6-Methylcoumarin

Somewhat dry, herbaceous (tonka-like) odor; also characterized as a delicate fig or date sweetness.

Coconut odor

Almost bitter taste above 50 ppm, turning sweet and vanilla-like at lower levels.

Sweet, coconut taste

Vanilla flavor

White, crystalline solid

White needles from benzene

Insoluble (NTP, 1992)

Very slightly sol in hot water; insol in petroleum ether; sol in oils.

soluble in alcohol /both alpha and beta forms/

Very soluble in ethanol, ether, benzene; slightly soluble in chloroform

Insoluble in water; soluble in oils

soluble (in ethanol)

266 °F (NTP, 1992)

577 °F at 725 mmHg (NTP, 1992)

304 °C

When heated to decomposition it emits acrid smoke and irritating fumes.

167 to 169 °F (NTP, 1992)

76.5 °C

Exists as alpha and beta forms, melting point(alpha): 90 °C, melting point (beta): 82 °C; both forms are soluble in alcohol; combustible

76.5 °C

6-methylcoumarin appears as white crystals with a flavor of vanilla. Insoluble in water. (NTP, 1992)

White solid; [HSDB]

Solid

White crystal solid; coconut-like aroma

1545；1564；1574；1545；1545

1588；1618

2551；2560；2630；2630

Congealing point: >73.5 °C

UV: 375 (Sadtler Research Laboratories Spectral Collection) /Coumarin, 3-methyl/

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]；H319 (95%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P264, P264+P265, P270, P280, P301+P317, P305+P351+P338, P330, P337+P317, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 1613 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: 2H-1-Benzopyran-2-one, 6-methyl-

Hazard Traits - Fragrance Allergen；Authoritative List - Annex III of the EU Cosmetics Regulation No. 1223/2009 - Fragrance Allergens；Report - if present in a rinse-off cosmetic product at a concentration at or above 0.01 percent (100 parts per million) or in a leave-on cosmetic product at a concentration at or above 0.001 percent (10 parts per million)

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

2H-1-Benzopyran-2-one, 6-methyl-: Does not have an individual approval but may be used under an appropriate group standard

IMAP assessments - Coumarins: Human health tier II assessment

This chemical is combustible. (NTP, 1992)

SYMPTOMS: This compound may cause photo-allergic reactions.；ACUTE/CHRONIC HAZARDS: This compound is a mild irritant. (NTP, 1992)

Emergency treatment: Coumarin; After an ingestion of 4 grams of coumarin, a patient developed muscle paralysis but no cardiovascular effects; Causes liver toxicity in rats, but humans are relatively resistant; Not active as an anti-coagulant; [HSDB] Causes seizures at lethal doses in mice; [RTECS] Caused photoallergic contact dermatitis when it was used as a fragrance in sunscreens; When patch tested, the antigen should be applied to the skin for no longer than 30 minutes before UVA exposure because it rapidly becomes inactive. [Marks, p. 224] Safe to use as a flavoring agent in food; [JECFA] Harmful by ingestion; A photosensitizer; [Aldrich MSDS]

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

BIBRA working group; TA:Toxicity profile. BIBRA Toxicology International:5 (1995).

Esters, such as 6-METHYLCOUMARIN, react with acids to liberate heat along with alcohols and acids. Generates heat with strong oxidizing acids. The reaction may be sufficiently exothermic to ignite the reaction products. Also generates heat with basic solutions. Generates flammable hydrogen with alkali metals and hydrides. Emits acrid smoke and irritating fumes when heated to decomposition.

Insoluble in water.

Acute Tox. 4 (100%)；Eye Irrit. 2 (95%)

Acute toxicity - category 4

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

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)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.；STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

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.

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)

The following drugs ... may increase ... response to coumarin or indandione derivatives: alcohol (acute intoxication), allopurinol, aminosalicylic acid, amiodarone, anabolic steroids, chloral hydrate, chloramphenicol, cimetidine, clofibrate, co-trimoxazole, danazol, dextrothyroxine sodium, diazoxide, diflunisal, disulfiram, erythromycin, ethacrynic acid, fenoprofen calcium, glucagon, ibuprofen, indomethacin, influenza virus vaccine, isoniazid, meclofenamate, mefenamic acid, methylthiouracil, metronidazole, miconazole, nalidixic acid, neomycin (oral), pentoxifylline, phenylbutazone, propoxyphene, propylthiouracil, quinidine, quinine, salicylates, streptokinase, sulfinpyrazone, sulfonamides, sulindac, tetracyclines, thiazides, thyroid drugs, tricyclic antidepressants, urokinase, vitamin E. /Coumarin & indandione derivatives/

The following drugs ... may ... decrease ... response to coumarin or indandione derivatives: alcohol (chronic alcoholism), barbiturates, carbamazepine, corticosteroids, corticotropin, ethchlorvynol, glutethimide, griseofulvin, mercaptopurine, methaqualone, oral contraceptives containing estrogen, rifampin, spironolactone, vitamin K. /Coumarin & indandione derivatives/

Neurotoxin - Other CNS neurotoxin；Dermatotoxin - PACD (photoallergic contact dermatitis).

