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Psychogenic chemical sensitivity: psychogenic pseudoseizures elicited by provocation challenges with fragrances.

A middle-aged woman with a 10-year history of disability attributed to chemical sensitivities complained that exposure to specific fragrances immediately elicited seizures. Video-EEG monitoring was performed in a hospital neurodiagnostic laboratory during provocative challenge studies employing fragrances identified by the patient as reliably inducing symptoms. The baseline clinical EEG was normal. Immediately after each provocation with air deodorant and perfume, she consistently showed both generalized tonic/clonic and multifocal myoclonic jerking, at times was nonresponsive, spoke with slurred speech, and complained of right-sided paralysis and lethargy. None of these events were associated with any EEG abnormalities. Psychological assessment (MMPI-2, MCMI-II) revealed personality traits that predisposed her to somatization and beliefs about environmental sensitivities. The convulsions were a manifestation of psychogenic pseudoseizures that had been iatrogenically reinforced.

Adult↗

Pathway for the biosynthesis of 4-methyl-1-hexanol volatilized from petal tissue of Nicotiana sylvestris.

Compounds volatilized from plant tissues play important roles in plant-insect and plant-herbivore interactions and are important to food quality/preference, and to the perfume and flavorant industries. While the chemistry of plant volatiles is well understood, less is known about the biosynthesis of this diverse group of compounds. This is particularly the case for non-terpenoid components such as volatile acyclic alcohols and their esters. Here we have studied metabolic pathways leading to formation of the anteiso-branched alcohol 4-methyl-1-hexanol volatilized by petal tissue of Nicotiana sylvestris. Evidence presented supports the involvement of steps in the pathways of both biosynthesis and degradation of isoleucine to form 2-oxo-3-methylvaleric acid then 2-methylbutyryl CoA. Results indicate that 2-methylbutyryl CoA is then elongated by addition of one acetate molecule via fatty acid synthase, followed by reduction to yield 4-methyl-1-hexanol. This pathway is in contrast to elongation of 2-oxo-3-methylvaleric acid via alpha-keto acid elongation leading to the formation of 4-methylhexanoyl acyl groups of tobacco leaf-trichome-secreted sugar esters.

Journal Article↗

Epidemic of haemorrhagic disease in Vietnamese infants caused by warfarin-contaminated talcs.

In August, 1981, paediatric hospitals in Ho Chi Minh City (formerly Saigon), Vietnam, began to report cases of a haemorrhagic syndrome in infants. The cause of this haemorrhagic phenomenon was identified as talcum powder contaminated with the anticoagulant warfarin. Analysis of talcum powders revealed warfarin in concentrations between 1.7% and 6.5%. 741 cases were detected and 177 patients died. The possibility of accidental contamination or substitution of a perfuming agent by warfarin can be rejected. In an experiment with two baboons, the animal exposed to the contaminated talc died five days later from haemorrhage. The accident and the animal study demonstrate the significant transcutaneous uptake of the anticoagulant.

Animals↗

Inhibition of cyclophosphamide-induced teratogenesis by beta-ionone.

Beta-ionone (BI) is a degraded (C 13) sesquiterpene found in plant essential oils. It has been used in the synthesis of perfume chemicals and vitamin A. Recently, it was reported that BI is a rather potent in vitro inhibitor of CYP2B1-catalysed reactions in rat liver microsomes. The present study was performed to investigate whether inhibition of CYP2B1 reactions by BI could lead to an attenuation of cyclophosphamide (CP)-induced embryotoxicity in the rat. In a preliminary experiment, a dose-dependent prolongation of pentobarbital sleeping time in male and female Wistar rats suggested that BI inhibits CYP2B1 in vivo as well. In a second experiment, rats were treated by gavage with BI (0, 250, 500, 750 or 1000 mg/kg body wt) 45 min prior to a subcutaneous injection of either CP (7.5 mg/kg body wt) or its vehicle (saline) on day 11 of pregnancy. BI alone, at the highest dose tested, caused a high proportion of resorptions. Lower doses of BI, however, clearly attenuated CP-induced embryolethality and teratogenicity. These results seem to support the view that, as far as rats are concerned, CYP2B1 plays an important role in the conversion of CP into its embryolethal and teratogenic metabolites.

