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PubMed2001

Exposing covert fragrance chemicals.

Fragrance is the most common cosmetic allergen found when dermatitis patients are patch tested in the United States and in many places worldwide. Fragrances are ubiquitous in our daily lives and are present in items ranging from toiletries to toilet tissue. Although fragrances enhance the smell or mask unpleasant odors of various cosmetics and household items, it becomes very difficult for fragrance-allergic patients to find products they can use. Many items labeled unscented and fragrance-free contain esoteric fragrance chemicals that most consumers would not recognize. This article details some covert fragrance agents to help physicians better educate their fragrance-sensitive patients.

Allergens↗
PubMed2004

Evaluation of the harmonizing effect of ylang-ylang oil on humans after inhalation.

Scientific evaluations of the effects of fragrances on humans are rather scarce. The aim of this investigation was to study the effects of ylang-ylang oil (Cananga odorata, Annonaceae) on hu-man physiological parameters and self-evaluation. Twenty-four healthy volunteers participated in the experiments. Fragrances were administered by inhalation. Physiological parameters recorded were skin temperature, pulse rate, breathing rate and blood pressure. Self-evaluation was assessed in terms of alertness, attentiveness, calmness, mood, relaxation and vigor. Additionally, fragrances were rated in terms of pleasantness, intensity and effect. The present investigation showed that ylang-ylang oil may be characterized by the concept of "harmonization" rather than relaxation/sedation. Compared to an odorless placebo, ylang-ylang oil caused significant decreases in blood pressure and pulse rate as well as significant increases of subjective attentiveness and alertness. Correlational analyses revealed that the observed effects are mainly due to a subjective odor experience.

Administration, Inhalation↗
PubMed2006

[The most frequent allergens in allergic contact dermatitis].

BACKGROUND AND OBJECTIVE: The prevalence of allergic contact dermatitis is high. Patch testing is the standard procedure to detect contact sensitivity. More than 3000 allergens are known, today. On the basis of the data of this study the top allergens are presented. PATIENTS AND METHODS: The retrospective analysis is based on the patch test results collected by the Information Network of Departments of Dermatology in 2004. Data of 9948 patients (6175 female und 3773 male) referred for the evaluation of suspected contact allergy were analysed to determine the frequency of sensitization to the 10 most common contact allergens. RESULTS: The top ten allergens were nickel sulphate (frequency of sensitization standardized for sex and age 17.2 %), fragrance mix (7.2 %), balsam of Peru (6.7 %), cobalt chloride (6.5 %), potassium dichromate (5.3 %), colophony (4.6 %), lanolin alcohol (4.3 %), p-phenylenediamine (4.2 %), ammoniated mercury (3.5 %) und methyldibromoglutaronitrile/phenoxyethanol (3.4 %) in 2004. CONCLUSIONS: Even after healing of the skin lesions of allergic contact dermatitis, it must be considered that sensitization persists indefinitely. Therefore, patients have to be informed exactly about their relevant contact allergens to ensure complete avoidance. To do so, physicians need a detailed knowledge of the most common contact allergens which are discussed in this paper.

Adult↗
PubMed2001

Patch testing discordance alert: false-negative findings with rubber additives and fragrances.

From July 1996 through June 1998, the North American Contact Dermatitis Group evaluated 318 patients for suspected contact dermatitis by patch testing simultaneously with Finn Chambers and the T.R.U.E. Test allergen system. Discrepancies between the two systems were found in some of the results, particularly with fragrance and rubber allergens. These results suggest that positive reactions to fragrance, thiuram, and carba mix allergens may be missed if the T.R.U.E. Test is used alone.

Allergens↗
PubMed2001

Evaluation of health risks caused by musk ketone.

Among the nitro musks, musk ketone (MK) as a synthetic compound with a typical musk odor is widely used in cosmetics. In the European Community the total amount used in fragrances has been reported to be 110 tons/a. Additionally, relevant amounts of MK are used in Indian joss sticks. As a result of its inherently low biodegradability MK has been detected in the aquatic environment (surface water, sediments, edible fish). Moreover, it has been shown that MK concentrates in human fatty tissue and breast milk, indicating that humans are constantly exposed. Several studies provided convincing evidence of lack of a genotoxic potential for MK. However, MK was identified as a strong inducer of phase I enzymes in rodents and a cogenotoxicant in vitro in human derived cells in rather low doses, suggesting that exposure to MK might increase the susceptibility to health hazards caused by carcinogens in humans.

