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Synthetic musks in environmental samples: indicator compounds with relevant properties for environmental monitoring.

Synthetic musks (nitro and polycyclic musks) are a group of chemicals offering a wide range of important properties for environmental monitoring programs. They are produced as odorous chemicals and added to a wide variety of perfumes, toiletry products and other household products. As such, they are directly applied in cosmetic products or in washed textiles to the human body in considerable concentrations and accumulate owing to dermal resorption. In addition, synthetic musks also enter the environment via waste water treatment. Several polycyclic musks are chiral. By using chiral gas chromatographic methods, it is possible to determine the enantiomeric ratio and assess their bioavailability. Although an comprehensive quality assurance program must be followed during the analysis of synthetic musks in environmental samples, the determination of these compounds is not very demanding and can be carried out by a standard analytical laboratory specialising in trace analysis of organic pollutants. Owing to the pheromone-like behavior of some synthetic musks, the induction of receptors in olfactory systems should be investigated. For HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran, e.g., Galaxolide), three-dimensional structural similarities with androstenone (5 alpha-androst-16-en-3-one), a mammalian steroid pheromone, were found, which support the hypothesis of HHCB as an artificial pheromone. Owing to their environmental abundance, their relation to human activities and their potential for pheromone-like environmental behavior, synthetic musks are especially valuable as future indicator chemicals for environmental monitoring.

Air Pollution, Indoor↗

Towards engineered topogenesis of cytochrome b(5) and P450 for in vivo transformation of xenobiotics.

Nature is endowed with catalysts capable of an unprecedented diversity of biotransformations, beyond the capabilities of synthetic chemistries. In a biotechnological context, there is a growing and emerging need to tap this catalytic potential. CYP (cytochrome P450) represents a superfamily of enzymes capable of a diverse array of catalytic activities. Distinct members are engaged in biosynthetic reactions within many organisms, while others have a role in the detoxification of foreign compounds. The latter substrates include medicines, pollutants, pesticides, carcinogens, perfumes and herbicides, representing considerable applied importance for pharmacology and toxicology. CYPs show a high degree of stereo- and regio-specificity for their reactions, which have wide industrial applications. Recombinant CYPs are commonly expressed as active recombinant cytosolic forms in Escherichia coli. However, selective permeability of E. coli to many substrates and products can cause problems with product recovery when using whole-cell systems. To overcome these problems, we have been developing approaches to facilitate export of functional recombinant haemoproteins to the inner membrane, periplasm and the outer membrane of E. coli. Here, we describe the progress in relation to cytochrome b(5) and CYPs.

Biotransformation↗

Prevalence of atopic dermatitis, asthma, allergic rhinitis, and hand and contact dermatitis in adolescents. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis.

BACKGROUND: Atopic diseases are common in children and adolescents. However, epidemiological knowledge is sparse for hand eczema and allergic contact dermatitis in this age group. Furthermore, no population-based studies have evaluated the prevalence of atopic diseases and hand and contact dermatitis in the same group of adolescents. OBJECTIVES: To assess prevalence measures of atopic dermatitis (AD), asthma, allergic rhinitis and hand and contact dermatitis in adolescents in Odense municipality, Denmark. METHODS: The study was carried out as a cross-sectional study among 1501 eighth grade school children (age 12-16 years) and included questionnaire, interview, clinical examination and patch testing. RESULTS: The lifetime prevalence of AD was 21.3% (girls 25.7% vs. boys 17.0%, P < 0.001) using predefined questionnaire criteria. The 1-year period prevalence of AD was 6.7% and the point prevalence 3.6% (Hanifin and Rajka criteria). In the interview the lifetime prevalence of inhalant allergy was estimated as 17.7% (6.9% allergic asthma, 15.7% allergic rhinitis). The lifetime prevalence of hand eczema based on the questionnaire was 9.2%, the 1-year period prevalence was 7.3% and the point prevalence 3.2%, with a significant predominance in girls. A significant association was found both between AD and inhalant allergy, and between AD and hand eczema using lifetime prevalence measures. The point prevalence of contact allergy was 15.2% (girls 19.4% vs. boys 10.3%, P < 0.001), and present or past allergic contact dermatitis was found in 7.2% (girls 11.3% vs. boys 2.5%). Contact allergy was most common to nickel (8.6%) and fragrance mix (1.8%). CONCLUSIONS: High prevalence figures were found for atopic diseases, hand eczema and allergic contact dermatitis, and the diseases were closely associated. A considerable number of adolescents still suffers from AD, and a considerable sex difference was noted for hand eczema and allergic contact dermatitis. Nickel allergy and perfume allergy were the major contact allergies. In the future this cohort of eighth grade school children will be followed up with regard to the course and development of atopic diseases, hand eczema and contact dermatitis.

