musk and musk-ketone

The polycyclic musk fragrances, mainly 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-ben zopyrane (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyltetrahydronaphthalene (AHTN) are synthetic musk fragrances which are used in almost all scented consumer products, such as perfumes, cosmetics and laundry detergents. Concerning their chemical structures the polycyclic musks are indane and tetraline derivatives highly substituted mainly by methyl groups. Their production has been increased continuously during the last years with a world-wide production volume today of about 6000 t/year. After their application in private households they are dumped via the sewage treatment plants into the aquatic environment. In this review the analysis of polycyclic musk compounds in environmental samples is shortly presented and all published data of polycyclic musk compounds in water, sediment, suspended particulate matter (SPM), sewage sludge, and biota are summarized and discussed. The highest HHCB and AHTN concentrations were analysed in water (maximum concentrations: 6 microg HHCB/l, 4.4 microg AHTN/1) and sludge (maximum concentrations: 63 mg HHCB/kg dry matter, 34 mg AHTN/kg dry matter) from sewage plants, and in fish (maximum concentrations: 159 mg HHCB/kg lipid, 58 mg AHTN/kg lipid) from sewage ponds. In all other samples from different aquatic ecosystems these chemicals were unequivocally detected in varying concentrations dependent on the distance to sewage treatment plants. Even in marine water samples from the German Bight HHCB and AHTN could be quantified at the lower ng/l level. Very often HHCB and AHTN formed the major organic contaminants, in all samples their concentrations exceeded those of musk xylene and musk ketone. Also several by-products and impurities of the commercial polycyclic musks were analysed in river and waste water samples in not negligible amounts. The apparently ubiquitous distribution of polycyclic musks in the aquatic environment demonstrates the persistence and lipophilicity of these pollutants. The high log K(ow) values of HHCB and AHTN (5.7-5.9) do not directly correlate with their relatively low bioconcentration factors (BCFs) derived from fish experiments, this discrepancy may be explained by a particular metabolism in fish. There are indications of a possible species dependent metabolisation. For a general risk assessment of this new group of environmental pollutants besides the missing toxicological data, further studies on

Topics: Animals; Benzopyrans; Fatty Acids, Monounsaturated; Fishes; Geologic Sediments; Naphthalenes; Perfume; Sewage; Water Pollutants, Chemical; Xylenes

Synthetic musk compounds (SMCs) have been extensively used in numerous consumer products, such as perfumes, cosmetics, soap, and fabric softener. Due to their bioaccumulative nature, these compounds have often been detected in the aquatic ecosystem. However, their effects on endocrine and behavioral effects in freshwater fish have rarely been investigated. In the present study, thyroid disruption and neurobehavioral toxicity of SMCs were investigated using embryo-larval zebrafish (Danio rerio). Three frequently used SMCs, i.e., musk ketone (MK), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta [g]- benzopyran (HHCB), and 6-acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN), were chosen. Experimental concentrations for HHCB and AHTN were selected to include the maximum levels reported in the ambient water. The 5-day exposure to either MK or HHCB led to significant decrease of T4 concentration in the larval fish at the levels as low as 0.13 μg/L, even though compensatory transcriptional changes, e.g., up-regulation of hypothalamic crhβ gene and/or down-regulation of ugt1ab gene, were taken place. In contrast, AHTN exposure resulted in up-regulation of crhβ, nis, ugt1ab, and dio2 genes but did not alter T4 level, suggesting its lesser thyroid disrupting potential. All tested SMCs caused hypoactivity of the larval fish. Several genes related to neurogenesis or development, e.g., mbp and syn2a, were down-regulated, but the patterns of transcriptional changes were different among the tested SMCs. The present observations demonstrate that MK and HHCB can decrease T4 levels and cause hypoactivity of the larval zebrafish. It requires attention that HHCB and AHTN could influence thyroid hormone or behavior of the larval fish even at the levels close to those observed in the ambient environment. Further studies on potential ecological consequences of these SMCs in freshwater environment are warranted.

