Malic acid

134.09

134.09

1723539

210-514-9

25941

DTXSID0027640

Colorless crystals|White, crystalline triclinic crystals

29181980

94.8

-1.26

DryPowder; OtherSolid, Liquid

1.601 g/ cu cm at 20 deg C

131 °C

167.16°C (rough estimate)

203 °C

H2O: 558 g/L (20 ºC);methanol: 0.1 g/mL, clear, colorless

2-8°C

<0.1 mm Hg ( 20 °C)

4.6 (vs air)

LD50 orally in Rabbit: > 3200 mg/kg

Characteristic

Smoothly tart

pH of a 0.001% aqueous solution is 3.80, that of 0.1% solution is 2.80, and that of a 1.0% solution is 2.34

Henry's Law constant = 8.4X10-13 atm-cu m/mol at 25 °C (est)

Ionization constants: K1 = 4X10-4; K2 = 9X10-6|pKa1 = 3.51; pKa2 = 5.03 at 20 °C /OECD Guideline 112 (Dissociation Constants in Water)/

115.9 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

Nearly odorless (sometimes a faint, acrid odor) /L-Malic Acid/|Exhibits isomeric forms (dl, l, and d)|Density: 1.601 (d or l form); MP: 128 °C (d or l form); BP: 140 °C with decomposition (d or l form)|Crystals from acetone, or acetone + chloroform; mp 100 °C; Decomposes at about 140 °C; specific optical rotation: -2.3 deg (conc = 8.5 g 1100 ml water); Solubilities at 20 °C: 60.66 g/100 g acetone, 74.35 g/100 g dioxane, 36.35 g/100 g water, practically insoluble in benzene, 197.22 g/100 g methanol, 2.70 g/100 g diethyl ether, 86.60 g/100 ethanol; L-(-)-Form/|BUFFERING INDEX: 3.26|SPECIFIC OPTICAL ROTATION: -5.7 DEG /L-FORM/, +5.2 DEG /D-FORM/ @ 18 °C (IN ACETONE)

-1.340 MJ/mol at 20 °C

1

22-37/38-41-36/37/38-42/43-34

26-39-37/39-36-36/39

ON7175000

Xn,Xi

Stable under recommended storage conditions.

P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, P362

H315

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/ Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. /Contaminated packaging/ Dispose of as unused product.

Bases, oxidizing agents, reducing agents, alkali metals.

Malic acid is an indirect food additive for use only as a component of adhesives.|Substance added directly to human food affirmed as generally recognized as safe (GRAS).|Malic 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.|Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. 1-Malic acid is included on this list.

Fuime MZ; Final report on the safety assessment of Malic Acid and Sodium Malate. Int J Toxicol 20 (Suppl 1): 47-55 (2001)[Fuime MZ; Int J Toxicol 20 (Suppl 1): 47-55 (2001)]

|Danger|H315 (79.02%): Causes skin irritation [Warning Skin corrosion/irritation]|P264, P280, P302+P352, P305+P351+P338, P310, P321, P332+P313, P337+P313, and P362|Aggregated GHS information provided by 1990 companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302 (12.88%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P310, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 326 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P310, P312, P321, P330, P332+P313, P362, P403+P233, P405, and P501|Warning|H315: Causes skin irritation [Warning Skin corrosion/irritation]|P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, and P362

/Skin protection/ Handle with gloves.|/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).|/Respiratory protection/ Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) 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).|/Body Protection/ Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Wear self-contained breathing apparatus for firefighting if necessary.|Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide

Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.|Do not let product enter drains.|ACCIDENTAL RELEASE MEASURES /Personal precautions, protective equipment and emergency procedures/ Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.

Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|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.|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.

A skin and eye irritant

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. Malic acid is produced, as an intermediate or a final product, by process units covered under this subpart.

Aerosol samples collected from a Hong Kong roadway tunnel during 2003-2004 monitoring contained malic acid levels of 2.2-9.1 ng/cu m(1); apparent occurrence of malic acid was reported as not detected to 6.63 ug/vehicle-km(1).

SOIL: Maleic acid was qualitatively detected in German soil samples(1).

