HuagongsheHuagongshe Chemistry Print Report · For research reference only
Skatole
SKATOLE · 3-METHYL-1H-INDOLE · Indole, 3-methyl- · FEMA 3019 · 3-Methylindole (skatole) · 3-MI · scatol · SCATOLE
Identifiers & Physical Properties
| CAS No. | 83-34-1 |
|---|---|
| Molecular formula | C9H9N |
| Average molar mass | 131.17 g/mol |
| Monoisotopic mass | 131.07349929 g/mol |
| SMILES | Cc1c[nH]c2ccccc12 |
| InChIKey | ZFRKQXVRDFCRJG-UHFFFAOYSA-N |
| PubChem CID | 6736 |
| ChEMBL | CHEMBL1329793 |
| ChEBI | CHEBI:9171 |
| EC No. | 201-471-7 |
| DTXSID | DTXSID8021775 |
Chemical & Physical Properties
| XLogP | 2.6 |
|---|---|
| Topological polar surface area | 15.8 |
| Hydrogen bond donors | 1 |
| Hydrogen bond acceptors | 0 |
| Rotatable bonds | 0 |
| Heavy atoms | 10 |
| Formal charge | 0 |
| Complexity | 122 |
| Chemical classes | Nitrogen Compounds -> IndolesWaste-water effluent contaminant |
| SpringerMaterials Properties | Angular frequency |
| Fragrances | Fragrance Ingredient (Skatole) -> IFRA transparency List |
| LogP (partition coefficient) | LogP= 2.60 |
| Odor | CHARACTERISTIC FECAL ODOR AT HIGH LEVELS, BECOMING PLEASANT, SWEET, AND WARM AT VERY LOW LEVELSindole-like odor |
| Taste | WARM, OVER-RIPE, FRUITY FLAVOR BELOW 0.1 PPM |
| Food additives | FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT -> FDA Substance added to food |
| Flavoring agents | EU Flavoring substances |
| Color/Form | LEAVES FROM PETROLEUM ETHERWHITE-BROWN SCALESWhite crystalline substance, browning upon aging. |
| Solubility | SOL IN HOT WATER, ALC, BENZENE, CHLOROFORM, ETHERSOL IN ACETONE, WATER, ETHANOL, ETHER0.498 mg/mLSoluble in boiling waterSoluble (in ethanol)6.8 [ug/mL] (The mean of the results at pH 7.4)Chloroform (Slightly), Methanol (Slightly)Soluble in water, Ether, Alcohols, Benzene, Acetone, Chloroform. |
| Boiling point | 265-266 °C @ 755 MM HG265.00 to 266.00 °C. @ 755.00 mm Hg265-266 °C (lit.) |
| Melting point | 95 °C97.5 °C92-97 °C (lit.) |
| Density | 1.0111 (estimate) |
| Refractive index | 1.6070 (estimate) |
| FEMA | 3019 | SKATOLE |
| FLAVIS Number | 14.004 | 3-Methylindole |
| Flash point | 132 °C |
| Storage conditions | Store below +30°C. |
| Physical state | Crystalline Powder or Flakes |
| pKa (acidity coefficient) | 17.30±0.30(Predicted) |
| Color | Almost white to pale brown |
| Odor threshold | 0.0000056ppm |
| Odor type | animal |
| Biological source | synthetic |
| Sensitivity | Light Sensitive |
| Merck | 14,8560 |
| JECFA Number | 1304 |
| BRN | 111296 |
| Henry's law constant | 2.9×10-5 mol/(m3Pa) at 25℃, Wetlaufer et al. (1964) |
| Stability | Stable, but light-sensistive. Stench! Incompatible with strong oxidizing agents, strong acids, acid ahydrides, acid chlorides. Combustible. |
| Major applications | flavors and fragrances |
| Cosmetics Ingredients Functions | PERFUMING |
| InChI | 1S/C9H9N/c1-7-6-10-9-5-3-2-4-8(7)9/h2-6,10H,1H3 |
| InChIKey | ZFRKQXVRDFCRJG-UHFFFAOYSA-N |
| SMILES | Cc1c[nH]c2ccccc12 |
| LogP (partition coefficient) | 2.60 |
| Substances Added to Food (formerly EAFUS) | SKATOLE |
| FDA 21 CFR | 172.515 |
| CAS DataBase Reference | 83-34-1(CAS DataBase Reference) |
| EWG's Food Scores | 1 |
| FDA UNII | 9W945B5H7R |
| NIST Chemistry Reference | 1H-Indole, 3-methyl-(83-34-1) |
| EPA Substance Registry System | 3-Methylindole (83-34-1) |
| UNSPSC Code | 85151701 |