Adolescent↗

Familial cases of poikiloderma of Civatte: genetic implications in its pathogenesis?

Poikiloderma of Civatte (PC) is a rather common, benign skin condition of obscure etiopathogenesis: cumulative exposure to UV radiation, hormonal changes associated with the menopause, and photo-allergic mechanisms have been implicated. We present seven cases of PC among the members of two unrelated Greek families, who have not shared common extrinsic influences. Literature review revealed no other reported familial cases. Familial tendencies, as well as the not unusual occurrence of PC in individuals with minimal sun exposure, and who are not using perfumes or cosmetics, provide support for the hypothesis that a genetic predisposition to the disease may exist; this predisposition is possibly transmitted as an autosomal dominant trait.

Female↗

Comparative evaluation of the antimicrobial activities of essential oils of Artemisia afra, Pteronia incana and Rosmarinus officinalis on selected bacteria and yeast strains.

Essential oils are frequently used for flavour and fragrance in the perfume, pharmaceutical, cosmetic and food industries. The antimicrobial activities of the essential oils of Artemisia afra, Pteronia incana and Rosmarinus officinalis were tested against 41 microbial strains. The test organisms were selected on the basis of their significance as food spoilage and/or poisoning, common human and plant pathogens. The agar diffusion assay was performed using nutrient agar and antibiotic medium. All the oils tested displayed some antimicrobial activities. However, the efficiency differed and depended both on the type and concentration of the oil, as well as the test microbial strain. Artemisia afra and R. officinalis showed similar and higher antimicrobial activity than P. incana. Due to their broad antimicrobial activities, the essential oils of the above plants growing in Eastern Cape may have preservative potential for the food and cosmetic industries.

Artemisia↗

Neuroendocrinology briefings 11: pheromones and reproduction.

The information humans receive from their nose is rarely of vital significance and although perfumers and masters of wine have developed a large vocabulary of descriptors, most of us categorize odours into pleasant and unpleasant. Not surprisingly therefore, most of our olfactory receptor genes are nonfunctional pseudogenes. Rodents, on the other hand, not only have a vast repertoire of olfactory genes (1000-1500) but also possess two additional sets of receptors in the vomeronasal organ that is specialized for pheromone reception.

Animals↗

Montelukast in the prophylaxis of migraine: a potential role for leukotriene modifiers.

OBJECTIVE: Clinical observation of a decrease in migraine frequency in patients with comorbid asthma taking montelukast, a specific D4 leukotriene receptor antagonist, or zafirlukast, another leukotriene receptor antagonist, prompted us to explore a possible role for leukotriene modifiers in the treatment of migraine. (A further prompt was a pharmacist colleague's observation that a number of patients on these agents reported a decreased sensitivity to perfume triggers and improvement in migraine.) BACKGROUND: Nonsteroidal anti-inflammatory agents have been used widely in the treatment of migraine. Another class of anti-inflammatory agents, known as leukotriene modifiers, have not been studied to date with regard to their possible role in the treatment of migraine. The name "leukotriene is derived both from the parent molecule, which was originally isolated from leukocytes, and from its three double-bond carbon backbone or triene structure. Both prostaglandins and leukotrienes are derived from the metabolism of arachidonic acid, with prostaglandins coming off the cyclooxygenase pathway and leukotrienes derived via the enzyme 5-lipoxygenase. Both prostaglandins and leukotrienes mediate inflammatory responses. The latter have been studied with regard to their role in the pathophysiology of asthma. METHODS: A prospective, open-label study evaluating the efficacy of montelukast, 10 mg or 20 mg, in the prophylaxis of migraine in 17 patients is presented in this paper. All 17 patients completed the study that consisted of a 2-month baseline run-in period and a 3-month treatment phase. RESULTS: Montelukast was extremely well tolerated, and no adverse events were reported by any of the patients. Fifty-three percent showed a reduction of greater than 50% (P<.025) in the frequency of severe attacks, with 41% showing a reduction of greater than 60%. Responders, including modest responders, rated the drug as excellent. CONCLUSIONS: We conclude, given the limitations of an open-label study design and the small sample size, that montelukast shows potential as an effective, well-tolerated prophylactic agent in migraine. Double-blinded, placebo-controlled studies are warranted. In addition, the leukotrienes, as suggested previously in the literature, may play a role in the pathogenesis of migraine.

