Ellagic acid

302.19

302.19

47549

207-508-3

19YRN3ZS9P

758198|656272|407286

DTXSID2020557

Cream colored needles from pyridine

29322090

134

1.1

tan to gray powder

2.1±0.1 g/cm3

>360 °C

363.24°C (rough estimate)

310.1±26.4 °C

1.895

H2O: <0.1 g/100 mL at 21 ºC;1 M NaOH: 10 mg/mL, dark green

Store at RT

2.81X10-15 mm Hg at 25 °C (est)

LD50 oral in rat: > 20gm/kg

pKa1 = 6.69 (phenol); pKa2 = 7.45 (phenol); pKa3 = 9.61(phenol); pKa4 = 11.50 (phenol) (est)

Needles from acetic anhydride, mp 340 °C /Tetraacetate/|Hydroxyl radical reaction rate constant = 1.48X10-11 cu cm/molec-sec at 25 °C (est)

Insoluble in water.

Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

ELLAGIC ACID reacts as a weak acid. Incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides. Flammable gas (H2) is often generated. Heat is also generated by the acid-base reaction between phenols and bases. May be sulfonated exothermically very readily (for example, by concentrated sulfuric acid at room temperature). May be nitrated very rapidly, even by dilute nitric acid.

NONH for all modes of transport

3

36/37/38

26-36-36/37

DJ2620000

Xi

Stable. Combustible. Incompatible with strong oxidizing agents.

P261-P305 + P351 + P338

H315-H319-H335

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.

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces 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. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

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)

Naturally occurring plant phenols with antimutagenic and anticarcinogenic activities were tested for their abilities to inhibit the biochemical and biological effects of the potent tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in mouse epidermis in vivo. When applied topically to mouse skin, tannic acid (TA), ellagic acid, and several gallic acid derivatives all inhibit TPA-induced ornithine decarboxylase activity, hydroperoxide production, and DNA synthesis, three biochemical markers of skin tumor promotion. Moreover, in the two-step initiation-promotion protocol, the same phenolic compounds also inhibit the incidence and yield of skin tumors promoted by TPA.|Resveratrol is shown to have a synergistic effect in vitro with both quercetin and ellagic acid for apoptosis ...|... Ellagic acid (EA) at a dose of 4 g/kg diet inhibited multiplicity of tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice by 54%. This inhibition was dose related between 0.06 and 4.0 g/kg diet ...|When administered in a semi-purified diet at concentrations of 0.4 and 4 g/kg, ellagic acid (EA) produced a significant (21 to 55%) decrease in the average number of N-nitrosobenzylmethylamine (NBMA)-induced esophageal tumors after 20 and 27 weeks of the bioassay. EA exhibited inhibitory effects toward preneoplastic lesions as well as neoplastic lesions. Tumors were not observed in vehicle-control rats or in rats that received EA alone.|For more Interactions (Complete) data for ELLAGIC ACID (6 total), please visit the HSDB record page.

/AQUATIC SPECIES/ The exposure of freshwater mussels Unio tumidus to phenolic compounds (tannic, ellagic and gallic acid) in vivo caused changes in proteins and DNA function of digestive gland cells. The mussels were exposed to various concentrations of tested polyphenols (60, 200 and 500 uM) for 24 and 48 hr and their antioxidant and pro-oxidant effects were determined. The number of SH-groups was quantified spectrophotometrically using Ellman's reagent. Oxidative modification of proteins increased in the digestive gland cells in a dose- and time-dependent manner. The level of nuclear DNA damage was investigated using the comet assay. The results revealed that polyphenolic acids induce single and double-strand breaks in DNA. The highest changes were observed for tannic and gallic acids and the smallest ones for ellagic acid. 1hr of DNA repair process was also studied using the same method. The data obtained in this experiment demonstrate that the most effective DNA repair occurs in the cells exposed to phenolic compounds for 24hr. A longer incubation (up to 48 hr) does not decrease the capacity of the repair mechanism. The antioxidant activity of the tested phenols was analyzed spectrofluorimetrically using a fluorescence probe DCFH-DA (dichlorofluorescein-diacetate). The experimental data showed that the tested acids can act as antioxidants when used at higher doses (200 and 500 uM) against the reactive oxygen species present in the digestive gland cells. The most effective was ellagic acid, also applied at the smallest dose of 60 uM, in comparison with tannic and gallic acids. In conclusion ... /the/ results demonstrate that chosen water-soluble polyphenols, which are located in various plant tissues and are also found in the aquatic environment, can influence organisms living in the water. They can be exposed to these chemicals that cause morphological alterations and changes in certain physiological processes in their organs (ie digestive gland cells of bivalve molluscs).