| NACRES | NA.24 |
| GHS pictogram | GHS09 |
| Signal word | Warning |
| GHS hazard statements | H411 |
| GHS precautionary statements | P273-P391-P501 |
| Hazard symbols | Xi,N |
| Risk statements (R) | 36/37/38-51/53 |
| Safety statements (S) | 26-36-61 |
| UN transport number | UN3077 - class 9 - PG 3 - DOT/IATA UN3335 - Environmentally hazardous substances, solid, n.o.s., HI: all (not BR) |
| Water hazard class (WGK) | 2 |
| RTECS number | NM0350000 |
| F | 8-13 |
| TSCA inventory status | TSCA listed |
| Customs code | 29339920 |
| Storage class | 11 - Combustible Solids |
| Hazard class | Aquatic Chronic 2 |
| Hazardous substances data | 83-34-1(Hazardous Substances Data) |
| Toxicity | MLD in frogs (mg/kg): 1000 s.c. (Bin-Ichi) |
| REACH registrations | Inactive |
Safety & Regulations
| GHS classification | This chemical does not meet GHS hazard criteria for 76% (304 of 400) of all reports.WarningH315 (19.5%): Causes skin irritation [Warning Skin corrosion/irritation]P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 400 reports by companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatory information | Chemical: 1H-Indole, 3-methyl-Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)Status: Cease Manufacture Update: 21-11-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/235051H-Indole, 3-methyl-: Does not have an individual approval but may be used under an appropriate group standard |
| Other safety information | IMAP assessments - 1H-Indole, 3-methyl-: Human health tier I assessment |
| Hazards summary | Caused no irritation in humans following 24 hour closed patch test (2% in petrolatum)[HSDB] Lethal doses by intravenous and oral routes produced pulmonary lesions in cattle[RTECS] Safe when used as a flavoring agent in food[JECFA] See Indole. |
| Hazard Classes and Categories | Skin Irrit. 2 (19.5%) |
| Cleanup methods | CHEM SCRUBBING SYSTEMS ARE ATTRACTIVE FOR CONTINUOUSLY HANDLING LARGE VOL OF GAS CONTAINING VERY LOW CONCN OF POTENT ODORANTS. THESE SYSTEMS USUALLY FUNCTION BY OXIDN OF THE ODORANT. THE ODOR CONTROL OF SKATOLE IS DISCUSSED FOR EACH OF THE OXIDIZERS: NAOCL, CL2, KMNO4, AND O3.TWO TYPES OF AIR WASHERS, CROSS-CURRENT AND COUNTERCURRENT, WERE INSTALLED IN THE VENTILATION OF THE EXHAUST SYSTEM IN LIVESTOCK AND POULTRY FARMS, TO DEODORIZE THE AIR. ACTIVATED SLUDGE FROM A SEWAGE PLANT WAS ADDED TO THE CIRCULATING WATER. WASH WATER SAMPLES CONTAINED SKATOLE. |
| Disposal methods | 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. |
| Environmental fate | TERRESTRIAL FATE: A methanogenic consortium, enriched from wetland soil completely mineralized 13 mg of 3-methylindole within 35 days(1). Based on a recommended classification scheme(2), an estimated Koc value of 600(SRC), indicates that 3-Methylindole will have low mobility in soil(SRC). Volatilization of 3-methylindole may occur slowly from moist soil surfaces(SRC) given an estimated Henry's Law constant of 2.1X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(3).AQUATIC FATE: Based on a recommended classification scheme(1), an estimated Koc value of 600(SRC), determined from a structure estimation method(2), indicates that 3-methylindole is expected to adsorb to suspended solids and sediment in water(SRC). 