Musk Moskene Research Articles

Analysis of nitro musk compounds and their amino metabolites in liquid sewage sludges using NMR and mass spectrometry.

A method using HRGC ion trap MS/MS for measuring simultaneously amino metabolites and the parent compounds, the nitro musks, an important group of organic fragrance components found in sewage sludges, was developed. The monoamino metabolites were synthesized and characterized by 1H/13C NMR and mass spectroscopy. Among the nitro musks, musk ketone was the major compound, found at an average concentration of 5 microg/kg of dry mass (dm) whereas musk xylene was detected in only one sample (30 microg/kg dm). Three amino metabolites were identified, namely, 1-tert-butyl-3,5-dimethyl-4-amino-2,6-dinitrobenzene, 1,1,3,3,5-pentamethyl-4-nitro-6-aminoindane, and 4-acetyl-1-tert-butyl-3,5-dimethyl-2-nitro-6-aminobenzene, the corresponding reduction products of the nitro musks xylene, moskene, and ketone. These metabolites were present in partly higher concentrations in the sludges than the corresponding nitro musk compounds. Musk xylene and musk moskene were mainly found as their monoamino metabolites, underlining the importance of anaerobic reduction processes in the sewage treatment plant.

Nitro musks, nitro musk amino metabolites and polycyclic musks in sewage sludges: Quantitative determination by HRGC-ion-trap-MS/MS and mass spectral characterization of the amino metabolites

Nitro- and polycyclic musks were quantified in sewage sludge samples from different catchment areas using high-resolution gas chromatography (HRGC) and ion-trap MS/MS. Collision induced dissociation (CID) turned out to be a useful tool for quantification of the analytes. Negative chemical ionization (NCI) quadrupole MS in the selected ion mode (SIM) showed similar sensitivities compared to ion trap MS/MS. Among the nitro musks, musk ketone (MK) and musk xylene (MX) were the main compounds in predominantly domestic sewage sludges, found at low μg/kg dry matter (d.m.) whereas polycyclic musks were present in domestic as well as in industrial sludges up to 12 mg/kg d.m. Galaxolide (HHCB) and Tonalide (AHTN) were the major polycyclic musks found in the sludges. Amino metabolites of the nitro musks, amino musk xylene (AMA), amino musk moskene (AMM) and amino musk ketone (AMK) were detected for the first time in sewage sludges, and reached partly higher concentrations compared to the parent compounds.

Toxicity of nitromusks in early lifestages of South African clawed frog ( Xenopus laevis) and zebrafish ( Danio rerio)

Musk xylene (MX), musk ketone (MK) and musk moskene (MM) are synthetic nitro-containing fragrances. Due to their inherent lipophilicity and environmental persistence, they are frequently detected in environmental samples and especially in aquatic ecosystems. Despite this, the current environmental toxicity database of nitromusks is limited. Although nitromusks have been shown to accumulate in aquatic organisms, little is known about their potential developmental effects in the respective aquatic species. To investigate the developmental toxicity of these compounds to amphibians and fish, early lifestages of xenopus ( Xenopus laevis) and zebrafish ( Danio rerio) were exposed to three nitromusks for 96 h to examine the developmental effects of these compounds in the two species. Nitromusk body concentration measurements were carried out in parallel for correlation with potential developmental effects. No increased mortality, malformation or growth inhibition was observed in either species following 96-h exposure to 400 μg/l MX, MK and MM. However, an approximately 20% reduced viability was observed in xenopus larvae when exposed to 400 μg/l MX, MK and MM for 11 days. Xenopus and zebrafish exposed to 10, 153, 871 and 1637 μg/l 14C-MX for 96 h resulted in whole-body concentrations of 0.7±0.1, 11.1±1.1, 38.7±1.9 and 76.3±18.3 μg/g, and 4.3±0.6, 73.3±11.8, 440.0±72.7 and 664.0±47.7 μg/g wet body weight, respectively. Exposure of xenopus larvae to 400 μg/l MX, MK and MM for 11 days, resulted in whole body concentrations (extrapolated from gas chromatographic determinations) of 4700±5000, 1300±300 and 4600±4800 μg/g wet weight for MX, MK and MM, respectively. The latter toxicity results, in conjunction with the fact that the concentrations used for the above experiments were between 400- and 10 000-fold higher than those detected in the environment, suggest that environmental concentrations of nitromusks are not hazardous for early lifestages of fish and amphibians.