Extracts from red raspberry leaves or seeds, pomegranates, or other sources are said to contain high levels of ellagic acid, and are available as dietary supplements in capsule, powder, or liquid forms. The best dose of these preparations is not known.

Ellagic acid is being investigated for use in follicular lymphoma, brain injury in intrauterine growth restricted babies, obese adolescents, and solar lentigines.

/EXPL THER/ Italian researchers found that ellagic acid seemed to reduce the side effects of chemotherapy in men with advanced prostate cancer, although it did not help slow disease progression or improve survival.|/EXPL THER/ Ellagic acid seems to have some anti-cancer properties. It can act as an antioxidant, and has been found to cause apoptosis (cell death) in cancer cells in the lab. In other lab studies, ellagic acid seems to reduce the effect of estrogen in promoting growth of breast cancer cells in tissue cultures. There are also reports that it may help the liver to break down or remove some cancer-causing substances from the blood. Some supporters have claimed these results mean that ellagic acid can prevent or treat cancer in humans. This has not been proven. Unfortunately, many substances showing promise against cancer in lab and animal studies have not been found to be useful in people. Ellagic acid has also been said to reduce heart disease, birth defects, liver problems, and to promote wound healing. The available scientific research does not support these claims at this time.|/EXPL THER/ ... Ellagic acid (EA) at a dose of 4 g/kg diet inhibited multiplicity of tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice by 54%. This inhibition was dose related between 0.06 and 4.0 g/kg diet ...|/EXPL THER/ When administered in a semi-purified diet at concentrations of 0.4 and 4 g/kg, ellagic acid (EA) produced a significant (21 to 55%) decrease in the average number of N-nitrosobenzylmethylamine (NBMA)-induced esophageal tumors after 20 and 27 weeks of the bioassay. EA exhibited inhibitory effects toward preneoplastic lesions as well as neoplastic lesions. Tumors were not observed in vehicle-control rats or in rats that received EA alone.|/EXPL THER/ Ellagic acid inhibited lung tumorigenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice. This inhibition was related to the logarithm of the dose of ellagic acid added to the diet. The biodistribution of ellagic acid was studied in mice gavaged with ellagic acid. Pulmonary levels of ellagic acid were directly proportional to the dose of ellagic acid between 0.2 and 2.0 mmol/kg ...

Ellagic acid is available in supplement form, but it has not been tested for safety. Some reports indicate it may affect certain enzymes in the liver, which could alter levels of some drugs in the body. For this reason, people taking medicines or other dietary supplements should talk with their doctors or pharmacists about all their medicines and supplements before taking ellagic acid. The raspberry leaf, or preparations made from it, should be used with caution during pregnancy because they may initiate labor.

Ellagic acid's therapeutic action mostly involves antioxidant and anti-proliferative/anti-cancer effects.