Absorption↗
PubMedDate not supplied

Structural analogues inhibit the sensitizing capacity of carvone.

The aim of the study was to investigate the effect of non-allergenic structural analogues on the sensitizing potential of carvone, a fragrance allergen. The possibility that one molecule might inhibit the allergenic activity of another molecule has been debated for 25 years. The Research Institute for Fragrance Materials states that the sensitizing activity from certain fragrance aldehydes is "quenched" by the addition of other specific chemicals. However, other studies do not confirm the results, although several attempts have been made. We used a guinea pig method designed to study the sensitizing capacity of fragrance allergens. Induction was performed with either carvone alone or with a mixture of carvone and one of two analogues. A significant difference in the response rates (p < 0.001) was observed between the animals induced with carvone alone and those induced with any of the mixtures. Our investigation shows that by using selected molecules it is possible to significantly reduce the sensitizing effect of a fragrance allergen.

Allergens↗
PubMedDate not supplied

Acute toxic effects of fragrance products.

To evaluate whether fragrance products can produce acute toxic effects in mammals, we allowed groups of male Swiss-Webster mice to breathe the emissions of five commercial colognes or toilet water for 1 h. We used the ASTM-E-981 test method to evaluate sensory irritation and pulmonary irritation. We used a computerized version of this test to measure the duration of the break at the end of inspiration and the duration of the pause at the end of expiration. Decreases in expiratory flow velocity indicated airflow limitation. We subjected the mice to a functional observational battery to probe for changes in nervous system function. The emissions of these fragrance products caused various combinations of sensory irritation, pulmonary irritation, decreases in expiratory airflow velocity, as well as alterations of the functional observational battery indicative of neurotoxicity. Neurotoxicity was more severe after mice were repeatedly exposed to the fragrance products. Evaluation of one of the test atmospheres with gas chromatography/mass spectrometry revealed the presence of chemicals for which irritant and neurotoxic properties had been documented previously. In summary, some fragrance products emitted chemicals that caused a variety of acute toxicities in mice.

Animals↗
PubMed1999

Haemoglobin binding of a musk xylene metabolite in man.

1. Musk xylene (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene) is used as a fragrance component in toiletries, detergents and skin care products. Musk xylene is widely distributed in the environment and has been identified as a persistent contaminant in fish and in mothers' milk. Experimental data in man indicate a slow elimination of musk xylene and a potential for accumulation. Nitroarenes may be biotransformed to the respective amines. Some aromatic amines are known to be tumorigenic in animals and in man. Quantitation of the binding of those aromatic amines to haemoglobin has been proposed as a biomarker of internal exposure. 2. To determine bioavailability, metabolic reduction and haemoglobin binding of musk xylene in man, we investigated the presence of musk xylene metabolites bound to haemoglobin in blood samples from rat and from 10 human volunteers not knowingly exposed to musk xylene. 3. Haemoglobin from the blood samples was isolated, and bound metabolites were liberated as amines by alkaline hydrolysis. In haemoglobin samples from all individuals, 1-tert-butyl-3,5-dimethyl-4-amino-2,6-dinitrobenzene and, after chemical derivatization, the corresponding N-perfluoropropyl amide were identified by GC/MS using electron-impact and electron-capture mass spectrometry. 4. The amounts of 1-tert-butyl-3,5-dimethyl-4-amino-2,6-dinitrobenzene bound to haemoglobin in the human blood samples ranged from 13 to 46 fmol/mg haemoglobin. 5. These data demonstrate that musk xylene is bioavailable in man. The use of haemoglobin binding as a biomarker for nitromusk exposure in the general population warrants further studies.

Adult↗
PubMedDate not supplied

Pectin gel vehicles for controlled fragrance delivery.

Using citronellal as a model compound, pectin gels formulations were evaluated for the controlled fragrance release by kinetic and static methods. The pectins with higher degrees of esterification induced a stronger molecular association with the nonpolar fragrance. This resulted in a prolonged duration of fragrance release and the limitation of fragrance adsorption to the receptor skin layers. The increase in pectin concentrations suppressed the fragrance release by a diffusion mechanism. Blocking the carboxyl groups of pectin with calcium ions reduces the hydrophilicity of pectin and provides physical barriers for citronellal diffusion. The pectin/calcium microparticles are promising materials for controlled fragrance release.

Acyclic Monoterpenes↗
PubMedDate not supplied

Ethanol and diethyl phthalate: vehicle effects in the local lymph node assay.

