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PubMed2005

A survey of polycyclic musks in selected household commodities from the United States.

Occurrence of the polycyclic musks, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronapthalene (AHTN), in wastewater influent and effluent, as well as in surface waters, has been reported. HHCB and AHTN were also reported to occur in human and wildlife tissues. The major sources for HHCB and AHTN to wastewater are thought to be consumer products such as shampoos, deodorants, laundry detergents, and household surface cleaners. However, the levels of HHCB and AHTN in consumer products are not known. For evaluation of the sources of human and environmental exposures, characterization of levels of HHCB and AHTN in consumer products is needed. In this study, we measured concentrations of HHCB (Galaxolide), AHTN (Tonalide), and HHCB-lactone (Galaxolidone) from a variety of consumer products, including perfumes, body lotions, and deodorants. Concentrations of HHCB, AHTN, and HHCB-lactone in consumer products ranged from <5 ng/g to over 4000 microg/g, <5 ng/g to 451 microg/g, and <5 ng/g to 217 microg/g, respectively. The highest concentrations were found in perfumes, body creams and lotions, and deodorants. The results suggest that a wide variety of source materials exist for HHCB and AHTN, and that these materials are used on a daily basis.

Benzopyrans↗
PubMed2005

A safety assessment of coumarin taking into account species-specificity of toxicokinetics.

Coumarin (1,2-benzopyrone) is a naturally occurring fragrant compound found in a variety of plants and spices. Exposure to the general public is through the diet and from its use as a perfume raw material in personal care products. High doses of coumarin by the oral route are known to be associated with liver toxicity in rodents. Chronic oral bioassays conducted in the 1990s reported liver tumors in rats and mice and lung tumors in mice, raising concerns regarding the safety of coumarin. Since then, an extensive body of research has focused on understanding the etiology of these tumors. The data support a conclusion that coumarin is not DNA-reactive and that the induction of tumors at high doses in rodents is attributed to cytotoxicity and regenerative hyperplasia. The species-specific target organ toxicity is shown to be related to the pharmacokinetics of coumarin metabolism, with data showing rats to be particularly susceptible to liver effects and mice to be particularly susceptible to lung effects. A quantitative human health risk assessment that integrates both cancer and non-cancer effects is presented, confirming the safety of coumarin exposure from natural dietary sources as well as from its use as a perfume in personal care products.

Animals↗
PubMed2002

Pheromonal influences on sociosexual behavior in young women.

A double-blind, placebo-controlled study of a synthesized putative female pheromone was conducted with regularly menstruating, university women (N=36, mean age=27.8). The pheromone formula was derived from earlier work investigating the underarm secretions of fertile, sexually active, heterosexual women. A vial of either synthesized pheromone or placebo was selected blindly and added to a subject's perfume. Subjects recorded seven sociosexual behaviors and reported them weekly across three menstrual cycles. Beginning with Day 8 of each cycle, the first cycle contained a 2-week baseline period followed by an experimental period of as many as 3 weeks each from the next two cycles for a maximum of 6 weeks. The 19 pheromone and 17 placebo subjects did not differ significantly in age, weight, body mass index, dating status or ethnicity nor in reported accuracy, back-filling data, perception of a positive effect or perfume use. Placebo subjects were significantly taller than pheromone subjects. Except for male approaches, subjects did not differ significantly at baseline in average weekly sociosexual behaviors. A significantly greater proportion of pheromone users compared with placebo users increased over baseline in frequency of sexual intercourse, sleeping next to a partner, formal dates and petting/affection/kissing but not in frequency of male approaches, informal dates or masturbation. Three or more sociosexual behaviors increased over baseline for 74% of pheromone users compared with 23% of placebo users. We conclude that this synthesized pheromone formula acted as a sex attractant pheromone and increased the sexual attractiveness of women to men.

Adult↗
PubMed2006

Questionnaire evaluation and risk factor identification for nonallergic vasomotor rhinitis.

