Musk Ambrette Research Articles

Measurement of urinary constituents and output using diposable napkins

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.

Drug-Induced Photoallergy

Over the past several years, the exponential growth in the use of topical and systemic medications and drugs has been accompanied by a concomitant increase in the incidence of adverse reactions associated with them. One type of reaction that has been of particular interest to dermatologists has been the development of immunologic photosensitivity to topically applied and orally administered substances. The majority of agents that have been identified as causing photoallergic reactions in a significant percentage of individuals are no longer utilized. However, because new products are introduced with increasing frequency, this type of photosensitivity disease promises to be an ongoing problem for the dermatologic community.

Identification, occurrence and mutagenicity in Salmonella typhimurium of two synthetic nitroarenes, musk ambrette and musk xylene, in Indian chewing tobacco and betel quid

During N-nitrosamine analysis of extracts of betel quid with tobacco and of the saliva of chewers of betel quid with tobacco for N-nitrosamines using a Thermal Energy Analyzer, two unknown compounds were detected. They were identified as synthetic nitro musks, musk ambrette (5- tert-butyl-1,3-dinitro-4-methoxy-2-methylbenzene, CAS No. 83-66-9) and musk xylene, (1- tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene, CAS No. 81-15-2), by gas chromatography-mass spectrometry and Fourier transform nuclear magnetic resonance spectroscopy. These compounds were detected in several samples of betel quid with tobacco and in perfurmed tobacco used for chewing in India in amounts ranging from 0.45–23.5 mg/g wet weight. Musk ambrette was found to be mutagenic in Salmonella typhimurium TA100 requiring metabolic activation by rat-liver postmitochondrial supernatant but musk xylene lacked mutagenicity.

A simple method of qualitative analysis for musk ambrette, musk ketone and musk xylene in cologne

Musk ambrette has become one of the commonest photosensitizers in many countries and is the cause of persistent light reactions in many patients. A simple method is presented for qualitative analysis for musk ambrette and other nitromusks in colognes using thin-layer chromatography with toluene as carrier solvent and visualization under UVL. It is useful for identifying such colognes so that proper recommendations can be given to patients sensitive to musk ambrette. 14 of 32 men's colognes, analysed by TLC and confirmed on GC/MS, were found to contain musk ambrette, the concentration varying from 0.02 to 0.39% w/v.

Photosensitivity to musk ambrette.

SUMMARYMusk ambrette is the most common known photosensitiser in Singapore. Twelve patients with photosensitivity to musk ambrette were studied and we observed that the majority of the patients belonged to the older age group (over 35 years of age). Their presentation was characteristic and 33 % were sensitive to this fragrance without UVL. Five patients remained photosensitive despite avoidance of this perfumed preparation, indicating the possibility of unidentified sources of musk ambrette in the environment.

Photosensitivity Diseases Related to Interior Lighting

The most frequently used source of indoor lighting is the fluorescent tube. Although there are major variations in phosphors, the majority of these lamps are safe, efficient, and economical illuminators. These fluorescent light sources are currently our primary source of visible light; however, they emit small amounts of ultraviolet A light (UVA) as well as a somewhat larger percentage of infrared radiation. Photosensitivity diseases have been reported in each of these three broad wavelength bands. Specific examples include heat urticaria from infrared exposure, contact photosensitivity of the phototoxic type following exposure to dyes and visible light, and two relatively rare but disabling conditions from ultraviolet A exposure--solar urticaria and contact photosensitivity of the photoallergic type (persistent light reaction). During the past five years, eight patients with photosensitivity induced by musk ambrette and UVA have been treated at Columbia-Presbyterian Medical Center; six of these have been severely disabled and satisfy the criteria for persistent light reactors. Fifteen patients with solar urticaria have also been observed. Ten of these had reactions in the UVA range. The clinical and laboratory findings of these two groups of patients were presented.