Topics: Animals; Ecosystem; Larva; Thyroid Hormones; Water Pollutants, Chemical; Zebrafish

Understanding olfaction process at a microscopic or molecular level needs more elucidation of the multiple stages involved in the olfaction mechanism. A worth full elucidation and a better understanding of this molecular mechanism, a necessary preamble should be achieved. The content of this work is a preamble for that. A study of the mouse and human olfactory receptors activation in response to two nitro musks stimuli, which are the musk xylol and the musk ketone, are considered here, first, for their wide expanded use in perfumery, but also to show some particular aspects of this process in the case of these two stimuli, which could help to deduce more details and more general aspects in the global olfactory mechanism. A statistical physics modeling using the monolayer model with two independent types of receptor binding sites of the response of the mouse olfactory receptor MOR215-1 and the human olfactory receptor OR5AN1, which are identified as specifically responding to musk compounds, is used to characterize the interaction between the two nitro musk molecules, the mouse and the human olfactory receptors and to determine the olfactory band of these two odorants through the determination of the molar adsorption energies and the adsorption energy distributions. The physico-chemical model parameters can be used for the steric characterization via the calculation of the receptor site size distributions. The docking computation between these two nitro musks and the human olfactory receptor OR5AN1 is performed demonstrating a large similarity in receptor-ligand detection process. Thus, docking finding results prove that the calculated binding affinities were belonging to the spectrum of adsorption energies.

Topics: Adsorption; Animals; Fatty Acids, Monounsaturated; Humans; Mice; Models, Chemical; Molecular Docking Simulation; Nitro Compounds; Odorants; Physics; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Receptors, Odorant; Smell; Xylenes

A Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) methodology followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis was developed to extract thirteen synthetic musk compounds (SMCs: cashmeran, celestolide, phantolide, traseolide, galaxolide, tonalide, musk ambrette, musk xylene, musk ketone, musk tibetene, musk moskene, ethylene brassylate and exaltolide) and six ultraviolet-filters (UVFs: 2-ethylhexyl 4-dimethylaminobenzoate, 3-(4'-methylbenzylidene) camphor, 2-ethylhexyl 4-methoxycinnamate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, benzophenone and drometrizole trisiloxane) from tomatoes. The proposed methodology was optimized: 2 g of freeze-dried tomato was extracted with 4 mL of water and 10 mL of ethyl acetate, adding 6 g of MgSO

Topics: Benzophenones; Benzopyrans; Dinitrobenzenes; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Indans; Solanum lycopersicum; Solid Phase Extraction; Tandem Mass Spectrometry; Tetrahydronaphthalenes; Water Pollutants, Chemical; Xylenes

Human activity in estuarine areas has resulted in pollution of the aquatic environment, but little is known about the levels of synthetic musks (SMs) in river water and sediments in estuarine areas. This study investigated the concentrations and distribution of SMs in the Jiaozhou Bay wetland, including celestolide, phantolide, traseolide, galaxolide (HHCB), tonalide (AHTN), musk xylene and musk ketone (MK). The SMs HHCB, AHTN and MK were detected at concentrations of 10.7-208, not detected (ND)-59.2 and ND-13.6 ng/L, respectively, in surface water samples and 13.1-27.3, 3.06-14.5 and 1.33-18.8 ng/g (dry weight; dw), respectively, in sediment samples. Based on the calculated total organic carbon (TOC) concentrations, there was no significant correlation between SMs and TOC in sediment samples (p > 0.05). The hazard quotients were 0.204, 0.386 and 0.059 for AHTN, HHCB and MK, respectively, which indicated no serious environmental impact, because these values are all less than 1. The concentrations of SMs decreased as the distance to the Xiaojianxi refuse landfill increased in both surface water and sediments. Compared with previous studies, the concentration of SMs in the Jiaozhou Bay wetland was relatively high. Therefore, more attention should be paid to SMs because of their persistent impact on human health and the environment.

