Fragrance and asthma bibliography

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Elberling, J, Duus Johansen, J, Dirksen, A, Mosbech, H Exposure of eyes to perfume: a
double-blind, placebo-controlled experiment. Indoor Air 2006 16(4):276-281.
Abstract: Environmental perfume exposure can elicit bothersome respiratory symptoms.
Symptoms are induced at exposure levels which most people find tolerable, and the
mechanisms are unclear. The aim of the study was to investigate patients with eye and
respiratory symptoms related to environmental perfume, by exposing the eyes to perfume
in a double-blind, placebo-controlled study. Twenty-one eczema patients with
respiratory symptoms elicited by perfume were compared with 21 healthy
volunteers in a sex- and age-matched case-control study. The participants completed a
symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to
perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching,
and tears) during perfume exposure than during placebo exposures, and eight of
these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true
positive eye reaction to perfume was significantly associated with identification of
perfume as an active exposure (P < 0.05). In this study, vapor of perfume elicited
irritation in the eyes independently of olfaction, but the relative importance of ocular
chemoperception in relation to elicitation of respiratory symptoms from common
environmental exposures to perfume remains unclear. Practical Implications: Vapors of
perfume provoked symptoms in the relevant eye in some patients and healthy control
persons, but under our exposure conditions, ocular chemesthesis failed to elicit
respiratory symptoms.
Elberling J, Linneberg A, Dirksen J. D. Johansen L, Frølund F, Madsen N, Nielsen
H, Mosbech, H Mucosal symptoms elicited by fragrance products in a populationbased sample in relation to atopy and bronchial hyper-reactivity. Clinical and
Experimental Allergy 2005 35(1), 75-81.
Abstract: To investigate both the localization and character of symptoms from the eyes
and airways elicited by fragrance products, and the associations between such symptoms
and skin prick test reactivity (atopy), methacholine bronchial hyper-reactivity (BHR),
allergic rhinitis and asthma. Methods A questionnaire on mucosal symptoms elicited by
fragrance products was posted to 1189 persons who had participated in a Danish
population-based study of allergic diseases in 1997/1998. The study included
measurement of BHR, atopy, forced expiratory volume in 1 s (FEV1), and serum
eosinophilic cationic protein (serum ECP). Results The response rate was 79.6%.
Symptoms from the eyes or airways elicited by fragrance products were reported by
42%. BHR (adjusted odds ratio 2.3, 95% confidence interval 1.5–3.5) was
independently associated with symptoms from the eyes and airways elicited by
fragrance products. There were no significant associations between these symptoms and
atopy, FEV1 or serum ECP. Conclusions Mucosal symptoms from the eyes and airways
were common in this population. BHR was a significant and independent predictor of
these symptoms. The lack of association with atopy suggested that IgE-mediated allergic
mechanisms do not play a major role in the development of these symptoms.
Su HJ, Chao CJ, Chang HY, Wu, PC The effects of evaporating essential oils on indoor
air quality. Atmospheric Environment 2007 41(6), 1230-1236
Abstract: Essential oils, predominantly comprised of a group of aromatic chemicals, have
attracted increasing attention as they are introduced into indoor environments through
various forms of consumer products via different venues. Our study aimed to characterize
the profiles and concentrations of emitted volatile organic compounds (VOCs) when
evaporating essential oils indoors. Three popular essential oils in the market, lavender,
eucalyptus, and tea tree, based on a nation-wide questionnaire survey, were tested.
Specific aromatic compounds of interest were sampled during evaporating the essential
oils, and analyzed by GC-MS. Indoor carbon monoxide (CO), carbon dioxide (CO2), total
volatile organic compounds (TVOCs), and particulate matters (PM10) were measured by
real-time, continuous monitors, and duplicate samples for airborne fungi and bacteria
were collected in different periods of the evaporation. Indoor CO (average
concentration 1.48 vs. 0.47 ppm at test vs. background), CO2 (543.21 vs.
