5-tert-Butyl-2,4,6-trinitro-m-xylol

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

Excerpt from ERG Guide 149 [Substances (Self-Reactive)]:

General First Aid:

General First Aid:

· Wear positive pressure self-contained breathing apparatus (SCBA).

· Wear positive pressure self-contained breathing apparatus (SCBA).

If material on fire or involved in fire: Use water in flooding quantities as fog. Solid streams of water may spread fire. Use foam, dry chemical, or carbon dioxide. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Keep run-off water out of sewers and water sources.

SRP: 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 air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

If material not on fire or involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers.

Personal protection: Avoid breathing dusts, and fumes from burning material ... Avoid bodily contact with the material. If contact with the material anticipated, wear appropriate chemical protective clothing.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Excerpt from ERG Guide 149 [Substances (Self-Reactive)]:

Immediate precautionary measure

Immediate precautionary measure

Excerpt from ERG Guide 149 [Substances (Self-Reactive)]:

Personal protection: Wear appropriate chemical protective gloves, boots and goggles. Wear positive pressure self-contained breathing apparatus when fighting fires involving this material.

Small Fire

Small Fire

Musk xylene was detected in 4 of 4 human adipose tissues samples, obtained from cadavers in Switzerland at autopsy, in 1983-84 and 11 of 11 samples collected in 1994 at concentrations ranging from 13 to 59 ng/g and 6.7 to 288 ng/g in samples from 1983-84 and 1994, respectively(1). Musk xylene was detected at 0.02 to 0.09 mg/kg fat in 19 human adipose tissue samples from males collected in Scheswig-Holstein (Germany) from May-June 1993 and at 0.02 to 0.22 mg/kg fat in 13 human adipose tissue samples from females collected in Scheswig-Holstein (Germany) from July 1992(2). Musk xylene was detected in 100% of milk samples from nursing mothers living in Southern Bavaria in 1992 (48 samples) and 1993 (343 samples) between 0.01-1.22 mg/kg fat with a mean concentration of 0.10 mg/kg fat(3). Musk xylene was at 0.02 to 0.19 mg/kg fat in 23 milk samples from nursing mothers from Scheswig-Holstein (Germany) from February 1992 to June 1993(4).

Musk xylene was detected at concentrations of 0.17-0.51 ug/g in maternal serum samples but not detected in any umbilical cord serum samples, all collected from 20 mothers in Seoul, Korea, sampling dates not provided(1). Musk xylene was detected in 79% of human blood plasma samples with a median concentration of 11 ng/L, collected from 100 healthy students of the Medical University of Vienna, dates not provided(2). Musk xylene was not detected in human blood samples, above the LOD (0.18 ng/L), collected from 50 hairdressers, and 10 normal adults(3).

/Researchers/ have studied the sensitizing properties of musk xylene in a photopatch test ... 13 Patients, suspected to suffer from a photoallergic contact dermatitis, were screened by means of a questionnaire and clinical tests. Dermal sensitivity to UV light was pre-tested after which nitromusks (amount and vehicle not specified) were applied on the skin under occlusive patches (two sites per substance). After 24 hours of contact the patches were removed under dim light and the skin examined for any signs of contact-dermatitis. Half of the contact sites were covered again and the other half was irradiated with ultra-violet light. All persons studied showed a photoallergic reaction to musk ambrette. In one person also a photoallergic reaction to musk xylene was observed. No reaction was seen at the non-irradiated site. The study is inconclusive as to whether this patient shows either cross-photoallergy between musk ambrette and musk xylene or that this patient shows a concomittant independent photo-allergy to two nitromusks. The study is also inconclusive as to the prevalence of the condition.