Acetates↗

Skin irritation and exposure to diisocyanates in orthopedic nurses working with soft casts.

BACKGROUND: Diisocyanates are widely used in industry, for example at hospitals as a constituent of Scotch Cast soft casts (3M, Glostrup, Denmark). They are a cause of occupational asthma and have been described as causing cutaneous problems both as irritants and as sensitizers. OBJECTIVE: The sensitizing potential of diisocyanates has previously only sporadically been described, predominantly in case reports. Therefore, we conducted this study to investigate eventual work-related skin sensitization to diisocyanates in a regularly exposed population. METHODS: The nursing staff of an orthopaedic outpatient clinic, consisting of 10 persons, were interviewed and subjected to patch testing using 5 types of diisocyanates and the TRUE Test (ECDRG Standard Series) to elucidate possible other type IV allergies with similar symptoms. Patch test results were evaluated according to the guidelines of the International Contact Dermatitis Group. RESULTS: We found no relationship between exposure time and severity of symptoms. Symptoms were mild, consisting of redness, itching, or both, lasting about 30 minutes. There was no suggestion that they result in any chronic skin problems. One nurse presented a doubtful reaction towards diaminophenylmethane (MDA) and isophorene diisocyanate (IPDI). Nine persons had no reactions to the 5 diisocyanates used in the patch test. Positive reactions were seen to nickel (4/10), thiomersal (2/10), and perfume mix (1/10). CONCLUSION: Our observations suggest that diisocyanates are primarily irritants rather than sensitizers in the professional setting studied. The skin symptoms of irritation were all mild and temporary.

Adult↗

Capsaicin inhalation test for identification of sensory hyperreactivity.

BACKGROUND: Patients with upper and lower airway symptoms and with pronounced sensitivity to chemical odours, such as perfumes, flower scents and tobacco smoke, have been suggested to have sensory hyperreactivity (SHR). The symptoms have been difficult to identify with physiological measurements and the effects of various medications are doubtful. However, these patients have been found to be more sensitive to inhalation of capsaicin than healthy people. The aim of this study was to establish limit values with the capsaicin inhalation test in patients with SHR. METHODS: Ninety-five consecutive patients with upper and lower airway problems, who were admitted for allergy testing, underwent a capsaicin inhalation test with three different concentrations. The number of coughs was registered during each challenge. Score systems were used for symptoms and influence on social life of sensitivity to odours. In relation to scored symptoms, the patients were grouped as SHR or not, and compared with 73 healthy controls. RESULTS: All patients and controls coughed on capsaicin in a dose-dependent manner. Symptom score of odour sensitivity in patients was positively correlated to the response of the test. Out of 95 patients, 15 (16%) were scored to SHR. Patients with SHR reacted more to the capsaicin inhalation test than the other patients and the healthy controls. The limit values for a positive capsaicin inhalation test for the SHR were determined to be 10, 35 and 55 coughs at 0.4, 2.0 and 10 microM capsaicin, respectively. CONCLUSION: The capsaicin inhalation test well reflects the degree of airway sensitivity to chemicals and to what extent the social life is influenced. The cut-off values of the test can distinguish patients with pronounced sensitivity to odours.

Administration, Inhalation↗

[Allergies in adults].