Abnormalities, Drug-Induced↗

Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.).

Saffron is harvested from the dried, dark red stigmas of Crocus sativus L. flowers. It is used as a spice for flavoring and coloring food and as a perfume. It is often used for treating several diseases. We assessed the antimutagenic, comutagenic and cytotoxic effects of saffron and its main ingredients using the Ames/Salmonella test system, two well known mutagens (BP, 2AA), the in vitro colony formation assay and four different cultured human normal (CCD-18Lu) and malignant (HeLa, A-204 and HepG2) cells. When only using the TA98 strain in the Ames/Salmonella test system, saffron showed non-mutagenic, as well as non-antimutagenic activity against BP-induced mutagenicity, and demonstrated a dose-dependent co-mutagenic effect on 2-AA-induced mutagenicity. The saffron component responsible for this unusual comutagenic effect was safranal. In the in vitro colony formation test system, saffron displayed a dose-dependent inhibitory effect only against human malignant cells. All isolated carotenoid ingredients of saffron demonstrated cytotoxic activity against in vitro tumor cells. Saffron crocin derivatives possessed a stronger inhibitory effect on tumor cell colony formation. Overall, these results suggest that saffron itself, as well as its carotenoid components might be used as potential cancer chemopreventive agents.

Anthracenes↗

Mutagenicity testing (+/-)-camphor, 1,8-cineole, citral, citronellal, (-)-menthol and terpineol with the Salmonella/microsome assay.

The essential oils and their monoterpenoid constituents have been widely used as fragrances in cosmetics, as flavouring food additives, as scenting agents in a variety of household products, as active ingredients in some old drugs, and as intermediates in the synthesis of perfume chemicals. The present study was undertaken to investigate the mutagenic potential of six monoterpenoid compounds: two aldehydes (citral and citronellal), a ketone ((+/-)-camphor), an oxide (1,8-cineole, also known as eucalyptol), and two alcohols (terpineol and (-)-menthol). It is part of a more comprehensive toxicological screening of monoterpenes under way at our laboratory. Mutagenicity was evaluated by the Salmonella/microsome assay (TA97a, TA98, TA100 and TA102 tester strains), without and with addition of an extrinsic metabolic activation system (lyophilized rat liver S9 fraction induced by Aroclor 1254). In all cases, the upper limit of the dose interval tested was either the highest non-toxic dose or the lowest dose of the monoterpene toxic to TA100 strain in the preliminary toxicity test. No mutagenic effect was found with (+/-) camphor, citral, citronellal, 1,8-cineole, and (-) menthol. Terpineol caused a slight but dose-related increase in the number of his+ revertants with TA102 tester strain both without and with addition of S9 mixture. The results from this study therefore suggest that, with the exception of terpineol, the monoterpenoid compounds tested are not mutagenic in the Ames test.

Acyclic Monoterpenes↗

Ocular effects of cosmetic products and procedures.

Cosmetic products and procedures can produce adverse effects on the ocular surface, ranging from mild discomfort to vision-threatening conditions. Complications of skin and eye products can be related to allergy or toxicity, often attributable to perfumes. Complications of blepharoplasty may be associated with overcorrection, scarring, or uneven contour of the lid margins, conditions that can cause significant ocular surface disease until they are corrected. Ocular surface effects of botulinum toxin injection include dry eye syndromes and also epiphora. More serious complications occur (rarely) and are dose- and location-related. Adverse effects of micropigmentation procedures involve pathological processes or, simply, poor cosmetic results. In certain youth cultures, special-effect contact lenses and even decorative conjunctival implants have gained popularity, presenting a wide variety of dangers, often attributable to poor education about care and hygiene.

Cosmetic Techniques↗

Asymmetric catalytic hydrogenation. Design of new Ru catalysts and chiral ligands: from laboratory to industrial applications.

