4-tert-ブチル-3-メトキシ-2,6-ジニトロトルエン

Insoluble (NTP, 1992)

Slightly soluble in ethanol; soluble in ethyl ether, chloroform

In water, 0.79 mg/L at temp. unspecified

275 °F at 16 mmHg (NTP, 1992)

185 °C at 16 mm Hg

183 to 187 °F (NTP, 1992)

85 °C

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P280, P301+P317, P302+P352, P321, P330, P332+P317, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 136 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

Chemical: Benzene, 1-(1,1-dimethylethyl)-2-methoxy-4-methyl-3,5-dinitro-

Benzene, 1-(1,1-dimethylethyl)-2-methoxy-4-methyl-3,5-dinitro-: Does not have an individual approval but may be used under an appropriate group standard

A moderate skin irritant; Causes spinal cord demyelination and changes in testicular weight in 90-day dermal studies of rats; Causes muscle weakness, weight loss, brain and spinal cord demyelination in repeated-dose oral studies of rats; [RTECS] Widely used fragrance implicated in contact photosensitivity. [ChemIDplus] Positive photopatch test results and photoallergic contact dermatitis have been reported; [HSDB] Evidence of photosensitivity, neurotoxicity, and penetration through human skin with slow excretion; No skin sensitization observed in maximization study of 25 volunteers; [EC: SCCNFP] A skin and moderate eye irritant; Toxic by ingestion; [Alfa Aesar MSDS]

Acute Tox. 4 (100%)

Acute toxicity - category 4

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.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a POTW is acceptable only after review by the governing authority. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must meet Hazardous Material Criteria for disposal.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol 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 alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate 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 an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Musk ambrette was detected in 3 of 4 human adipose tissues samples, obtained from cadavers in Switzerland at autopsy, in 1983-84 and 1 of 11 samples collected in 1994 at concentrations ranging from 5 ng/g to 67 ng/g and 18 ng/g in samples from 1983-84 and 1994, respectively(1). Musk ambrette was detected in 94% of milk samples from nursing mothers living in Southern Bavaria in 1992 (48 samples) and 1993 (343 samples) between <0.01-0.29 mg/kg fat with a mean concentration of 0.04 mg/kg fat(2).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 5,300(SRC), determined from a log Kow of 4.0(2) and a regression-derived equation(3), indicates that musk ambrette is expected to be immobile in soil(SRC). Volatilization of musk ambrette from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.05X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(4). However, adsorption to soil is expected to attenuate volatilization(SRC). Musk ambrette is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.31X10-5 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2009).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 5,300(SRC), determined from a log Kow of 4.0 (2)and a regression-derived equation(3), indicates that musk ambrette is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 7.05X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 85 days and 1.8 years, respectively(SRC). The volatilization half-life from a model pond is about 37 years when adsorption is considered(5). According to a classification scheme(6), an estimated BCF of 200(SRC), from a log Kow of 4.0(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). Biodegradation data were not available(SRC, 2009).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), musk ambrette, which has an estimated vapor pressure of 1.31X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase musk ambrette 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 11 days(SRC), calculated from its rate constant of 1.5X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase musk ambrette may be removed from the air by wet or dry deposition(SRC). Musk ambrette contains chromophores that absorb at wavelengths >290 nm(4) and may be susceptible to direct photolysis by sunlight(SRC).

The Koc of musk ambrette is estimated as 5,300( SRC), using a log Kow of 4.0 (1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that musk ambrette is expected to be immobile in soil.

/HUMAN EXPOSURE STUDIES/ The Scandinavian photopatch test procedure has been applied to 745 patients with suspected photodermatoses during the years 1980-1981. Our experience has been encouraging with the recording of several relevant reactions. A total of 132 positive photocontact reactions and 120 ordinary contact reactions were seen. Photocontact reactions to musk ambrette (19 cases) and PABA (19 cases) were surprisingly frequent. The next most common photocontact reactions were to promethazine (24), chlorpromazine (22 cases) and fentichlor (12). Ordinary contact reactions were observed to balsam of Peru (30), PABA (23), lichen mix (21), wood mix (14) and to perfume mix (10).

/HUMAN EXPOSURE STUDIES/ 495 patients were standard photopatch tested with Musk Ambrette 5% in petrolatum and in dimethyl phthalate. 4 cases gave positive photopatches; 3 were men and 1 a woman. 2 cases, both men, had current or past relevant reactions to Musk Ambrette presented with typical perfume dermatitis. The other 2 cases had positive reactions to Musk Ambrette of uncertain relevance. Photoallergic reaction to Musk Ambrette is a rare event. Only a few relevant reactions will be missed by excluding it from standard phototesting.