435.47 ppm), and TVOCs (0.74 vs. 0.48 ppm) levels have increased significantly
after evaporating essential oils, but not the PM10 (2.45 vs. 2.42 ppm). The antimicrobial activity on airborne microbes, an effect claimed by the use of many essential
oils, could only be found at the first 30–60 min after the evaporation began as the highest
levels of volatile components in these essential oils appeared to emit into the air,
especially in the case of tea tree oil. High emissions of linalool (0.092–0.787 mg m−3),
eucalyptol (0.007–0.856 mg m−3), d-limonene (0.004–0.153 mg m−3), ρ-cymene
(0.019–0.141 mg m−3), and terpinene-4-ol-1 (0.029–0.978 mg m−3), all from the
family of terpenes, were observed, and warranted for further examination for their
health implications, especially for their potential contribution to the increasing
indoor levels of secondary pollutants such as formaldehyde and secondary organic
aerosols (SOAs) in the presence of ozone.
Caress SM, Steinemann AC Prevalence of fragrance sensitivity in the American
population. J Env Health 2009 71(7) 46-50. Comment in:
J Environ Health. 2009 May;71(9):51-2; author reply 52.
This study determined the percentages of individuals who report adverse effects from
exposure to fragranced products in the U.S. population and in subpopulations of those
with asthma or chemical sensitivity. Data were collected through telephone interviews
from two geographically weighted, random samples of the continental U.S. in two
surveys during 2002-2003 and 2005-2006 (1,057 and 1,058 cases, respectively).
Respondents were asked if they find being next to someone wearing a scented product
irritating or appealing; if they have headaches, breathing difficulties, or other problems
when exposed to air fresheners or deodorizers; and if they are irritated by the scent from
laundry products, fabric softeners, or dryer sheets that are vented outside. Results
aggregated from both surveys found that 30.5% of the general population reported
scented products on others irritating, 19% reported adverse health effects from air
fresheners, and 10.9% reported irritation by scented laundry products vented
outside. This study reveals that a considerable percentage of the U.S. population
reports adverse health effects or irritation from fragranced products, with higher
percentages among those with asthma and chemical sensitivity.
Elberling, J, Linneberg A, Mosbech H, Dirksen A, Frolund L, Madsen F, Nielsen, NH
Johansen JD A link between skin and airways regarding sensitivity to fragrance
products? British Journal of Dermatology. 151(6):1197-1203, December 2004.
Abstract: To investigate if eye and airway symptoms elicited by fragrance products are
associated with perfume contact allergy or hand eczema in a population-based sample.
Methods: A questionnaire on eye and airway symptoms elicited by fragrance products
was mailed to 1189 individuals who had recently participated in a Danish
population-based study of allergic diseases. Results from the questionnaire about
localization and character of the symptoms were compared with data on patch testing
and 1-year prevalence of hand eczema collected during the health examination.
Results: Positive, independent and significant (P < 0.05) associations were found
between eye and airway symptoms elicited by fragrance products and perfume
contact allergy (adjusted odds ratios 2.0-3.7) and hand eczema (adjusted odds ratios
1.6-2.6). In further analysis, similar and consistent results were found regarding severity
of the symptoms. No associations were found between nickel contact allergy and the
symptoms. Female sex and psychological vulnerability were independently associated
with eye and airway symptoms elicited by fragrance products, but adjustment in
multivariate analysis did not change the results regarding perfume contact allergy and
hand eczema. Conclusions: Individuals with perfume contact allergy and/or hand
eczema, as opposed to those without, have more frequent and more severe eye or
airway symptoms after exposure to volatile fragrance products. Having hand eczema
has the greatest impact on reporting eye and airway symptoms elicited by fragrance
products.
Elberling J, Skov PS, Mosbech H, Holst, H, Dirksen A, Johansen JD Increased release of
histamine in patients with respiratory symptoms related to perfume. Clinical and
Experimental Allergy 2007, 37(11), 1676-1680.