3-Methylindole will volatilize from water surfaces(1,SRC) based on an estimated Henry's Law constant of 2.1X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). Estimated half-lives for a model river and model lake are 20 and 148 days, respectively(1,SRC). According to a classification scheme(5), an estimated BCF value of 56(1,SRC), from an experimental log Kow(4), suggests that bioconcentration in aquatic organisms is moderate, not high(SRC). When exposed to natural sunlight 3-methylindole may undergo photo-oxidative degradation. The aqueous rate constant for the photolysis of 3-methylindole was measured as 0.18 hr-1 with a half life of 3.8 hours(6). The major product of the aqueous photo-oxidative degradation of 3-methylindole is thought to be o-(N-formyl)aminoacetophenone(6).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3-Methylindole, which has an extrapolated vapor pressure of 0.005 mm Hg at 25 °C(4,SRC), will exist primarily as a vapor in the ambient atmosphere. Vapor-phase 3-methylindole 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 about 0.64 hours(3,SRC). |
| Food survey values | Cheese products obtained from dairy cattle in the French Alps were found to contain 3-methylindole(1). No concentration data are currently available. |
| Effluent Concentrations | Unspecified concentrations of 3-methylindole were detected in the secondary effluents of a municipal wastewater treatment facility in Addison Illinois(1). |
| Soil Adsorption/Mobility | The Koc of 3-methylindole is estimated as approximately 600(SRC), using an experimental log Kow of 2.60(1,SRC) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that 3-methylindole has low mobility in soil(SRC). The value of Koc may be influenced by the pH of the soil for this compound due to the basic nature of the amine group(SRC). |
| Natural Pollution Sources | ...AFRICAN CIVET CATCELTIS RETICULOSA, A JAVANESE TREE.Common naturally occurring sources of 3-methylindole are feces, beetroot, and nectrandra wood(1,2). |
| Human Toxicity Excerpts | TESTED AT 2% IN PETROLATUM IT PRODUCED NO IRRITATION AFTER A 48-HR CLOSED-PATCH TEST ON HUMAN SUBJECTS.SKATOLE AND ITS METABOLIC INTERMEDIATES MAY BE RELATED TO HUMAN PATHOLOGICAL CONDITIONS, INCL MALABSORPTION SYNDROMES AND CERTAIN ANEMIAS AND HEPATIC COMA. 6-HYDROXYSKATOLE, THE MAJOR METABOLITE OF SKATOLE IN MAN, MAY BE A PSYCHOTROPIC SUBSTANCEIT IS EXCRETED AS THE SULFATE IN ELEVATED AMOUNTS IN THE URINE OF SOME SCHIZOPHRENIC PT. |
| Artificial Pollution Sources | 3-Methylindole's production and use in the fragrance industry and as a food additive(1,2) may result in its release to the environment through various waste streams(SRC). |
| Environmental Biodegradation | A methanogenic consortium, enriched from wetland soil completely mineralized 13 mg of 3-methylindole within 35 days(1). |
| Environmental Bioconcentration | An estimated BCF value of 56 was calculated for 3-methylindole(SRC), using an experimental log Kow of 2.60(4) and a recommended regression-derived equation(2). According to a classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms is moderate, not high(SRC). |
