Diethyl malonate

160.17

160.17

774687

203-305-9

53A58PA183

8864

1993

DTXSID7021863

Colorless liquid|Clear, colorless liquid

29171910

52.6

1

Liquid

1.04460 g/cm³ @ Temp: 30 °C

-50 °C

200 °C

212 °F

n 20/D 1.413(lit.)

Miscible with ethyl alcohol, ether, chloroform and benzene. Slightly miscible with water.

Store below +30°C.

1 mm Hg ( 40 °C)

5.52 (vs air)

LD50 orally in Rabbit: 15720 mg/kg LD50 dermal Rabbit > 16000 mg/kg

0.8-12.8%(V)

Sweet ester odor

Sweet and fruity taste with apple and pineapple nuances

Henry's Law constant = 2.0X10-6 atm-cu m/mole at 25 °C (estimated from vapor pressure and water solubility)|Hydroxyl radical reaction rate constant = 3.4X10-12 cu-cm/molc sec at 25 °C (est)

64.7 kJ/mol

Critical temperature: 653 K (estimated); Critical pressure: 2780 kPa (estimated)

1993

1

36/37/38-36

24/25-26

OO0700000

Xi

Separated from strong oxidants. Ventilation along the floor. Store in an area without drain or sewer access.

Irritant

Stable. Combustible. Incompatible with strong oxidizing agents,

P210, P264, P273, P280, P305+P351+P338, P337+P313, P370+P378, P403+P235, P501

H227

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: This combustible material may be burned in a chemical incinerator equipped with an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Conditions to avoid: Heat, flames and sparks. Incompatible materials: Acids, Bases, Oxidizing agents, Reducing agents|can react with oxidizing materials.

Flammable - 2nd degree

|Warning|H319 (99.96%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P264, P280, P305+P351+P338, and P337+P313|Aggregated GHS information provided by 2462 companies from 14 notifications to the ECHA C&L Inventory.|H227: Combustible liquid [Warning Flammable liquids]|P210, P273, P280, P370+P378, P403+P235, and P501|P210, P264, P280, P305+P351+P338, P337+P313, P370+P378, P403+P235, 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).

Combustible liquid when exposed to heat or flame.

Water may be used to blanket fire.|To fight fire, use water to blanket fire, foam, CO2, dry chemical.|Extinguishing media: 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. Further information: Use water spray to cool unopened containers.

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. 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. Discharge into the environment must be avoided. 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. Keep in suitable, closed containers for disposal.

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.|Avoid inhalation of vapor or mist. Keep away from sources of ignition - No smoking. Take measures to prevent the build up of electrostatic charge.|ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. 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. Discharge into the environment must be avoided.|Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|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.

Eye irritation in rabbits: moderately irritating.|A skin irritant.

| 1 - Materials that, under emergency conditions, can cause significant irritation.| 2 - Materials that must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur. Materials would not under normal conditions form hazardous atmospheres with air, but under high ambient temperatures or under moderate heating could release vapor in sufficient quantities to produce hazardous atmospheres with air.| 0 - Materials that in themselves are normally stable, even under fire conditions.

IDENTIFICATION AND USE: Diethyl malonate is used in chemical synthesis. It is also used in food, beverages, and in fragrances. HUMAN STUDIES: A maximization test was reported in 23 volunteers. 4% of the test substance in petrolatum produced no sensitization reactions. Tested at 4% in petrolatum it produced no irritation after a 48-hr closed-patch test on human subjects. ANIMAL STUDIES: Diethyl malonate causes moderate irritation to rabbit's eyes and is non-irritating to rabbit's skin. Application of 0.005 mL of undiluted diethyl malonate to the rabbit cornea caused severe burning. Diethyl malonate fed to rats for 90 days at more than 100 times the equivalent of the human daily dietary intake (averaging 35.93 mg/kg bw per day for males and 41.14 mg/kg bw per day for females) had no adverse effects. The maximum time for inhalation of the concentrated vapor of diethyl malonate by rats without deaths was found to be 8 hr. Mutagenicity test in Salmonella typhimurium TA98, TA 100, TA 1535, TA 1537, TA 1538 was negative with and without activation at concentrations of 8, 40, 200, 1000, 5000 ug/plate 5000 ug/plate (maximal concentration).

Because it inhibits dehydrochlorinase activity, diethyl malonate (10-40 ppm) increased the toxicity of DDT (2 ppm) to DDT-resistant mosquitoes Culex fatinans.

LD50 Rat oral 15 g/kg|LD50 Rat oral 15,794 mg/kg bw|LD50 Mice oral 6400 mg/kg|LD50 Rabbits dermal > 5 g/kg|LD50 Guinea pigs dermal > 10 mL/kg

Diethyl malonate is reportedly found in pineapple, bilberry, Cape gooseberrys, grapes and strawberries(1). Diethyl malonate is present in guava fruit, melon, concord grape, pineapple, and blackberry(2). The related diester (dimethyl malonate) occurs in pineapple, bananas and blackberries(3).

