Musk Ambrette Research Articles

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.

Determination of Musk Ambrette in Fragrance Products by Capillary Gas Chromatography with Electron Capture Detection: Interlaboratory Study

A gas chromatographic method that uses an internal standard additions techniques is described for the determination of musck ambrette (MA) in fragrance products. A solution containing the product and a known amount of an internal standard, musk tibetene (MT), is injected directly into a gas chromatograph equipped with an electron capture detector. The chromatographic separation of the components on a wide-bore fused silica capillary column is recorded and a response constant is calculated from MA and MT peak heights. A similar response constant is also calculated for a standard solution containing known concentrations of MA and MT. The MA content of the fragrance product is then calculated. Average recoveries of MA from fragrance products ranged from 97.6 to 102.3%. The method was also evaluated collaboratively by 6 laboratories. In this study, the reproducibility relative standard deviation for MA in 6 fragrance test samples ranged from 2.78 to 22.87%.

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.

Nitro musks in human milk

391 milk samples (48 in the year 1991 and 343 in 1992) of nursing mothers living in Southern Bavaria, Germany, were analyzed by GC/ECD for the synthetic nitro musks musk xylene (CAS No. 81-15-2), musk ketone (CAS No. 81-14-1), and musk ambrette (CAS No. 83-66-9). Musk ambrette and musk ketone were detected in similar amounts ranging from < 0.01 – 0.29 mg/kg fat and < 0.01 – 0.24 mg/kg fat, respectively. The mean content for both compounds was 0.04 mg/kg fat. Concentrations of musk xylene were about 2 – 3 times higher, ranging from 0.01 – 1.22 mg/kg fat with a mean content of 0.10 mg/kg fat. The toxicology of nitro musks is summarized to assess a possible hazard posed by these compounds.

Induction of cytochrome P450 1A2 by musk analogues and other inducing agents in rat liver

We characterized the inducing effects of two musk analogues, musk xylene and musk ambrette, on phase I and phase II drug-metabolizing enzymes in rat liver and compared their effects with 3-methylcholanthrene, isosafrole and 2(3)-tert-butylhydroxyanisole (BHA) at 0.1 mmol/kg dose level. Musk xylene and isosafrole increased more efficiently the metabolic activation of 2-amino-6-methyldipyrido[1,2-a:3′,2′-d]imidazole (Glu-P-1) to mutagen than that of benzo(a)pyrene. Musk ambrette increased both the activation of Glu-P-1 and benzo(a)pyrene to the same extent. Western blot analyses revealed that musk xylene, musk ambrette, isosfrole and BHA induced more stronly cytochrome P450 1A2 (CYP1A2) in microsomes than CYP1A1. 3-Methylcholanthrene induced CYP1A1 in preference to CYP1A2. On the other hand, all drugs except for 3-methylcholanthrene did not show remarkable increases in phase II enzyme activities, such as DT-diaphorase, glutathione S-transferase and UDP-glucuronyltransferase, at 0.1 mmol/kg dose level. These results show that musk xylene, musk ambrette, isosafrole and BHA at the dose level used in this study posses the potency to induce CYP1A2 without remarkable induction of CYP1A1 and phase II enzyme activities as observed for 3-methylcholanthrene, although they have been considered to induce both phase I and phase II drug-metabolizing enzymes at higher doses.

Photoallergic Contact Dermatitis

Over a 6-year period, 187 patients with a history of photosensitivity were photopatch tested using standard techniques. Seventy-six patients were male and 111 were female. Most patients were white (151 patients). Two thirds of the patients were between the ages of 31 and 60 years.Testing revealed a total of 63 positive reactions: 14 plain contact, 41 photocontact, and eight combined contact and photocontact in 37 (20%) patients. Careful history taking resulted in a diagnosis of clinically relevant photoallergic contact dermatitis in 54% of these 37 patients or 11% (20) of the total tested. Ten of the relevant responses were due to fragrance ingredients (musk ambrette and 6-methylcoumarin); 18 were due to sunscreen agents (nine to p-aminobenzoic acid and esters, nine to oxybenzone). The fragrance reactions occurred in the early years of the study (1985, 1986, and 1987) while the sunscreen agents accounted for all but two of the 14 positive reactions in the last 3 years of the study (1988, 1989, and 1990).These data suggest that the incidence of photoallergy due to fragrances is declining, while reactions to sunscreen agents, in particular oxybenzone, are increasing. This trend may reflect an altered use pattern by the general population for products containing these chemicals.

