Emodin

less than 1 mg/mL at 66 °F (NTP, 1992)

Practically insoluble in water; soluble in alcohol, aqueous alkali hydroxide solutions (cherry red color), sodium carbonate and ammonia solutions.

Solubility @ 25 °C (g/100 ml of satd solution): ether 0.140; chloroform 0.071; carbon tetrachloride 0.010; carbon bisulfide 0.009; benzene 0.041

Practically insoluble in water; soluble in ethanol; moderately soluble in aqueous alkali solutions

Soluble in alcohol; insoluble in water

493 to 495 °F (NTP, 1992)

256-257 °C

Brick red monoclinic needles; mp: 207 °C /3-Methyl ether/

Pale yellow needles; mp: 225 °C /Trimethyl ether/

266 - 268 °C

Emodin appears as orange needles or powder. (NTP, 1992)

Solid

154.6 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID5025231]

158.74 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

161.3 Ų [M+H]+ [CCS Type: DT; Method: stepped-field]

156.4 Ų [M-H]-

Warning

H315 (92.3%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 52 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

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.

If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated sufaces with acetone followed by washing with a soap and water soln. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone 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.

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

Where the neat chemical is weighed and diluted, wear a NIOSH approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter).

Emodin is moderately cytotoxic and can inhibit the growth of many cell types by interfering with the cell cycle, possibly by stimulating the expression of p53 and p21. Alternatively, it may do this by creating DNA strand breaks and/or non-covalently binding to DNA and inhibiting the catalytic activity of topoisomerase II. It may also induce apoptosis by inhibiting the electron transport chain, producing reactive oxygen species. Emodin is a strong inhibitor of tyrosine-protein kinase Lck and other tyrosine kinase receptors, which likely contributes to its growth suppressing activity. It may act as a chemopreventive agent by activating DNA repair machinery. Emodin can also inhibit metastasis by interfering with the activity of matrix metalloproteinases, either directly or through through inhibition of focal adhesion kinase, mitogen-activated protein kinase, and RAC-alpha serine/threonine-protein kinase activation, and partial inhibition of transcription factor AP-1 and nuclear factor NF-kappa-B (NF-kB) transcriptional activities. Emodin exerts its purgative effects by acting directly or indirectly on colon epithelial cells. This activates the underlying smooth muscle cells, leading to muscle contractility. Possible mechanisms for this effect includes enhancing the hormone motilin, activating muscarinic receptors by triggering the release of acetylcholine, stimulating the protein kinase C-alpha pathway for increased calcium sensibility, inhibiting the secretion of the hormone somatostatin, increasing fluid electrolyte accumulation in the distal ileum and colon, and inhibiting the activity of Na+/K+-ATPase and/or potassium channels. Emodin's antiinflammatory action is due to its specific inhibition of the transcription factor NF-kB. It also regulates angiogenesis by inhibiting the enzymes casein kinase II and nitric oxide synthase and has shown potent estrogen receptor binding affinity. Emodin can induce the microsomal enzyme cytochrome P-450 1A1, perpetuating its own metabolic activation. (A3043, A3044, A3045, A3046, A3047, A3048, A3049, A3050, A3051, A3052, A3053, A3054)

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=518-82-1]

Emodin

TR-493: Toxicology and Carcinogenesis Studies of Emodin (CASRN 518-82-1) in F344/N Rats and B6C3F1 Mice (Feed Studies) (2001 )