URBAN/SUBURBAN: In a monitoring study sampling the atmospheric aerosol in the atmosphere of urban Tokyo, Japan during 1988 and 1989, malic acid was detected at concentrations ranging from 3.2 to 100 ng/cu m with an average concentration of 23 ng/cu m(1). Ambient aerosol monitoring conducted throughout 1982 in the Los Angeles, CA area found respective annual ambient average malic acid concentrations of 7.8, 14.3, 16.0, 22.1 and <0.02 ng/cu m at West Los Angeles, downtown Los Angeles, Pasadena, Rubidoux and San Nicolas Island, respectively(2). Aerosol samples (PM2.5) collected in Nanjing China between July 2004 and January 2005 contained mean maleic acid concentrations of 1.89-31.6 ng/cu m during daytime and 1.18-18.1 ng/cu during nightime(3). Aerosol samples collected in Tokyo Japan in 1992 contained malic acid concentrations of 21-33 ng/cu m(4).|RURAL/REMOTE: Fine aerosol samples collected at the Great Smoky Mountain National Park, Tennessee between July 15 to August 25, 1995 contained malic acid in 9 of 21 daytime samples (2.5-38.5 ng/cu m) and 2 of 10 nighttime samples (4.7-14 ng/cu m)(1). Arctic aerosol samples collected from Alert, Canada during 1987-1988 contained a mean malic acid concentration of 0.026 ng/cu m with a range of <0.003-0.14 ng/cu m(2); elevated diacid levels occurred during extended sunlight times, as opposed to dark periods, suggesting the presence of the diacids (such as malic acid) was due to photooxidation generation from other atmospheric compounds(2). Aerosol samples collected at a forest area in Hungary between June 4 and July 10, 2003 contained a mean malic acid concentration of 40 ng/cu m (range of 16.5-78 ng/cu m)(3).

Malic acid has been identified as a component of tobacco smoke(1).

IDENTIFICATION AND USE: Malic acid forms colorless crystals with a characteristic sour taste. It is used as a cosmetic and food ingredient. Malic acid has been tested as experimental therapy for various conditions. HUMAN EXPOSURE AND TOXICITY: Malic acid and its salts are considered as strongly irritant to the skin and mucosa and as a particular risk to the eyes. Exposure via inhalation for those handling the additives is also considered to present a risk. Malic acid was irritating in clinical tests, with less irritation seen as pH of the applied material increased. Patients patch tested with malic acid, placed on a diet that avoided foods containing malic or citric acid, and then challenged with a diet high in malic and citric acid had both immediate urticarial and delayed contact dermatitis reactions. In the absence of data on inhalation toxicity, inhalation of the malate additive should be considered as hazardous. Because of the particle size distribution of the additives and the high dusting potential of the malate salts, it is likely that handling the additives could result in a production of respirable dust that could present a risk to unprotected workers. ANIMAL STUDIES: Malic acid is a component of the Kreb's cycle. Malic acid was relatively nontoxic in acute toxicity studies using animals. In a chronic oral study, feeding malic acid to rats resulted only in weight gain changes and changes in feed consumption. Malic acid did not cause reproductive toxicity in mice, rats, or rabbits. Malic acid was a moderate to strong skin irritatant in animal tests, and was a strong ocular irritant. Malic acid was not mutagenic across a range of genotoxicity tests.

