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Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Metabolite of Sodium oxybate

Cosmetic ingredients (Succinic Acid) -> CIR (Cosmetic Ingredient Review)

Buffering

log Kow = -0.59

-0.59

-0.61

Very acid taste

TART TASTE; PURE AQ SOLN ARE SLIGHTLY BITTER & TASTE BUILD UP IS SLOW

1.572 at 68 °F (NTP, 1992) - Denser than water; will sink

1.572 @ 25 °C/4 °C

BULK DENSITY: 55 LB/CU FT; NONHYGROSCOPIC

1.154 @ 15°C

This chemical does not meet GHS hazard criteria for 3.4% (78 of 2311) of reports.

Danger

H318 (82.6%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

P264+P265, P280, P305+P351+P338, P305+P354+P338, P317, and P337+P317 (click each P-code to see the statement)

Aggregated GHS information provided per 2311 reports by companies from 28 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Butanedioic acid

Regulation (EC) No 1831/2003 (amended)

Butanedioic acid is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Butanedioic acid 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)

Status: Active Update: 25-04-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/15265

Butanedioic acid: Does not have an individual approval but may be used under an appropriate group standard

Maximum tolerated dose was 2-2.5% when given in drinking water to rats; Caused severe weight loss in the 10% group, and all the rats died within the first 4 weeks; Has anxiolytic activity when given orally to rats at 3-6 mg/kg; [HSDB] Causes somnolence in lethal-dose feeding studies; [RTECS] A skin, eye, mucous membrane, and upper respiratory tract irritant; [CAMEO] An irritant; [MSDSonline]

Substance added directly to human food affirmed as generally recognized as safe (GRAS).

Succinic acid used as a general purpose food additive in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.

Succinic acid is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.

SUCCINIC ACID reacts exothermically to neutralize bases, both organic and inorganic. Can react with active metals to form gaseous hydrogen and a metal salt. Such reactions are slow in the dry, but systems may absorb water from the air to allow corrosion of iron, steel, and aluminum parts and containers. Reacts slowly with cyanide salts to generate gaseous hydrogen cyanide. Reacts with solutions of cyanides to cause the release of gaseous hydrogen cyanide. May generate flammable and/or toxic gases and heat with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. May react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Can be oxidized exothermically by strong oxidizing agents and reduced by strong reducing agents. May initiate polymerization reactions.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Succinic acid is produced, as an intermediate or a final product, by process units covered under this subpart.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure 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, aquatic, and plant life; and conformance with environmental and public health regulations.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Incineration: Succinic acid should be combined with paper or other flammable material. An alternate procedure is to dissolve it in a flammable solvent and spray the solutions into the fire chamber.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit 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.

4.0 [mg/m3]

75 [mg/m3]

450 [mg/m3]

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

At acute doses or exposures succinic acid is a skin irritant. Chronically high doses of succinate can lead to succinylation or succination of a variety of enzymes. Partial succinate dehydrogenase deficiency (15% to 50% of normal reference enzyme activity) in skeletal muscle leads to elevated succinate levels and causes mitochondrial myopathy with various symptoms, for example, brain involvement, cardiomyopathy, and/or exercise intolerance.

EC50 Daphnia magna (first instar; immobilization) 374.2 mg/L/48 hr (95% confidence limits: 350-400 mg/L); static, 22 °C, hardness: 154.5 mg/L as CaCO3, pH of 7.7, alkalinity of 137.7 mg/L as CaCO3, conductivity of 290.4 umohs/cm, Ca of 32.7 mg/L, Mg of 19.7 mg/L, Na of 2.4 mg/L, and K of 1.3 mg/L

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 11(SRC), determined from a log Kow of -0.59(2) and a regression-derived equation(3), indicates that succinic acid is expected to have very high mobility in soil(SRC). Volatilization of succinic acid from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.6X10-13 atm-cu m/mole(SRC), derived from its vapor pressure, 1.91X10-7 mm Hg(4), and water solubility, 8.32X10+4 mg/L(5). Succinic acid is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure of 1.91X10-7 mm Hg at 25 °C(4). The anion form, which is the dominant form in the environment (pKa 4.16 and 5.6), will also not volatilize(SRC). Succinic acid has been observed to biodegrade in soil at rates ranging from 52 to 89% in 7 days to 71 to 95% in 84 days at an initial concn of 1000 ppm(6), suggesting biodegration may be an important environmental fate process in soil.