Only few epidemiological studies have assessed allergic diseases in adults. In a follow-up study of the MONICA survey S3 (1994/95), which was performed 1997-1999, a total of 1,537 persons were interviewed and tested by skin prick and patch test. Furthermore data of the MONICA survey (RAST, cholesterol, food diaries) could be used. Within survey S4 (1999/2001) a total of 4,261 subjects were interviewed concerning their personal history of atopic diseases and the corresponding history of their partners. In survey S3 the prevalence of allergic sensitisation was 20.5 % for persons without formal graduation from school and 48.1 % for those with a university degree. 20.8 % reported a hypersensitivity to food and about one quarter exhibited a positive reaction in skin prick test. Atopic eczema and hay fever increased over quartiles of HDL cholesterol. Similar, allergic sensitisation (RAST) increased over quartiles of uptake of unsaturated fatty acids in men. 40 % of those who were patch tested exhibited a positive reaction, with perfume mix, nickel, thimerosal and balsam of Peru being the most prominent allergens. Inhabitants of the City of Augsburg were sensitised more often (34.0 % overall, 23.9 % pollen) than inhabitants of villages with (29.4 %, 17.0 %). Full time farmers were sensitised less frequently (22.0 %, 8.4 %). In survey S4 the lifetime prevalence of atopic diseases diagnosed by doctors was 5.1 % for atopic eczema, 6.1 % for asthma and 13.7 % for hay fever. Subjects who lived together with a partner who suffered from hay fever were affected in 19.6 % whereas 13.1 % had hay fever when the partner was not affected. Future studies will offer an unique opportunity to analyse the incidence and remission of manifestations of atopy in adults.

Adult↗

Headspace constituents of opium.

The headspace of medicinal opium (Ph. Ned. 8) was analyzed by means of GC-FID, (+EI)-GC-MS (low and high resolution), and GC-FTIR. After olfactoric evaluation of the headspace sample by professional perfumers by the use of the GC-sniffing technique and after correlation tests with trained police dogs, more than 70 components were identified. With regard to the characteristic olfactoric properties of opium only one class of components, namely pyrazines, is of special interest. The synthetic mixture of 2-methyl-, 2,5-, and 2,6-dimethylpyrazine with 2-methoxy-3-isopropyl- and 2-methoxy-3-isobutylpyrazine was found to represent the original opium odour quite well.

Animals↗

[Disorders of smell and taste. Standard and recent methods in diagnosis and therapy].

Compared to disorders of the ears and eyes, diseases of smell and taste seem to be far less outstanding: however, the unimpaired perception of odours and flavours comprises an important part of our well-being, as can be seen in the perfume industry or in drinking and eating habits. The ENT-specialist covers organic causes of these senses, as he has the tools to explore and treat in the depth of the nasal and oral cavities. The "Arbeitsgemeinchaft Olfaktologie/Gustologie der Deutschen Gesellschaft für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie" therefore is in process of establishing a new set for a standardised smell and taste test, which is based in part on the sniffin'sticks, which were developed by Prof. Kobal, Erlangen. The examination procedure of nasal and oral chemosensory performance requires a high test-retest reliability and an efficiency comparable to internationally established measurements in order to render valid results in diagnostic and therapeutic procedures. The new test kit with the sniffin'sticks is presented in this paper, followed by an overview on some disorders of smell and taste perception and proposals for actual therapeutic procedures.

Ageusia↗

[Sense of smell].

About two million Americans suffer from anosmia. Most result from nasal obstruction, head injuries, and viral infections. Brain disorders like epileptic seizures, tumours, and dementia can distort can distort the sense of smell. Anosmia adversely affects patient well-being. Patients cannot detect spoiled food, gas leakage, or dangerous smoke. They are unable to distinguish flavour and smell the springtime or the ocean. Many products as soaps, cat litter, toilet paper, etc. are perfumed because consumers will more readily buy a product that smells nice than one that has no smell at all. Historically, the importance of odors was very different. The ancient Romans loved exotic aromas during their banquets and orgies. In the Middle Ages the church did not like fragrances. The French revolution of 1789 brought a revolution of deodorization to Europe. Today, fragrance companies' increasing sales are an indication of the power of odor.