After oral consumption, ellagic acid reaches maximum concentrations in about 1 hour.|Ellagic acid is eliminated from the body in about 4 hours.|The present study was initiated to determine ... the distribution of (14)C-ellagic acid (EA) and (3)H-N-methyl-N-nitrosourea (MNU) in the rat whole embryo culture model system ... (14)C-EA (50 uM for 2 hr, known embryoprotective concentration; no MNU added) was used to demonstrate access of EA to the embryo within the 2 hr exposure period. The majority of EA (99.5%) remained in the media while tissue concentrations of 57.0 and 47.9 pmol/mg were attained in the yolk sacs and embryos, respectively.|Ellagic acid (EA), derived from fruit ellagitannins, is known to be antimutagenic and anticarcinogenic in various animal tumor models. In this study, EA at a dose of 4 g/kg diet inhibited multiplicity of tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice by 54%. This inhibition was dose related between 0.06 and 4.0 g/kg diet. In contrast, two related compounds, esculin and esculetin, had no effect on lung tumorigenesis. The biodistribution of ellagic acid (EA) /in A/J mice/ was studied as a function of dose and time after gavage of EA. The levels of EA in the lung were directly proportional to the dose of EA between 0.2 and 2.0 mmol. The maximum level of EA, corresponding to 21.3 nmol/g, was observed 30 minutes after gavage with 2.0 mmol of EA/kg body wt, which corresponds to only 70 ppm of the administered dose. The levels in liver tissues were 10-fold lower and reached a maximum 30 minutes after gavage. At this interval, the blood level of EA was 1 nmol/mL. The inclusion of EA in cyclodextrin doubles the level of EA in lung tissues. These results demonstrate that EA localizes preferentially in lung tissues ...|... Ellagic acid (EA), a dietary antioxidant associated with poor biopharmaceutical properties, was encapsulated into poly(lactide-co-glycolide) (PLGA) and polycaprolactone (PCL) nanoparticles to improve oral bioavailability ... The antioxidant potential of the didodecyldimethyl ammonium bromide (DMAB)-stabilized nanoparticulate formulations was evaluated against cyclosporine A (CyA)-induced nephrotoxicity in rats ... From in situ permeation studies in rats, it was evident that intestinal uptake of EA as DMAB-stabilized nanoparticles was significantly higher as compared to the sodium carboxymethyl cellulose suspension and the polyvinyl alcohol (PVA)-stabilized particles. EA and EA nanoparticles were able to prevent the CyA-induced nephrotoxicity in rats as evident by biochemical parameters as well as kidney histopathology.