Use of the occlusive patch to evaluate the photosensitive properties of chemicals in guinea-pigs

Guinea-pig tests were conducted on a known photocontact allergen, tetrachlorosalicylanilide (TCSA), a known phototoxin, 8-methoxypsoralen, two reportedly weak photoallergens, musk ambrette and 6-methylcoumarin, and a negative control, octylphenoxy polyethoxyethanol (Triton X-15). The data show that under the test conditions used, photosensitivity responses can be produced, and combinations of these as well as the other biological responses can be readily defined. The results indicate that musk ambrette is photoallergenic, that 8-methoxypsoralen is phototoxic and that Triton X-15 is only a slight irritant. On the other hand, results with TCSA suggest that it is a strong contact allergen and photoallergen, while 6-methylcoumarin would be considered to be a weak contact allergen with weak phototoxic properties. Previous reports that barrier destruction or adjuvanticity is necessary to produce photoallergy to musk ambrette were not confirmed; by ensuring occlusion using standard methods, the photoallergic nature of the response to this material was clearly demonstrated. A device described elsewhere (Newmann & Parker, Fd Chem. Toxic. 1985, 23, 683) has made it possible to develop methods that can be used to differentiate clearly among the possible biological responses that can occur in guinea-pigs when photoreactive materials are applied to their skin and irradiated. The probable biological responses that need to be defined, under the above conditions, are primary irritation, delayed contact hypersensitivity, phototoxicity and/or photoallergenicity.

The Clinical Spectrum of the Persistent Light Reactor

Eight patients had a chronic photodermatitis of five to 19 years' duration. The clinical and photobiological features were consistent with the pattern observed in persistent light reactors. Severity and clinical presentation, however, were quite variable, ranging from a few isolated papules to extensive lichenification involving the entire exposed skin. Three had positive photopatch tests to halogenated salicylanilides, while the remaining five reacted to musk ambrette. Exposure of the uninvolved skin to UV-B or solar-simulated radiation provoked abnormal delayed papular or infiltrated reactions. Histological evaluation of these reactions in three cases disclosed moderate to dense perivascular lymphocytic infiltrates with occasional eosinophils, focal exocytosis, and epidermal spongiosis. We conclude that persistent light reactivity associated with photoallergic contact dermatitis shows a spectrum of disease activity and photosensitivity. Recognition of the subtle forms of this disease is important.

Transient and persistent photosensitivity due to musk ambrette. Clinical and photobiological studies

Musk ambrette caused contact photosensitivity in five patients. One patient showed transient light reactivity and four showed persistent light reactivity. Tests with artificial radiation were performed on normal skin without musk ambrette being added. All patients reacted abnormally to UV-B and three to UV-A. In particular the patient with transient light reactivity showed abnormal responses to UV-B and UV-A. The patients were not always aware of the role of sunlight in the development of their eruption and the clinical features were not always typical of a photodermatitis.

Neurotoxic properties of musk ambrette

Musk ambrette (2,6-dinitro-3-methoxy-4- tert-butyltoluene), a nitro-musk compound widely used as a fixative in fragrance formulations and found to a lesser degree in flavor compositions, produces hindlimb weakness when administered in the diet or applied to skin of rats for periods up to 12 weeks. Underlying neuropathologic changes consist of primary demyelination and distal axonal degeneration in selected regions of the central and peripheral nervous system. Murine neurological disease induced by musk ambrette occurs at doses well above estimated maximum daily human exposure. Lifetime experimental neurotoxicology studies using lower concentrations of musk ambrette for prolonged periods would be needed for the estimation of human risk.

SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS—VI. IDENTIFICATION OF THE FREE RADICALS GENERATED DURING THE PHOTOLYSIS OF MUSK AMBRETTE, MUSK XYLENE AND MUSK KETONE