/HUMAN EXPOSURE STUDIES/ Photosensitivity to musk ambrette was confirmed in 15 men previously photopatch tested and in a further 4 men currently attending the clinic. 6 of the recalled patients continued to react adversely to sunlight due either to unrecognised exposure to musk ambrette or to their having become persistent light reactors. Positive photopatch tests, possibly cross reactions, were seen in 3 of the 19 patients with the structurally-related nitromusks, moskene and musk xylene but not with musks ketone and tibetine. Musk ambrette elicited a positive patch test without light in 3 of the 19 patients.

/CASE REPORTS/ A patient with persistent photosensitivity and positive photopatch tests to musk ambrette and an after-shave lotion is reported. Phototests showed extreme sensitivity to UV radiation, especially UVB. Patch tests with the European Standard Series and some plant allergens were negative. Histology showed a granulomatous reaction with epithelioid and giant cells in the dermis.

For more Human Toxicity Excerpts (Complete) data for MUSK AMBRETTE (14 total), please visit the HSDB record page.

Musk ambrette

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 65: (1996) Printing Processes and Printing Inks, Carbon Black and Some Nitro Compounds

1996

1995

An estimated BCF of 200 was calculated in fish for musk ambrette(SRC), using a log Kow of 4.0(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high (SRC), provided the compound is not metabolized by the organism(SRC).

The Henry's Law constant for musk ambrette is estimated as 7.05X10-7 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that musk ambrette is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river(2) is estimated as 85 days(SRC). The volatilization half-life from a model lake(2) is estimated as 1.8 years(SRC). The volatilization half-life from a model pond is about 37 years when adsorption is considered(3). Musk ambrette's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Musk ambrette is not expected to volatilize from dry soil surfaces(SRC) based upon a an estimated vapor pressure of 1.3X10-5 mm Hg(SRC), determined from a fragment constant method(4).

Used as a perfume fixative; [HSDB] Used as a flavoring agent; [FDA] Used in organic synthesis; [NTP] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]

Prohibited for use as a fragrance ingredient in the EU; [EC: SCCNFP]

... Perfume fixative

Use in fragrances in the USA amounts to approximately 100,000 lb/yr.

Usual concentration in final product (%): soap 0-03 (0-2 max); detergent 0-003 (0-02 max); creams, lotions 0-01 (0-07 max); perfume 0-2 (2-0 max)

Musk ambrette

Benzene, 1-(1,1-dimethylethyl)-2-methoxy-4-methyl-3,5-dinitro-; 1-tert-Butyl-2-methoxy-4-methyl-3,5-dinitrobenzene; 4-tert-Butyl-3-methoxy-2,6-dinitrotoluene; 6-tert-Butyl-3-methyl-2,4-dinitroanisole; 1-(1,1-Dimethylethyl)-2-methoxy-4-methyl-3,5-dinitrobenzene; 2,6-Dinitro-3-methoxy-1-methyl-4-tert-butylbenzene; 2,6-Dinitro-3-methoxy-4-tert-butyltoluene; 2,4-Dinitro-3-methyl-6-tert-butylanisole

IFRA_STD_168.pdf

40

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

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

By nitration of the corresponding benzene derivative ...

Musk ambrette is now prepared commercially by the following multistep synthesis. The potassium salt of meta-cresol is methylated with dimethyl sulfate to give the methyl ether, which is then butylated using isobutyl chloride in the presence of aluminium chloride. The resulting tert-butylcresyl methyl ether is obtained in yields of 55 to 60% and is purified with fractionation. Nitration at temperatures below 0 °C with fuming nitric acid leads to the formation of the dinitro derivatives in yields of 45 to 60%. The pure product is obtained by crystallization from 95% ethanol. The by-products in this case consist of the mononitro derivative, 4,6-dinitro-meta-cresol methyl ether and smaller amounts of trinitro derivatives

Benzene, 1-(1,1-dimethylethyl)-2-methoxy-4-methyl-3,5-dinitro-: ACTIVE

In public use before the 1920s

The Council of Europe (1974) included musk ambrette at a level of 1 ppm in the list of artificial flavoring substances that may be added to foodstuffs without hazard to public health, and FEMA (1965) has given musk ambrette GRAS status.