Interactions of nitromusk parent compounds and their amino-metabolites with the estrogen receptors of rainbow trout ( Oncorhynchus mykiss) and the South African clawed frog ( Xenopus laevis)

Nitromusks, musk xylene (MX), musk ketone (MK) and musk moskene (MM) are synthetic fragrances. 4-Amino-MX (4X), 2-amino-MX (2X) and 2-amino-MK (2K) are nitromusk metabolites formed during the sewage treatment process and have been detected in effluent and surface water at concentrations four to 40 times higher than their parent compounds. To date, data to the aquatic toxicity of nitromusk compounds are limited to the parent compounds and the determination of acute and subacute effects in aquatic organisms. No data are available regarding the potential endocrine modulating effects of these compounds and/or their metabolites in aquatic organisms. Therefore, the competitive binding capability of nitromusks and their metabolites to the estrogen receptors (ER) in rainbow trout and xenopus was investigated. No binding of MX, MK and MM to the ER of either species was observed. In contrast, binding to the ER was observed for 4X, 2X and 2K in both species. The IC 50 (competitive binding at the ER) of 2X in rainbow trout was 1.3±1.1 mM. In contrast, 4X, 2X and 2K bound to the xenopus ER with an IC 50 of 30.8±28.5, 12.9±10.3 and 70.1±88.3 μM, respectively.

Genotoxicity of nitro musks in the micronucleus test with human lymphocytes in vitro and the human hepatoma cell line Hep G2

The nitro musk compounds musk xylene (1-tert.-butyl-3,5-dimethyl-2,4,6-trinitrobenzene), musk ketone (4-tert.-butyl-3, 5-dinitro-2,6-dimethylacetophenone), musk ambrette (1-tert.-butyl-4-methyl-6-methoxy-3,5-dinitrobenzene), musk moskene (1,1,3,3,5-pentamethyl-4,6-dinitroindane) and musk tibetene (1-tert.-butyl-3,4,5-trimethyl-2,6-dinitrobenzene) were tested for their genotoxic activity in the micronucleus test (MN) with human lymphocytes in vitro and the human hepatoma cell line Hep G2. Compound concentrations were employed up to cytotoxic doses. Musk xylene, musk ketone, musk ambrette, musk moskene and musk tibetene revealed no genotoxicity in the micronucleus test with human lymphocytes and with the human hepatoma cell line Hep G2.

Nitro musk compounds genotoxic activity

Five nitro musk compounds are widely used as fragrance ingredients in perfumes, lotions and detergents; as food additives in cigarettes and fish baits, and in such technical products as herbicide formulations and explosives. Several studies identified nitro musk compounds in aquatic environment samples, human milk and fat samples as highly lipophilic and persistent bioaccumulating environmental pollutants. To examine the compounds for genotoxic activity, musk xylene (1-tert.-butyl-3, 5-dimethyl-2, 4, 6-trinitrobenzene), musk ketone (4-tert.-butyl-3, 5-dinitro-2, 6-dimethylacetophenone), musk ambrette (l-tert.-butyl-4-methyl-6-methoxy-3, 5-dinitrobenzene), musk moskene (l, 1, 3, 3, 5-pemamethyl-4, 6-di-nitroindane) and musk tibetene (1-tert.-butyl-3, 4, 5-trimethyl-2, 6-dinitrobenzene) were tested for SOS inducing potency in the SOS chromotest with E. coli PQ37 and for sister-chromatid exchange inducing activities in human lymphocytes in vitro both in the presence and absence of an exogenous metabolizing system from rat liver S9-Mix. Nitro musks revealed no genotoxicity either in the SOS chromotest with E. coli PQ37 or in the sister-chromatid exchange test with human lymphocytes.

Occurrence of nitro and non-nitro benzenoid musk compounds in human adipose tissue

Nitro benzenoid musk compounds (Musk tibetene [CAS no. 145-39-1], Musk ambrette [83-66-9], Musk moskene [116-66-5], Musk ketone [81-14-1] and Musk xylene [81-15-2]) and non-nitro benzenoid musks (Celestolide® [13171-00-1], Galaxolide® [1222-05-5]) and Fixolide® [1506-02-1] [21445-77-7]) were analysed in 15 human adipose tissue samples from Switzerland by gas chromatography / high resolution mass spectrometry. The levels of Musk xylene and Galaxolide ranged up to 288 ng/g lipids and 171 ng/g lipids, respectively. The concentrations of non-nitro benzenoid musks found in human adipose tissue raise concern since very few toxicological data are available.