The exact mechanism of action of ellagic acid in its different potential indications is still being investigated.|Induction of glutathione S-transferase (GST) enzymes can increase detoxification of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To determine if the anticarcinogen ellagic acid induces cellular enzymes which detoxify carcinogens ... the effect of ellagic acid on the expression of glutathione S-transferase-Ya /was examined/. Rats fed ellagic acid demonstrated significant increases in total hepatic GST activity, hepatic GST-Ya activity and hepatic GST-Ya mRNA. To determine if the observed increase in GST-Ya mRNA was due to ellagic acid inducing transcription of the GST-Ya gene, transfection studies were performed with plasmid constructs containing various portions of the 5' regulatory region of the rat GST-Ya gene. The transfection studies demonstrated that ellagic acid increased GST-Ya mRNA by inducing transcription of the GST-Ya gene and demonstrated that this induction is mediated through the antioxidant responsive element of the GST-Ya gene.|Induction of cellular detoxification enzymes can increase detoxification of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To determine if the dietary anticarcinogen ellagic acid induced enzymes which detoxify xenobiotics and carcinogens ... the effect of ellagic acid on the expression of the phase II detoxification enzyme NAD(P)H:quinone reductase (QR) /was examined/. QR is induced by xenobiotics and antioxidants interacting with the xenobiotic responsive and antioxidant responsive elements of the 5' regulatory region of the QR gene. Ellagic acid is structurally related to the antioxidants which induce QR and we proposed that ellagic acid would induce QR expression through activation of the antioxidant responsive element of the QR gene. Rats fed ellagic acid demonstrated a 9-fold increase in hepatic and a 2-fold increase in pulmonary QR activity, associated with an 8-fold increase in hepatic QR mRNA. To determine if this increase in QR mRNA was due to activation of the antioxidant responsive element, transient transfection studies were performed with plasmid constructs containing various portions of the 5' regulatory region of the rat QR gene. These transfection studies confirmed that ellagic acid induces transcription of the QR gene and demonstrated that this induction is mediated through the antioxidant responsive element of the QR gene.|A principal mechanism by which these chemopreventive compounds exert their protective effects is likely to be via induction of carcinogen detoxification. This can be mediated by conjugation with glutathione, which is synthesized by the sequential actions of glutamate-cysteine ligase (GLCL) and glutathione synthetase ... /It was/ demonstrated that dietary administration of the naturally occurring chemopreventive agents, ellagic acid, coumarin or alpha-angelicalactone caused an increase in GLCL activity of between approximately 3- and 5-fold in rat liver. Treatment with the synthetic antioxidant ethoxyquin or the classic inducer phenobarbital caused < 2-fold induction of GLCL activity in rat liver, which was not found to be significant. The increases in GLCL activity were accompanied by increases (between 2- and 4-fold) in levels of both the catalytic heavy subunit (GLCLC) and regulatory light subunit (GLCLR). No substantial induction of GLCL was observed in rat kidney. The glutathione S-transferase (GST) subunits A1, A3, A4, A5, P1 and M1 were all found to be inducible in rat liver by most of the agents. The greatest levels of induction were observed for GST P1, following treatment with coumarin (20-fold), alpha-angelicalactone (10-fold) or ellagic acid (6-fold), and GST A5, following treatment with coumarin (7-fold), alpha-angelicalactone (6-fold) and ethoxyquin (6-fold). Glutathione synthetase was induced approximately 1.5-fold by coumarin, alpha-angelicalactone, ellagic acid and ethoxyquin. The expression of glutathione-related enzymes was also examined in preneoplastic lesions induced in rat liver by aflatoxin B(1). The majority of gamma-glutamyltranspeptidase (GGT)-positive preneoplastic foci contained increased levels of GLCLC relative to the surrounding tissue. This was usually found to be accompanied by an increase in GLCLR. Cells in the inner cortex of rat kidney were found to contain the highest levels of both GLCLC and GLCLR. The same cells showed the strongest staining for GGT activity.|... Specific in vitro assays ... found ellagic acid ... to be /a/ potent inhibitors of the catalytic activities of the two /human DNA/ topoisomerases. The minimum concentration required to inhibit > or = 50% of catalytic activity (IC50) of ellagic acid was determined at 0.6 and 0.7 ug/mL for topo I and topo II, respectively ... Unlike topoisomerase poisons ... /the/ plant phenol did not trap the enzyme-DNA reaction intermediate, known as the cleavable complex. In contrast, ellagic acid prevented other topo I and topo II poisons from stabilizing the cleavable complex, suggesting that the mode of its action is that of an antagonist. Structure-activity studies identified the 3,3'-hydroxyl groups and the lactone groups as the most essential elements for the topoisomerase inhibitory actions of plant phenols. On the basis of these findings and other properties of ellagic acid, a mechanistic model for the documented anticarcinogenic effects of the agent is proposed.

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

/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 the 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. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. 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 ... . Anticipate seizures 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 ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/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. 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 if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ALTERNATIVE and IN VITRO TESTS/ ... Specific in vitro assays ... found ellagic acid ... to be /a/ potent inhibitors of the catalytic activities of the two /human DNA/ topoisomerases. The minimum concentration required to inhibit > or = 50% of catalytic activity (IC50) of ellagic acid was determined at 0.6 and 0.7 ug/mL for topo I and topo II, respectively ... Unlike topoisomerase poisons ... /the/ plant phenol did not trap the enzyme-DNA reaction intermediate, known as the cleavable complex. In contrast, ellagic acid prevented other topo I and topo II poisons from stabilizing the cleavable complex, suggesting that the mode of its action is that of an antagonist. Structure-activity studies identified the 3,3'-hydroxyl groups and the lactone groups as the most essential elements for the topoisomerase inhibitory actions of plant phenols. On the basis of these findings and other properties of ellagic acid, a mechanistic model for the documented anticarcinogenic effects of the agent is proposed.

Acid, Benzoaric