BACKGROUND: Chronic rhinitis, a prevalent primary care disorder associated with significant comorbidities, is often incorrectly diagnosed. As a result, inappropriate treatment leads to higher health care costs and poor clinical outcomes. OBJECTIVE: To verify whether responses to specific questions may help in the diagnosis of nonallergic vasomotor rhinitis (NAVMR). METHODS: A questionnaire listing allergic and nonallergic triggers was blindly distributed to 100 random new patients with chronic rhinitis in an allergist's office. Questionnaire and physician diagnoses were compared. Allergic triggers included cat, dog, feathers, other furry animals, and symptoms during the spring, summer, and fall seasons. Nonallergic triggers included temperature changes, diesel and car exhaust, tobacco smoke, perfumes and fragrances, incense, cleaning products, newsprint, hairspray, and alcoholic beverages, spicy foods, or eating. RESULTS: The construct validity and internal consistency indicated that the questionnaire was a good tool for diagnosing NAVMR. Multivariate analysis revealed that the absence of outdoor symptoms in the spring (odds ratio [OR], 7.76; 95% confidence interval [CI], 1.18-51.22; P = .03), no parental history of allergy (OR, 5.16; 95% CI, 1.05-25.20; P = .04), no symptoms around cats (OR, 3.82; 95% CI, 0.59-24.83; P = .16), the presence of symptoms around perfumes and fragrances (OR, 4.875; 95% CI, 1.05-22.60; P = .04), and age at symptom onset (OR, 1.08; 95% CI, 1.02-1.14; P = .008) were predictive of NAVMR. CONCLUSIONS: Specific questionnaire responses may help primary care physicians accurately diagnose NAVMR. Questions asked of patients by physicians to diagnose allergic rhinitis do not correlate well with physician diagnosis.

Adult↗
PubMed2004

Near-infrared spectroscopy of the adult human olfactory cortex.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a non-invasive method for investigating activation of the human cortex. The applicability of NIRS to the olfactory cortex was investigated. MATERIAL AND METHODS: The relative oxy- and deoxy-hemoglobin levels of the orbito-frontal cortex during olfactory stimulation in healthy subjects were measured using NIRS. RESULTS: When perfumed strips containing the odorants beta-phenyl ethyl alcohol, iso-valeric acid and gamma-undecalactone were presented, the oxy-hemoglobin level increased but the deoxy-hemoglobin level did not change. The increase in the oxy-hemoglobin level was observed bilaterally. A placebo perfumed strip did not elicit a change in the hemoglobin level. It was also observed that the odorant intensity affected the oxy-hemoglobin level. Although the orbito-frontal cortices seemed to be activated bilaterally during olfaction, the right cortex was activated to a greater extent than the left. CONCLUSION: NIRS appears to be an adequate method for investigating the human olfactory cortex.

Adult↗
PubMed1990

[Cosmetic dermatitis. Its relationship with positive patch test results, clinical features and atopy].

Although cosmetic manufacturing has progressed significantly, we still see a lot of skin problems caused by cosmetics. We patch tested 307 patients who showed signs of cosmetic contact dermatitis on the face from using their own cosmetics. The most common sensitizers were hair dyes, especially paraphenylenediamine (PPDA). Eighty-six of the 307 patients were assessed with patch tests for 23 perfumes, 16 tar dyes, preservatives, bases and 7 other items. Perfumes were frequently identified as allergens such as hidroxycitronellal, which turned out to be the most common sensitizer. The eighty-six patients were divided into 7 groups according to the clinical features and were discussed in terms of the period of onset and their age distribution. The relationship between positive patch test results and atopy is also reported.

Age Factors↗
PubMed1979

Airway response to hair spray in normal subjects and subjects with hyperreactive airways.

Short-term 20-second exposure to hair sprays A and B failed to show significant decreases in maximum expiratory flow rates at low pulmonary volumes in normal subjects; however, significant decreases were observed with hair spray B in eight subjects with hyperractive airways (abnormal response to inhalation of methacholine). On the partial flow-volume curves, flows at 40 percent and 25 percent of forced vital capacity decreased 8.9 to 10.3 percent and 14 to 18.7 percent, respectively. The hair sprays differed in their content of perfume and plasticizer, and since the latter is generally considered nontoxic at room temperature, the perfume may be the responsible agent. It would appear from this study that normal healthy individuals are at little risk, at least from brief exposure to hair spray; however, in the presence of hyperreactive airways, as seen in asthmatic subjects and in some people with allergic rhinitis and viral respiratory infections, an immediate response of the airways may result from exposure to some hair sprays.