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.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+4(SRC), determined from a log Kow of 4.9(2) and a regression-derived equation(3), indicates that musk xylene is expected to be immobile in soil(SRC). Volatilization of musk xylene from moist soil surfaces may be an important, relatively slow, fate process(SRC) given an estimated Henry's Law constant of 5.9X10-7 atm-cu m/mole(SRC) derived from its vapor pressure, 2.25X10-7 mm Hg(4), and water solubility, 0.15 mg/L(5). Additionally, adsorption to soil is expected to attenuate volatilization(SRC). Musk xylene is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure at 25 °C(4). A 2% of theoretical BOD using activated sludge in the Japanese MITI test(6) suggests that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+4(SRC), determined from a log Kow of 4.9(2) and a regression-derived equation(3), indicates that musk xylene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 5.9X10-7 atm-cu m/mole(SRC) derived from its vapor pressure, 2.25X10-7 mm Hg(5), and water solubility, 0.15 mg/L(6). According to a classification scheme(7), measured BCF values ranging from 1,400 to 68,100(6-10) suggest that bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). A 2% of theoretical BOD using activated sludge in the Japanese MITI test(8) suggests that biodegradation is not 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), musk xylene, which has a vapor pressure of 2.25X10-7 mm Hg at 25 °C(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase musk xylene 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 19 days(SRC), calculated from its rate constant of 8.3X10-13 cu cm/molecule-sec at 25 °C(SRC), that was derived using a structure estimation method(3). Particulate-phase musk xylene may be removed from the air by wet and dry deposition(SRC). Musk xylene contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

ENVIRONMENTAL: Musk xylene was detected in 100% of milk samples from nursing mothers living in Southern Bavaria in 1992 (48 samples) and 1993 (343 samples) between 0.01-1.22 mg/kg fat with a mean concentration of 0.10 mg/kg fat(1). Musk xylene was at 0.02 to 0.19 mg/kg fat in 23 milk samples from nursing mothers from Scheswig-Holstein (Germany) from February 1992 to June 1993(2). In a 1999 survey of human milk samples from 10 mothers in Denmark, musk xylene was present at concentrations ranging from below the detection limit to 46.4 ug/kg with a mean concentration of 23.6 ug/kg milk fat(3). Musk xylene was below the LOQ in 31 of 101 samples of human milk collected from 1996 to 2003 and detected in 70 samples at concentrations up to 83.9 ng/g lipid, with a median value of 9.5 ng/g(4). Musk xylene was detected in 9 of 20 human milk samples from Seoul, Korea, at concentrations ranging from 0.015-0.22 with a mean concentration of 0.031, sampling dates not provided(5).

From 108 women milk was taken and analyzed for several polycyclic musks and nitromusks ... A mean and a median fat content of 3.67 and 3.40%, respectively, were found in the mother's milk. The concentration of musk xylene in breast milk showed a mean value of 7.43 ug/kg milk fat with a standard deviation of 9.58. The minimum and maximum value found were close to zero (detection limit less than 1 ug/kg milk fat) and 68.3 ug/kg milk fat, respectively. There was no convincing correlation of musk xylene levels in the milk with maternal age, body mass, loss of body mass and weight and pregnancy and lactation variables. It was stated that there was no significant correlation with the use of skin products and with fish consumption (this could not be verified as the report was not complete). Milk samples (391) from nursing mothers living in Southern Bavaria (Germany) were analyzed for musk xylene in 1991 (48 samples) and 1992 (343 samples). Levels of musk xylene varied from 10 to 1,220 ug/kg milk fat, with a mean of 100 ug/kg milk fat (one outlier of 1,220 ug/kg milk fat, rest less than 700 ug/kg milk fat; 90- and 95- percentile 210 and 290 ug/kg milk fat, respectively). In a study in 23 human milk samples from 1992/1993 in Northern Germany, musk xylene levels up to 190 (average 78) ug/kg milk fat were found. These milk samples showed fat contents of 0.1 - 5.1%. Another study showed the presence of musk xylene in mother's milk of various research-centers throughout Germany between 1992-1994. The mean concentrations varied from 11-90 ug/kg milk fat (with one extreme mean value of 245 ug/kg milk fat due to an extremely high individual value of 3 mg/kg milk fat).

Milk samples (391) from nursing mothers living in Southern Bavaria (Germany) were analyzed for musk xylene in 1991 (48 samples) and 1992 (343 samples). Levels of musk xylene varied from 10 to 1,220 ug/kg milk fat, with a mean of 100 ug/kg milk fat (one outlier of 1,220 ug/kg milk fat, rest /less than/ 700 ug/kg milk fat; 90- and 95- percentile 210 and 290 ug/kg milk fat, respectively).