This Account covers the design of Ru catalysts and ligands. Two classes of chiral phosphine ligands are prepared: the electron-rich trans-2,4-substituted phosphetanes, readily available from optically pure 1,3-diol cyclic sulfates, and atropoisomeric ligands (SYNPHOS, MeO-NAPhePHOS, bearing heterotopic biaryl moieties, and a chiral water-soluble diguanidinium binaphthyl diphosphine, Digm-BINAP). Applications of these ligands to rhodium- and ruthenium-mediated hydrogenation of ketones and olefins have been reported with high enantioselectivities. The recognition abilities of Ru-SYNPHOS for a wide range of ketones is superior to those observed with BINAP, MeO-NAPhePHOS, and MeO-BIPHEP. Several biologically active compounds have been prepared through dynamic kinetic resolution. This work gives access to a number of highly active catalysts of the type [Ru(biphosphane)(H)(eta(6)-cot)]BF(4). These catalysts have demonstrated their utility in the enantioselective hydrogenation of the tetrasubstituted cyclopentenone "dehydrodione", which leads to the commercially important perfume component Paradisone (Firmenich).

Alkenes↗

Concentrations and sources of VOCs in urban domestic and public microenvironments.

Concentrations of 15 VOCs including 1,3-butadiene, benzene, and styrene were measured in a wide range of urban microenvironments, viz: homes, offices, restaurants, pubs, department stores, coach and train stations, cinemas, libraries, laboratories, perfume shops, heavily trafficked roadside locations, buses, trains, and automobiles. For most target VOCs-including 1,3-butadiene and benzene-mean concentrations at heavily trafficked roadside locations were exceeded by those in automobiles and were comparable to those in pubs and train stations. With regard to indoor-outdoor relationships in homes, this study revealed higher mean indoor concentrations, no correlation between simultaneously measured indoor and outdoor concentrations, and significantly different patterns of diurnal variation. Thus-in poorly ventilated buildings-indoor emission source strength is considered a more significant influence on VOC concentrations than infiltration of outdoor air. In the six smoking homes studied, environmental tobacco smoke (ETS) was found to make a substantial contribution to concentrations of 1,3-butadiene. This finding was based on the significantly higher concentrations detected in smoking compared to nonsmoking homes, the significant correlation between 1,3-butadiene concentrations and those of 3-ethenylpyridine (an ETS marker), factor analysis, and the results of a source apportionment exercise based on ratios of 1,3-butadiene to 3-ethenylpyridine.

Air Pollution, Indoor↗

Thermodynamics of nitroaromatic compound adsorption from water by smectite clay.

Nitroaromatic compounds enter the environment through their use as explosives, pesticides, solvents, and synthetic intermediates in the manufacturing of dyes, perfumes, and drugs. Recent studies have found that many nitroaromatic compounds are strongly retained by smectites, especially K+-saturated smectites. Sorption occurs when nitroaromatic compounds replace water associated with the clay and form complexes between K+ and -NO2 groups. This study seeks to further understand nitroaromatic-clay interactions from the viewpoint of energetics. Adsorption isotherms of 1,3-dinitrobenzene, 1,4-dinitrobenzene, and 1,3,5-trinitrobenzene from aqueous solution by K+- and Ca2+-saturated smectite (SWy-2) were measured at several temperatures between 4 degrees C and 37 degrees C to determine the molar differential adsorption enthalpies. Adsorption was found to be an exothermic process on both homoionic K+- and Ca2+-smectite. The smaller adsorption enthalpy on Ca-SWy-2 was consistent with its much smaller adsorption capacity for nitroaromatics compared to K-SWy-2. Our best estimate forthe enthalpy of 1,3,5-trinitrobenzene interactions with K-SWy-2 is -124 kJ/mol, which is referenced to gas-phase 1,3,5-trinitrobenzene, corrected forthe displacement of interlayer water, and can be directly compared with quantum chemical enthalpies from the literature. Our comparable estimates for 1,3- and 1,4-dinitrobenzene interaction enthalpies are near -90 kJ/mol. We conclude that our adsorption enthalpy results are consistent with the hypothesis that nitroaromatic compounds are sorbed strongly by K-smectites because they form inner- and/or outer-sphere complexes with K+ cations in clay interlayers. Indeed, the basal spacings of rewetted clay films in the presence of nitroaromatic compounds imply that water molecules cannot effectively compete with the adsorbed nitrobenzenes for reactive sites on K-SWy-2.