Aerosols↗
PubMed1997

[The golden panacea. Alchemy and distillation in the court of Philip II (1527-1598)].

This study analyzes the relationships between Philip II and the two main goals of Alchemy: obtaining or forging alchemical gold, and preparing chemical drugs, liquors and perfumes. The first part of the study shows that throughout his reign Philip II maintained contacts with alchemists of several nationalities (Flemish, German, Italian, English and Spanish) in the Low Countries and Spain who were determined to obtain gold and silver. Their activities were overseen by high-level bureaucrats. Despite the disapproval of the Church and intense repression by the Holy Office, the alchemists had no difficulties during his reign, although their situation changed markedly after his death. In relation with distillation, Philip II ordered stills to be installed in all his gardens in Madrid, Aranjuez and the Escorial. He hired a corps of Flemish distillers who worked at all three sites in the preparation of chemical drugs, liquors and perfumes for the royal household. Their activities, and records conserved at the library of the Escorial, bear witness to a new route for the introduction of Paracelsism in Spain. Philip II organized the distillers' activities and brought them under the oversight of his apothecaries and protophysicians. The distillers' activities were later regulated by the by-laws fo the Royal Apothecary, inaugurated in 1594.

Alchemy↗
PubMed2003

Evaluation of contact sensitization in vulvar lichen simplex chronicus. A proposal for a battery of selected allergens.

OBJECTIVE: To determine the role of contact sensitization in vulvar lichen simplex chronicus and to select appropriate batteries of allergens to test. STUDY DESIGN: Between 1993 and 2000, 61 women affected by vulvar lichen simplex chronicus were enrolled to evaluate the role of contact hypersensitivity. All the patients underwent patch tests with the Italian standard series and with a wide battery of allergens (preservatives, perfumes, emulsifiers, medicaments) and products they used routinely. RESULTS: Of the women, 47.5% had at least one positive patch test, and relevant positivities were observed in 26%. The relevant allergens were usually medicaments and preservatives. CONCLUSION: It would be acceptable to reduce the number of allergens tested, in particular omitting the perfume series. Patch tests are a helpful diagnostic tool in vulvar lichen simplex chronicus and improve prescribing practice.

Adult↗
PubMed2005

[Hypothesis on generating and tracer gas study regarding transmission of severe acute respiratory syndrome through ventilation system in a general hospital].

OBJECTIVE: By measuring airflow and ventilation distribution of ward building, to explore and verify the hypothesis of airborne transmission and risk factor of severe acute respiratory syndrome (SARS) nosocomial infection. METHODS: Tracer gas (perfume of plant oil) was emitted to the bathroom of wards when SARS index patient lived. Six different experimental situations were designed to control the status of exhaust fan in bathrooms, exhaust fan in the top of building and fresh air exchange system. The concentration of perfume was separately measured by 4 groups of lab workers and recorded blindly by the scores of "tenth degree". RESULTS: Tracer gas was detected from the wards of 8th to 13th floor. CONCLUSION: Architecture and ventilation system of the inpatient building in the hospital contributed to the aerodynamic condition of SARS nosocomial infection through airborne transmission. The distribution of tracer gas in the wards was associated with SARS patients in this building. It was possible that SARS could have been transmitted to for distance by aerosol or other carriers.

Air Microbiology↗
PubMed1995

[Certification of oral hygiene agents from a microbiological viewpoint].