The vehicle in which an allergen is presented to the skin has been recognized to have an effect on the skin-sensitizing potency of the allergen. Typical vehicles used to evaluate the skin sensitization potential of fragrance materials include ethanol, diethyl phthalate, or a combination of the two. The authors conducted a series of studies to evaluate each of these vehicles for their utility in the murine local lymph node assay and to investigate the potential differences in skin sensitization resulting from their use. Four fragrance materials were tested in four different vehicles. The test materials were p-t-butyl-alpha-methylhydrocinnamic aldehyde, geraniol, eugenol, and hydroxycitronellal. The vehicles were diethyl phthalate, 1:3 ethanol:diethyl phthalate, 3:1 ethanol:diethyl phthalate, and ethanol. Each of the fragrance materials was tested at five dose levels ranging from 0.3% to 50% w/v. In all four vehicles, each material tested elicited positive responses, exhibiting weak to moderate skin sensitization potential. Overall, p-t-butyl-alpha-methylhydrocinnamic aldehyde exhibited the most potency, followed by eugenol, geraniol, and hydroxycitronellal. The sensitization potential of both p-t-butyl-alpha-methylhydrocinnamic aldehyde and geraniol was greatest when the vehicle was ethanol. The sensitization potential of eugenol was greatest in 3:1 ethanol:diethyl phthalate, but the sensitization potential for hydroxycitronellal was greatest in 1:3 ethanol:diethyl phthalate. The strength of the sensitization response was observed to vary with the vehicle; however, the results did not show any clear pattern of one vehicle over another regarding skin sensitization.

Administration, Topical↗
PubMedDate not supplied

Evaluation of the developmental toxicity of alpha-methyl-3,4-methylene-dioxyhydrocinnamic aldehyde in rats.

The developmental toxicity of alpha-methyl-3,4-methylene-dioxyhydrocinnamic aldehyde (MMDHCA), a widely used fragrance ingredient, was evaluated for developmental toxicity in Sprague-Dawley rats (25/group; cesarean-sectioning identified 21 to 25 pregnant rats/group). Oral dosages of 0 (corn oil), 62, 125, or 250 mg/kg/day were administered by gavage on days 7 through 17 of gestation (GDs 7 through 17). Rats were observed for viability, clinical signs, body weights, and feed consumption. Necropsy and cesarean sectioning occurred on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Numbers of corpora lutea were also recorded. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. Analysis of dosage preparations verified calculated dosages +/-10%. No deaths occurred. Excessive salivation occurred in all groups, but the incidence was increased at 250 mg/kg/day. The 250 mg/kg/day dosage also was associated with a significant increase in the incidences of a clear, red or yellow perioral and/or red perivaginal substance and significant reductions in mean feed consumption and body weight gains (11.6% and 7.4%, respectively) during the entire dosage period. No gross changes attributable to MMDHCA were observed at necropsy. Cesarean section or litter parameters, as well as fetal alterations, were not affected by MMDHCA at 250 mg/kg/day or either of the lower dosages tested. Based on these data, maternal and developmental no-observable-effect levels (NOAELs) of 125 and >250 mg/kg/day, respectively, were established for MMDHCA. It is concluded that MMDHCA is not a developmental toxicant in rats under the conditions of this study and dosing regimen.

Animals↗
PubMedDate not supplied

The effects of vehicles on the human dermal irritation potentials of allyl esters.

Allyl esters, frequently used in the fragrance industry, often contain a certain percentage of free allyl alcohol. Allyl alcohol is known to have a potential for delayed skin irritation. Also present in the finished product are different solvent systems, or vehicles, which are used to deliver the fragrances based upon their intended application. This study was conducted to determine whether different vehicles affect the skin irritation potential of five different allyl esters. The allyl esters tested were allyl amyl glycolate, allyl caproate, allyl (cyclohexyloxy)acetate, allyl cyclohexylpropionate, and allyl phenoxyacetate in the vehicles diethyl phthalate, 3:1 diethyl phthalate:ethanol, and 1:3 diethyl phthalate:ethanol at concentrations of 0.1%, 0.5%, 1.0%, and 2.0% (w/w). A modified cumulative irritation test was conducted in 129 human subjects. Test materials (0.3 ml) were applied under occlusion to skin sites on the back for 1 day (24 h) using Hill Top chambers. Irritation was assessed at 1, 2, 4, and 5 days following application of test materials. Cumulative irritation scores varied considerably among test materials. There were no delayed irritation observations. The highest irritation scores were observed at the 2.0% concentration for all test materials. The irritation scores for allyl amyl glycolate, allyl (cyclohexyloxy)acetate, and allyl phenoxyacetate were highest in 1:3 diethyl phthalate:ethanol, thus the resulting calculated no-observed-effect levels, 0.12%, 0.03%, and 0%, respectively, were much lower for this vehicle compared to the diethyl phthalate vehicle, 0.33%, 0.26%, 0.25%, respectively. These data showed a trend for lower concentration thresholds to induce irritation when higher levels of ethanol were used in the vehicle.