| Volatilization from Water/Soil | The Henry's Law constant for 3-methylindole is estimated as 2.1X10-6 atm-cu m/mole(SRC) from its extrapolated value for vapor pressure, 0.005 mm Hg(1), and experimental water solubility, 498 mg/l(2). This value indicates that 3-methylindole will volatilize from water surfaces(3,SRC). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec) is estimated as approximately 20 days(3,SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec) is estimated as approximately 148 days(3,SRC). 3-Methylindole's Henry's Law constant(1,2,SRC) indicates that volatilization from moist soil surfaces will not be important(SRC). |
| Non-Human Toxicity Excerpts | IN FROGS, THE MINIMUM LETHAL DOSE OF SKATOLE ADMIN SC OR INTO THE ABDOMINAL LYMPH SAC WAS 1 G/KGA PARALYTIC ACTION ON THE CENTRAL NERVOUS SYSTEM RESULTED IN A COMPLETE ABOLITION OF SPONTANEOUS REFLEX AND RESP MOVEMENTS. AN ORAL DOSE OF 0.3 G SKATOLE/KG GIVEN TO GOATS PRODUCED DIFFUSE PULMONARY EDEMA WHICH RESULTED IN DEATH, AND ORAL OR IV ADMIN TO COWS CAUSED PULMONARY LESIONS. DEATH FROM PULMONARY EDEMA & EMPHYSEMA RESULTED IN 3/3, 0/2 AND 1/3 COWS GIVEN 0.2 (ORAL), 0.1 (ORAL) AND 0.06 G/KG (IV IN PROPYLENE GLYCOL), RESPECTIVELY.MICE TREATED ORALLY WITH 100 MG SKATOLE/KG SHOWED NO SIGNS OF PULMONARY DISEASE. ORAL INGESTION OF 200 MG/KG BY MICE ALSO FAILED TO INDUCE PULMONARY EMPHYSEMA, BUT PULMONARY CONGESTION DID OCCUR, AS SHOWN BY A REDUCTION IN THE PHOSPHOLIPID CONTENT OF THE LUNG AND INCREASES IN HEMOGLOBIN CONTENT. ...WHEN MICE WERE GIVEN SKATOLE (10 MG/KG BODY WT) IP FOR 15 CONSECUTIVE DAYS...LESIONS OF THE LIVER, SPLEEN, KIDNEY AND LUNGS WERE PRESENT BUT SHOWED MARKED REGENERATION AFTER THE DOSE WAS STOPPED.RABBITS INJECTED IN THE KNEE JOINT WITH A SINGLE DOSE OF SKATOLE (0.26 MMOL IN 1 ML AQUEOUS 50% PROPYLENE GLYCOL) DEVELOPED ACUTE ARTHRITIS AND AN ACUTE INFLAMMATION ORIGINATING IN THE SYNOVIAL TISSUE, WHILE RABBITS INJECTED IN THE KNEE JOINT WITH 0.04-0.26 MMOL SKATOLE ONCE WEEKLY FOR 6 WK DEVELOPED CHRONIC ARTHRITIS, THE SEVERITY INCREASING WITH INCREASING DOSAGES. ...SKATOLE APPLIED FULL STRENGTH TO INTACT OR ABRADED RABBIT SKIN FOR 24 HR UNDER OCCLUSION WAS NOT IRRITATING.3-METHYLINDOLE (3MI) WAS ORALLY ADMIN AS A SINGLE DOSE OF 0.1-0.2 G/KG WHICH THEN PRODUCED ACUTE PULMONARY EDEMA IN CATTLE. LUNG TISSUE COLLECTED AFTER 72 HR REVEALED VESICULATION AND DESQUAMATION OF ALVEOLAR TYPE I CELLS AS WELL AS HYPERPLASIA OF THE ALVEOLAR TYPE II CELLS. HYALINE MEMBRANE FORMATION, ALONG WITH MASSIVE ACCUMULATION OF TUBULAR MYELIN IN THE ALVEOLAR SPACES, WAS OBSERVED. PULMONARY CAPILLARIES WERE OCCLUDED WITH MICROTHROMBI, AND LEUKOCYTES INFILTRATED THE INTERSTITIUM AS WELL AS THE ALVEOLI. ACCUMULATION OF LARGE AGGREGATES OF GLYCOGEN IN THE ALVEOLAR TYPE II CELLS WERE THE MOST UNUSUAL CHANGES SEEN IN EXPTL ANIMALS.THE PATHOLOGIC FEATURES OF BRONCHIOLITIS WERE STUDIED IN HORSES AND PONIES FROM 30 MIN TO 27 DAYS AFTER AN ORAL DOSE OF 3-METHYLINDOLE (3MI). FROM 30 MIN TO 3 HR, LESIONS WERE LIMITED TO NONCILIATED BRONCHIOLAR EPITHELIAL (CLARA) CELLS, WHICH LOST APICAL CAPS AND CYTOPLASMIC GRANULES AND HAD DILATED SMOOTH ENDOPLASMIC RETICULUM (SER). AT 12 HR, NECROTIC CLARA CELLS WERE EXFOLIATEDDEGENERATION AND NECROSIS WERE EVIDENT, IN BRONCHIOLAR CILIATED CELLS. RARE EPITHELIAL CELLS WITH HYPERPLASTIC SER APPEARED ON THE DENUDED BASAL LAMINA AT 24 HR. INFLAMMATORY CELLS, EPITHELIA, FIBROBLASTLIKE CELLS, COLLAGEN, AND DEBRIS OCCLUDED MANY BRONCHIOLAR LUMENS FROM 3 TO 6 DAYS. REORGANIZATION RESULTED IN A SIMPLE COLUMNAR BRONCHIOLAR EPITHELIUM WITH RELATIVELY NORMAL CILIATED CELLS AND FEWER FIBROBLASTLIKE CELLS. HOWEVER, MATURE CLARA CELLS WERE RARE AT 27 DAYS, AND COLLAGENOUS BANDS STILL DIVIDED BRONCHIOLAR LUMENS. |
