Phototoxicity testing of fragrance raw materials.
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The objectives of the present study were to test odor identification ability in patients with multiple sclerosis (MS) and to examine possible correlations between smell identification test scores and various clinical variables. We performed a case-control study comparing the Cross Cultural Smell Identification Test scores of 40 patients with definite multiple sclerosis with those obtained in 40 age-, sex- and smoking-habit-matched healthy controls. The neurological impairment, the disability, the cognitive performances and the psychological functioning were also assessed. Patients with multiple sclerosis scored significantly poorer than controls on the Cross-Cultural Smell Identification Test (P<0.001). Olfactory function was borderline normal in four (10%) and abnormal in five (12.5%) MS patients, whereas it was normal in all controls (P<0.02). Significant correlations between the smell identification score and symptoms of anxiety (r=-0.43, P=0.006), depression (r=-0.42, P=0. 008) and severity of neurological impairment (r=-0.32, P=0.05) were found. Only two (5%) patients with multiple sclerosis reported having episodes of smell loss, suggesting a low level of awareness of this problem. Although smell changes are rarely reported, olfactory function is impaired in a considerable number of patients with MS. The observed association between decreased odor identification ability and symptoms of anxiety and depression in our patients suggests that mood and anxiety disorders have to be considered in assessing olfaction in MS patients. Clearly, smell disturbances deserve greater attention from health professionals and caregivers dealing with such patients.
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An environmental risk assessment has been carried out for musk ketone and musk xylene according to the EU Technical Guidance Document for Environmental Risk Assessment for New and Existing Substances [1]. Musk ketone and musk xylene are used in fragrances for cosmetics and household products. For the fragrance industry these are important fragrance ingredients because of their excellent substantivity as well as for their unique smell, which determines largely the odor of a product. The initial environmental risk assessment is based on information provided by the fragrance industry as represented in the Netherlands by its association NEA, by the Research Institute for Fragrance Materials (RIFM) and data reported in the international open literature. The risk assessment includes and evaluation of the risks for aquatic organisms in surface water and sediment and for soil organisms in soil after application of sewage sludge. Secondary poisoning of fish-eating birds and mammals is considered as well. For each compartment the Predicted Environmental Concentration (PEC) is compared to the Predicted No Effect Concentration (PNEC) to obtain PEC/PNEC ratios. Since monitoring data are available in water, sediment and fish, similar ratios are obtained with measured concentrations instead of the predicted ones. For both substances, PEC/PNEC ratios are at or below 0.1 for organisms in the aquatic environment, including sediment organisms. PEC/PNEC ratios for fish-eating predators are 0.01. Ratios based on monitoring data are below 0.01 for all of these organisms. For soil organisms the PEC/PNEC ratio is 0.5 for musk ketone and 1.3 for musk xylene. Although in the Netherlands (as well as in some other European countries), sewage sludge presently finds no application as fertilizer on agricultural soil, the aim of environmental policy is to upgrade the sludge quality to enable future applications on agricultural and grassland. The reliability of the predicted soil concentrations can be greatly improved by obtaining experimental data on fate and behaviour of musk ketone and musk xylene in digested sludge and soil. The risk assessment provides reassurance for the aquatic compartment while pointing the way for obtaining additional data for the soil compartment.
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 microgram/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.
By means of the environmental fate and distribution models laid down in the Technical Guidance Documents (TGD) and implemented in the European Union System for the Evaluation of Substances (EUSES) environmental concentrations of the polycyclic musk fragrance HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-[g]-2- benzopyrane; trade name: e.g. Galaxolide) were calculated for the aquatic environment under consideration of various scenarios. The results were then compared to monitoring data from the region of North Rhine-Westphalia (River Ruhr). An uncertainty analysis was carried out to determine sensitive parameters, to integrate environmental variability and to confirm the model's calculations. The standard scenario of EUSES overestimates the measured concentrations, which confirms the conservative nature of the calculations. The regional-specific scenarios lead to lower deviations from the measured values than the standard scenario. Deviations range from one to two orders of magnitude in the effluent of sewage treatment plants; they amount to one order of magnitude for surface water concentrations on a local scale and conform to monitoring data on a regional scale. The use of measured bioconcentration factors for fish instead of estimated ones reduces deviations remarkably. The investigation reveals that unrealistic worst-case calculations of HHCB can at best be ameliorated by the application of more realistic emission rates and measured bioconcentration factors. The use of regional-specific parameters also diminishes the deviations of the calculations from the measured concentrations.