Abstract—Musk ambrette (4‐tert‐butyl‐3‐methoxy‐2,5‐dinitrotoluene), a common component of perfumes, soaps, and some food flavorings, can cause cutaneous photosensitization reactions including photoallergy. These may be mediated through free radicals formed during photolysis. When musk ambrette was photolyzed under nitrogen in basic methanol, two distinct nitro anion radicals were identified by electron spin resonance. One radical was centered on a nitro group in the plane of the aromatic ring, while the other was centered on a nitro group twisted out of the plane of the ring due to steric hindrance by bulky substituents on either side of the group: the two radicals appeared to interconvert and maintain an equilibrium concentration ratio. Two closely related compounds which are also used in perfumes, but have not been reported to cause photosensitizing reactions, also produced free radicals during photolysis. Musk xylene (2,4,6‐trinitro‐1,3‐dimethyl‐5‐tert‐butylbenzene) generated two nitro anion radicals, both of which were centered on twisted nitro groups, while musk ketone (3,5‐dinitro‐2,6‐dimethyl‐4‐tert‐butylacetophenone) produced only one nitro anion radical, which is also twisted. Athough these nitro anion radicals are probably the first step in the photolysis of these nitroarornatic molecules, it seems likely that in vivo they will undergo further reduction to produce more reactive species including the corresponding nitroso and hydroxylamine derivatives. In addition, autoxidation of the nitro anion radical intermediate forms superoxide.

Study of artificial flavouring substances for mutagenicity in the salmonella/microsome, Basc and micronucleus tests

Seventy-six compounds used as artificial flavouring substances in food products were studied for mutagenic properties by the use of the Salmonella/mammalian microsome test (Ames test), Basc test on Drosophila melanogaster and micronucleus test on mouse bone marrow. The following four compounds were mutagenic in Ames tests: ethyl nitrite, ethyl 3-phenylglycidate, 6-methylquinoline and musk ambrette. Of these, ethyl nitrite and musk ambrette also induced a significant (P ⩽ 0.01) increase in sex-linked recessive lethal mutations in Drosophila. Two further compounds, ethyl 3-methyl-3-phenylglycidate and 4-n-propylanisole, appeared weakly mutagenic in Drosophila only. The result with 4-n-propylanisole was judged to be of equivocal biological significance. None of the flavouring substances induced micronuclei, i.e. cytogenetic damage in the bone marrow of mice.

Mechanisms of Contact Photosensitivity in Mice

The photoallergenic potential of various chemicals was assessed in mice. Mice were sensitized with applications of the test agent on the shaved abdomen; they underwent irradiation with black light on days 0 and 1. On day 5, ear lobes were painted with the chemicals and underwent irradiation with black light. The degree of the sensitivity was assessed by measuring the ear thickness 24 hours after challenge. Tetrachlorosalicylanilide, tribromsalan, bithionol, and chlorpromazine were photosensitizers. Hexachlorophene and sulfanilamide induced contact photosensitivity after pretreatment of mice with cyclophosphamide. Reactions of the recently discovered photosensitizers such as musk ambrette, 6-methylcoumarin, 7-methylcoumarin, and benzocaine were enhanced by cyclophosphamide pretreatment. Salicylanilide, salicylic acid, and 3,4-dichloroaniline failed to demonstrate photosensitization potential. This mouse model and cyclophosphamide pretreatment is a useful technique to determine photosensitization potentials for a variety of new chemicals.

Nitro Musk Fragrances as Potential Contaminants in Pesticide Residue Analysis

Abstract Synthetic nitro musks, fragrance ingredients of soaps, lotions, and other products commonly used in the home and laboratory, are potential interferences in analyses of foods for pesticide residues. These fragrances are recovered by extraction-cleanup procedures of the AOAC multiresidue method for fatty and nonfatty foods and have electron capture gas-liquid chromatographic properties similar to the organochlorine residues for which the method has official status. This report presents the analytical evidence that led to the identification of musk xylol (1-[1,1-dimethylethyl]-3,5-dimethyl-2,4,6-trinitrobenzene) as a contaminant in a sample of fish; mass spectra and data on the behavior in the AOAC multiresidue method of musk xylol, musk ambrette (1-[1,1-dimethylethyl]-2-methoxy-4-methyl - 3,5 - dinitrobenzene), musk tibetene (1-[1,1-dimethylethyl]-3,4,5-trimethyl-2,6-dinitrobenzene), and musk ketone (1-[4-(1,1-dimethylethyl)-2,6-dimethyl - 3,5 - dinitrophenyl] ethanone); and information on some sources of these chemicals in the laboratory environment.

The guinea pig as a model for predicting photoallergic contact dermatitis.