Topics: Bays; Benzopyrans; China; Fatty Acids, Monounsaturated; Humans; Perfume; Risk Assessment; Tetrahydronaphthalenes; Water Pollutants, Chemical; Wetlands; Xylenes

Synthetic musk compounds are widely used in the formulation of several cosmetics, personal care and household products. Due to their massive and widespread use, together with some health concerns, they are considered emerging pollutants and have been detected in different environmental compartments. This study focused on the evaluation of the concentration of synthetic musks (five nitro, five polycyclic and one macrocyclic musks) in beach sands, from Oporto coastal area (Portugal), contributing to the enhancement of the knowledge of levels, trends and behaviour of these compounds in this particular matrix. To accomplish this task, a QuEChERS methodology ("Quick, Easy, Cheap, Effective, Rugged, and Safe") coupled to gas chromatography-mass spectrometry (GC-MS) was successfully used to determine synthetic musks from beach sand. The chosen methodology proved to be suitable, achieving satisfactory results for precision (relative standard deviation values below 15%), accuracy (average recovery of 97%) and limits of detection (below 38 pg g

Topics: Bathing Beaches; Benzopyrans; Cosmetics; Dinitrobenzenes; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Portugal; Seasons; Tetrahydronaphthalenes; Water Pollutants, Chemical; Xylenes

The levels of 12 synthetic musks and one musk metabolite in 24 pooled human milk samples were examined in order to assess the health risks of these contaminants to breast-feeding infants of China. The 24 pooled samples comprised of 1237 individual human milk samples collected from 12 provinces of China according to WHO guidelines. Among the 13 target analytes, OTNE ([1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethylnaphthalen-2yl]ethan-1-one), HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[γ]-2-benzopyran), AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene), musk ketone (4-tert-butyl-2,6-dimethyl-3,5-dinitroacetophenone, MK), Musk T (1,4-dioxacyclohepta decane-5,17-dione), HHCB-lactone (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl cyclopenta[γ]-2-benzopyran-1-one) and musk ambrette (1-(1,1-dimethylethyl)-2-methoxy-4-methyl-3,5-dinitrobenzene, MA), were found in the milk samples analysed with mean (median) concentrations of 3.96 (3.91), 18.03 (15.10), 10.30 (9.38), 4.68 (4.45), < 3.70 (< 3.70), 10.02 (9.20) and < 5.20 (< 5.20) ng g(-1) lipid weight, respectively, whereas ADBI (4-acetyl-1,1-dimethyl-6-tert-butylindan), AHDI (6-acetyl-1,1,2,3,3,5-hexamethylindan), ATII (5-acetyl-1,1,2,6-tetramethyl-3-isopropylindan), musk xylene (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene, MX), musk tibetene (1-tert-butyl-3,4,5-trimethyl-2,6-dinitrobenzene, MT) and musk moskene (1,1,3,3,5-pentamethyl-4,6-dinotroindane, MM) were not detected. Significantly positive associations were observed in concentration levels between HHCB and AHTN (p < 0.001), HHCB and HHCB-lactone (p < 0.05), AHTN and HHCB-lactone (p < 0.001), and MK and OTNE (p < 0.05). No statistical difference was found in musk concentrations between rural and urban areas in China (p > 0.05). The mean (median) estimated daily intakes by infants were 20.5 (20.2), 93.4 (78.2), 53.4 (48.6), 24.2 (23.0) and 51.9 (47.6) ng kg(-1) body weight for OTNE, HHCB, AHTN, MK and HHCB-lactone, respectively. The musk exposure levels of infants in China via breast feeding were very low according to the current toxicological information.

Topics: Adolescent; Adult; China; Dinitrobenzenes; Fatty Acids, Monounsaturated; Female; Humans; Indans; Infant; Milk, Human; Recommended Dietary Allowances; Tetrahydronaphthalenes; Water Pollutants, Chemical; Xylenes

A new analytical method for the simultaneous determination of eight synthetic musks compounds (SMs) including five polycyclic musks (PCMs) and three nitro musks (NMs) was validated for sediment samples based on a simple QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) sample preparation procedure followed by gas chromatography-mass spectrometry (GC-MS). Good analytical performances were obtained for all the target compounds. For the validation of the method, internal calibration (IC) and internal calibration with QuEChERS (ICQ) were compared. Good linearity was obtained for both calibration methods with determination coefficients (R

Topics: Benzopyrans; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Tetrahydronaphthalenes; Tunisia; Xylenes