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 11(SRC), determined from a log Kow of -0.59(2) and a regression-derived equation(3), indicates that succinic acid is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.6X10-13 atm-cu m/mole(SRC), derived from its vapor pressure, 1.91X10-7 mm Hg(4), and water solubility, 8.32X1+4 mg/L(5). One of the pKa values of succinic acid is 4.21(6), indicating that this compound will exist in the dissociated form in the environment and anions generally do not adsorb more strongly to suspended solids and sediment than their neutral counterparts(7), and will not volatilize. According to a classification scheme(8), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(9), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Succinic acid, present at 100 mg/L, reached 78% of its theoretical BOD in 14 days using an activated sludge inoculum at 30 mg/L and the Japanese MITI test(10), suggesting biodegradation may be an important environmental fate process in water.

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), succinic acid, which has a vapor pressure of 1.91X10-7 mm Hg at 25 °C(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase succinic acid 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 6 days(SRC), calculated from its rate constant of 2.8X10-12 cu cm/molecule-sec at 25 °C that was derived using a structure estimation method(3). Particulate-phase succinic acid may be removed from the air by wet and dry deposition(SRC).

Succinic acid was identified as a flavoring constituent of gari, 0.04% and farine, 0.002%(1). Aerosol emission rates of succinic acid from frying hamburger meat was 2.3 mg/kg of meat cooked; emission rates from charbroiling hamburger was 7.6 mg/kg of meat cooked for extra-lean hamburger (approx. 10.0% fat) and 12.0 mg/kg of meat cooked for regular hamburger (approx. 21% fat)(2).

Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org

Succinate can inhibit the activities of α-KG–dependent oxygenases (KDMs) and the TET family of 5-methlycytosine (5mC) hydroxylases. Succinate also mediates allosteric inhibition of hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs). Inhibition of HIF PHDs leads to activation of HIF-mediated pseudohypoxic response, whereas inhibition of KDMs and TET family of 5mC hydroxylases causes epigenetic alterations that ultimately cause cancer. Succination of KEAP1 in FH deficiency results in the constitutive activation of the antioxidant defense pathway mediated by NRF2, conferring a reductive milieu that promotes cell proliferation. Succination of the Krebs cycle enzyme Aco2 impairs aconitase activity in Fh1-deficient MEFs. Succination also causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

/AQUATIC SPECIES/ ...A series of insulated, round, stainless steel tubs were used for water baths. The water was obtained from Rochat Creek, and a chemical analysis of the water was made during summer when the stream flows were low. The pH of the water was 7.2, alkalinity was 7 ppm, and hardness was 0-17 ppm. The baths were served by a common refrigerated reservoir through which temperature-controlled water was recirculated. Each tub held 9.5 L plastic aquaria, and each aquarium was aerated by a single stone air-breaker and lined with a disposable polyethylene poultry bag. The bag was closed at the top to prevent fish from escaping. Fish were acclimatized at about the temperatures of the assay vessels. The acclimatizing period varied from 3-24 hours, but most fish were conditioned at least overnight. The test fish were starved during acclimatization and transferred to the assay vessel approximately 2 hours prior to addition of 10 ppm of test substance. Usually 1 squawfish and 1 each of 2 species of salmonid were placed together in 1 vessel in 4 L of water, the load being approximately 5 g of fish/L solution. /The fish used measured 5-10 cm./ Water temperature was taken several times during each test, with only the highest temperature recorded in a 24-hr test period reported. The times at which a fish lost its equilibrium and died were recorded. Equilibrium was defined as lost when a fish was no longer able to remain right-side-up, and death was designated when a fish ceased visible movement. ...In Ptychocheilus oregonensis (Northern squawfish), loss of equilibrium occurred in 4-8 hours at 10 ppm, but was regained by 17 hours. No deaths were reported. At 15 ppm neither loss of equilibrium nor death occurred. In Oncorhynchus tshawytscha and kisutch (Chinook salmon and Coho salmon, silver salmon), neither loss of equilibrium nor death occurred at 10 or 15 ppm.