The influence of some frequent dietary constituents on gastrointestinal absorption of aluminum from drinking water and diet was investigated in mice. Eight groups of male mice received lactic (57.6 mg/kg/day), tartaric (96 mg/kg/day), gluconic (125.4 mg/kg/day), malic (85.8 mg/kg/day), succinic (75.6 mg/kg/day), ascorbic (112.6 mg/kg/day), citric (124 mg/kg/day), and oxalic (80.6 mg/kg/day) acids in the drinking water for one month. At the end of this period, animals were killed and aluminum concentrations in liver, spleen, kidney, brain, and bone were determined. All the dietary constituents significantly increased the aluminum levels in bone, whereas brain aluminum concentrations were also raised by the intake of lactic, gluconic, malic, citric, and oxalic acids. The levels of aluminum found in spleen were significantly increased by gluconic and ascorbic acids, whereas gluconic and oxalic acids also raised the concentrations of aluminum found in kidneys.|The interactions of aqueous solutions of chlorine with some fruit acids (citric acid, DL-malic acid, and L-tartaric acid) different pH values were studied diethyl ether extraction followed by GC/MS analysis indicated that a number of mutagens certain chlorinated propanones and chloral hydrate) are present as major products in some of these samples. A number of fruit juices (orange, grape, apple, pineapple, and grapefruit) were also treated with aqueous solutions of chlorine at their pH values. The products were analyzed by GC/MS. The same mutagens that were formed by the pure acids (citric acid and DL-malic acid) were identified as major products in ether extracts of these samples. All of the major products observed in the chlorination of all five fruit juices are potentially derived from reactions aqueous solutions of chlorine with citric or malic acid and with trace amounts of acetaldehyde and acetone in the juices.|The relative efficacy of citric, malic, malonic, oxalic and succinic acids, and deferoxamine mesylate (DFOA) on the toxicity, distribution and excretion in mice exposed to aluminum were compared. To determine the effect of the various chelators on the toxicity of aluminum various doses of aluminum nitrate (938-3l88 mg/kg) were administered intraperitoneally, followed by one of the chelators. Survival was recorded at the end of 14 days. Malic and succinic acids were the most effective. Malic and succinic acids were the most effective in increasing the urinary excretion of aluminum.|Eight groups of female Sprague-Dawley rats were treated with 281 mg aluminum hydroxide/kg/day by gastric intubation five times a week for fives weeks. Concurrently, animals in seven groups received ascorbic acid (56.3 mg/kg/day), citric acid (62 mg/kg/day), gluconic acid (62.7 mg/kg/day), lactic acid (28.8 mg/kg/day), malic acid (42.9 mg/kg/day), oxalic acid (28.8 mq/kg/day), and tartaric acid (48 mg/kg/day) in the drinking water. The eighth group did not receive any dietary constituent in the water and was designated as the control group. Animals were placed in plastic metabolic cages and urine was collected during the treatment period. The liver, spleen, kidney, brain and bone aluminum levels of each rat were measured, as well as the total amount of aluminun excreted into urine. All the dietary constituents significantly increased the aluminum concentrations in most of the tissues, with ascorbic and citric acids showing the highest rate of aluminum accumulation.

LD50 Mouse oral 1600-3200 mg/kg|LD50 Mouse ip 50-100 mg/kg|LD50 Rat oral greater than 3200 mg/kg|LD50 Rat ip 100-200 mg/kg|LD50 Rabbit oral 3000 mg/kg

Malic acid occurs in apples and many other fruits and plants(1). Malic acid occurs in plants such as apricot, mango, rose, plum, elderberry, buckwheat, strawberry, pineapple, papaya, orange, tangerine, potato, grape, soybean, grapefruit, lettuce, onion, celery, oats, cauliflower, cabbage, brussel sprouts, tobacco, carrot, olive, sunflower, tomato, ginseng, opium poppy, pea, raspberry, sage, and corn(2). Malic acid may occur in atmospheric samples as a result of volatilization from naturally occurring sources or from the atmospheric oxidation of precursor aldehydes(3). Malic acid and other dicarboxylic acids are probably formed in the atmosphere via photooxidation of organic compounds that occur in the atmosphere(4,5).

Malic acid's production and use as a chemical intermediate in the synthesis of esters, salts and compounds, as a chelating and buffering agent and as a flavoring agent and acidulant in foods(1,2) may result in its release to the environment through various waste streams(SRC). Malic acid's identification as a chemical component of tobacco smoke(2) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that malic acid is expected to have very high mobility in soil(SRC). The pKa values of malic acid are 3.51 and 5.03(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of malic acid from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.4X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Malic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an extrapolated vapor pressure of 3.28X10-8 mm Hg at 25 °C(5). A 73% of theoretical BOD in 2 weeks using activated sludge in the Japanese MITI test indicates that malic acid is readily biodegradable(6). Results of other screening studies also indicate that malic acid biodegrades readily(7,8). Using C14-radio-labeled malic acid and a 1-hr incubation period, a 6.7% CO2 evolution was observed in a natural soil degradation study(9) demonstrating that biodegradation is expected to be an important fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that malic 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 8.4X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of -1.26(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A 73% of theoretical BOD in 2 weeks using activated sludge in the Japanese MITI test indicates that malic acid is readily biodegradable(6). Results of other screening studies also indicate that malic acid biodegrades readily(7,8). Malic acid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), malic acid, which has an extrapolated vapor pressure of 3.28X10-8 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase malic 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 2 days(SRC), calculated from its rate constant of 8.3X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase malic acid may be removed from the air by wet and dry deposition(SRC). Malic acid has been detected in atmospheric particulate matter and in rain and snow(4,5). Malic acid does not absorb at wavelengths >290 nm(6) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of malic acid with photochemically-produced hydroxyl radicals has been estimated as 8.3X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the reaction of malic acid with hydroxyl radicals in aqueous solutions at pH 1.5-14 is 8.2X10+8 L/mol-sec(2); this corresponds to an aquatic half-life of 2.6 years at an aquatic concentration of 1X10-17 hydroxyl radicals per liter(3). Malic acid does not absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). Malic acid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(5).