Adsorption↗

Ti-crossed-Claisen condensation between carboxylic esters and acid chlorides or acids: a highly selective and general method for the preparation of various beta-keto esters.

Ti-crossed-Claisen condensation between a 1:1 mixture of carboxylic esters and acid chlorides promoted by TiCl4-Bu3N-N-methylimidazole proceeded successfully to give various beta-keto esters in good yields with excellent selectivities (19 examples, approximately 48-95% yield; cross/self-selectivity = approximately 96/4-99/1). The present method was extended to the condensation between a 1:1 mixture of carboxylic acids and carboxylic esters (six examples, approximately 70-92% yield; cross/self-selectivity = approximately 91/9-99/1). To demonstrate the utility of the present two Ti-crossed-Claisen condensations, we performed a couple of efficient short-step syntheses of two natural, representative, and useful perfumes, cis-jasmone and (R)-muscone.

Carboxylic Acids↗

Effect of cis/trans isomerism of beta-carotene on the ratios of volatile compounds produced during oxidative degradation.

beta-Carotene is, when cleaved, an important source of flavor and aroma compounds in fruits and flowers. Among these aroma compounds, the main degradation products are beta-ionone, 5,6-epoxy-beta-ionone, and dihydroactinidiolide (DHA), which are associated by flavorists and perfumers with fruity, floral, and woody notes. These three species can be produced by degradation of beta-carotene through an attack by enzyme-generated free radicals and a cleavage at the C9-C10 bond. This study investigated the influence of cis/trans isomerism at the C9-C10 bond on the production of beta-carotene degradation compounds, first with a predictive approach and then experimentally with different isomer mixtures. beta-Carotene solutions containing high ratios of 9-cis-isomers produced more DHA, suggesting a different pathway than for the transformation of all-trans-beta-carotene to ionone and DHA. These results are important in the search for financially viable processes to produce natural carotene-derived aroma compounds.

Flowers↗

The association of respiratory problems in a community sample with self-reported chemical intolerance.

This epidemiological study evaluated respiratory histories in those individuals reporting chemical intolerance (CI) in a community population sample. The subsample of 181 completed standard Respiratory Health Questionnaires. CI was determined from self-ratings of feeling 'moderately' to 'severely' ill from exposure to at least three of five common chemicals (paint, pesticides, car exhaust, new carpet, and perfume); the prevalence rate was 22.7%. The comparison group (CN) (31.5% of the sample) were selected from their reports of 'never' feeling ill from the same chemicals. The prevalence rate of CI in females was over twice that in males (28% vs 12.9%), a significant difference. There were no significant differences in smoking, age, or education between CI and CN. Prevalence rates for symptoms and Relative Risk Ratios (RR) indicated that the CI were significantly more likely to report chronic cough, phlegm, wheeze, chest tightness, exertional dyspnea, acute respiratory illnesses, hay fever, child respiratory trouble, and physician confirmed asthma. Several of these respiratory symptoms were significantly, though differentially, related to 'current' asthma and hay fever reports. Results suggest a potential vulnerability to and greater interference from respiratory illness for the CI, which have implications for women's health and quality of life.

Adolescent↗

Ability of honeybee, Apis mellifera, to detect and discriminate odors of varieties of canola (Brassica rapa and Brassica napus) and snapdragon flowers (Antirrhinum majus).

Honeybees (Apis mellifera) use odors to identify and discriminate among flowers during foraging. This series of experiments examined the ability of bees to detect and discriminate among the floral odors of different varieties of two species of canola (Brassica rapa and Brassica napus) and also among three varieties of snapdragons (Antirhinnum majus). Individual worker honeybees were trained using a proboscis extension assay. The ability of bees to distinguish a floral odor from an air stimulus during training increased as the number of flowers used during training increased. Bees conditioned to the odor of one variety of flower were asked to discriminate it from the odors of other flowers in two different training assays. Bees were unable to discriminate among flowers at the level of variety in a randomized presentation of a reinforced floral odor and an unreinforced floral odor. In the second type of assay, bees were trained with one floral variety for 40 trials without reinforcement and then tested with the same variety or with other varieties and species. If a bee had been trained with a variety of canola, it was unable to differentiate the odor of one canola flower from the odor of other canola flowers, but it could differentiate canola from the odor of a snapdragon flower. Bees trained with the odor of snapdragon flowers readily differentiated the odor of one variety of a snapdragon from the odor of other varieties of snapdragons and also canola flowers. Our study suggests that both intensity and odor quality affect the ability of honeybees to differentiate among floral perfumes.