Succinic acid has been identified as a component of pulp mill effluent(1). Trace amounts, less than 0.5 mg/l, of succinic acid were detected in industrial waste samples from the Hercules, Inc. plant site near Wilmington, NC(2). Succinic acid was identified in the acidic fraction of sewage and sludge from the Iona Island Sewage Treatment Plant, British Columbia(3). Succinic acid was detected in an automobile exhaust sample from a 1982 Toyota Corolla at a concn of 24.3 nmol/cu m and a diesel exhaust sample from a 1971 Mercedes Benz 220D at a concn of 65.7 nmol/cu m(4). Succinic acid emission rates from pine wood, oak wood, and synthetic logs burned were 0.89 mg/kg, 11.68 mg/kg, and not detected, respectively(5).

The Koc of succinic acid is estimated as 11(SRC), using a log Kow of -0.59(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that succinic acid is expected to have very high mobility in soil. One of the pKa values of succinic acid is 4.21(4), indicating that this compound will exist in anion form in the environment and anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts(5).

Substance added directly to human food affirmed as generally recognized as safe (GRAS).

Succinic acid used as a general purpose food additive in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.

Succinic acid is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Succinic acid is produced, as an intermediate or a final product, by process units covered under this subpart.

Succinate is an essential component of the Krebs or citric acid cycle and serves an electron donor in the production of fumaric acid and FADH2. It also has been shown to be a good "natural" antibiotic because of its relative acidic or caustic nature (high concentrations can even cause burns). Succinate supplements have been shown to help reduce the effects of hangovers by activating the degradation of acetaldehyde - a toxic byproduct of alcohol metabolism - into CO2 and H2O through aerobic metabolism. Succinic acid has been shown to stimulate neural system recovery and bolster the immune system. Claims have also been made that it boosts awareness, concentration and reflexes.

Succinic acid is a normal intermediary metabolite and a constituent of the citric acid cycle. It is readily metabolized when administered to animals, but may be partly excreted unchanged in the urine if large doses are fed.

Succinic acid can be converted into fumaric acid by oxidation via succinate dehydrogenase.

CIR ingredient: Succinic Acid

Found in fossils, fungi, and lichens; [Merck Index] Present in nearly all plant and animal tissues; Used to make lacquers, dyes, esters for perfumes, alkyd resins, pharmaceuticals, plasticizers, lubricants, and pesticides; Also used in photography, as a sequestrant in foods, a buffering and neutralizing agent, for radiation dosimetry, and to promote plant growth and increased yields in food crops; [HSDB]

Farming (Pesticides) [Category: Industry]

Organic synthesis, manufacture of lacquers, dyes esters for perfumes, photography, in foods as sequestrant, buffer, neutralizing agent

Flavoring agent /Disodium succinate/

Uses of succinic acid range from scientific applications such as radiation dosimetry and standard buffer solutions to applications in agriculture, food, medicine, plastics, cosmetics, textiles, plating, and waste-gas scrubbing

Hydrogenation of maleic acid, maleic anhydride, or fumaric acid produces good yields of succinic acid.

1,4-Butanediol can be oxidized to succinic acid in several ways: (1) with O2 in an aqueous solution of an alkaline-earth hydroxide at 90-110 °C in the presence of Pd-C; (2) by ozonolysis in aqueous acetic acid; or (3) by reaction with N2O4 at low temperature.

Succinic acid can ... be obtained by phase-transfer-catalyzed reaction of 2-haloacetates, electrolytic dimerization of bromoacetic acid or ester, oxidation of 3-cyanopropanal, and fermentation of n-alkanes.

Succinic acid is derived from fermentation of ammonium tartrate.

Food additives

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Cosmetics -> Buffering

Environmental transformation -> Pesticide transformation products (metabolite, successor)

Textiles, apparel, and leather manufacturing

Butanedioic acid: ACTIVE