An estimated BCF of 3 was calculated in fish for malic acid(SRC), using a log Kow of -1.26(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 malic acid can be estimated to be 1(SRC). According to a classification scheme(2), this estimated Koc value suggests that malic acid is expected to have very high mobility in soil. The pKa values of malic acid are 3.51 and 5.03(3), indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The Henry's Law constant for malic acid is estimated as 8.4X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that malic acid is expected to be essentially nonvolatile from water surfaces(2). In addition, the pKa values of malic acid are 3.51 and 5.03(3), indicating that this compound will exist partially in anion form in the environment and the anion form of malic acid will not volatilize from water(SRC). Malic acid's Henry's Law constant indicates that volatilization from moist soil surfaces will not occur(SRC). Malic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an extrapolated vapor pressure of 3.28X10-8 mm Hg(4).

RAIN/SNOW: Malic acid was detected in rainwater samples collected from New Brunswick, NJ during 1999-2000 sampling(1). Snow, sleet and rain samples collected in Tokyo Japan in 1992 contained malic acid concentrations of 0.49-6.76 ug/L(2).

Malic acid has been found in apples and many other fruits and plants(1). An analysis of Caribbean cassava vegetables found a 0.2% constituent of malic acid(2). Malic acid was detected in six wild edible mushroom species (Amanita caesarea, Boletus edulis, Gyroporus castaneus, Lactarius delicious, Suillus collinitus and Xerocomus chrysenteron)(3). Malic acid occurs in fruits and edible plants such as apricot, mango, rose, plum, elderberry, strawberry, pineapple, papaya, orange, tangerine, potato, grape, soybean, grapefruit, lettuce, onion, celery, oats, cauliflower, cabbage, brussel sprouts, carrot, olive, sunflower, tomato, ginseng, poppy, pea, raspberry, sage, and corn(4).|Reported food use categories for malic acid include baked goods, frozen dairy, nonalcoholic beverages and soft candy(1). Malic acid occurs in maple sap, apple, melon, papaya, beer, grape wine, cocoa, sake, kiwifruit and chicory root(1).

According to the 2012 TSCA Inventory Update Reporting data, 2 reporting facilities estimate the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of malic acid in the United States may be as low as 25-49 workers and as high as 100-499 workers per plant; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).|NIOSH (NOES Survey 1981-1983) has statistically estimated that 80,674 workers (51,609 of these were female) were potentially exposed to malic acid in the US(1). Occupational exposure to malic acid may occur through inhalation and dermal contact with this compound at workplaces where malic acid is produced or used. Monitoring data indicate that the general population may be exposed to malic via inhalation of ambient air and tobacco smoke, ingestion of food and beverages, and dermal contact with consumer products containing malic acid(SRC).