IDENTIFICATION AND USE: Musk xylene is a solid with sweet, musky odor. It is used in large quantities in inexpensive perfumes for soap and household products. HUMAN STUDIES: Some patients develop a persistent light reaction/chronic actinic dermatitis (pruritic dermatitis with lichenification on the light-exposed areas), which can persist for years, in spite of the patient having removed the exposure. The mechanism behind this reaction is not known. It can cause photoallergic contact dermatitis. Significant associations were reported between musk xylene levels in blood and the frequency of cosmetics use (especially with perfumes), the level of androstanediol-glucuronide, and obstetric history. Musk xylene did not induced sister chromatid exchanges in human lymphocytes with and without metabolic activation. In an in vitro micronucleus test, musk xylene at doses up to 135 and 350 uM did not increase the frequency of micronuclei in human lymphocytes and in the human hepatoma cell line Hep G2, respectively. ANIMAL STUDIES: Musk xylene is not an eye irritant in rabbits. Musk xylene does not produce photoallergy in guinea pigs. In an acute toxicity test musk xylene was given by gavage to mice at doses of 125, 250, 500, 1,000, 2,000, or 4,000 mg musk xylene/kg bw. The mice were observed for 14 days. Tremor was observed 3-18 hours after treatment in males and females given 4,000 mg/kg bw. Three groups of 50 male and 50 female mice received a diet containing musk xylene 0, 750 or 1500 mg/kg for 80 weeks. Musk xylene increased the incidence of liver adenomas in both sexes and of liver carcinomas in males. In male mice, the incidence of Harderian gland adenomas was also increased. In developmental studies musk xylene produced maternal toxicity in rats at 60 and 200 mg/kg bw. However, reproduction and litter parameters were unaffected by musk xylene administration. Extra thoracic ribs and increased ossification of hyoid sites and forepaw phalanges were observed in the 200 mg/kg group. A musk xylene mutagenicity test was negative in 4 strains of Salmonella typhimurium, and in Escherichia coli with or without metabolic activation. Musk xylene was evaluated in a battery of short-term genotoxicity tests that included the mouse lymphoma assay, an in vitro cytogenetics assay in Chinese hamster ovary (CHO) cells, the in vitro unscheduled DNA synthesis (UDS) assay in primary rat hepatocytes and an in vivo UDS assay. Musk xylene gave uniformly negative results in these genotoxicity tests. These observation, combined with previously reported negative Ames tests, suggest a non-genotoxic mechanism for the induction of mouse liver tumors by musk xylene. ECOTOXICITY STUDIES: In teleost Danio rerio and the Dicentrarchus labrax embryonic cells musk xylene exhibited a genotoxic activity even after short exposure times.

/AQUATIC SPECIES/ Certain ATP binding cassette (ABC) transporter proteins, such as zebrafish Abcb4, are efflux pumps acting as a cellular defense against a wide range of different, potentially toxic chemical compounds thus mediating so called multixenobiotic resistance (MXR). Certain chemicals target MXR proteins and, as so called chemosensitizers, inhibit the activity of these proteins thus increasing the toxicity of other chemicals that would normally be effluxed. In this study 14 pharmaceuticals and personal care products (PPCPs) that are being increasingly detected in aquatic systems, were assessed for interference with the MXR system of zebrafish (Danio rerio). ... Eight of the tested PPCPs showed effects on Abcb4 ATPase activity indicating that their effects in the dye accumulation assay may have indeed resulted from interference with Abcb4-mediated rhodamine 123 efflux. Slight stimulatory effects were found for musk xylene, nerol, isoeugenol, alpha-amylcinnamaldehyde, alpha-hexylcinnamaldehyde and simvastatin indicating Abcb4 substrate/competitive inhibitor properties of those compounds.

/AQUATIC SPECIES/ ... The aim of this research was to evaluate the genotoxic activity of an artificial musk (musk xylene, MX) and the potential anti-genotoxicity against this chemical compound of two antioxidant substances (alpha-tocopherol and an anthocyanins enriched extract). ... The results of this study showed that MX exhibited a genotoxic activity even after short exposure times. The anti-genotoxicity experiments evidenced that both alpha-tocopherol and Anthocyanin were able to contrast the genotoxic effects induced by MX, both in vivo and in vitro.