Photoallergic contact dermatitis. Results of photopatch testing in New York, 1985 to 1990.

Over a 6-year period, 187 patients with a history of photosensitivity were photopatch tested using standard techniques. Seventy-six patients were male and 111 were female. Most patients were white (151 patients). Two thirds of the patients were between the ages of 31 and 60 years. Testing revealed a total of 63 positive reactions: 14 plain contact, 41 photocontact, and eight combined contact and photocontact in 37 (20%) patients. Careful history taking resulted in a diagnosis of clinically relevant photoallergic contact dermatitis in 54% of these 37 patients or 11% (20) of the total tested. Ten of the relevant responses were due to fragrance ingredients (musk ambrette and 6-methylcoumarin); 18 were due to sunscreen agents (nine to p-aminobenzoic acid and esters, nine to oxybenzone). The fragrance reactions occurred in the early years of the study (1985, 1986, and 1987) while the sunscreen agents accounted for all but two of the 14 positive reactions in the last 3 years of the study (1988, 1989, and 1990). These data suggest that the incidence of photoallergy due to fragrances is declining, while reactions to sunscreen agents, in particular oxybenzone, are increasing. This trend may reflect an altered use pattern by the general population for products containing these chemicals.

Successful treatment of musk ketone-induced chronic actinic dermatitis with cyclosporine and PUVA

We describe a patient with chronic actinic dermatitis whose photopatch tests revealed reactions to musk ketone and musk ambrette, both of which were found in his aftershave lotion. Minimal erythema doses of UVA and UVB were decreased. After initial unsuccessful treatment with PUVA therapy the patient was successfully treated with a combination of cyclosporine and PUVA.

Examination of Tetrachlorosalicylanilide (TCSA) Photoallergy Using In Vitro Photohapten-Modified Langerhans Cell-Enriched Epidermal Cells

Lymphocytes from BALB/c mice photosensitized in vivo to tetrachlorosalicylanilide (TCSA) were investigated to determine whether they could be stimulated to proliferate when cultured with Langerhans cell-enriched cultured epidermal cells (LC-EC) photohapten-modified in vitro with TCSA + UVA radiation. Cultured LC-EC were photohapten-modified in vitro by irradiation in TCSA-containing medium using a 1000-watt solar simulator equipped with filters to deliver primarily UVA radiation (320-400 nm). Lymphocytes from TCSA-photosensitized mice were incubated with LC-EC that had been treated in vitro with 0.1 mM TCSA and 2 J/cm2 UVA radiation (TCSA + UVA). Responder lymphocytes demonstrated a significant increase in their blastogenesis response compared to lymphocytes that were incubated with LC-EC irradiated with UVA prior to treatment with TCSA (UVA/TCSA) or with LC-EC that had received no treatment. Lymphocytes from naive mice or mice photosensitized with musk ambrette (MA) demonstrated a significantly lower response to LC-EC modified with TCSA + UVA, indicating the specificity of the response. Maximum blastogenesis response was achieved when LC-EC were treated with 0.1 mM TCSA and a UVA radiation dose of at least 0.5 J/cm2. Epidermal cells depleted of LC by treatment with anti-Ia antibody plus complement or by an adherence procedure were unable to stimulate this blastogenesis response. Epidermal cells treated in vitro with TCSA + UVA demonstrated enhanced fluorescence compared to control cells. The fluorescence observed was not restricted to any specific epidermal cell type; however, fluorescence microscopy studies revealed that dendritic Ia-positive cells, presumably LC, were also TCSA fluorescent. Flow cytometry showed that Ia-positive epidermal cells demonstrated the greatest UV fluorescence when treated with TCSA + UVA compared to both cells irradiated with UVA and subsequently treated with TCSA and untreated cells. This is consistent with the enhanced antigen presentation capability of TCSA + UVA treated LC-EC, which leads to the conclusion that LC photohapten-modified in vitro with TCSA + UVA demonstrate enhanced TCSA fluorescence and are capable of stimulating lymphocytes from TCSA photosensitized mice in an antigen-specific manner.

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.