The authors validate the necessity of hygienic certification including microbiological control of perfumes and cosmetics, to which oral hygiene means belong. They consider that the absence of sanitary regulations for some goods, toothpastes included, is one of the causes, responsible for the absence of a proper sanitary control on the part of State Epidemiological Survey of the Russian Federation. In accordance with the resolution "On Certification of Perfumes and Cosmetics" issued in 1994, Central Research Institute of Stomatology is appointed the central institution responsible for certification of means of oral hygiene, and at present its main task is development of sanitary regulations, standards, methods of investigation, and training of personnel for institutions which are to carry out certification.

Child↗
PubMed1996

Genetic and environmental factors associated with asthma.

We investigate the familial and environmental risk factors associated with asthma among United Arab Emirates schoolchildren aged 6-14 years. A cross-sectional study of 850 schoolchildren living in both urban and rural areas (average age 9.36 +/- 2.11 years; 46.8% boys, 53.2% girls) was conducted using self-administered questionnaires between October 1992 and May 1993. The population sample had a high prevalence rate of diagnosed asthma (13.6%) and allergic rhinitis (22.9%). The frequency of asthma, allergic rhinitis, and eczema among parents and siblings reflected the same pattern as that seen in the children. Environmental risk factors associated with asthma were pets, medicine, plants, dust storm, physical exercise, humidity, and perfume. All other factors, such as foods, climate, and parental smoking, showed no apparent relation to the development of asthma. The logistic regression analysis showed that parental asthma, plants, perfume, dust storm, humidity, and pets were the only significant predictors after adjusting for sex and other confounding covariates in the model. In conclusion, risk factors for asthma identified by our study are similar to those found in other community-based studies. Consistencies and discrepancies between our findings and those from other studies with respect to asthma risk factors support the hypothesis that asthma is a multifactorial disease related to both familial and environmental influences.

Adolescent↗
PubMed1997

Characterization of the effects of musk ketone on mouse hepatic cytochrome P450 enzymes.

Nitroaromatic musks, including musk ketone (MK; 2,6-dimethyl-3,5-dinitro-4-t-butylacetophenone), are chemicals used as perfume ingredients in household products, cosmetics, and toiletries. Musk xylene (MX; 1,3,5-trinitro-2-t-butylxylene), another nitromusk, is not genotoxic but has been reported to produce mouse liver tumors in a chronic bioassay. In addition, MX has been shown to both induce and inhibit mouse liver cytochrome P450 2B (CYP2B) isozymes. The ability of MX to inhibit CYP2B enzyme activity is attributable to inactivation of the enzyme by a specific amine metabolite. MK is structurally similar to MX, but lacks the nitro substitution that is reduced to the inactivating amine metabolite. Therefore, we hypothesized that MK would induce, but not inhibit, CYP2B isozymes. To test this hypothesis, and to evaluate the effects of MK on mouse liver cytochrome P450 enzymes, two sets of experiments were performed. To evaluate the ability of MK to induce cytochromes P450, mice were dosed daily by oral gavage at dosages ranging from 5 to 500 mg/ kg MK for 7 days. This treatment resulted in a pleiotropic response in mouse liver, including increased liver weight, increased total microsomal protein, and centrilobular hepatocellular hypertrophy. At the highest dose tested, MK caused a 28-fold increase in CYP2B enzyme activity and a small (approximately 2-fold) increase in both cytochromes P450 1A and 3A (CYP1A and CYP3A) enzyme activities over control levels. Protein and mRNA analyses confirmed the relative levels of induction for CYP2B, CYP1A, and CYP3A. In addition, the no-observable-effect level (NOEL) for CYP2B induction by MK was 20 mg/kg. To evaluate the ability of MK to inhibit phenobarbital-induced CYP2B activity, mice were given 500 ppm phenobarbital (PB) in the drinking water for 5 days to induce CYP2B isozymes, followed by a single equimolar (0.67 mmol/kg) oral gavage dose of either MK (198 mg/kg) or MX (200 mg/kg), and microsomes were prepared 18 h later. While MX inhibited more than 90% of the PB-induced CYP2B activity in the microsomes, MK caused only a small (about 20%) reduction in PB-induced CYP2B enzyme activity. These results indicate that, like MX. MK is a PB-type inducer of mouse liver CYP2B isozymes, but unlike MX, MK does not effectively inhibit PB-induced CYP2B enzyme activity.