Animals↗

To fix or not to fix: the role of 2-phenoxyethanol in rabbit, Oryctolagus cuniculus, chin gland secretion.

The European rabbit (Oryctolagus cuniculus) uses the secretion of the chin gland to maintain dominance hierarchies in the wild. Recent work has investigated changes in the secretion when social status is manipulated in the rabbit. When a rabbit becomes dominant, a new compound appears in his secretion, 2-phenoxyethanol. This compound is used as a fixative in the perfume industry. This study investigates whether the compound performs a similar function in the secretion of the rabbit. 2-Phenoxyethanol is not detected olfactorially by rabbits, and slows the release rate of some of the compounds that occur naturally in rabbit chin gland secretion. We suggest that when a rabbit becomes dominant, he adds a fixative to his secretion so that his scent will persist in the environment and not dissipate. He will thus come to dominate the olfactory environment, in much the same way as he does the physical environment.

Animals↗

Asthma and allergies at school--a Swedish national position paper.

The marked rise in allergies during the past decade has been increasingly perceptible for school personnel. A quarter of Swedish parents of children with allergies are unsatisfied with the school environment and how the schools are organized around their children. The Association of School Physicians has, together with six other medical, teaching and patient organizations, developed written guidelines for the management of asthma and allergies in Swedish schools. The aim was to regulate the responsibility of the school and its personnel for students with asthma and allergies, and to strengthen safety arrangements within schools. A secondary aim was to describe how the curriculum, teaching equipment, excursions, and other school activities, could be arranged appropriately and safely for students with asthma and allergies. Five-hundred copies of the document were circulated to all of Sweden's municipalities, county councils and pediatric departments. There was general agreement regarding the schools' responsibility that no child should risk becoming ill or having exacerbation of symptoms due to conditions at school. Recommendations regarding smoking on school premises and the use of perfumes were criticised. The strength of this document is that all organizations actively involved with schools have agreed upon these recommendations. This document serves to suggest a minimum level of activities thus ensuring that even students with asthma and allergies will receive appropriate schooling.

Asthma↗

Gas chromatography: an investigative tool in multiple allergies to essential oils.

Essential or fragrant oils are volatile odourous mixtures of organic chemical compounds that are widely used in aromatherapy and in the perfume industry. Because of their frequent use, allergy to essential oils is being increasingly recognized. We report 2 cases of multiple allergies to essential oils in professional aromatherapists. Gas chromatography/mass spectrometry was used to analyse the oils in order to identify a common allergen responsible for the contact dermatitis. In both the cases, alpha- and beta-pinene were found to be the most common constituent in the oils and thus appeared to be key allergens. alpha-pinene was confirmed as an allergen on repeat patch testing with pure alpha-pinene in both cases. 12 controls tested were negative for the same. Gas chromatography-mass spectrometry was found to be an extremely useful tool that could be utilized in investigating multiple allergies to essential oils.

Allergens↗

Influence of training and experience on the perception of multicomponent odor mixtures.

This study examined whether a previously established (D. G. Laing & G. W. Francis, 1989) limited capacity to discriminate and identify the components of olfactory mixtures resulted from the participants' lack of familiarity with the task, training designed to optimize cognitive and perceptual performance, or professional experience in odor discrimination. The participants were a trained panel of 10 women (23-43 years old), and an expert panel of 8 male professional perfumers and flavorists (25-55 years old). The individual chemical stimuli were 7 common dissimilar odorants of equal moderate intensity. An air dilution olfactometer delivered a single odorant or a mixture containing up to 5 odorants. The results indicated that for both panels only 3 or 4 components of a complex mixture could be discriminated and identified and that this capacity could not be increased by training. Therefore, the limit may be imposed physiologically or by processing constraints.

Adult↗