| Environmental Abiotic Degradation | When exposed to natural sunlight the aqueous rate constant for the photolysis of 3-methylindole was measured as 0.18 hr-1 with a half life of 3.8 hours(1). The major product of the photo-oxidative degradation of 3-methylindole is thought to be o-(N-formyl)aminoacetophenone(1). The vapor-phase reaction of 3-methylindole with photochemically-produced hydroxyl radicals has been estimated as 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(2,SRC). This corresponds to an atmospheric half-life of about 0.64 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(3,SRC). |
| F | 8-13 |
| Water hazard class (WGK) | 2 |
| TSCA inventory status | TSCA listed |
| RTECS number | NM0350000 |
| UN transport number | UN3077 - class 9 - PG 3 - DOT/IATA UN3335 - Environmentally hazardous substances, solid, n.o.s., HI: all (not BR) |
| Customs code | 29339920 |
| Toxicity | MLD in frogs (mg/kg): 1000 s.c. (Bin-Ichi) |
| Risk statements (R) | 36/37/38-51/53 |
| Signal word | Warning |
| GHS pictogram | GHS09 |
| Hazard symbols | Xi,N |
| Safety statements (S) | 26-36-61 |
| Storage class | 11 - Combustible Solids |
| GHS hazard statements | H411 |
| REACH registrations | Inactive |
| Hazard class | Aquatic Chronic 2 |
| GHS precautionary statements | P273-P391-P501 |
| Hazardous substances data | 83-34-1(Hazardous Substances Data) |
Applications & Uses
Occurrence
Skatole is an indole derivative with a strong fecal odor that occurs naturally in feces formed due to the degradation of tryptophan. It is found in several flowers such as jasmine owing to its flowery smell when present in low concentration. Skatole is also one of the key contributors to the development of boar taint in fat samples.Reported found in beetroot, feces, coal tar, Swiss cheese, Gruyere cheese, mozarella cheese, butter, milk, goat and sheep milk, boiled egg, fatty fish, coffee, tea, trassi, rice bran, dried bonito and squid.
Uses
3-Methylindole is a naturally abundant pneumotoxin, found primarily in mammalian feces providing its strong fecal odor. In lower concentrations however, the compound has a pleasent aroma, giving orange blossoms and ja smine their pleasing scent. It is often a component of commercial fragrances and perfumes.It helps fluorescent guanosine analogue, which in a dimethoxytrityl, phosphoramidite protected form, can be site-specifically inserted into oligonucleotides through a 3'-5' phosphodiester linkage using an automated DNA synthesizer.
General Description
3-Methylindole (3-MI), commonly found in wine, dairy products, and other foodstuffs, leads to an unpleasant fecal like odor in pig meat products. It is reported to be produced in the intestines of several species by the microbial degradation of tryptophan.
Preparation & Synthesis
Preparation
Prepared synthetically from the phenylhydrazone of propionaldehyde or by cyclization of o-toluidides (Bedoukian, 1967).Industrial synthesis of 3-Methylindole: Propionaldehyde phenylhydrazone is obtained by heating propionaldehyde and phenylhydrazine to remove water molecules, and then heating with zinc chloride or sulfuric acid to remove ammonia molecules to obtain 3-Methylindole.3 Step Synthesis of 3-Methylindole (Skatole) via Hydroboration and Cyclization