Diethyl malonate's production and use as a chemical intermediate for the production of agrochemicals, pharmaceuticals (barbiturates) and other compounds(1,2) and as a food and fragrance additive(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that diethyl malonate is expected to have very high mobility in soil(SRC). Volatilization of diethyl malonate from moist soil surfaces may occur(SRC) given an estimated Henry's Law constant of 2.0X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.19 mm Hg(3), and water solubility, 2.0X10+4 mg/L(4). In chemical stimulant studies simulating chemical warfare agents, diethyl malonate deposited to dry soil and foliar surfaces was rapidly lost through volatilization processes with observed half-lives on soil of about 2 hours (fast) to 5-16 hours (residual material)(4); foliar half-lives ranged from 1 to 242 hours(5). Two screening studies found diethyl malonate to be readily biodegradable(6,7). An 86% of theoretical BOD in two weeks using activated sludge in the Japanese MITI test(6) suggests that biodegradation is an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that diethyl malonate 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 2.0X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.19 mm Hg(4), and water solubility, 2.0X10+4 mg/L(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 23 and 173 days, respectively(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of 0.96(7) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Two screening studies found diethyl malonate to be readily biodegradable(8,9). An 86% of theoretical BOD in two weeks using activated sludge in the Japanese MITI test(8) suggests that biodegradation is an important environmental fate process in water(SRC). Diethyl malonate hydrolyzes readily in neutral and alkaline water, but slowly in acidic water(10). Respective hydrolysis half-lives at pH 4, pH7 and pH 9 are <10% after 5 days (50 °C), 137.5 hr (25 °C) and <2.4 hr (50 °C)(10).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diethyl malonate, which has a vapor pressure of 0.19 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase diethyl malonate 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 3.1 days(SRC), calculated from its rate constant of 3.4X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Diethyl malonate contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of diethyl malonate with photochemically-produced hydroxyl radicals has been estimated as 3.4X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3.1 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The hydrolysis of diethyl malonate was studied using OECD Guideline 111(2). At pH 4 and 50 °C), hydrolysis was <10% after 5 days; at pH 7, the hydrolysis half-life was 15.9 and 137.5 hr at 50 and 25 °C respectively; at pH 9, the half-life was <2.4 hr at 50 °C(2). It was noted that the hydrolysis initially yielded the monoester followed by hydrolysis to malonic acid(2). Diethyl malonate contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). The rate constant for the OH radical reaction of diethyl malonate with hydroxyl radicals in aqueous solutions at pH 6-7 is 6.5X10+8 L/mol-sec(4); this corresponds to an aquatic half-life of 3.38 years at an aquatic concentration of 1X10-17 hydroxyl radicals per liter(5).

An estimated BCF of 3 was calculated in fish for diethyl malonate(SRC), using a log Kow of 0.96(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 diethyl malonate can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that diethyl malonate is expected to have very high mobility in soil(SRC).

The Henry's Law constant for diethyl malonate is estimated as 2.0X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 0.19 mm Hg(1), and water solubility, 2.0X10+4 mg/L(2). This Henry's Law constant indicates that diethyl malonate is expected to volatilize from water surfaces(3). 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)(3) is estimated as 23 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)(3) is estimated as 173 days(SRC). Diethyl malonate's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). In chemical stimulant studies simulating chemical warfare agents, diethyl malonate deposited to dry soil and foliar surfaces is rapidly lost through volatilization processes with observed half-lives on soil of about 2 hours (fast) to 5-16 hours (residual material)(4); foliar half-lives ranged from 1 to 242 hours(4).

DRINKING WATER: Diethyl malonate has been detected in US drinking water at a reported maximum concentration of 0.01 ug/L(1).

Diethyl malonate is reported found in pineapple, bilberry, Cape gooseberry, cognac, malt whiskey, apple brandy, grape brandy port cider, sherry, and red wine, white and strawberry wines. It is used as a flavor additive in alcoholic beverages, baked goods, frozen dairy, gelatins, puddings, hard candy, non-alcoholic beverages and soft candy(1).