A comparative study of five nitro musk compounds for genotoxicity in the SOS chromotest and Salmonella mutagenicity

Five nitro musk compounds widely used in cosmetics and detergents were examined for DNA-damaging and mutation-inducing properties. For this purpose two short-time assays were used, the SOS chromotest and the Salmonella/mammalian microsome test. Musk ambrette showed mutagenicity in Salmonella typhimurium TA 100 requiring metabolic activation by rat liver postmitochondrial supernatant (S9) but it lacked mutagenicity in the absence of S9 and genotoxicity in the SOS chromotest. Musk xylene, musk ketone, musk moskene and musk tibetene showed neither mutagenicity nor genotoxicity in the presence and absence of S9.

Nitro musk fragrances in biota from freshwater and marine environment

The nitro musks - musk xylene, musk ketone, musk ambrette, musk moskene, and musk tibetene - are intensively used as fragrances in cosmetics and detergents. The residue analysis (clean-up and GC/ECD analysis) of nitro musks in biota from freshwater and marine environment is described. In particular musk xylene and musk ketone were determined in a total of 145 samples of fish, mussels and shrimps originating from domestic and foreign aquacultures, some rivers in northern Germany, from Baltic Sea and North Sea coast. The residue levels ranged from <0.01 to 1.06 mg musk xylene/kg lipid and from <0.01 to 0.38 mg musk ketone/kg lipid, respectively. Our results seem to indicate the high bioconcentration potential and the ubiquitous distribution of this new group of contaminants in biota from freshwater and marine ecosystems.

Crystal studies of musk compounds. XI. Molecular structures of musk moskene and two homologues

The crystal structures of 1,1,3,3,5-pentamethyl-4,6-dinitroindan (1), 1,1,2,3,3,6-hexamethyl-5-nitroindan (2) and 1,1,2,3,3,5-hexamethyl-4,6-dinitroindan (3) have been established by X-ray crystallography. (1) and (3) are strong musks. Some of the structures described show disorder in the cyclopentene ring and/or in the nitro groups. This manifests itself in relatively high displacement parameters and in deviating bond distances and angles. The endocyclic angles of the cyclopentene ring, at the fusion with the aromatic ring, are significantly larger than reported in a study of the geometry of small rings [Allen (1981). Acta Cryst. B37, 900-906]

Nitro musks in human adipose tissue and breast milk

The nitro musks - musk xylene, musk ketone, musk ambrette, musk moskene and musk tibetene - which are extensively utilized as fragrances in cosmetics and detergents, were determined in a total of 32 human adipose tissue samples and 23 human milk samples from northern Germany. The residue levels ranged from 0.02 to 0.22 mg musk xylene/kg fat and from 0.01 to 0.09 mg musk ketone/kg fat, respectively (1 fat sample contained 0.22 mg musk ketone/kg fat). In a few samples musk ambrette and musk moskene were detected at low levels. Musk tibetene could not be detected at all. Apart from alimentary intake, the dermal sorption of these compounds from cosmetics and detergents is discussed as possible contamination routes.

Pigmented Contact Dermatitis Due to Musk Moskene

Musk moskene is a soft, sweet fragrance resembling musk ambrette which introduces a very desirable creamy powder note for cosmetic fragrance. Because of its advantages, which include low cost, oil solubility, and less sensitive to sunlight, musk moskene has recently increased its share of the market. In this paper, we reported a case with pigmented contact dermatitis from musk moskene in cheek rouges. Patch test positive reactions to cheek rouges resulted in hyperpigmentation. Both the perfume used in the cheek rouges and musk moskene, which was a component of that perfume, showed strongly positive reactions. Residual hyperpigmentation was seen on the regions of the perfume and musk moskene patch testings. Hyperpigmentation on cheeks of the patient gradually diminished after discontinuing use of the causative cheek rouge.

Photoallergic potential in the guinea‐pig of the nitromusk perfume ingredients musk ambrette, musk moskene, musk xylene, musk ketone, and musk tibetene

Synopsis The nitromusk perfume ingredient, musk abrette, has been reported to cause photoallergic reactions in man. The potential of alternative, chemically related, nitromusks to cause photoallergy has been studied using the Colworth guinea-pig photoallergy test. The results showed that, compared with musk ambrette, musk moskene had a weak potential for inducing photoallergy, and that the musks xylene, ketone and tibetene had only very weak potentials. A study of photo-crossreaction to musk ambrette showed that musk moskene was active, musk xylene was weakly active, while the musks ketone and tibetene were inactive. We conclude that musk moskene is likely to be less hazardous for man than musk ambrette, but caution should be used in selection of concentrations for use on sun-exposed skin. The musks xylene, ketone and tibetene are likely, photobiologically, to be acceptable alternatives to musk ambrette. The photoallergic potential of the nitromusks can, probably, be related to chemical structure.