Humans↗

[Laurel allergy. Cause, effect and sequelae of the external application of a so-called nature remedy].

Self-medication of rheumatic complaints in the upper arm, by one woman, and of a lipoma on the thigh, by another, with pure laurel oil caused within two weeks severe contact dermatitis and swellings far from the point of application. Sesquiterpene lactone, contained within laurel oil, proved to be the cause of the induced contact allergy. Since the acquired specific hypersensitivity of the eczema type is directed primarily against the alpha-methylene group of the lactone, cross-reactions were observed against a large number of other plans which are botanically unrelated but contain substances of a similar class. Those allergic to laurel oil should therefore avoid many cosmetics, articles of hygiene, foods, drinks and medicinal preparations which contain herbs, as well as gardening, certain cut flowers and perfumes, especially those of the family Compositae. The present trend "back to nature" makes further sensitizations against laurel oil likely. This would seem to justify the inclusion of these substances among the group of potentially harmful environmental and occupational products.

Arm↗

Symptomatology and etiology of multiple chemical sensitivities in the southeastern United States.

A questionnaire was administered to individuals who had reported a hypersensitivity to common chemical products in an earlier epidemiological study in the Atlanta, Georgia, metropolitan area. The questionnaire investigated the nature of the symptoms and factors that potentially initiated hypersensitivity and subsequently triggered reactions. Also examined were associated lifestyle modifications and the relationships of hypersensitivity with other illnesses. The authors found that a majority of hypersensitive individuals (52.2%) experienced either "severe" or "somewhat severe" symptoms. The most common triggers of symptoms were cleaning products (88.4%), tobacco smoke (82.6%), perfume (81.2%), pesticides (81.2%), and car exhaust (72.5%). Only 1.4% of the subjects had a prior history of emotional problems, whereas 37.7% developed such problems after the emergence of their hypersensitivity. Lifestyle modifications varied; 76.8% changed their household cleaning/personal hygiene products, 47.8% began using water and/or air filtration systems, and 13% found it necessary to change residence. Although hypersensitivity was more common in females than males, the condition affects individuals in all categories of race/ethnicity, age, household income, and educational level.

Adult↗

Possible time-dependent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult population.

The present paper summarizes key features of time-dependent sensitization (TDS) in neuropharmacology (progressive amplification of behavioral, neuronal, endocrine, and/or immune responses to repeated intermittent exposures to an environmental agent or cross-sensitizing agents) as a possible model for cacosmia (subjective sense of feeling ill from low levels of environmental chemical odors) in nonindustrial and industrial populations; and extends previous cacosmia research in nonpatient populations to an elderly sample. This study examined the symptom and psychological profiles of 263 older adults (aged 60-90 y, 71% women, 29% men); 57% reported that at least one chemical and 17% reported that at least four of five chemicals (pesticide, automobile exhaust, paint, new carpet, perfume) made them feel ill. Cacosmia ratings correlated weakly and negatively with age (r = -0.19, p = .001) over the whole sample. Cacosmia correlated significantly with self-reported illness from foods that may mobilize or generate opioid peptides (wheat, dairy, eggs) (r = 0.32, p < .0001) and with illness from opiate drugs (r = 0.23, p < .0001). When the sample was divided into four cells on the basis of above-versus below-median total chemical-induced illness score (CI) and total food-induced illness score (FI), the high CI and high FI, high CI only, and high FI only groups had more frequent indigestion, and the high CI group had more frequent difficulty concentrating than the groups below median for illness from both chemicals and foods (NOILL), even after covarying for age and anxiety. The most cacosmic subjects noted higher prevalence of physician-diagnosed allergies and irritable bowel than did noncacosmic subjects. In contrast with previous young adult cohort studies, the older illness groups did not differ with regard to sex distribution, depression, shyness, or repressive defensiveness. When considered with prior surveys of young adults, the present findings are consistent with the presence of previously established, time-dependent sensitization to multiple xenobiotic agents in susceptible individuals for whom psychological variables do not explain the symptom of cacosmia. If cacosmia is a symptom of TDS, then the neuropharmacology literature suggests the possibility of excitatory amino acid, hypothalamic-pituitary-adrenal axis, dopaminergic, and/or opioid involvement. Prospective studies with objective measures testing the possible induction of TDS to specific chemicals are indicated.

