코우마린

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Use water spray, foam, powder, carbon dioxide.

Fresh air, rest.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Refer for medical attention .

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.

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 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% 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 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.

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.

Incineration: Coumarin should be combined with paper or other flammable material. An alternate procedure is to dissolve the solid in a flammable solvent and spray the soln into the fire chamber.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants.

...Substitution of less irritating substances, ...redesign of operations...prevent contact, provision of a physical barrier against contact, proper washing facilities, work clothing and storage facilities, protective clothing, and barrier creams. Medical control... .

In 387 expired air samples from 54 normal subjects, 63.1% contained coumarin(1). The geometric mean concentration was 1.0(1). As part of EPA's National Human Adipose Tissue Survey, 46 composite adipose fat samples in FY82 were analyzed(2). One of these samples, from an over 45 yr age group from the northeast, contained coumarin.

Coumarin was a moderate inhibitor of 7,12-dimethylbenz(a)anthracene-induced neoplasia of rat mammary gland. It also inhibited benzo(a)pyrene-induced neoplasia of mouse forestomach.

The possibility that pretreatment with coumarin would inhibit the genotoxicity of benzo(a)pyrene was investigated in ICR mice. Male and female mice weighing 21 to 24 g were given coumarin in olive oil at doses of 65 g/kg or 139 mg/kg body weight by oral gavage. Controls received only olive oil. The animals were treated daily for 1 week with 1 day of no treatment at midweek. After the six treatments the animals were given benzo(a)pyrene injections (150 mg/kg in olive oil). At various times (12-72 hr) after the BP injection, ... bone marrow smears were examined for the presence of micronuclei in polychromatic erythrocytes. ... Pretreatment with coumarin alone did not cause formation in polychromatic erythrocytes in both males and females. In male animals treated with coumarin prior to benzo(a)pyrene treatment there was a statistically significant reduction in the number of micronucleated polychromatic erythrocytes. To clarify that this reduction was not due to a phase shift in the start of micronuclei production studies were conducted at several time intervals after benzo(a)pyrene injection. Again there was no micronuclei induction by coumarin alone and there was a significant reduction in benzo(a)pyrene induced micronuclei when male mice were pretreated with coumarin. This protective effect of coumarin pretreatment was not seen in female animals.

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/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a log Kow of 1.39(2) and a regression-derived equation(3), indicates that coumarin is expected to have high mobility in soil(SRC). Volatilization of coumarin from moist soil surfaces is not expected to be an important fate process(SRC) based upon a Henry's Law constant of 9.9X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 9.8X10-4 mm Hg(4), and water solubility, 1,900 mg/l(5). Coumarin is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 9.8X10-4 mm Hg(4). Coumarin is confirmed to be biodegradable according to the standard test of the Japanese Ministry of Industry and Trade (MITI) that employs a mixed inoculum obtained from freshwater, soil, and sludge(6). Therefore, biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a log Kow of 1.39(2) and a regression-derived equation(3), indicates that coumarin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon a Henry's Law constant of 9.9X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 9.8X10-4 mm Hg(3), and water solubility, 1,900 mg/l(4). According to a classification scheme(5), a BCF <10 in golden orfe(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). The lactone is hydrolyzed by alkalies to the corresponding salts of coumarinic acid or o-hydroxy-cis-cinnamic acid(8); however, no data are available concerning the hydrolysis of coumarin under environmental conditions. Coumarin is confirmed to be biodegradable according to the standard test of the Japanese Ministry of Industry and Trade (MITI) that employs a mixed inoculum obtained from freshwater, soil, and sludge(7). Therefore, biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), coumarin, which has a vapor pressure of 9.8X10-4 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase coumarin 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 29 hrs(SRC), calculated from its rate constant of 1.3X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase coumarin may be removed from the air by wet and dry deposition(SRC). 59.2% of the initial concn of coumarin was mineralized to CO2 when exposed to UV radiation >290 nm for 17 hr(4).