/AQUATIC SPECIES/ Synthetic musks are widely used as perfuming agents in products, such as cosmetics, detergents, and soaps. The increased detection of these substances in the aquatic environment and their high bioconcentration potential raises concerns about potential effects on aquatic species. This work aimed at assessing the interactions of the most widely used musks: nitromusks (musk xylene, musk ketone) and polycyclic musks (celestolide, galaxolide, and tonalide) with fish enzymatic systems involved in both xenobiotic and endogenous metabolism. Therefore, CYP catalyzed pathways were investigated in carp liver microsomes (CYP1A, CYP3A), ovarian microsomes (CYP19) and testicular mitochondria (CYP17 and CYP11beta) using standard substrates. Phase II activities (UDP-glucuronosyltransferases and sulfotransferases) were determined in carp liver microsomes and cytosol, respectively. Polycyclic musks (galaxolide and tonalide) were stronger inhibitors of CYP3A- (IC(50): 68-74 uM), CYP17- (IC(50): 213-225 uM), CYP11beta- and CYP19-catalyzed activities than nitromusks, while the latter showed higher ability to interfere with CYP1A (IC(50): 35-37 uM). The sulfation of estradiol was also significantly inhibited by tonalide and galoxolide (IC(50): 140-294 uM). Overall, polycyclic musks showed the highest potential to interfere with those activities involved in the synthesis and metabolism of steroids while nitromusks mainly interfered with xenobiotic metabolism (CYP1A-catalyzed reactions). The obtained data suggest that CYP isoforms are potentially sensitive targets of synthetic musk substances in fish.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of July 27, 2017: http://actor.epa.gov/dashboard/]

Musk xylene was detected in 18 effluent samples from three treatment plants along the river Tama (Japan) in 1981 at 0.025-0.036 ug/L, median concentration 0.035 ug/L(1). Musk xylene was detected in effluent samples collected over a 3-day period from an activated sludge wastewater treatment plant in Loveland, OH in September 1997 and from a trickling filter wastewater treatment plant in Glendale, OH in October 1997 at concentrations of 5 and 31 ng/L, respectively(2). Musk xylene was detected in the effluent from a variety of types of European and U.S. wastewater treatment plants at concentrations ranging from 10 to 95 ng/L and from <1 to 112 ng/L, respectively, depending on the type of wastewater treatment plant(3). In the City of Lubbock, TX, musk xylene was not detected in waste water treatment plant influent and effluent sampled in Winter 2009, Spring 2010, Summer 2010, Fall 210, and Winter 2010(4). In waste water treatment plants of Beijing, China sampled in Jan and Sept 2008, musk xylene was detected in influent at concentrations below the limit of quantification up to 22.95 ng/L and not detected in effluent(5).

The Koc of musk xylene is estimated as 1.2X10+4(SRC), using a log Kow of 4.9(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that musk xylene is expected to be immobile in soil. An experimental Koc for musk xylene of 16,300 L/kg was reported from a laboratory desorption experiment utilizing 25 mg suspended matter spiked with approx 10 ug/g musk xylene(4).

URBAN/SUBURBAN: Musk xylene was detected in 25 of 26 air samples and 4 of 24 airborne particulate-phase samples collected from Milwaukee (Wisconsin) in June 2001 at average concentrations of 0.032 ng/cu m and 0.010 ng/cu m, respectively; the reported concentrations were not corrected for the concentrations in the field blanks so the actual values are likely to be lower(1).

INDOOR: Musk xylene was detected in dust samples collected from barbershops (n = 55; ave 210 ng/g; med 50.6 ng/g), bathhouses (n = 2; ave 34.9 ng/g; med 34.9 ng/g), dormitories (n = 28 and 23 for female and male, respectively; ave 10.5 ng/g; med 0.50 ng/g), and households (n = 36; ave 45.7 ng/g; med 7.48 ng/g), sampled in Tianjin, China during April and July, 2012(1).

RURAL/REMOTE: Musk xylene was detected in 11 of 11 air samples collected from Lake Michigan from June 1991 and May 2000 at an average concentration of 0.014 ng/cu m; the reported concentration was not corrected for the concentration in the field blanks so the actual value is likely to be lower(1).

SOURCE DOMINATED: Musk xylene was not detected in air sampled at two landfills in Northern Germany in 2009(1).