Aged↗

Increased cardiopulmonary disease risk in a community-based sample with chemical odor intolerance: implications for women's health and health-care utilization.

Chemical intolerance, or reported illness from odors of common environmental chemicals (e.g., car exhaust, pesticides), is emerging as an important environmental and public health-care issue. Epidemiologic methods provide relevant heuristic devices for studies of complex disorders, such as chemical intolerance. The authors examined personal and reported parental cardiopulmonary disease prevalence rates in a community sample of chemically intolerant and control individuals. A county government (Tucson, Arizona) employee and kin subset (N = 181; 113 households) completed standard health questionnaires. Investigators determined chemical intolerance (n = 41/181) from self-reports of individuals who felt "moderately" to "severely" ill from exposure to at least three of five chemicals (i.e., car exhaust, pesticides, paint, new carpet, and perfume) on a Chemical Odor Intolerance Index. The authors chose the control group (n = 57/181) on the basis of self-reports of "never" feeling ill on the Chemical Odor Intolerance Index. The chemically intolerant group, which primarily comprised women (78% versus 51% of controls, p < .05), was significantly more likely to report-and to have sought--medical attention for heart problems, bronchitis, asthma, and pneumonia. Reports of heart problems in the chemically intolerant index cases and the occurrence of heart disease in both of their parents were significant (Fisher's p < .05). The chemically intolerant individuals were also significantly more likely to report maternal histories of chest problems (e.g., inhalant allergens, tuberculosis) than controls. The findings of the study suggested that the chemically intolerant individuals (a preponderance of whom were women [sex-related risk]) were more likely to have (a) reported cardiopulmonary problems (i.e., greater health risk); (b) actively sought medical care for these problems (i.e., increased medical utilization); and (c) reported more parental illnesses-particularly heart disease, asthma, and diabetes (i.e., genetic risk). Additional community-based studies of chemical intolerance are needed.

Adult↗

Symptom and personality profiles of young adults from a college student population with self-reported illness from foods and chemicals.

Despite much debate over a presumptively somatic vs psychological etiology of nonatopic food and chemical sensitivities, little systematic research has addressed the issues. The present study investigated self-reported illness from several common foods (wheat, dairy, eggs) and chemicals (pesticide, car exhaust, paint, perfume, new carpet), symptom patterns, and psychological profiles of a sample of young adult college students (n = 490, age 19.4 +/- 2.4, 52% female/48% male). Subjects were divided into 4 groups on the basis of sample medians for frequency of illness from the foods (FI) and chemicals (CI); high FI with high CI (FI/CI), high FI alone, high CI alone, and NOILL (low FI and CI). FI was associated with more defensiveness (denial of negativity) while CI was linked with more shyness (avoidance of novelty). Women outnumbered men in all groups (FI/CI: 61%; FI: 80% CI: 55%) except the NOILL (40% women). Nevertheless, the FI/CI, FI, and/or CI groups still had significantly higher total symptom scores as well as more indigestion, headache, and memory trouble than did the NOILL group, even after depression, anxiety, shyness, defensiveness, and gender were covaried. The illness groups reported significantly more limitation of foods that mobilize endogenous opioids or generate exogenous opioids (sweets, fats, bread) as well as more illness from opiate drugs, small amounts of beverage alcohol, and late meals. Nasal symptoms from pollens or animals were more common in the FI/CI (42%) and CI (42%) than in FI (26%) or NOILL (28%) groups. Premenstrual tension syndrome and irritable bowel were also more common in the FI/CI group. The findings indicate that young adults outside the clinical setting who are relatively higher in FI and/or CI have distinctive symptom and psychological patterns. Covariate analyses suggest that important symptoms in FI and CI individuals such as indigestion, headache, and memory problems may occur in addition to rather than as simply part of emotional distress. The data are consistent with a previously hypothesized role of olfactory-limbic and hypothalamic pathways and with a time-dependent sensitization model for illness from foods and chemicals.

Adolescent↗