernels at concentrations ranging from 200 to 380 ug/kg(3). 2,3-Pentanedione has been reported as a volatile compound of commercial rice cakes at concentrations ranging from 91 to 250 ppb(4). 2,3-Pentanedione has been reported as an aroma constituent in raw and roasted earth almonds (Cyperus esculentus)(5). 2,3-Pentanedione was identified but not quantified in frankfurters(6).

IDENTIFICATION AND USE: 2,3-Pentanedione is a yellow liquid. It is used as flavoring agent (butter flavoring) including many e-cigarette brands. HUMAN EXPOSURE AND TOXICITY: Inhalation of butter flavoring by workers in the microwave popcorn industry may result in "popcorn workers' lung." Cultured human bronchial/tracheal epithelial cells (NHBEs) were exposed for 6 hours to diacetyl or 2,3-pentanedione vapors (25 or >/= 60 ppm) and the effects on short circuit current and transepithelial resistance (Rt) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na+ transport, without affecting Cl- transport or Na+,K+-pump activity. Concentrations (100-360 ppm) of diacetyl and 2,3-pentanedione reported to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 hours post-exposure. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro. ANIMAL STUDIES: Rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis. To investigate delayed toxicity, additional rats inhaled 318 (range, 317.9-318.9) ppm 2,3-pentanedione for 6 hours and were sacrificed 0 to 2, 12 to 14, or 18 to 20 hours after exposure. Respiratory epithelial injury in the upper nose involved both apoptosis and necrosis, which progressed through 12 to 14 hours after exposure. Olfactory neuroepithelial injury included loss of olfactory neurons that showed reduced expression of the 2,3-pentanedione-metabolizing enzyme, dicarbonyl/L-xylulose reductase, relative to sustentacular cells. Caspase 3 activation occasionally involved olfactory nerve bundles that synapse in the olfactory bulb (OB). An additional group of rats inhaling 270 ppm 2,3-pentanedione for 6 hours 41 minutes showed increased expression of IL-6 and nitric oxide synthase-2 and decreased expression of vascular endothelial growth factor A in the OB, striatum, hippocampus, and cerebellum using real-time PCR. Claudin-1 expression increased in the OB and striatum. In other experiment, male and female rats and mice were exposed to 0, 50, 100, or 200 ppm 2,3-pentanedione 6 hr/d, 5 d/wk for up to 2 weeks. Bronchoalveolar lavage fluid (BALF) was collected after 1, 3, 5, and 10 exposures, and histopathology was evaluated after 12 exposures. MCP-1, MCP-3, CRP, FGF-9, fibrinogen, and OSM were increased 2- to 9-fold in BALF of rats exposed for 5 and 10 days to 200 ppm. In mice, only fibrinogen was increased after 5 exposures to 200 ppm. The epithelium lining the respiratory tract was the site of toxicity in all mice and rats exposed to 200 ppm. Significantly, 2,3-pentanedione also caused both intraluminal and intramural fibrotic airway lesions in rats. In third experiment, rats exposed to 150 or 200 ppm 2,3-pentanedione developed bronchial fibrosis. In mice, 2,3-pentanedione was not a dermal irritant when tested at concentrations up to 50%. However, concentration-dependent increases in lymphocyte proliferation were observed following exposure to 2,3-pentanedione in mice.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 2,3-pentanedione can be estimated to be 1(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2,3-pentanedione is expected to have very high mobility in soil.

/ALTERNATIVE and IN VITRO TESTS/ Inhalation of butter flavoring by workers in the microwave popcorn industry may result in "popcorn workers' lung." In previous in vivo studies rats exposed for 6 hr to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance, we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity. We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 hr to diacetyl or 2,3-pentanedione vapors (25 or >/= 60 ppm) and the effects on short circuit current and transepithelial resistance (Rt) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na+ transport, without affecting Cl- transport or Na+,K+-pump activity. Rt was unaffected. Na+ transport recovered 18 hr after exposure. Concentrations (100-360 ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 hr (immediately) post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro.