Parenteral nutrition

EXPL THER An efficcacy and safety test of a tablet containing 200 mg malic acid (and 50 mg magnesium) was conducted using patients with primary fibromyalgia syndrome. In the first part of the test, 24 patients were given three tablets twice daily (bid) for 4 weeks. In the second part, 16 patients started with three tablets bid and increased the dosage every 3 to 5 days as necessary; at month 6, the average dose was 8.8 tablets per day. (For a 50-kg person, ingestion of six tablets would be equivalent to 24 mg of malate/kg of body weight). In the first part of the study, one test patient reported diarrhea, one reported nausea, and one reported dyspepsia. (In the placebo group, two patients reported diarrhea and one reported dyspepsia.) In the second part of the study, five test patients reported diarrhea, one reported nausea, one reported dyspepsia, one reported panic attacks, and one reported dizziness.|EXPL THER Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components of Fructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. In in vivo rat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-alpha, and platelet aggregation. In vitro experiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient of Fructus Choerospondiatis responsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease. /L-Malic Acid/|EXPL THER Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a placebo. Both of them were administered on demand for 2 weeks. Dry Mouth Questionnaire (DMQ) was used in order to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. All the statistical analyses were performed by using SPSS software v17.0. Different DMQ scores at the earliest and final stage of the trial were analysed by using Mann-Whitney U test, whereas Student's T-test was used to analyse salivary flows. Critical p-value was established at p<0.05. Results: DMQ scores increased significantly (clinical recovery) from 1.21 to 3.36 points (p<0.05) after malic acid (1%) application whereas DMQ scores increased from 1.18 to 1.34 points (p>0.05) after placebo application. After two weeks of treatment with malic acid, unstimulated salivary flow increased from 0.17 to 0.242 mL/min whereas the stimulated one increased from 0.66 to 0.92 mL/min (p<0.05). After placebo application unstimulated flow ranged from 0.152 to 0.146 mL/min and stimulated flow increased from 0.67 to 0.70 mL/min (p>0.05). Conclusions: Malic acid 1% spray improved antihypertensive-induced xerostomia and stimulated the production of saliva.|Fourteen patients, 11 males and 3 females, with various forms of ichthyosiformdermatoses were used to evaluate the therapeutic potential of more than 60 chemicals, including malic acid. Malic acid was dissolved in either water or ethanol and incorporated into a hydrophilic ointment of plain petrolatum. The ointment, containing 5% malic acid (pH not specified), was applied twice daily to the appropriate test site for 2 weeks. Daily to weekly observations were made. Malic acid provided 3+ (disappearance of scales from lesions) or 4+ (restoration to normal looking skin) improvement in all patients except one with epidermolytic hyperkeratosis.

Upon oral and IP administration of radioactive malic acid to rats, most of the radioactivity was excreted as carbon dioxide.

Acidulents. Like l-(14)C4 malic acid, dl-(14)C4 malic acid, when admin ip or orally to rats was extensively metabolized; 90-95% of (14)C was excreted through lungs as (14)CO2. ... Metabolized at same rate irrespective of route admin ... . /L- & dl-malic acid/|Malic acid is an intermediate in the citric acid cycle. It is formed from fumaric acid and is oxidized to oxaloacetic acid. It is also metabolized to pyruvic acid by malic enzyme which is present in many biologic systems, including bacteria and plants. L-Malic and dl-malic acid are both rapidly metabolized in the rat. Orally or ip administered l- or dl-malic acid was extensively eliminated as carbon dioxide (83 to 92%). No differences between the two forms were found in the rates (90 to 95% in 24 hr) or routes of excretion.|Malates are normal constituents of the diet of humans and animals and, when ingested, are rapidly and completely metabolized to CO2. /Malates/|... Both enantiomers of malic acid are readily metabolised by laboratory animals and humans and that there was no reason to distinguish between L-malic acid and DL-malic acid when considering their safe use in food.|Upon oral and IP administration of radioactive Malic Acid to rats, most of the radioactivity was excreted as carbon dioxide.

... contents of fumaric and maleic acids are ... 7.5 and <500 ppm, respectively.

/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 as 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/ The effect of malic acid on cell renewal was assessed using the dansyl chloride method. Two mg/sq cm of 1 M malic acid in a simple liquid vehicle (15% ethanol [SD 40], 5% ethoxydiglycol, and 5% butylene glycol) was applied to the volar forearm which was stained with dansyl chloride twice daily until all the stain was removed. An 18%, 10%, and 5% increase in cell renewal was observed at pH 3, 5, and 7, respectively.|/HUMAN EXPOSURE STUDIES/ Thirty-four patients with atopic dermatitis were tested to determine their sensitivity to foods containing malic (and citric) acid. The patients were first patch tested with malic (and citric) acid applied as a 10% aqueous solution under occlusive patches for 48 hours. For 2 weeks, the patients followed a diet that avoided processed foods in which malic (and citric) Acid were used, and then challenged themselves with a diet high in malic (and citric) acid the during the third week. Eighteen patients reacted to both malic and citric acid and 6 patients reacted to only malic acid. Both immediate reactions (seasonal allergic rhinitis and urticaria) and delayed reactions (contact dermatitis) were present. Patch-test results were reliable in predicting results of the challenge with diet.|/HUMAN EXPOSURE STUDIES/ The subjective skin irritation potential of malic acid was evaluated by applying 2 mg/sq cm of 1 M malic acid in vehicle (15% ethanol [SD40], 5% ethoxydiglycol, and 5% butylene glycol) to the nasal fold area of at least 10 subjects. Irritation was graded on a scale of 0 to 4 everyminute for 15 minutes. The irritation scores, as an average of the summation of each individual irritation score over the 15-minute test period, were 39.4, 37.1, and 23.1 for pH 3, 5, and 7, respectively.|/SIGNS AND SYMPTOMS/ Malic acid and its salts are considered as strongly irritant to the skin and mucosa and as a particular risk to the eyes. Exposure via inhalation for those handling the additives is also considered to present a risk.|For more Human Toxicity Excerpts (Complete) data for MALIC ACID (6 total), please visit the HSDB record page.