Administration, Oral↗
PubMed1999

Olfaction and symptoms in the multiple chemical sensitivities syndrome.

Whereas most idiosyncratic environmental sensitivity complaints do not fit known diagnoses, the multiple chemical sensitivities syndrome (MCS) is an extreme presentation that has defined diagnostic criteria. MCS symptomatics claim that they acquired a sensitized state as the result of a chemical exposure, usually to a solvent or pesticide, but not to a fragrance. Before this exposure, they did not experience symptoms. Following sensitization, symptoms increasing in number and severity with time are attributed by the MCS symptomatic to various exposures that are innocuous to most individuals. Although phenomenological studies have provided no evidence that particular odors elicit MCS symptoms, low levels of fragrances and perfumes are frequently associated with the reporting of MCS symptoms. This evaluation examines proposed mechanisms by which odorants and fragrances might cause either sensitization or elicitation of MCS symptoms, including altered odor sensitivity, primary irritancy or irritancy-induced upper airway reactivity, neurogenic switching of trigeminal irritancy signals, time-dependent sensitization and limbic kindling, CNS toxicity, and various psychiatric conditions. In no case was there persuasive evidence that any olfactory mechanism involving fragrance underlies either induction of a sensitized state or the triggering of MCS symptoms. Fragrances and other odorants could, however, be associated with symptoms as claimed by MCS symptomatics, because they are recognizable stimuli, but fragrance has not been demonstrated to be causal in the usual sense.

Environmental Exposure↗
PubMed2002

Consumer exposure to fragrance ingredients: providing estimates for safety evaluation.

To fully apply already published procedures for the safety evaluation of fragrance ingredients, it is necessary to estimate exposure through different routes and leading to different potential endpoints. Worst-case scenario calculations indicate that deposition on the surface of the skin following use of cosmetics represents the major route of exposure to fragrance ingredients when conservative estimates for evaporation, rinsing, and other forms of product removal are employed. Hydroalcoholic perfumes and colognes deliver the highest dose after single product use. Surveys of formulas used in this type of product allow the calculation of average maximum or upper 97.5th percentile concentration of the ingredient in formulas. With this type of exaggeration, the use of estimates of "typical" cosmetic use can be maximized to take account of excessive consumption patterns for both short-term and long-term exposure estimates. In the latter case, multiple product use must be considered. Short-term exposure (single product doses) of an ingredient found at an average maximum use level of P% in fragrances is taken to be 0.2 x P% or 3P microg/cm(2). Using upper 97.5th percentile concentrations (P(97.5)) of individual ingredients in fragrances, the long-term exposure is taken to be P(97.5) x 2,547 microg/kg body wt/day. The estimates of long-term exposure incorporate a number of highly conservative assumptions (e.g., over a long period, every product used will contain a fragrance with this ingredient at this high (P(97.5)) level).

Administration, Cutaneous↗
PubMed1997

Induction and inhibition of mouse cytochrome P-450 2B enzymes by musk xylene.