Persistent Light Reaction Associated with Photoallergic Contact Dermatitis to Musk Ambrette and Allergic Contact Dermatitis to Fragrance Mix

A 57-year-old man suffering from persistent light reaction with photocontact allergy to musk ambrette and contact allergy to fragrance mix was evaluated. A lowered minimal erythema dose to UV-B (MED-UV-B) was seen. Reactions to long-wave UV-A and visible radiation were normal. A skin biopsy from one MED-UV-B, taken 24 h after irradiation, showed acute spongiotic dermatitis.

ChemInform Abstract: Crystal Studies of Musk Compounds. Part 1. 4‐tert.‐Butyl‐3‐methoxy‐2,6‐dinitrotoluene (Musk Ambrette)

ChemInformVolume 21, Issue 26 Physical Organic Chemistry ChemInform Abstract: Crystal Studies of Musk Compounds. Part 1. 4-tert.-Butyl-3-methoxy-2,6-dinitrotoluene (Musk Ambrette) D. J. A. DE RIDDER, D. J. A. DE RIDDER Lab. Crystallogr., Univ. Amsterdam, Amsterdam, Neth.Search for more papers by this authorK. GOUBITZ, K. GOUBITZ Lab. Crystallogr., Univ. Amsterdam, Amsterdam, Neth.Search for more papers by this authorH. SCHENK, H. SCHENK Lab. Crystallogr., Univ. Amsterdam, Amsterdam, Neth.Search for more papers by this author D. J. A. DE RIDDER, D. J. A. DE RIDDER Lab. Crystallogr., Univ. Amsterdam, Amsterdam, Neth.Search for more papers by this authorK. GOUBITZ, K. GOUBITZ Lab. Crystallogr., Univ. Amsterdam, Amsterdam, Neth.Search for more papers by this authorH. SCHENK, H. SCHENK Lab. Crystallogr., Univ. Amsterdam, Amsterdam, Neth.Search for more papers by this author First published: June 26, 1990 https://doi.org/10.1002/chin.199026054Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume21, Issue26June 26, 1990 RelatedInformation

Chronic Actinic Dermatitis

Persistent light reactivity, photosensitive eczema, photosensitivity dermatitis, or actinic reticuloid? Increasing experience indicates that these syndromes (Table), which were defined 15 or more years ago and generally occur in elderly men, represent arbitrary, confusing, and largely unnecessary subclassifications, and in this issue of theArchivesLim et al 1 rightly suggest that the conditions should be considered as variants of a single condition, namely chronic actinic dermatitis. The syndrome of persistent light reactivity was first recognized in 1962 by Wilkinson 2 after an epidemic of photoallergy to tetrachlorosalicylanilide, an antibacterial agent incorporated into soaps and hair toiletries. Following an episode of photoallergy caused by epicutaneous contact with a photoallergen such as one of these halogenated salicylanilides, musk ambrette 3 or quinoxaline dioxide, 4 some subjects develop persistent photosensitivity of both exposed and covered skin despite removal of the offending chemical from the environment. Whereas the action spectrum for the initiating

A predictive mouse ear-swelling model for investigating topical photoallergy

The photoallergic potential of various compounds was assessed using a mouse ear-swelling model, which offers the advantage of being quantifiable and more objective than models based on subjective evaluation of erythematous skin reactions. Cyclophosphamide pretreated BALB/c mice were induced by topical treatment of the dorsal skin surface on 3 consecutive days and challenged on the ears 5 days after the last induction. For each induction and challenge treatment, mice were consecutively irradiated with ultraviolet (UV) A (10 J/cm 2) and UVB (45 mJ/cm 2) radiation 30 min to 1 hr after test material application. The photoallergic response to musk ambrette, a known human photoallergen, was significantly augmented when three consecutive induction exposures were used as compared with one or two inductions. The photoallergic potential of nine other known human photoallergens (tetrachlorosalicylanilide, bithionol, 6-methylcoumarin, chlorpromazine, sodium omadine, bisphenol A, sulphanilamide, fentichlor and p-aminobenzoic acid) was successfully detected using the mouse model. In each experiment, the ear thickness changes observed in the photoallergy test mice were significantly greater than the changes observed in the contact allergy, vehicle/radiation and phototoxicity control mice. Coumarin and homosalate, two agents not traditionally associated with causing photoallergy in humans or animals, did not demonstrate contact photoallergy using this model. With three of the photoallergens, musk ambrette, bithionol and tetrachlorosalicylanilide, the ear swelling response obtained was due to photoallergy alone and not due to the co-existence of both contact photoallergy and contact allergy. In addition, irradiating mice 24 hr, rather than 1 hr, following application of the test material during the induction phase resulted in a significantly reduced photoallergic response with both musk ambrette and tetrachlorosalicylanilide. These results indicate that the mouse ear-swelling model is a potentially useful model for investigative and predictive photoallergy testing.

