Dihydrocoumarin

Herbal

Odor similar to coumarin at room temp or reminiscent of nitrobenzene at higher temp.

Coconut odor

Hay-like

Sweet then bitter

Burning

1.169 at 64 °F (NTP, 1992) - Denser than water; will sink

1.169 @ 18 °C

1.186-1.192

Leaflets

White to light yellow, oily liquid

Colorless crystals

less than 1 mg/mL at 68 °F (NTP, 1992)

Slightly soluble in ether and carbon tetrachloride

1:2.5-3.5 IN 70% ALCOHOL

Soluble in chloroform.

Soluble in chlorinated solvents

In water, 3,000 mg/l at 37 °C

266 °F (NTP, 1992)

130 °C

130 °C

522 °F at 760 mmHg (NTP, 1992)

272 °C

271.00 to 272.00 °C. @ 760.00 mm Hg

272 °C

77 °F (NTP, 1992)

25 °C

25 °C

13.4 mmHg at 77 °F ; 19.5 mmHg at 108 °F; 27.4 mmHg at 145 °F (NTP, 1992)

13.4 [mmHg]

Index of refraction: 1.5563 @ 20 °C/D

1.555-1.559

3,4-dihydrocoumarin is a white to pale yellow clear oily liquid with a sweet odor. Solidifies around room temperature. (NTP, 1992)

White to light yellow liquid; Colorless solid; [HSDB] Low melting solid; mp = 24-26 deg C; [MSDSonline]

Solid

colourless to pale yellow liquid; coconut-like aroma

Warning

H302 (> 99.9%): Harmful if swallowed [Warning Acute toxicity, oral]；H317 (97.4%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P261, P264, P270, P272, P280, P301+P317, P302+P352, P321, P330, P333+P317, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 1702 reports by companies from 11 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, 3,4-dihydro-

Commission Regulation (EC) No 1565/2000 (Repealed by Com.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

Status: Active Update: 05-05-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/22066

Dihydrocoumarin: Does not have an individual approval but may be used under an appropriate group standard

Emergency treatment: Coumarin; After an ingestion of 4 grams of coumarin, a patient developed muscle paralysis but no cardiovascular effects; Has liver toxicity in rats, but humans are relatively resistant; Not active as an anti-coagulant; [HSDB] Safe when used as a flavoring agent in food; [JECFA] A tumorigen and irritant; Caused somnolence in lethal-dose feeding studies of rats; [RTECS] A skin, eye, and mucous membrane irritant; [CAMEO] An irritant; [MSDSonline] See Coumarin.

Opdyke DL; J Food Cosmet Toxicol 12 (4): 521 (1974). Review with 9 references on irritation, sensitization and toxicity of dihydrocoumarin.

DHHS/NTP; Toxicology & Carcinogenesis Studies of 3,4-Dihydrocoumarin in F344/N Rats and B6C3F1 Mice (Gavage Studies) Technical Report Series No. 423 (1993) NIH Publication No. 93-3154

3,4-DIHYDROCOUMARIN is a lactone (behaves as an ester). Esters react with acids to liberate heat along with alcohols and acids. Strong oxidizing acids may cause a vigorous reaction that is sufficiently exothermic to ignite the reaction products. Heat is also generated by the interaction of esters with caustic solutions. Flammable hydrogen is generated by mixing esters with alkali metals and hydrides. This chemical may hydrolyze under alkaline or acidic conditions. (NTP, 1992)

Acute Tox. 4 (> 99.9%)；Skin Sens. 1 (97.4%)

Acute toxicity - category 4；Skin sensitisation - category 1

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: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% 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 at ambient temperatures. STORE AWAY FROM SOURCES OF IGNITION. (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/

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=119-84-6]

3,4-Dihydrocoumarin

TR-423: Toxicology and Carcinogenesis Studies of 3,4-Dihydrocoumarin (CASRN 119-84-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies) (1993 )

06/23/92

Some Evidence

No Evidence

No Evidence

/LABORATORY ANIMALS: Acute Exposure/ ...Decreased /nasal/ P450 levels were observed /in rats/ at 24 hr, 48 hr, and 7 days following /a single ip injection of 50 mg/kg coumarin/, with minimal levels seen at 48 hr. The decr in P450 levels was accompanied by necrosis, cell loss, and basal cell metaplasia in the olfactory mucosa. Ip injection of 7-hydroxycoumarin or 3,4-dihydrocoumarin at 50 mg/kg did not result in depletion of nasal P450... .

/LABORATORY ANIMALS: Acute Exposure/ ...3,4-Dihydrocoumarin (DHC), which is not a mouse lung carcinogen, did not cause Clara cell injury when dosed to mice at 800 mg/kg. This finding suggests, because DHC lacks a 3,4-double bond, that bioactivation of coumarin to a 3,4-epoxide intermediate may contribute to mouse lung Clara cell toxicity. ...