calcium (hydroxy-1-malate) hexahydrate

Dry beverage powders 50%; carbonated & still beverages, 25%; food & candy, 15%; metal cleaning & finishing, 5%; miscellaneous, 5% (1983)

Uva ursi, this is volatile oil containing a glucoside, arbutin, tannin, & gallic & malic acids.|Grades: Technical, active and inactive; Food Chemical Codex. The natural material is levorotatory, but the synthetic material is /optically/ inactive.

Electrical equipment, appliance, and component manufacturing|Butanedioic acid, 2-hydroxy-: ACTIVE|Malic acid [6915-15-7] (hydroxysuccinic acid, hydroxybutanedioic acid, or 1-hydroxy-1,2-ethanedicarboxylic acid), C4H6O5, is a white, crystalline material. The levorotatory isomer, S(-)-malic acid [97-67-6] (l-malic acid), is a natural constituent and common metabolite of plants and animals. The racemic compound, R,S-malic acid [617-48-1] (dl-malic acid), is a widely used food acidulant. This material is also used in some industrial applications as a sequestrant and as a buffer for pH control. R(+)-Malic acid [636-61-3] (d-malic acid) is available only as a laboratory chemical.|In the United States, Canada, and Europe, only the synthetic R,S-malic acid is produced commercially, whereas both the S and R,S forms are produced in Japan.|Although its degree of ionization in water ... is same as citric acid, it has much stronger apparent acidic taste. ... Smaller amt are usually required to obtain same taste effect. It does not have as strong an apparent taste ... as fumaric acid.|... One of ingredients specified by internal revenue service for rendering volatile fruit-flavored concn nonpotable when they contain 6 to 15% alcohol & have to be transferred from place of mfr to winery.|For more General Manufacturing Information (Complete) data for MALIC ACID (7 total), please visit the HSDB record page.

9.123, 22.073. CORDIALS & LIQUEURS /OF/ ... TOTAL MALIC ACID (LEVO & INACTIVE) /DETERMINED/ BY CHROMATOGRAPHIC METHOD. 9.124, 22.081. CORDIALS & LIQUEURS /OF/ LEVO-MALIC ACID /DETERMINED BY/ POLARIZATION. /L-MALIC ACID/|12.020, 22.073. BEVERAGES: NONALCOHOLIC & CONCENTRATES /OF/ TOTAL MALIC ACID /DETERMINED BY/ CHROMATOGRAPHIC METHODS. 12.021, 22.081. BEVERAGES: NONALCOHOLIC & CONCENTRATES /OF/ LEVO MALIC ACID /DETERMINED BY/ POLARIZATION. /L-MALIC ACID/|11.047, 22.088. BEVERAGES: WINES /OF/ ... CITRIC & MALIC ACIDS /DETERMINED BY/ POLARIZATION.|31.184-31.188. MAPLE PRODUCTS /OF/ MALIC ACID, /DETERMINED BY/ SPECTROPHOTOMETRY @ 390 NM.|For more Analytic Laboratory Methods (Complete) data for MALIC ACID (8 total), please visit the HSDB record page.

EPA Safer Chemical Functional Use Classes -> Processing Aids and Additives|Safer Chemical Classes -> Green circle - The chemical has been verified to be of low concern|Food additives|Human Drugs -> EU pediatric investigation plans|Flavouring Agent -> FLAVOURING_AGENT; -> JECFA Functional ClassesFood Additives -> ACIDITY_REGULATOR; -> JECFA Functional Classes|Cosmetics -> Buffering

Flavouring Agent -> FLAVOURING_AGENT; Food Additives -> ACIDITY_REGULATOR;