Musk is widely used in clinical practice for its anti-cancer properties. Here, we treated various types of cancer using musk to determine which cancers are sensitive to musk treatment. We also compared effects of native musk and synthetic musk ketone in cancer cells. Furthermore, we investigated mechanisms underlying effects of musk.. Twenty two cancer cell lines were treated with musk. Cell proliferation and apoptosis analyses were carried out. Native musk and synthetic musk ketone were analyzed by gas chromatograph-mass spectrometer (GC-MS) assay. Differentially expressed genes were determined by microarray and quantitative real-time polymerase chain reaction.. Native musk strongly induced the growth repression and the apoptosis in the majority of cancer cell lines in a dose-dependent manner, but distinct types of cancer showed significantly different reactions. Cancer cells which originated from epithelial cells showed higher sensitivity for musk treatment. By contrast, leukaemia and lymphoma cells were not sensitive. GC-MS analysis demonstrated that native musk contains more than 30 contents in which musk ketone is a major component; synthetic musk ketone was consistent with natural musk ketone, and the used sample of synthetic musk ketone contained only sole component. Similar to native musk, synthetic musk ketone induced the growth repression and the apoptosis of cancer cells. Additionally, numerous genes were differentially expressed in lung cancer cells after native musk treatment. These differentially expressed genes were involved in many signalling pathways. Among these pathways, apoptosis-related pathways included interleukin family, tumor necrosis factor family, and MAPK signalling pathway. Native musk and synthetic musk ketone can up-regulate IL-24 (interleukin family) and DDIT3 (MAPK signalling pathway) in lung cancer cells.. This research provided strong evidence that native musk and synthetic musk ketone can induce the growth repression and the apoptosis of cancer cells. However, the selection of sensitive cancer patient for individualized treatment is a key step in clinical application. Synthetic musk ketone can substitute for native musk to treat cancer patients. Musk might induce the growth repression and the apoptosis of lung cancer cells through up-regulating IL-24 and DDIT3 expressions.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Humans; Lung Neoplasms; Signal Transduction; Xylenes

Human breast milk samples collected from mothers (n=110) who lived in Chengdu, Sichuan Province, southwestern China in 2009 were analyzed to determine the concentrations of 13 musk compounds. Possible relationships between musk concentrations and some personal characteristics were also studied. Only five target analytes were detected in the milk samples analyzed, with median concentration values of 16.5, 11.5, 7.85, <1.5 and <1.4ngg(-1)lipid weight for AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene), HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[γ]-2-benzopyran), HHCB-lactone (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[γ]-2-benzopyran-1-one), OTNE ([1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethylnaphthalen-2yl]ethan-1-one) and musk ketone (4-tert-butyl-2,6-dimethyl-3,5-dinitroacetophenone, MK), respectively. Mothers who reported high use of hand-cleaning agents, body-cleaning agents, shampoo and hair conditioners, hair dyes and hair gels had significantly elevated milk concentrations of HHCB whereas elevated milk concentrations of AHTN were observed among mothers reporting high use of body-cleaning agents, body lotions, shampoos, hair dyes and hair gels. Younger age showed a significantly positive effect on milk concentrations of both HHCB and AHTN whereas BMI after delivery, the number of children nursed and place of residence (urban or rural) had no significant effect. The estimated median daily intakes of synthetic musks for breast-fed infants were considerably lower than the current provisional tolerable daily intake amounts suggested for adults.

Topics: Benzopyrans; China; Fatty Acids, Monounsaturated; Female; Household Products; Humans; Infant; Maternal Age; Milk, Human; Mothers; Naphthalenes; Risk Assessment; Tetrahydronaphthalenes; Urban Population; Xylenes

To investigate the occurrence of 13 kinds of synthetic musk and triclosan in breast milk samples collected from Beijing, and to estimate the exposure of breastfed infants.. Target compounds in 65 milk samples collected from 4 districts of Beijing in 2004 were analyzed by means of gas chromatography - tandem mass spectrometry (GC - MS/MS) and quantified by internal standards. The exposure of infants was analyzed statistically by SPSS software.. HHCB, AHTN, OTNE, MT and Triclosan were detected in milk samples in the range of 0.6 - 174.1 ng/g lipid, with some difference in 4 districts. It is estimated that the intake of synthetic musks and triclosan for each infant from breast milk would be 13.5 - 3917 ng/d.. Commonly used synthetic musks and tricloson were generally detected in breast milk. Further study should be focused on monitoring and tracing the possible source of pollution.