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ...The effects of ...admin over a 13 wk period of coumarin and three coumarin derivatives, dihydrocoumarin (DHC), 3,4-dimethylcoumarin (3,4-DMC), and 6-methylcoumarin (6-MC) were compared. Coumarin was administered at dietary levels of 0.5 and 0.75% and 3,4-DMC was administered at equimolar dietary levels of 0.6 and 0.9%, respectively. DHC and 6-MC were administered at dietary levels of 0.76 and 0.82%, respectively, equimolar to the 0.75% coumarin dietary level. ...Rats fed equimolar doses of DHC, 3,4-DMC, or 6-MC showed increased relative liver weight and hepatic gamma-glutamyltransferase activity; however, these compounds did not produce any marked hepatotoxic effects. ...

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ...Under the conditions of these 2 yr gavage studies, there was some evidence of carcinogenic activity of 3,4-dihydrocoumarin in male F344/N rats based on increased incidences of renal tubule adenomas and focal hyperplasia. The transitional cell carcinomas in two 600 mg/kg males may also have been chemical related. There was no evidence of carcinogenic activity of 3,4-dihydrocoumarin in female F344/N rats receiving 150, 300, or 600 mg/kg. There was no evidence of carcinogenic activity of 3,4-dihydrocoumarin in male B6C3FI mice receiving 200, 400, or 800 mg/kg. There was some evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined).

/GENOTOXICITY/ Results from two Salmonella typhimurium gene mutation tests with or without S9 were negative.

Toxicity and carcinogenicity studies were conducted by administering 3,4-dihydrocoumarin (99% pure) in corn oil by gavage to groups of male and female F344/N rats and B6C3F1 mice for ... 2 yr. ... 2 YEAR STUDY IN MICE: Groups of 70 male and 70 female mice received 3,4-dihydrocoumarin in corn oil by gavage at doses of 0, 200, 400 or 800 mg/kg body weight. ... 2 YEAR STUDY IN RATS: Groups of 60 male and female rats received 3,4-dihydrocoumarin in corn oil by gavage at doses of 0, 150, 300, or 600 mg/kg body weight. ... CONCLUSIONS: Under the conditions of these 2 yr gavage studies, there was some evidence of carcinogenic activity of 3,4-dihydrocoumarin in male F344/N rats based on increased incidences of renal tubule adenomas and focal hyperplasia. The transitional cell carcinomas in two 600 mg/kg males may also have been chemical related. There was no evidence of carcinogenic activity of 3,4-dihydrocoumarin in female F344/N rats receiving 150, 300, or 600 mg/kg. There was no evidence of carcinogenic activity of 3,4-dihydrocoumarin in male B6C3FI mice receiving 200, 400, or 800 mg/kg. There was some evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined).

LD50 Rat oral 1460 mg/kg

LD50 Mouse ip 200 mg/kg

LD50 Guinea pig oral 1760 mg/kg

Chemical: 2H-1-Benzopyran-2-one, 3,4-dihydro-

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

Status: Active Update: 05-05-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/22066

Dihydrocoumarin: Does not have an individual approval but may be used under an appropriate group standard

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

Used in perfumes and flavors--has GRAS status in US; [HSDB]

...Used in perfumery industry for its haylike odor.

It has GRAS status and can be used as a food flavor ingredient with a sweet caramel-like taste.

... In woodruff-type flavor compositions.

(1977) 2.00X10+5 GRAMS (PRINCPL CUSTMS DISTS)

(1979) 2.25X10+5 GRAMS (PRINCPL CUSTMS DISTS)

(1974) 4.5X10+6 G-MAX CONSUMPTION AS FRAGRANCE

(1979) PROBABLY GREATER THAN 1.36X10+6 GRAMS

The U.S. market is estimated at 50 tons/yr.

Dihydrocoumarin

Dihydrocoumarin; 1,2-Benzodihydropyrone; 2H-1-Benzopyran-2-one, 3,4-dihydro-; Chroman-2-one; 2-Chromanone; 3,4-Dihydro-2H-1-benzopyran-2-one; o-Hydroxydihydrocinnamic acid lactone; Melilotic acid lactone; Melilotic lactone (commercial name)

IFRA_STD_029.pdf

51

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

Restriction: This material should be used only in the limited quantity as stated in the Standard

Fragrance Ingredients

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

2H-1-Benzopyran-2-one, 3,4-dihydro-: ACTIVE

Regulatory status of direct food additives: limitations; dihydrocoumarin, synthetic flavor.

Reported uses: non-alcoholic beverages, 7.8 ppm; ice cream, ices, etc, 21 ppm; candy, 44 ppm; baked goods, 28 ppm; gelatins and puddings, 10 ppm; chewing gum, 78 ppm. Regulatory status: FDA status not fully defined; FEMA No 2381.

Useful in vanilla, butter, cream soda, tobacco flavors.

By reduction of coumarin under pressure in presence of nickel at 160-200 °C (Tetralin Gesellschaft, German Patent 355,650) or in presence of palladium-barium sulfate in alcoholic solution (Paal & Schiedewitz, ber Dtsch Chem Ges, 63, 775, 1930).

0.038 [Products applied to the lips]

0.011 [Products applied to the axillae]

0.23 [Products applied to the face/body using fingertips]

0.21 [Products related to fine fragrances]

0.053 [Products applied to the body using the hands (palms), primarily leave-on (Body lotion)]

0.053 [Products applied to the face using the hands (palms), primarily leave-on (Face moisturizer)]