05/21/99

No Evidence

Equivocal Evidence

Equivocal Evidence

/LABORATORY ANIMALS: Acute Exposure/ This compound has caused gastrointestinal effects in experimental animals.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... The effect of emodin on hepatic fibrosis in rats /was investigated/. The rat hepatic fibrosis model was induced by the subcutaneous injection of 40% CCl4 (twice a week for 6 weeks) dissolved in olive oil. The emodin-treated rats were treated with low-dose, intermediate-dose and high-dose emodin (20, 40 and 80 mg/kg body weight, once a day for 42 days) dissolved in 0.5% sodium carboxymethylcellulose (CMC), except receiving CCl4. Control group received only olive oil and 0.5% CMC... Compared with model group, the emodin-treated rats showed (1) liver functions were improved, alanine transaminase (ALT) and alkaline phosphatase (AKP) were obviously reduced, and total protein (TP) and albumin (ALB) were significantly increased; (2) serum hyaluronic acid and laminin were markedly reduced; (3) liver hydroxyproline was significantly decreased; (4) the degrees of fibrosis were reduced. The changes of parameters mentioned above were significant (P < 0.05 or P < 0.01). Emodin has effect on hepatic fibrosis in rats. The hepatoprotective of emodin /SRP: may effect liver fibrosis/.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Emodin and cassiamin B /were examined as cancer chemopreventive agents/ ... These compounds exhibited the remarkable anti-tumor promoting effect on two-stage carcinogenesis test of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter by both topical application. Furthermore, emodin exhibited potent inhibitory activity on two-stage carcinogenesis test of mouse skin tumors induced by nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide as an initiator and TPA as a promoter.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ EMOD /emodin/ was administered in feed to timed-mated Sprague-Dawley (CD) rats (0, 425, 850, and 1,700 ppm; gestational day (gd) 6 to 20), and Swiss albino (CD-1) mice (0, 600, 2,500; or 6,000 ppm; gd 6 to 17). Ingested dose was 0, 31, 57, and 80-144 mg EMOD/kg/day (rats) and 0, 94, 391, and 1,005 mg EMOD/kg/day (mice). ...There were no maternal deaths; discolored, soft or loose feces were observed at the high dose in mice. In rats, maternal body wt decreased at the high dose (gd 9, 12); wt gain was reduced at the mid (gd 6-9) and high dose (gd 6-9; 6-20). Maternal body wt (gestation) and wt gain (corrected for gravid uterine weight (GUW)) exhibited a decreasing trend. In mice, maternal body wt and wt gain decreased at the high dose. Prenatal mortality, live litter size, fetal sex ratio, and morphological development were unaffected in both rats and mice. At the high dose, rat average fetal body wt/litter was unaffected, but was significantly reduced in mice. The rat maternal LOAEL was 1,700 ppm based on maternal body weight and weight gain; the NOAEL was 850 ppm. The rat developmental toxicity NOAEL was greater than 1,700 ppm; a LOAEL for rat developmental toxicity was not established. In mice, the maternal toxicity LOAEL was 6,000 ppm based on reduction of maternal body wt and wt gain; the NOAEL was 2,500 ppm. The developmental toxicity LOAEL was 6000 ppm, based on reduction of fetal body wt; the NOAEL was 2,500 ppm.

For more Non-Human Toxicity Excerpts (Complete) data for EMODIN (10 total), please visit the HSDB record page.

SKIN CONTACT: 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. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. 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 Respirator Recommendation.

EYE CONTACT: 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.

INGESTION: 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. Generally, the induction of vomiting is NOT recommended outside of a physician's care due to the risk of aspirating the chemical into the victim's lungs. However, if the victim is conscious and not convulsing and if medical help is not readily available, consider the risk of inducing vomiting because of the high toxicity of the chemical ingested. Ipecac syrup ... may be used in such an emergency. IMMEDIATELY transport the victim to a hospital. 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.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The anthraquinone mycotoxins emodin and skyrin were examined for the inhibitory effects on murine leukemia L1210 culture cells, oxidative phosphorylation of rat liver mitochondria, and Na+, K+-activated ATPase activity of rat brain microsomes to find the differences between their modes of toxic action. Skyrin exhibited a stronger inhibitory effect than emodin on the growth of L1210 culture cells. Emodin showed a stronger uncoupling effect than skyrin on mitochondrial respiration. Skyrin inhibited Na+, K+-activated ATPase activity of rat brain microsomes but emodin did not inhibit.

... Emodin induces apoptotic responses in the human hepatocellular carcinoma cell lines (HCC) Mahlavu, PLC / PRF / 5 and HepG2. The addition of emodin to these three cell lines led to inhibition of growth in a time- and dose-dependent manner. Emodin generated reactive oxygen species (ROS) in these cells which brought about a reduction of the intracellular mitochondrial transmembrane potential (Deltaym), followed by the activation of caspase-9 and caspase-3, leading to DNA fragmentation and apoptosis.

Emodin inhibited the activity of TPK and CK2 and the degradation of I-kappaB.

... Emodin-induced apoptosis of CH27 cells does not involve modulation of endogenous Bcl-X(L) protein expression, but appears to be associated with the increased expression of cellular Bak and Bax proteins.

For more Mechanism of Action (Complete) data for EMODIN (9 total), please visit the HSDB record page.