IDENTIFICATION: Coumarin occurs in fruits, roots, bark, stalks, leaves and branches of a wide variety of plants including Tonka bean, cassie, levender, lovage, yellow sweet clover, deer tongue and woodruff. It is used as a flavoring agent in food; a fixative and enhancer for the odor of essential oils in perfumes; in toilet soaps, toothpastes and in hair preparations; in tobacco products to enhance and fix the natural taste, flavor and aroma; and in industrial products to mask disagreeable odors. HUMAN EXPOSURE: Four male and four female volunteers were given 200 mg each of coumarin in a capsule. Most of dose was excreted in the first 24 hr, primarily as 7-hydroxycoumarin and another metabolic product O-hydroxyphenylacetic acid. Blood concentration time profiles calculated after oral or iv administration of coumarin to four male and two female adults indicated an open two compartment model. The major site of metabolism is the liver and the glucuronidation of the metabolites may occur at several sites, including the liver and intestinal wall along with other tissues. ANIMAL STUDIES: Coumarin administered to female Albino rats caused hyperglycemia which lasted about 24 hr. An oral dose of coumarin dissolved in Arachis oil administered daily for seven dats to virgin female Wistar rats resulted in a decrease in serum progesterone levels. Groups of six male rats were given coumarin in Arachis oil daily for seven days by oral intubation. There was no increase in relative liver weight at lower doses; however, there was a dose related increase at the highest dose tested. Histological changes at the highest dose consisted of fatty change abd vacuolar degeneration in the centrilobular hepatocytes. A centrilobular loss of G6P and aniline hydroxylase resulted at the two highest doses. Lysosomal and ultrastructural changes also occurred at the two highest doses; the latter consisted of hypertrophy and dilation of the rough endoplasmic reticulium in centrilobular hepatocytes, increases in the size of lysosomes and the number of autophagic vacoules. Dose related depression in cytochrome p-450 and aminopyridine demethylase also occurred at the two highest dose levels. Coumarin was fed for 32 weeks in the diet to DBA/2 mice and to CH3/HeJ mice. Minimal increases in serum glutamate oxalate transferase, gamma-glutamyl transferase and sorbitol dehydrogenase activities were noted, but no gross or microscopic liver lestions were reported. Coumarin was found to inhibit Uvr repair of ultraviolet induced lesions in Escherichia coli. Groups of pregnant mice were fed in the diet on days 6-17 of pregnancy. No increase in malformations at any dose was noted although delayed ossification and increased still births at the high dose group was found. Groups of three male and three female Orsborne-Mendel rats were fed coumarin in the diet for four weeks. Marked growth retardation, testicular atrophy and slight to moderate liver damage was noted. Liver damage consisted of dead and dying cells, a decrease in oxyphillia and cytoplasm in the centrilobular cells and proliferation of bile ducts. One male and one female dog were given coumarin by capsures 6 days/wk for up to 16 days. The male was sacrificed in extremis after nime days and the female was found dead on day 16. The livers were yellow colored and had a nutmeg appearance. Microscopically there was marked disorganization of the lobular pattern, moderate increase in the size of liver cells, vacoulation, a large amount of diffusely distributed fat, focal necrosis, fibrosis and a very slight to moderate bile duct proliferation. The spleen was pale colored and the bone marrow was thin and fatty and the gall bladder moderately distended. Groups of 4 to 8 male baboons of several species were fed coumarin in the diet for two years. No changes in body weight were noted. Relative liver weights were increased in the high dose animals. No treatment related effects on liver histology were observed in six to ten month biopsy specimens. No biliary hyperplasia or fibrosis was seen at any dose. Marked dilation of the endoplasmic reticulum was seen upon sultrastructural examination of the liver in three high dose animals.[

/ACCIDENTAL POISONINGS/ Coumarin, contained in sweetclover hay (melilotus spp), is converted to dicoumarin by molds under certain conditions. This compound interferes with prothrombin synthesis and results in hemorrhagic disease when molded sweetclover hay is ingested over period of time.

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=91-64-5]

Coumarin was detected in fine particle emissions from fireplace combustion of northeastern US woods at the following concns: 0.077, 0.049, 0.359, 0.110, 0.080, and 0.067 mg/g organic carbon from the residential fireplace burning of red maple, northern red oak, paper birch, eastern white pine, eastern hemlock, and balsam fir, respectively(1).