This report describes modifications in the techniques used for both the induction and elicitation of photoallergic contact dermatitis (PACD) in the guinea pig. These changes have improved the reliability of this animal as the model of choice for screening chemicals or products for their tendency to produce PACD. The induction period consists of 15 exposures of the test substance to shoulder skin that has been abraded with a nylon brush rotating at 13,000 rpm. One hour later, the test site is irradiated with broadband UVA from a source having some irradiance below 320 nm (UVA/b). The animals receive 450 J/cm2 of UVA during the three-week induction period. The elicitation (challenge) test is repeated for two consecutive days. Each day, the test material, if a liquid, is applied to two sites every 30 to 60 min for 6 h; then one of the sites receives 20 J/cm2 of UVA. These photo-induction and photo-induction and photo-elicitation procedures have demonstrated that low-level concentrations (0.25% range) of 6-methyl coumarin or musk ambrette will both induce and elicit PACD in the guinea pig. This report adds more evidence that the induction of PACD in the guinea pig is dependent on broadband UVA.

Persistent Photosensitivity Caused by Musk Ambrette

Persistent photosensitivity developed in a man after use of an after-shave lotion containing musk ambrette. His eruption, present over ligh-exposed areas of the face, the "V" area of the neck, and the dorsa of the hands, has persisted for more than three years despite therapy. The patient demonstrated a minimal erythema after an ultraviolet B dose of 5 s, and was strongly ultraviolet A photosensitive to a 2% musk ambrette solution in petrolatum and to the after-shave lotion that contained musk ambrette. A persistent light reactivity induced by musk ambrette has most likely developed in this patient.

Persistent photosensitivity caused by musk ambrette

Persistent photosensitivity caused by musk ambrette

Photoallergic contact dermatitis to musk ambrette: action spectra in guinea pigs and man.

Abstract— Positive photopatch tests to musk ambrette were elicited using narrow band radiation in two patients with photoallergic contact dermatitis to musk ambrette and in photosensitized guinea pigs. The most effective wavelength range in the two patients was between 334 and 394 nm. Control subjects did not respond to the same light doses either in the presence or absence of musk ambrette. One patient exhibited maximum sensitivity at 346 nm. The action spectrum in guinea pigs extended from 322 to 406 nm with maximum response at 322 nm. Below 322 nm, erythema was observed at the same or higher doses than those required for evoking a minimal erythema response in non‐sensitized animals. Morphologically and histologically the response below 322 nm appeared to be normal delayed erythema. No erythema was elicited by radiation between 322 and 430 nm in non‐photosensitized animals which had received musk ambrette.

Photoallergic contact dermatitis to musk ambrette: Clinical report of two patients with persistent light reactor patterns

Two male patients with photoallergic contact dermatitis to musk ambrette, 2-methoxy-3,5-dinitro-4-methyl-t-butylbenzene, are reported. Musk ambrette is a synthetic fragrance material commonly used in foods and cosmetics. The clinical distribution of lesions presented by these patients strongly suggested an adverse reaction to light. Over a period of several years no etiology had been determined in these cases despite extensive testing and hospitalization. Photopatch tests to musk ambrette were positive. No other etiology for photosensitivity was found. This report emphasizes that exposure to household or cosmetic products represents a potential source of contact photosensitivity. Patients presenting with dermatoses of unknown origin confined to the light-exposed areas should have fragrances considered as possible etiologic agents.

Photochemie aromatischer Nitroverbindungen, XV. Photo‐Vergilbung von Ambrette‐Moschus (4‐tert‐Butyl‐3‐methoxy‐2,6‐dinitrotoluol) in methanolischer Alkalilauge

Photochemistry of Aromatic Nitro Compounds, XV. Photo‐yellowing of Musk Ambrette (4‐tert‐Butyl‐3‐methoxy‐2,6‐dinitrotoluene) in Methanolic Sodium Hydroxide SolutionPhotolysis (λ ≥ 280 nm) of musk ambrette (1) in 0.1 N methanolic sodium hydroxide solution gives rise (via photoreduction) to the corresponding azoxybenzene 2, which undergoes secondary photolysis to the hydroxyazobenzene 5, and to the by‐products 3 and 4 via intramolecular photo‐cyclizations.