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=92-48-8]

/HUMAN EXPOSURE STUDIES/ A Maximization test was carried out on 25 human volunteers. The material was tested at a concn of 4% in petrolatum and produced no sensitization reactions.

/HUMAN EXPOSURE STUDIES/ 6-Methylcoumarin, a fragrance material, is a photocontact allergen.

/HUMAN EXPOSURE STUDIES/ The test agent is applied for 24 hr followed by exposure to 3 minimal erythema doses (med) of solar simulated radiation twice weekly for 3 wk (6 exposures) in a panel of 25 white caucasians. The subjects are challenged 2 wk later with long-wave uv radiation. 6-Methylcoumarin gave a high rate of sensitization.

/SPECIAL STUDIES/ ...Topical pretreatment of /human reconstituted epidermis/ (Episkin), with weak phototoxic compounds /including methyl coumarin/ induced, after UVA exposure, a dose-dependent decr in cell viability, in concordance with an increasing IL-1alpha release. Moreover, compared to chlorpromazine, the lower IL-1alpha release observed with 6-methylcoumarin and ofloxacin could be linked to their weak phototoxic potential. ...

/LABORATORY ANIMALS: Acute Exposure/ 15 exposures of 6-methylcoumarin to the shoulder skin of guinea pigs that had been abraded with a nylon brush rotating @ 13,000 rpm and irradiated with broadband uv irradiation for a 3 wk induction period induced and elicited photoallergic contact dermatitis.

/LABORATORY ANIMALS: Acute Exposure/ More than 85% of the guinea pigs tested developed photoallergic contact dermatitis. The sensitivity could be detected in 45% of the sensitized animals using 1%, although no reaction was seen with 0.1%.

/LABORATORY ANIMALS: Acute Exposure/ ...Applied full strength to intact or abraded rabbit skin for 24 hr under occlusion was mildly irritating...

/LABORATORY ANIMALS: Acute Exposure/ A male dog fed 150 mg.../kg had to be killed after 39 days because of weakness, emaciation and dehydration, and showed moderate to severe hepatitis and slight to moderate muscle atrophy.

For more Non-Human Toxicity Excerpts (Complete) data for METHYL COUMARIN (12 total), please visit the HSDB record page.

Human exposure to second-generation and indandione anticoagulants produces symptoms consistent with anticoagulation effects (e.g., hematomas, hematemesis, hematuria, easy bruisability). Treatment of cases of exposure, particularly of substantial and repeated exposure, may require vitamin K1 therapy and monitoring of prothrombin times for periods of many months.

LD50 Rat oral 1,680 mg/kg

LD50 Mouse subcutaneous 253 mg/kg

Chemical: 2H-1-Benzopyran-2-one, 6-methyl-

Hazard Traits - Fragrance Allergen；Authoritative List - Annex III of the EU Cosmetics Regulation No. 1223/2009 - Fragrance Allergens；Report - if present in a rinse-off cosmetic product at a concentration at or above 0.01 percent (100 parts per million) or in a leave-on cosmetic product at a concentration at or above 0.001 percent (10 parts per million)

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

2H-1-Benzopyran-2-one, 6-methyl-: Does not have an individual approval but may be used under an appropriate group standard

...6-Methylcoumarin... undergoes direct photolysis with an estimated half-life of 83 min when illuminated with mid-latitude U.S., noon-centered, equinox sunlight and a quantum yield for photolysis at 313 nm of phi=3 x 10(-3). .../There is/ evidence that singlet molecular oxygen ((1)O2) is formed in illuminated solns containing 6-MC. An estimated value of phi=0.01 is reported for the (1)O2 quantum yield at 313 nm. Formation of (1)O2 is significant because it is known to react with a variety of biomolecules and it is possible that (1)O2 formation is at least partially responsible for reports of 6-MC photoallergenicity and phototoxicity.