/HUMAN EXPOSURE STUDIES/ To evaluate the contact-sensitizing potential of musk xylene twenty-five healthy adult males received an application of 5% musk xylene in petrolatum on the skin for 5 alternate day 48-hour periods under occlusion. Pretreatment with sodium lauryl sulfate was omitted because the test solution caused mild irritation. Following a 10-day rest period, occlusive challenge patches were applied to fresh skin sites for 48 hours. The challenges were evaluated at 48 and 72 hours. No reactions were observed.

/HUMAN EXPOSURE STUDIES/ A study was performed to determine the frequency of reactivity to a series of commonly used fragrances (amongst others musk xylene) in dermatological patients. In a pilot study on a total of 1,069 patients in 11 centers, the appropriate test concentration and vehicle were examined for each fragrance. In the main study, a set of 5 to 10 fragrances at 2 concentrations was patch tested in each center on a minimum of 100 consecutive patients seen in the patch test clinic. With respect to musk xylene, 0.1% and 1% concentrations in petrolatum were patch tested on 192 patients (116 females, 76 males) in the test center Menne, Copenhagen. Patches were applied to the back and kept in place for two days. Two to three reactions, rated as 'irritant' or 'doubtful positive', were observed for the 0.1 and 1% musk xylene concentrations, respectively, but no allergic reactions were observed.

/HUMAN EXPOSURE STUDIES/ /Researchers/ have studied the sensitizing properties of musk xylene in a photopatch test ... 13 Patients, suspected to suffer from a photoallergic contact dermatitis, were screened by means of a questionnaire and clinical tests. Dermal sensitivity to UV light was pre-tested after which nitromusks (amount and vehicle not specified) were applied on the skin under occlusive patches (two sites per substance). After 24 hours of contact the patches were removed under dim light and the skin examined for any signs of contact-dermatitis. Half of the contact sites were covered again and the other half was irradiated with ultra-violet light. All persons studied showed a photoallergic reaction to musk ambrette. In one person also a photoallergic reaction to musk xylene was observed. No reaction was seen at the non-irradiated site. The study is inconclusive as to whether this patient shows either cross-photoallergy between musk ambrette and musk xylene or that this patient shows a concomittant independent photo-allergy to two nitromusks. The study is also inconclusive as to the prevalence of the condition.

/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.

Musk xylol is used in ... inexpensive perfumes for soap and household products.

Fragrances are complex mixtures, prepared by blending many fragrance ingredients in varying concentrations. They are nearly always liquids, in which musk xylene has to be dissolved. Musk xylene is partly used in cosmetic products and partly in detergents, fabric softeners, household cleaning products and other fragranced products.

Musk xylene is used as fragrance and fragrance enhancer in fragrance mixtures for detergents, fabric softeners, fabric conditioners, cleaning agents, air fresheners and other household products.

Use in fragrances in the USA amounts to approximately 150,000 lb/yr.

Usual concentration in final product (%): soap 0.03 (0.15 maximum); detergent 0.003 (0.015 maximum); creams, lotions 0.01 (0.05 maximum); perfume 0.2 (0.5 maximum)

Musk xylene

2,4,6-Trinitro-1,3-methyl-5-tert-butylbenzene; 1-tert-Butyl-3,5-dimethyl-2,4,6-trinitrobenzene; Benzene, 1-(1,1-dimethylethyl)-3,5-dimethyl-2,4,6-trinitro-; Musk xylol

IFRA_STD_170.pdf

44

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

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

Benzene, 1-(1,1-dimethylethyl)-3,5-dimethyl-2,4,6-trinitro-: ACTIVE

Of the few aromatic, nitrogen-containing fragrance substances, the nitro musk material musk ketone is still important commercially as an inexpensive and tenacious musk fragrance. The other artificial nitro musks, musk ambrette and musk xylene, have lost their significance on account of their toxicological and ecotoxicological properties.

In public use since the 1900s.

Musk xylene is a vPvB /very persistent and very bioaccumulative/ substance according to Article 59 of REACH; it has been included on the candidate list (28/10/2008; ED/67/2008) and included into Annex XIV of REACH (Commission Regulation (EU) No 143/2011) with a sunset date of 21 August 2014.