... The metabolism of emodin (1,3,8-trihydroxy-6-methylanthraquinone) /was studied/... With rat liver microsomes, the formation of two emodin metabolites, omega-hydroxyemodin and 2-hydroxyemodin, was observed. The rates of formation of omega-hydroxyemodin were not different with microsomes from rats that had been pretreated with inducers for different cytochrome P450 enzymes. Thus, the formation of omega-hydroxyemodin seems to be catalyzed by several cytochrome P450 enzymes at low rates. The formation of 2-hydroxyemodin was increased in liver microsomes from 3-methylcholanthrene-pretreated rats and was inhibited by alpha-naphthoflavone, by an anti-rat cytochrome P450 1A1/2 antibody, and, to a lesser degree, by an anti-rat cytochrome P450 1A1 antibody. These data suggest the involvement of cytochrome P450 1A2 in the formation of this metabolite. However, other cytochrome P450 enzymes also seem to catalyze this reaction. The anthraquinone chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is transformed, in a cytochrome P450-dependent oxidation, to aloe-emodin (1, 8-dihydroxy-3-hydroxymethylanthraquinone) as the major product formed.

The hepatic microsomes derived from various animal species transformed emodin (1,3,8-trihydroxy-6-methylanthraquinone), into an unidentified anthraquinone, along with 2-hydroxy-, 4-hydroxy- and 7-hydroxyemodins. ... This major metabolite /was identified/ as omega-hydroxy-emodin (1,3,8-trihydroxy-6-hydroxymethylanthraquinone). Among 7 animal species, the highest activity to produce this omega-hydroxyemodin was observed in the hepatic microsomes of guinea pig and rat, followed by mouse and rabbit. The microsomal activity to convert emodin into omega-hydroxyemodin was accelerated by the pretreatment of animals with phenobarbital, and inhibited by SKF 525A. The microsomal hydroxylation reactions of the methyl residue and the anthraquinoid nucleus of emodin were presumed to be catalyzed regiospecifically by multiple forms of cytochrome P-450.

... Emodin was biotransformed by the microsomal enzymes into at least 5 quinonoid metabolites, among which one pigment, identified as 2-hydroxyemodin (1,2,3,8-tetrahydroxy-6-methyl-anthraquinone), was proven to be a direct mutagen to the test strain, and the remaining 4 quinonoid metabolites were negative or far less active than this active principle.

Emodin has known human metabolites that include Emodin 3-hydroxy-glucuronide.

Emodin is biotransformed by the microsomal cytochrome P450 enzymes into active hydroxyemodins such as omega-hydroxyemodin and 2-hydroxyemodin. Emodin glycoside is carried unabsorbed to the large intestine, where it is metabolized to the active aglycones by intestinal bacterial flora. (A3043, A3046)

Agents that are used to stimulate evacuation of the bowels.

Agents that inhibit PROTEIN KINASES.

Absorption, excretion, tissue distribution and metabolism of the anthraquinone [14C]emodin was studied after a single oral administration (approx. 50 mg/kg) to rats. Urinary excretion amounted to 18(+/- 5)% dose in 24 hr and to 22(+/- 6)% in 72 hr. Metabolites found in pooled urine (0-72 hr) were mostly free anthraquinones (emodin and emodic acid, 16% dose); 3% was conjugated and 3% was non-extractable radioactivity. In 24 hr, 48 +/- 11% and in 120 hr, 68 +/- 8% dose was excreted in the faeces, mostly in the free anthraquinone form. In two cannulated rats biliary excretion reached a maximum at approx. 6 hr and amounted to 49% dose within 15 hr; 70% of biliary activity was in the form of conjugated emodin. The content of radioactivity in most organs decreased significantly between 3 and 5 days. In kidneys, however, the 14C activity was still equiv. to 4.33 ppm. emodin after five days. Mesenterium and fat tissue showed increasing 14C activity from 72 to 120 hr.

Medicine (cathartic)

This compound is used as a cathartic and a dye intermediate.

Emodin is a mycotoxin and naturally occurring anthraquinone present in the roots and barks of numerous plants, such as rhubarb. It is an active ingredient of Chinese herbs, including Rheum officinale and Polygonam cuspidatum. Emodin is also produced as a secondary metabolite by molds and lichens such as Aspergillus wentii. It has been used as a laxative and also investigated as a potential chemotherapeutic drug. (A3043)