The Koc of coumarin is estimated as 140(SRC), using a log Kow of 1.39(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that coumarin is expected to have high mobility in soil.

REPORTED IN TONKA BEAN (DIPTERYX ODORATA) SEED, THE FLOWERS OF MELILOTUS OFFICIALIS, THE LEAVES OF MELILOTUS ALBUS, IN LIATRIS ODORATISSIMA, ASPERULA ODOROSA, WILD VANILLA (ACHLYS TRIPHYLLA), LAVENDER OIL, & SEVERAL VARIETIES OF ORCHID.

...FOUND IN EDIBLE PLANTS SUCH AS STRAWBERRIES, BLACKCURRENTS, APRICOTS, & CHERRIES...

Coumarin is a naturally occurring compound found in a large number of plants belonging to many different families, including tonka beans, lavender oil, woodruff (Asperula species), cassia, meliot and sweet clover (Melilotus)(1,2).

(a) Coumarin is the chemical 1,2-benzopyrone, C9H6O2. It is found in tonka beans and extract of tonka beans, among other natural sources, and is also synthesized. It has been used as a flavoring agent. (b) Food containing any added coumarin as such or as a constituent of tonka beans or tonka extract is deemed to be adulterated under the act, based upon an order published in the Federal Register of March 5, 1954 (19 FR 1239).

Occurs naturally in the tonka beans, Cassia, and lavender oils; [Marks, p. 172] Used in soaps, tobacco, pharmaceuticals, and rubber products; Also used in the fragrance industry and in the electroplating industry to polish chrome-plated steel; Coumarin banned in US since 1954 as a flavor in food, it may contaminate vanilla imported from Mexico and Caribbean countries; [HSDB] The anticoagulant warfarin (Coumadin) is synthesized from 4-hydroxycoumarin and benzalacetone with pyridine as a catalyst; Many coumarins are effective laser dyes; [Ullmann]

Electroplating [Category: Plate]

For Coumarin (USEPA/OPP Pesticide Code: 127301) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Formerly important as a flavor and perfume in foods and pharmaceuticals.

As deodorizing and odor enhancing agent in soaps, tobacco and rubber products.

Pharmaceutic aid (flavor).

2023: 8,500,000 - <10,000,000 lb

(1990) >500 tons

Coumarin

2H-1-Benzopyran-2-one; 2H-chromen-2-one; 1,2-Benzopyrone; cis-o-Coumaric acid lactone; Coumarinic anhydride; 2-Oxo-1,2-benzopyran; Tonka bean camphor

IFRA_STD_023.pdf

49

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

...Made synthetically by heating salicylic aldehyde, sodium acetate, and acetic acid anhydride.

From o-cresol and carbonyl chloride followed by chlorination of the carbonate and fusion with a mixture of alkali acetate, acetic anhydride, and a catalyst.

Synthesis from salicyladehyde by the Perkin reaction. In the presence of sodium acetate, salicylaldehyde reacts with acetic anhydride to produce coumarin and acetic acid. The reaction is carried out in the liquid phase at elevated temperatures.

Synthesis from o-cresol by the Raschig process. The hydroxyl group of o-cresol is protected by a carbonate or phosphate group, and the ester can be converted into the corresponding benzal chloride derivative by chlorination of the methyl group. Reaction of this intermediate with acetic anhydride yields o-acetylsalicylaldehyde and acetyl chloride. Ring closure of the aldehyde with acetic anhydride gives coumarin.

Cosmetics product ingredient: 2H-1-Benzopyran-2-one (COUMARIN)

Information on 416 consumer products that contain Coumarin in the following categories is provided:

Fragrance Ingredients

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Cosmetics -> Masking

Wholesale and Retail Trade

2H-1-Benzopyran-2-one: ACTIVE

Commercially, in detergents, soaps, and cosmetics, and as flavoring agent for cattle medicines.

Use in foods not permitted in USA.

... Is widely distributed in the plant kingdom but most of it has been produced synthetically for many years for commercial use.

0.089 [Products applied to the lips]

0.08 [Products applied to the axillae]

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

1.5 [Products related to fine fragrances]

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

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