Topics: Adult; Breast Feeding; Environmental Exposure; Environmental Pollutants; Fatty Acids, Monounsaturated; Female; Gas Chromatography-Mass Spectrometry; Humans; Infant; Milk, Human; Perfume; Tandem Mass Spectrometry; Triclosan; Xylenes

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 microM), CYP17- (IC(50): 213-225 microM), CYP11beta- and CYP19-catalyzed activities than nitromusks, while the latter showed higher ability to interfere with CYP1A (IC(50): 35-37 microM). The sulfation of estradiol was also significantly inhibited by tonalide and galoxolide (IC(50): 140-294 microM). 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.

Topics: Animals; Aromatase; Benzopyrans; Carps; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP3A; Fatty Acids, Monounsaturated; Female; Glucuronosyltransferase; Gonads; Indans; Liver; Male; Perfume; Steroid 17-alpha-Hydroxylase; Sulfotransferases; Tetrahydronaphthalenes; Water Pollutants, Chemical; Xenobiotics; Xylenes

Synthetic musk fragrances have been measured in water, air, sediments, sewage sludge, and biota worldwide. As the study of the environmental fate and impacts of these compounds progresses, the need for Standard Reference Materials (SRMs) for these compounds to facilitate analytical method improvement and interlaboratory comparisons becomes increasingly important. The National Institute of Standards and Technology (NIST) issues environmental matrix SRMs with certified concentrations for a variety of persistent organic pollutants including polycyclic aromatic hydrocarbons (PAHs), chlorinated pesticides, and polychlorinated biphenyl congeners (PCBs). Until now synthetic musk fragrance concentrations have not been reported in NIST SRMs. The objective of this study was to provide reference values for several commonly detected synthetic musk fragrances in several NIST natural matrix SRMs. In this study five polycyclic musk fragrances [HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran), AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene), ADBI (4-acetyl-1,1-dimethyl-6-tert-butylindane), AHMI (6-acetyl-1,1,2,3,3,5-hexamethylindane), and ATII (5-acetyl-1,1,2,6-tetramethyl-3-isopropylindane] and two nitro musk fragrances [musk xylene (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene) and musk ketone (4-tert-butyl-3,5-dinitro-2,6-dimethylacetophenone)] were measured in selected environmental SRMs. Gas chromatography-electron impact mass spectrometry (GC/EI-MS) was used for all analyses. HHCB was the most frequently detected synthetic musk fragrance and was detected in SRM 2585 Organic Contaminants in House Dust, SRM 2781 Domestic Sludge, SRM 1974b Organics in Mussel Tissue (Mytilus edulis), and SRM 1947 Lake Michigan Fish Tissue. It was not detected in SRM 1946 Lake Superior Fish Tissue or SRM 1945 Organics in Whale Blubber. Concentrations of HHCB in these SRMs ranged from 1.12 ng/g in SRM 1947 to 92,901 ng/g in SRM 2781. All of the polycyclic musk fragrances were detected in SRM 2781 and all of the target compounds were detected in SRM 2585.

Topics: Animals; Bivalvia; Chemistry Techniques, Analytical; Dust; Environmental Monitoring; Environmental Pollutants; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Models, Chemical; Mytilus; Organic Chemicals; Reference Standards; Reproducibility of Results; Xylenes

A full life-cycle (

Topics: Animals; Benzopyrans; Cell Line; Copepoda; Drosophila melanogaster; Endocrine System; Fatty Acids, Monounsaturated; Female; Indans; Larva; Life Tables; Male; Odorants; Perfume; Population Dynamics; Reproduction; Tetrahydronaphthalenes; Water Pollutants, Chemical; Xylenes

Topics: Dinitrobenzenes; Fatty Acids, Monounsaturated; Xylenes