Esters↗
PubMedDate not supplied

Evaluation of the developmental toxicity of acetyl cedrene.

The developmental toxicity of acetyl cedrene (AC), a widely used fragrance ingredient, was evaluated in pregnant Sprague-Dawley rats (25/group). Gavaged dosages of 0 (corn oil), 25, 50, or 100 mg/kg/day were administered on days 7 through 17 of gestation (GDs 7 to 17). First and last day dosing suspensions were analyzed for AC content. All rats were observed daily for viability, clinical signs, abortions, and premature deliveries. Body weights were recorded at frequent intervals. Cesarean-sectioning and necropsy examinations were performed on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. The number of corpora lutea in each ovary was also recorded. Fetuses were weighed and examined for gender and gross external changes and soft tissue or skeletal alterations. Totals of 25, 23, 21, and 24 rats became pregnant in the 0 (control), 25, 50 and 100 mg/kg/day groups, respectively, and analysis of dosage preparations verified that administered dosages reflected calculated dosages +/-10%. No deaths or premature deliveries occurred in the study. Clinical signs included excessive salivation, which was attributed to the administration of AC. When compared to controls, significant reductions in feed consumption and body weight gains occurred only at 100 mg/kg/day. Both absolute (g/day) and relative (g/kg/day) feed consumption values were significantly decreased on GDs 7 to 12. Relative values were decreased significantly on GDs 15 to 18. Body weight gains were significantly reduced on GDs 7 to 10. Mean maternal body weights remained significantly lower than controls on GDs 9 to 14, but a marked compensatory increase in feed consumption on GDs 15 to 18 prevented further deterioration in body weight gains. No cesarean-sectioning or litter parameters were affected by dosages of AC and necropsy of the dams after cesarean section did not reveal any gross changes attributable to AC. No gross external, soft tissue, or skeletal fetal alterations (malformations or variations) were attributed by dosages AC. The average number of ossifications sites per fetus per litter did not differ among the groups. Based on these data, maternal and developmental no-observable-adverse-effect levels (NOAELs) of 50 and 100 mg/kg/day, respectively, were established for AC.

Animals↗
PubMed2006

Is there evidence that methyl heptine carbonate causes allergic contact dermatitis?

The fragrance material methyl heptine carbonate has been cited as a moderately frequent cause of cosmetics-related allergic contact dermatitis. A review of the literature shows that when the underlying clinical data are analyzed, there is only one published case where a possible causal link to a cosmetic product has been established. Predictive tests in a computational model, in animal systems, and in volunteers have demonstrated a significant sensitization potential for this substance but reports of clinical cases of allergy are rare with no new reports appearing in the last two decades. The infrequence of reported cases of allergy may be linked to risk management procedures put in place by the International Fragrance Association (IFRA) more than 20 years ago.

Animals↗
PubMed1995

Comparison of models of odor interaction.

Subjects rated the overall perceived intensity of concentrations of the odorants cineole, geraniol, hexyl salicylate, and linalyl acetate smelled alone and in binary mixtures. The subjects also rated intensity of specified constituents (e.g. amount of cineole in cineole, and in mixtures of cineole and linalyl acetate). The intensity of the stronger component alone offered a close description of perceived intensity. In addition to the Stronger Component model, two other psychological models (Vector and U model) and two psychophysical models (UPL2 and Equiratio Mixture model) offered descriptions ranging from fair to very good. Psychological models gave better fits, but lack explanatory power. Some results indicated that weaker odors add more potently than stronger odors, an outcome incompatible with these models. The psychophysical models, based on the additivity of single components, generally overestimated perceived intensity. Judgments of individual qualities gave only slight encouragement to any expectation of differences in masking or maskability among odorants. The results highlight the need to test particular critical hypotheses regarding how people perceive mixtures.

Acyclic Monoterpenes↗