Human nasal secretions are comprised of lysozyme and albumin as their main protein components. Lysozyme, an anti-microbial substance, is produced by nasal serous cells while albumin is obtained, primarily, from increased nasal vasculature permeability. We measured lysozyme levels in nasal secretions following challenge by a variety of non-infectious environmental contaminants. The methodology given presents a simple and rapid method of collecting nasal secretions and determining their lysozyme content, a technique which can be used for a host of environmental irritants.
A nitro musk (musk ketone) and three polycyclic musks (Tonalide, Galaxolide and Celestolide) were tested for acute and subchronic effects on a marine crustacean, the calanoid copepod Acartia tonsa. Sublethal effects on A. tonsa larvae were investigated with a rapid and cost effective bioassay, which is based on the easily detectable morphological change from the last nauplius to the first copepodite stage during copepod larval development. The inhibition of larval development after 5 days exposure was a very sensitive endpoint, with 5-d-EC(50)-values as low as 0.026 mg/l (Tonalide), 0.059 mg/l (Galaxolide), 0.066 mg/l (musk ketone) and 0.160 mg/l (Celestolide), respectively. These values were generally more than one order of magnitude below the 48-h-LC(50)-values found for adults, which were 0.47 mg/l (Galaxolide), 0.71 mg/l (Celestolide), 1.32 mg/l (musk ketone) and 2.5 mg/l (Tonalide). Since the synthetic musks strongly inhibited larval development in A. tonsa at low nominal concentrations, they should be considered as very toxic. The larval development test with A. tonsa is able to provide important aquatic toxicity data for the evaluation of synthetic musks, for which there is little published ecotoxicological information available regarding Crustacea. It is suggested that subchronic and chronic copepod toxicity tests should be used more frequently for risk assessment of environmental pollutants.
Nitro musks are a group of nitrated benzenes mainly used by the fragrance industry as a substitute for natural musk. Two of the most common nitro musks, musk xylene and musk ketone, have been detected in water, fish, human adipose tissue, as well as in human breast milk. In this study, female zebrafish were dietary-exposed to musk ketone, prior to spawning with unexposed males. The fish were exposed for 8 weeks at two different dose levels. Accumulation of the compound in the fish as well as reproductive success were studied. Exposed females had reduced body weight and length, as well as reduced liver- and gonad somatic index. The results from the reproduction study showed a dose-dependent reduction in fecundity. Early life-stage mortality was increased and the median survival time was reduced. In addition, an embryo/larvae toxicity test was performed, using newly fertilized zebrafish eggs from unexposed parental fish. Eggs were exposed to a series of different concentrations of musk ketone via the surrounding water. A NOEC value of 10 micrograms/l and a LOEC value of 33 micrograms/l was determined. Conclusively, the present study clearly shows that musk ketone negatively affects reproduction and early life-stage survival in zebrafish.
A full life-cycle (</=26 days exposure) toxicity test with the harpacticoid copepod Nitocra spinipes was used to study the effects of one nitro musk (musk ketone) as well as three polycyclic musks (Tonalide, Celestolide and Galaxolide). A subchronic individual life-table endpoint, the larval development rate, was recorded after 7-8 days exposure of juveniles and was significantly decreased in copepods exposed to sublethal concentrations of musk ketone, Celestolide and Galaxolide. However, none of the Tonalide concentrations had any effect on larval development. The lowest Galaxolide concentration (0.02 mg/l), which affected juvenile development, was about 100 times below the adult 96-h-LC(50)-value of 1.9 mg/l (95% confidence interval: 1.4-2.7 mg/l). However, none of the four musks had any agonistic or antagonistic activity in the ecdysteroid-sensitive Drosophila melanogaster B(II)-cell line. This indicates that the decrease in larval development rate was due to pharmacological effects rather than steroid receptor-mediated endocrine disruption. A modified Euler-Lotka equation was used to calculate a population-level endpoint, the intrinsic rate of natural increase (r(m)), from individual life-table endpoints, i.e. mortality rate, time of release of first brood, sex ratio, the fraction of ovigerous females among all females as well as the number of nauplii per ovigerous female. The second highest musk ketone concentration (0.1 mg/l) was the only treatment, which significantly affected r(m) (***P<0.001). At the highest musk ketone (0.3 mg/l) and Celestolide (0.3 mg/l) concentrations, all copepods were dead at the end of the exposures. This shows that a sensitive individual life-table endpoint is protective over the population-level endpoint r(m). Though we think that it is necessary to obtain population-level endpoints from standardised toxicity test, for ecologically successful risk characterisation of synthetic musks as well as other chemicals. The results from the present study show that it is possible to obtain population-level data from the full life-cycle test with N. spinipes. However, there seems to be little risk that synthetic musks are harmful to copepods at present environmental concentrations.
Natural aroma compounds are of major interest to the flavor and fragrance industry. Due to the limited sources for natural aromas, there is a growing interest in developing alternative sources for natural aroma compounds, and in particular aromatic aldehydes. In several microbial species aromatic aldehydes are detected as intermediates in the degradation pathway of phenylpropanoids. Thus, bioconversion of phenylpropanoids is one possible route for the production of these aroma compounds. The present work describes the isolation of microbial strains, capable of producing vanillin from isoeugenol. Bacterial strains isolated from soil, were screened for their ability to transform isoeugenol to vanillin. One of these strains, strain B2, was found to produce high amounts of vanillin when grown in the presence of isoeugenol, and was also capable of growing on isoeugenol as the sole carbon source. Based on its fatty acids profile, strain B2 was identified as a Bacillus subtilis sp. The bioconversion capabilities of strain B2 were tested in growing cultures and cell free extracts. In the presence of isoeugenol, a growing cultures of B. subtilis B2 produced 0.61 g l-1 vanillin (molar yield of 12.4%), whereas cell free extracts resulted in 0.9 g l-1 vanillin (molar yield of 14%).
During 64 months (1977 to 1983), twelve dermatologists from various sections of the United States studied a total of 713 patients with cosmetic dermatitis out of an estimated total of 13,216 patients with contact dermatitis. The number of patients seen for all causes during this period was 281,100. An important finding was that half of the patients or physicians were unaware that a cosmetic was responsible for their dermatitis. Skin care products, hair preparations (including colors), and facial makeup were responsible for the majority of the reactions. The most important objective was identification of causative ingredients. Eighty-seven percent of the subjects had patch tests. Fragrance, preservatives (Quaternium-15, formaldehyde, imidazolidinyl urea, and parabens), p-phenylenediamine, and glyceryl monothioglycolate were the most frequently identified allergic sensitizers, in that order. In addition to the clinical data, the study permitted assessment of the frequency of cosmetic reactions, although the data may not be entirely representative of the country at large because of the special interests of the dermatologists involved.
A general review is given of airborne-induced contact dermatoses, particularly of the irritant and allergenic types. Because the reports in the literature often omit the term airborne, 12 volumes of Contact Dermatitis (January 1975-July 1985) were screened, and the cases cited were classified in function of the anamnesis, lesion locations, causative irritants and allergens, and other factors. The present article also discusses differential diagnoses, in particular with regard to contact dermatitis of the face, ears, and neck. Finally, seven case reports of occupational and nonoccupational contact dermatitis problems caused by airborne agents are presented. In some of the cases the allergens have not been mentioned in published literature previously.
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