According to the 2016 TSCA Inventory Update Reporting data, 9 reporting facilities estimate the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of diethyl malonate in the United States may be as low as <10 workers and as high as 25-50; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).|Occupational exposure to diethyl malonate may occur through inhalation and dermal contact with this compound at workplaces where diethyl malonate is produced or used. Monitoring data indicate that the general population may be exposed to diethyl malonate via inhalation of volatile aromas from fruits, ingestion of food, and dermal contact with consumer products containing diethyl malonate. (SRC)

A shower decontamination bench model has been used to assess quantitatively the importance of several variables (water pressure and temperature, surfactant concentration in the decontamination fluid, nozzle type, and shower time) on decontamination of nontoxic chemical warfare-agent simulants diethyl malonate and thickened diethyl malonate from pig skin in vitro. Diethyl malonate was validated as a simulant for 1,2,2-trimethylpropyl methylphosphonofluoridate (soman) by comparison of the skin penetration and decontamination of radiolabeled diethyl malonate to the radiolabeled phosphonofluoridate in shower decontamination trials of pig skin in vitro. Percutaneous penetration of diethyl malonate was significantly greater than that of the phosphonofluoridate during the 15-min period after application. However, both were less than 0.1% of the applied dose. Showering or thickener had no significant effect on the percutaneous penetration of diethyl malonate or the phosphonofluoridate. Most of the phosphonofluoridate removed by showering or scrubbing the skin was inactivated. The quantity of intact 1,2,2-trimethylpropyl methylphosphonofluoridate that penetrated through the skin was below the detection limit of the enzymatic analysis. There was no statistically significant difference between the phosphonofluoridate and diethyl malonate in efficacy of shower decontamination. The presence of thickener did not have a significant effect on decontamination efficacy.|The in vitro distribution and fate of [(14)C]diethyl malonate and [(14)C]diisopropyl fluorophosphate were evaluated on normal and heat-treated pig skin. The extent of hydrolysis from the skin surface, skin, and receptor fluid was determined. A significant skin-mediated hydrolysis (15-35% of applied dose) was observed for diethyl malonate in normal skin, but not in heat-treated skin. These results indicated that a heat labile process (e.g., enzymatic hydrolysis) was in part responsible for the degradation of diethyl malonate after topical application to normal skin. Heat treatment tripled the skin penetration of diisopropyl fluorophosphate and reduced the amount of recovered hydrolysis product, diisopropyl phosphoric acid. Enzymatic and spontaneous hydrolysis, as well as impurity, accounted for the presence of degradation product.

Hydrolysis of diethyl malonate would produce ethanol and malonic acid, which is a relatively strong acid and acts as an inhibitor of enzymes, including succinic dehydrogenase.|Diethyl malonate was hydrolyzed by adipose-tisue lipase and to the monoester by alpha-chymotrypsin.

In some cases, the use of conventional GC/FTIR technique is limited due to its lower detectability to micro-components in organic mixtues in comparison to GC/MS. In this paper, an integration of LG/GC using retention gap technique with partially concurrent solvent evaporation, as a efficient chromatographic system for sample preconcentration and preseparation, was coupled into FTIR system in order to overcome the detectability problems of GC/FTIR analysis. The applicability of the on-line LG-GC/FTIR method is demonstrated by analysis of the isomers of divinylbenzene in purified diethyl malonate under conditions of hexane/dichloromethane (85:15) used as mobile phase in LC, solvent evaporation temperature of 75 degrees C and inlet pressure of 0.20MPa etc.

/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. /Organic acids and related compounds/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist respirations if necessary. 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 ... . 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. Activated charcoal is not effective ... . Do not attempt to neutralize, because of exothermic reaction. Cover skin burns with dry, sterile dressings after decontamination ... . /Organic acids and related compounds/|/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. Early intubation, at the first sign of upper airway obstruction, may be necessary. 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 (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organic acids and related compounds/

/HUMAN EXPOSURE STUDIES/ Tested at 4% in petrolatum it produced no irritation after a 48-hr closed-patch test on human subjects.|/HUMAN EXPOSURE STUDIES/ A maximization test was reported in 23 volunteers. 4% of the test substance in petrolatum produced no sensitization reactions.

diethyl malonate

Construction|Propanedioic acid, 1,3-diethyl ester: ACTIVE|Diethyl malonate is diethyl ester of malonic acid. Acylation of diethyl malonate using magnesium chloride and triethylamine is reported. K2CO3-catalyzed 1,4-addition reaction of diethyl malonate with various substituted 1,2-allenic ketones yields polyfunctionalized beta,gamma-unsaturated enones.

In some cases, the use of conventional GC/FTIR technique is limited due to its lower detectability to micro-components in organic mixtues in comparison to GC/MS. In this paper, an integration of LG/GC using retention gap technique with partially concurrent solvent evaporation, as a efficient chromatographic system for sample preconcentration and preseparation, was coupled into FTIR system in order to overcome the detectability problems of GC/FTIR analysis. The applicability of the on-line LG-GC/FTIR method is demonstrated by analysis of the isomers of divinylbenzene in purified diethyl malonate under conditions of hexane/dichloromethane (85:15) used as mobile phase in LC, solvent evaporation temperature of 75 degrees C and inlet pressure of 0.20 MPa etc.

EPA Safer Chemical Functional Use Classes -> Fragrances|Safer Chemical Classes -> Green circle - The chemical has been verified to be of low concern|Food additives -> Flavoring Agents|Flavoring Agents -> JECFA Flavorings Index|Fire Hazards -> Flammable - 2nd degree

Flavoring Agents