/OTHER TOXICITY INFORMATION/ Over the last decade, concerns have been raised about potential respiratory health effects associated with occupational exposure to the flavoring additives diacetyl and 2,3-pentanedione. Both of these diketones are also natural components of many foods and beverages, including roasted coffee. To date, there are no published studies characterizing workplace exposures to these diketones during commercial roasting and grinding of unflavored coffee beans. In this study, we measured naturally occurring diacetyl, 2,3-pentanedione, and respirable dust at a facility that roasts and grinds coffee beans with no added flavoring agents. Sampling was conducted over the course of three roasting batches and three grinding batches at varying distances from a commercial roaster and grinder. The three batches consisted of lightly roasted soft beans, lightly roasted hard beans, and dark roasted hard beans. Roasting occurred for 37 to 41 min, and the grinding process took between 8 and 11 min. Diacetyl, 2,3-pentanedione, and respirable dust concentrations measured during roasting ranged from less than the limit of detection (<LOD) to 0.0039 ppm, <LOD to 0.018 ppm, and <LOD to 0.31 mg/cu m, respectively. During grinding, diacetyl, 2,3-pentanedione, and respirable dust concentrations ranged from 0.018 to 0.39 ppm, 0.0089 to 0.21 ppm, and <LOD to 1.7 mg/cu m, respectively. For any given bean/roast combination and sample location, diketone concentrations during grinding were higher than those measured during roasting. During grinding, concentrations decreased with increased distance from the source. Measured concentrations of both diketones were higher during grinding of soft beans than hard beans. The results indicate that airborne concentrations of naturally occurring diacetyl and 2,3-pentanedione associated with unflavored coffee processing: (1) are similar to the concentrations that have been measured in food flavoring facilities; (2) are likely to exceed some recommended short-term occupational exposure limits, but; (3) based on previous analyses of exposure response relationships in animal studies, are far below the concentrations that are expected to cause even minimal responses in the human respiratory tract.

/OTHER TOXICITY INFORMATION/ Diacetyl and 2,3-pentanedione inhalation have been suggested as causes of severe respiratory disease, including bronchiolitis obliterans, in food/flavoring manufacturing workers. Both compounds are present in many food items, tobacco, and other consumer products, but estimates of exposures associated with the use of these goods are scant. A study was conducted to characterize exposures to diacetyl and 2,3-pentanedione associated with cigarette smoking. The yields (ug/cigarette) of diacetyl and 2,3-pentanedione in mainstream (MS) cigarette smoke were evaluated for six tobacco products under three smoking regimens (ISO, Massachusetts Department of Public Health, and Health Canada Intense) using a standard smoking machine. Mean diacetyl concentrations in MS smoke ranged from 250 to 361 ppm for all tobacco products and smoking regimens, and mean cumulative exposures associated with 1 pack-year ranged from 1.1 to 1.9 ppm-years. Mean 2,3-pentanedione concentrations in MS smoke ranged from 32.2 to 50.1 ppm, and mean cumulative exposures associated with 1 pack-year ranged from 0.14 to 0.26 ppm-years. We found that diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/flavoring workers who smoke. This suggests that previous claims of a significant exposure-response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded, because none of the investigations considered or quantified the non-occupational diacetyl exposure from cigarette smoke, yet all of the cohorts evaluated had considerable smoking histories. Further, because smoking has not been shown to be a risk factor for bronchiolitis obliterans, our findings are inconsistent with claims that diacetyl and/or 2,3-pentanedione exposure are risk factors for this disease.

Identified in fatty fish, shrimp, oyster, and clam(1). 2,3-Pentanedione has been reported as a volatile component of anchovy (Engraulis japonica) paste and big eyed herring (Harengula zunasi) paste at mean concentrations of 669 and 1450 ng/g(2). 2,3-Pentanedione has been identified as a volatile compound of leg, body, and carspace meat of edible crabs (Charybdis feriatus) at concentrations of 27.7, 29.6, and 74.2 ug/kg (dry weight), respectively(3). 2,3-Pentanedione has been identified, but not quantified, as a volatile component of cooked mussels (Mytilus edulis)(4) and fish oil enriched by milk(5).

2,3-Pentanedione 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.

We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 hr to diacetyl or 2,3-pentanedione vapors (25 or >/= 60 ppm)... Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively.

Used as flavoring agent or adjuvant; [FDA] Used as a substitute for diacetyl in food flavoring and food production; [Reference #1]

Flavors of butterscotch and chocolate type

... used as aroma components in alcohol-free beverages and in baked goods.

2,3-Pentanedione and acetoin were detected in 23 and 46 of the 51 flavors /of e-cigarettes/ tested at concentrations up to 64 and 529 ug/e-cigarette, respectively.

Reported uses (ppm):

By oxidation of methyl propyl ketone with excess NaNO2 and diluted HCl in the presence of hydroxylamine hydrochloride under a nitrogen blanket.

Processes used include oxidation of the corresponding diols over a copper or silver catalyst, or selective oxidation of the methylene group in the corresponding methyl alkyl ketones with oxygen in the presence of catalysts such as nickel.

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes