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Content and reactivity to product perfumes in fragrance mix positive and negative eczema patients. A study of perfumes used in toiletries and skin-care products.

The aim of the study was to investigate the elicitation potential of perfumes from 17 commonly sold lower-price cosmetic products. 8 of the perfumes were from stay-on cosmetics and 9 were from wash-off cosmetics. Each perfume was tested in 500 consecutive eczema patients, who also were tested with the European standard patch test series. 4.2% reacted to 1 or more of the wash-off product perfumes and 3.2% to 1 or more of the stay-on product perfumes. Concordant positive reactions between the fragrance mix and the product perfumes were found in 81.3% of positive reactions to the stay-on product perfumes and in 52.4% of the reactions to the wash-off product perfumes. Compared to the fragrance mix alone, only 1 additional case of contact allergy to the product perfumes was detected by balsam of Peru. Chemical analysis revealed that between 1 and 5 of the chemically-defined constituents of the fragrance mix were present in all of the product perfumes. Geraniol was found in 12 of the 17 perfumes and was most often detected. The concentration of the target fragrance materials ranged from 0.005%-1.35 w/v%. It is concluded that the allergenic constituents of the fragrance mix are impossible to avoid if perfumed cosmetics are used. Furthermore, patients suspected of perfume allergy need to be tested with their own perfumed products, as far from all cases of perfume allergy are detected by the fragrance mix and/or balsam of Peru in the European standard patch test series.

Acyclic Monoterpenes↗

The effect of perfume "ageing" on the allergenicity of individual perfume ingredients.

An ingredient of a perfume which is a sensitizer may become hypoallergenic by interacting with other ingredients during the ageing process of the perfume. Thus, a patient with an exquisite allergic sensitivity to cinnamic aldehyde tolerates two perfumes containing cinnamic aldehyde without acquiring a dermatitis. There are several theories of why cinnamic aldehyde can become a non-sensitizer in a perfume mixture. Testing with a mature perfume may be much more significant than testing with individual ingredients.

Aldehydes↗

Perfume sensitivity in adult females. A study of contact sensitivity to a perfume mix in two groups of student nurses.

The incidence of contact sensitivity to a perfume mix was investigated in two groups of student nurses by questionnaire and patch testing. Twenty-nine of ninety gave a history of dermatitis on exposure to fragrances or perfumed cosmetics. Fifteen of eighty-five showed a positive patch test reaction to a perfume mix comprising 2% concentrations of eight different perfume ingredients, and twelve of the fifteen had a positive history. Chi-square analysis of the data indicates that the results of the two methods of measurements are significantly related (p < 0.0001).

Dermatitis, Contact↗

Odds and Trends: Recent Developments in the Chemistry of Odorants Note on trademarks: Words which we know or have reason to believe constitute registered trademarks (R) are designated as such. However, neither the presence nor absence of such designation should be regarded as affecting the legal status of any trademark. Note on perfume analysis: The quoted percentages of perfume raw materials in market products are rounded figures. They are often derived from area percentages from the GC (FID) analysis, and are thus subject to analytical error.

Fragrance chemistry is, together with the closely related area of flavor chemistry, one of the few domains, if not the only one, in which chemists can immediately experience structure-activity relationships. This review presents structure-odor correlations and olfactophore models for the main odor notes of perfumery: "fruity", "marine", "green", "floral", "spicy", "woody", "amber", and "musky". New trendsetters and so-called captive odorants of these notes are introduced, and recent activities and highlights in fragrance chemistry are summarized. The design of odorants, their chemical synthesis, and their use in modern perfumery is discussed. Our selection is guided and illustrated by creative fragrances, and features new odorants which encompassed current trends in perfumery. New odorants for grapefruit and blackcurrant, for galbanum, and leafy top notes are presented. Compounds with fashionable marine, ozonic, and aquatic facets are treated, as well as new odorants for classical lily-of-the-valley, rose, and jasmine accords. Compounds with sweet and spicy tonalities are also discussed, as are the most recent developments for woody notes such as sandalwood and vetiver. We conclude with musky and ambery odorants possessing uncommon or unusual structural features. Some odor trends and effects are illustrated by microencapsulated fragrance samples, and areas where there is need for the development of new synthetic materials and methodologies are pointed out. Thus, chemists are invited to explore fragrance chemistry and participate in the design and synthesis of new odorants. This review gives the latest state of the art of the subject.

Journal Article↗

Exposure of eyes to perfume: a double-blind, placebo-controlled experiment.

Environmental perfume exposure can elicit bothersome respiratory symptoms. Symptoms are induced at exposure levels which most people find tolerable, and the mechanisms are unclear. The aim of the study was to investigate patients with eye and respiratory symptoms related to environmental perfume, by exposing the eyes to perfume in a double-blind, placebo-controlled study.Twenty-one eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case-control study. The participants completed a symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching, and tears) during perfume exposure than during placebo exposures, and eight of these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true positive eye reaction to perfume was significantly associated with identification of perfume as an active exposure (P < 0.05). In this study, vapor of perfume elicited irritation in the eyes independently of olfaction, but the relative importance of ocular chemoperception in relation to elicitation of respiratory symptoms from common environmental exposures to perfume remains unclear. We investigated the hypothesis of an association between respiratory symptoms related to perfume and ocular perfume sensitivity by exposing the eyes to perfume in a double blind, placebo-controlled experiment. Vapors of perfume provoked symptoms in the relevant eye in some patients and healthy control persons, but under our exposure conditions, ocular chemesthesis failed to elicit respiratory symptoms.

Adult↗

Inhalation challenge effects of perfume scent strips in patients with asthma.

BACKGROUND: Perfume- and cologne-scented advertisement strips are widely used. There are, however, very few data on the adverse effects of perfume inhalation in asthmatic subjects. OBJECTIVES: This study was undertaken to determine whether perfume inhalation from magazine scent strips could exacerbate asthma. METHODS: Twenty-nine asthmatic adults and 13 normal subjects were included in the study. Histories were obtained and physical examinations performed. Asthma severity was determined by clinical criteria of the National Heart, Lung, and Blood Institute (NHLBI). Skin prick tests with common inhalant allergens and with the perfume under investigation were also performed. Four bronchial inhalation challenges were performed on each subject using commercial perfume scented strips, filter paper impregnated with perfume identical to that of the commercial strips, 70% isopropyl alcohol, and normal saline, respectively. Symptoms and signs were recorded before and after challenges. Pulmonary function studies were performed before and at 10, 20, and 30 minutes after challenges. RESULTS: Inhalational challenges using perfume produced significant declines in FEV1 in asthmatic patients when compared with control subjects. No significant change in FEV1 was noted after saline (placebo) challenge in asthmatic patients. The percent decline in FEV1 was significantly greater after challenge in severely asthmatic patients as compared with those with mild asthma. Chest tightness and wheezing occurred in 20.7% of asthmatic patients after perfume challenges. Asthmatic exacerbations after perfume challenge occurred in 36%, 17%, and 8% of patients with severe, moderate, and mild asthma, respectively. Patients with atopic asthma had greater decreases in FEV1 after perfume challenge when compared with patients with nonallergic asthma. CONCLUSIONS: Perfume-scented strips in magazines can cause exacerbations of symptoms and airway obstruction in asthmatic patients. Severe and atopic asthma increases risk of adverse respiratory reactions to perfumes.

Administration, Inhalation↗

The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume.

Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate to the site of the symptoms in the airways and was not associated with increased capsaicin cough responsiveness. In conclusion, respiratory symptoms elicited by perfume may reflect local hyperreactivity related to defensive reflexes in the airways, and measurements of the capsaicin cough reflex are relevant when patients with lower respiratory symptoms related to environmental perfume exposures are investigated.

Adult↗

The influence of shaving method on perfume allergy.

Among men, the most frequent contact allergens are perfumes (fragrance mix and balsam of Peru). Considering that the main cause of nickel allergy is ear-piercing, shaving with a razor blade might be the cause of perfume contact allergy, by creating small wounds that increase the penetration of applied perfume substances derived from soaps, shaving foams and after-shave lotions. 19 males with contact allergy to fragrance mix and/or to balsam of Peru were interviewed about their shaving habits by letter. 17 responded (89%), of whom 12 (71%) had been using razor blades continuously for a period of at least 1 year. At our clinic, the frequency of razor blade usage was found to be 45% in patch tested men without perfume contact allergy. When comparing the frequencies of razor blade usage among patch tested men with and without perfume contact allergy, there was a statistically significant over-representation (p = 0.047) among those with perfume allergy. The risk of perfume allergy when using razor blades was found to be 2.9 (odds ratio).

Aged↗

Effect of Types of Perfume Compounds on the Hydrophile-Lipophile Balance Temperature.

The effect of added perfume compounds (d-limonene (LN), alpha-hexylcinnamic aldehyde (HCA), beta-ionone (IN), benzyl acetate (BA), linalool (LL), geraniol (GL), eugenol (EL), and cis-3-hexenol (HL)) on the three-phase behavior was investigated in water/octaethylene glycol dodecyl ether (C(12)EO(8))/perfume compound systems. The HLB (hydrophile-lipophile balance) temperatures are considerably lower than those of saturated hydrocarbon systems and are in the order LN > HCA > IN > BA > LL > GL > EL > HL. It is considered that the perfume molecules tend to be solubilized in the vicinity of the interface of the water-hydrocarbon moieties of the surfactant or the surfactant palisade layer. To confirm this, the location of the solubilized perfume compound in aggregates of liquid crystals was investigated by small-angle X-ray scattering (SAXS). In the LN, HCA, IN, BA, LL, and GL systems, the hexagonal liquid crystalline phase changes to lamellar liquid crystals on addition of each perfume compound, whereas the hexagonal liquid crystalline phase is directly changed to a reverse micellar solution phase in the EL and HL systems. The effective cross-sectional area per surfactant molecule, a(s), was calculated by using interlayer spacing measured by SAXS. Perfume compounds, which reduce the HLB temperature greatly, tend to penetrate into the surfactant palisade layer and increase a(s). Thus, the perfume molecules change the surfactant curvature from positive to negative. The more the perfume compound penetrates into the palisade layer, the lower the HLB temperature becomes. Copyright 1999 Academic Press.

Journal Article↗

Phototoxic properties of perfumes containing bergamot oil on human skin: photoprotective effect of UVA and UVB sunscreens.

As part of an international cooperative study of the photophysical, photomutagenic and photocarcinogenic properties of bergamot oil and the effect of UVA and UVB sunscreens, the phototoxic properties of model perfumes containing 5, 15 and 50 ppm 5-methoxypsoralen (5-MOP) in bergamot oil with and without a sunscreen have been investigated on human skin. It has been confirmed that the photosensitivity of human skin is maximal 2 h after perfume application. Interestingly the addition of a UVA sunscreen is more efficient for decreasing the phototoxic properties of bergamot oil than is a UVB sunscreen. The addition of sunscreens in a model perfume containing 50 ppm 5-MOP in bergamot oil can reduce the phototoxic properties of this perfume to a toxicity equivalent to that produced by the application of a model perfume containing 15 ppm 5-MOP without sunscreens. However, despite their promising protective effect in vitro, UVB and UVA sunscreens at low concentration (0.5%-1%) in perfumes cannot suppress the phototoxicity of bergamot oil on human skin.

Adult↗

Placebo-controlled challenges with perfume in patients with asthma-like symptoms.

A group of nine patients with respiratory symptoms after nonspecific irritating stimuli, but without any IgE-mediated allergy or demonstrable bronchial obstruction, were referred to the asthma/allergy outpatient department for evaluation of suspected asthma. In order to find a provocation model and objectively assess these patients' symptoms in controlled studies, provocation with perfume or placebo was performed. The same patients were also subjected to perfume provocation with or without a carbon filter mask to ascertain whether breathing through a filter with active carbon could prevent the symptoms. The patients breathed through the mouth during the provocations, as they used a nasal clamp to prevent any smell of perfume. We found that the patients' earlier symptoms could be verified by perfume provocation. Breathing through the carbon filter had no protective effect. The conclusion is that symptoms suggesting hyperreactivity of the respiratory tract and asthma can be provoked by perfume without the presence of bronchial obstruction, and that using a carbon filter mask has no preventive effect. The symptoms are not transmitted via the olfactory nerve, since the patients could not smell the perfume, but they may have been induced by a trigeminal reflex via the respiratory tract or by the eyes.

Adult↗

Psi-screen, an in vitro toxicity test system: applications in the bioassay of perfumes and fragrance chemicals.

The effects of 65 perfume formulations (perfume oils, perfumes, eau de parfum, eau de toilette) on mitochondrial membrane potential (Psim) and mitochondrial respiration have been investigated using a mitochondria-based assay for (Psim, termed Psi-Screen. All the perfume formulations tested are highly active in the Psi-Screen assay, and the major site of inhibition in all cases is NADH-ubiquinone reductase (Complex I). This is confirmed in studies on the inhibition of NADH oxidase and NADH-ubiquinone reductase. Some formulations also inhibit succinate oxidation at either Complex II or Complex III. Evidence for the inhibition of mitochondrial ATPase is presented, as well as for the induction of reactive oxygen species production by perfume inhibition of Complex I. Thus, perfume formulations are multiple inhibitor mixtures which inhibit multiple bioenergetic functions at high dilutions. The implications of these findings are discussed with respect to cell toxicity via necrosis and/or apoptosis. Twenty candidate fragrance chemicals were investigated and all inhibited Complex I (5 at <35 microM). Mass screening strategies and high-throughput screening assays are discussed.

Animals↗

Contact allergy to popular perfumes; assessed by patch test, use test and chemical analysis.

The frequency of contact allergy to the 10 best-selling women's perfumes was studied in 335 consecutive female eczema patients by patch testing. The diagnostic ability of the fragrance mix, in relation to these products, was evaluated. Of eczema patients, 6.9% had a positive patch test to one or more of the perfumes, and 56.5% of these had a concurrent positive reaction to the fragrance mix. Hence, testing with the patients' own cosmetics is a significant part of diagnosing perfume allergy. The clinical relevance of the patch-test reactions to the commercial perfumes was equal to that of the fragrance mix, as judged from the patient's history and use testing with one of the perfumes. At least three of the chemically defined sensitizers in the fragrance mix were detected in all the perfumes by gas chromatography-mass spectrometry, which indicates that the fragrance mix is a good imitation of actual exposure.

Adolescent↗

Occupational acute anaphylactic reaction to assault by perfume spray in the face.

BACKGROUND: Perfumes have been associated with rashes in employees exposed to scented soaps or with allergic conditions, such as rhinitis or asthma, in employees exposed to perfumes or fragrances in the air. METHODS: Reported here is a case of an anaphylactic reaction and respiratory distress as a result of a deliberate assault with a perfume spray. The medical literature was searched using the key words "fragrances," "respiratory distress," "assault," and "health care workers." RESULTS: A female medical assistant with no history of asthma or reactions to fragrances was assaulted by a patient, who pumped three sprays of a perfume into her face. The employee experienced an acute anaphylactic reaction with shortness of breath, a suffocating sensation, wheezes, and generalized urticaria, and required aggressive medical treatment, a long period of oral bronchodilator therapy, and, finally, weaning from the medications. CONCLUSIONS: Perfumes are complex mixtures of more than 4,000 vegetable and animal extracts and organic and nonorganic compounds. Fragrances have been found to cause exacerbations of symptoms and airway obstruction in asthmatic patients, including chest tightening and wheezing, and are a common cause of cosmetic allergic contact dermatitis. In many work settings the use of fragrances is limited. Assault is becoming more common among workers in the health care setting. Workers should be prepared to take immediate steps should an employee go into anaphylactic shock.

Adult↗

A liquid chromatography-mass spectrometric method for the determination of oak moss allergens atranol and chloroatranol in perfumes.

This paper describes a validated liquid chromatographic-tandem mass spectrometric method for quantitative analysis of the potential oak moss allergens atranol and chloroatranol in perfumes and similar products. The method employs LC-MS-MS with electrospray ionization (ESI) in negative mode. The compounds are analysed by selective reaction monitoring (SRM) of 2 or 3 ions for each compound in order to obtain high selectivity and sensitivity. The method has been validated for the following parameters: linearity; repeatability; recovery; limit of detection; and limit of quantification. The limits of detection, 5.0 ng/mL and 2.4 ng/mL, respectively, for atranol and chloroatranol, achieved by this method allowed identification of these compounds at concentrations below those causing allergic skin reactions in oak-moss-sensitive patients. The recovery of chloratranol from spiked perfumes was 96+/-4%. Low recoveries (49+/-5%) were observed for atranol in spiked perfumes, indicating ion suppression caused by matrix components. The method has been applied to the analysis of 10 randomly selected perfumes and similar products.

Allergens↗

Quantitative analysis of the 26 allergens for cosmetic labeling in fragrance raw materials and perfume oils.

The adoption of the 7th amendment of the European Cosmetic Directive 76/768/EEC requires any cosmetic product containing any of 26 raw materials identified by the Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers as likely to cause a contact allergy when present above certain trigger levels to be declared on the package label. Of these 26, 24 are volatile and can be analyzed by GC. This paper describes a method for the quantitative analysis of these volatile raw materials in perfume ingredients as well as complex perfume compositions. The method uses sequential dual-column GC-MS analysis. The full-scan data acquired minimize the false-positive and false-negative identifications that can be observed with alternate methods based on data acquired in the SIM mode. For each sample, allergen levels are determined on both columns sequentially, leading to two numerical results for each allergen. Quantification limits for each allergen in a perfume mixture based on the analysis of a standard are <4 mg/kg. This is well below the level that would trigger label declaration on the consumer good. Calibration curves for all allergens are linear (r > 0.999) and stable for multiple days. Studies on perfumes spiked with multiple allergens at 30, 50, and 70 mg/kg show recoveries close to nominal values.

Allergens↗

Chloroatranol, an extremely potent allergen hidden in perfumes: a dose-response elicitation study.

Oak moss absolute is a long-known, popular natural extract widely used in perfumes. It is reported as the cause of allergic reactions in a significant number of those with perfume allergy. Oak moss absolute has been the target of recent research to identify its allergenic components. Recently, chloroatranol, a hitherto unknown fragrance allergen, was identified in oak moss absolute. The objective was to assess the clinical importance of chloroatranol as a fragrance allergen by characterizing its elicitation profile. 13 patients previously showing a positive patch test to oak moss absolute and chloroatranol were included, together with a control group of 10 patients without sensitization to either of the 2 materials. A serial dilution patch test was performed on the upper back with concentrations ranging from 200 to 0.0063 p.p.m. of chloroatranol in ethanol. Simultaneously, the participant performed an open test simulating the use of perfumes on the volar aspect of the forearms in a randomized and double-blinded design. A solution with 5 p.p.m. chloroatranol was used for 14 days, and, in case of no reaction, the applications were continued for another 14 days with a solution containing 25 p.p.m. All test subjects (13/13) developed an allergic reaction at the site of application of the solution containing chloroatranol. Among them, 12/13 (92%) gave a positive reaction to the 5 p.p.m. solution and 1 to 25 p.p.m. None of the controls reacted (P < 0.001). The use test was terminated at median day 4. The dose eliciting a reaction in 50% of the test subjects at patch testing was 0.2 p.p.m. In conclusion, the hidden exposure to a potent allergen widely used in perfumes has caused a highly sensitized cohort of individuals. Judged from the elicitation profile, chloroatranol is the most potent allergen present in consumer products today.

Adult↗