90-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat

Musk ketone, musk xylene, musk tibetene and moskene, synthetic musks used in fragrances, were applied dermally to rats in daily doses of 240 (musk ketone and musk xylene only), 75, 24 or 7.5 mg/kg body weight for 90 days. The chemically related musk ambrette, a known neurotoxin in rats, was used as a positive control. While musk ambrette was clearly neurotoxic and caused testicular atrophy, as had been previously reported, the other compounds tested caused neither effect. The only effects of application of these materials were some organ weight changes at the higher doses, but these were not associated with histopathological changes in any of the tissues. The no-effect levels were: musk ketone, 75 mg/kg for males and females; musk xylene, 75 mg/kg for males and 24 mg/kg for females; moskene, 24 mg/kg for males and 75 mg/kg (highest dose administered) for females; and musk tibetene, 75 mg/kg (highest dose) for males and females.

Screening test for phototoxins using solutions of simple biochemicals

The feasibility of using solution photochemistry for in vitro phototoxicology testing was examined. Solutions of substrate and test chemical, in binary aqueous/organic solvent to ensure solubility, were exposed to ultraviolet/visible radiation. Quantum efficiencies for photosensitized oxidation of substrate were calculated. The phototoxins rose bengal, anthracene and acridine were good photooxidizers of histidine, in contrast to the other chemicals studied. Solution photochemistry using histidine may be a useful screening test for molecules that photooxidize by the singlet oxygen pathway. Other indications of in vivo activity may be gained from the molecular weight, ionic nature, lipophilicity and photodegradation (photoinactivation). The photoallergens tetrachlorosalicylanilide, tribromosalicylanilide and musk ambrette, and the photomutagen 8-methoxypsoralen, were detected qualitatively by these studies, but in vivo potency could not be predicted.

Contact photoallergy testing of sunscreens in guinea pigs.

The potential of 3 sunscreens (p-aminobenzoic acid, 4-isopropyldibenzoylmethane and homosalate) and 2 known human photoallergens (musk ambrette and tetrachlorosalicylanilide) to cause photoallergy, phototoxicity, and/or contact sensitization was determined using a guinea pig photoallergy model, as previously described by Harber and associates. The model was slightly modified by employing 6 exposures over 2 weeks and using Hill Top Chambers for application of the test material. Contact photoallergy was detected in guinea pigs treated with musk ambrette or tetrachlorosalicylanilide (TCSA), although with TCSA, a lower incidence of contact sensitivity and phototoxicity was also detected. The results of studies conducted with sunscreens showed that p-aminobenzoic acid was photoallergenic, whereas homosalate and 4-isopropyl-dibenzoylmethane (Eusolex 8020) were not. However, contact sensitization, and to a lesser degree primary irritation, was detected with Eusolex 8020 at the concentrations employed in this study. The results of these studies suggest that this guinea pig model is a suitable model for assessing the photoallergic potential of various compounds, including the sunscreens tested in this study.

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.

Photopatch testing: A six-year experience

The results of photopatch testing performed at the Mayo Clinic from 1980 through 1985 were analyzed. During the 6 years, 70 patients underwent photopatch testing. Of the 70 patients, 27 (38.5%) had positive photopatch test reactions and 22 (31%) had ordinary contact reactions. Of the 27 patients with photocontact reactions, 14 had relevant reactions. The most frequent positive reactions were to chlorpromazine (13 patients), musk ambrette (nine patients), and promethazine (eight patients). Photopatch testing is an essential part of the evaluation of patients who are suspected of having photosensitive dermatitis. In some patients with recalcitrant eruptions, testing may help in excluding photosensitivity as a possible contributing factor.

Contact photoallergy to musk ambrette.

SummaryPhotoallergic dermatitis due to musk ambrette is reported in six patients, and the literature on this sensitivity is reviewed. The condition presents with a typical pattern involving the neck and cheeks, and the diagnosis can be confirmed by photopatch testing with musk ambrette.