Musk xylene (MX) (1,3,5-trinitro-2-t-butylxylene) is a nitromusk perfume ingredient that although uniformly negative in a battery of genotoxicity tests, produces a high incidence of liver tumors in mice. The purpose of this work was to characterize the profile and dose-response relationship of microsomal enzyme induction following exposure to MX. MX was dosed by gavage to male B6C3F1 mice for 7 days at 0, 1, 5, 10, 20, 50, 100, and 200 mg/kg after which microsomes were prepared. At 200 mg/kg, MX increased liver weight by about 65% and increased microsomal cytochrome P-450 content 2-fold over control. MX increased microsomal activity for O-dealkylation of 7-ethoxy and 7-methoxyresorufin 4- and 2-fold, respectively, and increased the N-demethylation of erythromycin approximately 2-fold. These results were generally consistent with increased CYP1A1, 1A2, and 3A protein levels determined by Western blotting. In contrast, whereas no increase in O-dealkylation of 7-pentoxyresorufin (PROD) was observed, MX treatment increased CYP2B protein levels about 25-fold over control at 200 mg/kg. Furthermore, a single dosage of MX (200 mg/kg) increased Cyp2b-10 mRNA to a maximal level and with a time course similar to phenobarbital (PB). To study inhibition of CYP2B enzymes in vivo, mice were treated with PB (0.05% in drinking water for 5 days), then given a single dosage of corn oil or MX (200 mg/kg) at 2 or 18 hr before necropsy. PB treatment increased PROD activity 25-fold, and at 2 hr after MX treatment (associated with peak plasma levels of MX), there was no change in the PB-induced PROD activity. However, at 18 hr, MX treatment decreased PROD activity by 90%. Despite the in vivo inhibition, in vitro studies indicated that MX did not cause mechanism-based inactivation of CYP2B enzymes. The potential for nitroreduction of MX (catalyzed by anaerobic intestinal bacteria) to contribute to the inhibition of CYP2B enzyme activity was evaluated in a separate group of PB-induced mice that were dosed orally with a regimen of broad spectrum antibiotics (neomycin, tetracyline, and bacitracin) to reduce gut flora prior to administration of MX. In these animals, MX (200 mg/kg) did not inhibit PB-induced PROD activity. In summary, MX treatment produced general hepatic changes consistent with induction of CYP2B enzymes in mice and caused a large increase in CYP2B protein and mRNA levels. These data indicate that MX is a PB-like inducer of cytochrome P-450 enzymes and may cause liver tumors in a manner analogous to PB. However, no increase in CYP2B enzyme activity was observed, suggesting that MX or metabolites of MX also inhibit this enzyme. When the intestinal flora was eliminated by antibiotic treatment, MX no longer inhibited the CYP2B enzyme, indicating that anaerobic bacteria are capable of metabolizing MX, and suggesting that amine metabolites formed by nitroreduction are involved in the inhibition of mouse CYP2B enzymes.

Administration, Oral↗
PubMed1992

trans,trans-Muconic acid, a reliable biological indicator for the detection of individual benzene exposure down to the ppm level.

trans,trans-Muconic acid (2,4-hexadienedioic acid) (t,t-MA) is a minor benzene metabolite which can be used as a biological indicator for benzene exposure. The purpose of the study was to evaluate the limits of use of t,t-MA for detection and quantification of occupational exposures to benzene, particularly on an individual scale, phenol being used as the metabolite of reference. A simple and sensitive method previously described by the authors was carried out to analyse t,t-MA in 105 end-of-shift urinary samples from 23 workers exposed to benzene used as an extraction solvent for "concretes" recovery in the perfume industry. Good correlations were found between atmospheric benzene and both metabolites (uncorrected or corrected for creatinine) or between the metabolites themselves, with correlation coefficients from 0.81 to 0.91 (P < 0.0001). Correlation- coefficients were not improved after correction for creatinine. The overall individual benzene exposure range, median, and arithmetic mean were respectively 0.1-75, 4.5, and 9.0 ppm with corresponding t,t-MA excretion of 0.1-47.9, 5.2 and 8.9 mg/l (uncorrected) and phenol excretion of 1.4-298, 30.9, and 42.2 mg/l (uncorrected). In the control group (145 determinations for t,t-MA and 76 for phenol from 79 individuals) the range, median, and arithmetic mean were respectively < 0.04-0.66, 0.08, and 0.13 mg/l (uncorrected t,t-MA) and 1.5-42.0, 9.85 and 11.3 mg/l (uncorrected phenol). t,t-MA was far more specific than phenol and could be easily and practically used to estimate with a given probability the upper or lower corresponding benzene concentrations down to around the ppm level.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational↗
PubMed1994

Nitro musk.

The detection of nitro musk compounds in breast milk and in human adipose tissue is mainly due to the use of such substances as perfume in detergents from which they enter the sewage and finally the whole freshwater system. Due to their low degradability and a high biological concentration factor, they enter the food chain without the toxicological investigations to date allowing any certain conclusions on the effect of such accumulation in the human organism or on the effect of accumulation in ecological systems.

Animals↗