Both 4-hydroxycoumarin derivatives and indandiones (also known as oral anticoagulants) are antagonists of vitamin K. Their use as rodenticides is based on the inhibition of the vitamin K-dependent step in the synthesis of a number of blood coagulation factors. The vitamin K-dependent proteins ...in the coagulation cascade... are the procoagulant factors II (prothrombin), VII (proconvertin), IX (Christmas factor) and X (Stuart-Prower factor), and the coagulation-inhibiting proteins C and S. All these proteins are synthesized in the liver. Before they are released into the circulation the various precursor proteins undergo substantial (intracellular) post-translational modification. Vitamin K functions as a co-enzyme in one of these modifications, namely the carboxylation at well-defined positions of 10-12 glutamate residues into gamma-carboxyglutamate (Gla). The presence of these Gla residues is essential for the procoagulant activity of the various coagulations factors. Vitamin K hydroquinone (KH2) is the active co-enzyme, and its oxidation to vitamin K 2,3-epoxide (KO) provides the energy required for the carboxylation reaction. The epoxide is than recycled in two reduction steps mediated by the enzyme KO reductase... . The latter enzyme is the target enzyme for coumarin anticoagulants. Their blocking of the KO reductase leads to a rapid exhaustion of the supply of KH2, and thus to an effective prevention of the formation of Gla residues. This leads to an accumulation of non-carboxylated coagulation factor precursors in the liver. In some cases these precursors are processed further without being carboxylated, and (depending on the species) may appear in the circulation. At that stage the under-carboxylated proteins are designated as descarboxy coagulation factors. Normal coagulation factors circulate in the form of zymogens, which can only participate in the coagulation cascade after being activated by limited proteolytic degradation. Descarboxy coagulation factor

Cytoplasm；Extracellular

Used in perfumes and flavors; Coumarin banned in US since 1954 as a flavor in food; It may contaminate vanilla imported from Mexico and Caribbean countries; [HSDB]

Perfumes; Flavoring

Useful in coconut flavors, vanilla, caramel.

6-Methylcoumarin

2H-1-Benzopyran-2-one, 6-methyl; 6-Methyl-2h-1-benzopyran-2-one; 6-Methylbenzopyrone; 6-Methyl coumarin; 6-Methyl-cis-o-coumarinic lactone; 5-Methyl-2-hydroxyphenylpropenoic acid lactone; Toncarine (commercial name)

IFRA_STD_160.pdf

40

IFRA 51st Amendment - Guidance for the use of IFRA Standards

Prohibition: This material should not be used as a fragrance ingredient

By heating 6-methyl coumarin-3-carboxylic acid to 300-340 °C; by condensation of p-cresoldisulfonic acid with fumaric acid in the presence of H2SO4; by condensation of p-homosalicylic aldehyde with malonic acid in the presence of aniline, followed by heating to form the lactone; from salicylaldehyde with propionic anhydride and sodium propionate.

Cosmetics product ingredient: 6-Methylcoumarin (6-Methyl Coumarin)；6-Methyl coumarin is a fragrance allergen. Fragrance allergens are hazardous only to individuals who suffer from fragrance allergies. The Cosmetic Fragrance and Flavor Ingredient Right to Know Act of 2020 requires fragrance allergens included in Annex III of the EU Cosmetics Regulation No. 1223/2009 be reported to the California Department of Public Health. Fragrance allergens are only required to be reported if present in a rinse-off cosmetic product at a concentration at or above 0.01 percent (100 parts per million) or in a leave-on cosmetic product at a concentration at or above 0.001 percent (10 parts per million).；For more information, you can visit the fragrance allergens webpage on the California Safe Cosmetics Program website:；https://www.cdph.ca.gov/Programs/CCDPHP/DEODC/OHB/CSCP/Pages/FragranceAllergens.aspx；Product count: 9

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

2H-1-Benzopyran-2-one, 6-methyl-: ACTIVE

Non-alcoholic beverages 5.2 ppm; ice cream, ices 4.8 ppm; candy 21 ppm; baked goods 24 ppm; gelatins and puddings 39 ppm; chewing gum 0.80-15 ppm.

In public use since the 1920's. Use in fragrances in the USA amount to <1,000 lb/yr. Concentration in final product (%): soap: usual 0.01, max 0.1; detergent: usual 0.001, max 0.01; creams, lotions: usual 0.005, max 0.03; perfume: usual 0.04, max 0.4.

FEMA NUMBER 2699

6-Methylcoumarin was given GRAS status by /the Flavor and Extract Manufacturers Association/ (FEMA) (1965). The council of Europe (1974) included 6-methylcoumarin at a level of 30 ppm in the list of artificial flavoring substances that may be added to foodstuffs without hazard to public health.