ABSTRACT The study aimed to investigate whether basophils from patients with
respiratory symptoms related to perfume released more histamine in the presence of
perfume as compared with healthy volunteers. Methods Histamine release was measured
by the glass fibre method. Blood was obtained from healthy volunteers (n=20) and
patients with respiratory symptoms related to perfume (n=17) attending a
dermatological outpatient clinic for patch testing. The effect of an international brand
perfume was investigated using the basophil histamine release test with perfume.
Furthermore, basophils from a healthy non-atopic donor were incubated with participant's
sera and histamine release induced by perfume was measured. Results In both groups,
incremental perfume concentrations showed a positive and significant (P<0.001)
dose-response effect on the release of histamine. At the highest perfume
concentration, the basophils released significantly (P<0.05) more histamine in
patients as compared with healthy volunteers. No difference was found between the
groups when sera were incubated with basophils from a healthy non-atopic donor.
Conclusion Perfume induces a dose-dependent non-IgE-mediated release of
histamine from human peripheral blood basophils. Increased basophil reactivity to
perfume was found in patients with respiratory symptoms related to perfume.
Curtis, L Letter to the Editor: Toxicity of fragrances EHP 2004 112(8) A461
Anderson R, Anderson J. 1998. Acute toxic effects of fragrance products. Arch Environ Health
53(2):138–146.
Ashford N, Miller C. 1991. Chemical Exposures: Low Levels and High Stakes. New York: Von
Nostrand Reinold.
Kumar P, Caradonna-Graham VM, Gupta S, Cai X, Rao PN, Thompson J. Inhalation challenge
effects of perfume scent strips in patients with asthma. 1995. Annals Allergy 75(5):429–433.
Millqvist E, Lowhagen O. 1996. Placebo controlled challenges with perfume in patients with
asthma-like symptoms. Allergy 51(6):434–439.
Shim C, Williams MH. 1986. Effect of odors in asthma. Am J Med 80(1):18–22.
Spencer PS, Bischoff-Fenton MC, Moreno OM, Opdyke DL, Ford RA. 1984. Neurotoxic
properties of musk ambrette. Toxicol Appl Pharmacol 75(3):571–575.
Steinemann, AC Fragranced consumer products and undisclosed ingredients.
Environmental Impact Assessment Review 2009, 29(1): 32-38
Abstract Fragranced consumer products—such as air fresheners, laundry supplies,
personal care products, and cleaners—are widely used in homes, businesses, institutions,
and public places. While prevalent, these products can contain chemicals that are not
disclosed to the public through product labels or material safety data sheets (MSDSs).
What are some of these chemicals and what limits their disclosure? This article
investigates these questions, and brings new pieces of evidence to the science, health, and
policy puzzle. Results from a regulatory analysis, coupled with a chemical analysis of
six best-selling products (three air fresheners and three laundry supplies), provide
several findings. First, no law in the U.S. requires disclosure of all chemical ingredients
in consumer products or in fragrances. Second, in these six products, nearly 100 volatile
organic compounds (VOCs) were identified, but none of the VOCs were listed on any
product label, and one was listed on one MSDS. Third, of these identified VOCs, ten are
regulated as toxic or hazardous under federal laws, with three (acetaldehyde,
chloromethane, and 1,4-dioxane) classified as Hazardous Air Pollutants (HAPs). Results
point to a need for improved understanding of product constituents and mechanisms
between exposures and effects.
Thyssen J P, Menne T, Linneberg A, Johansen, J D Contact sensitization to fragrances
in the general population: a Koch's approach may reveal the burden of disease. British
Journal of Dermatology 2009 160(4):729-735.
Abstract: Background: Contact sensitization to fragrance mix (FM) I and Myroxylon
pereirae (MP) is common among European patients with dermatitis. Recently, FM II was
included in the European baseline series as an additional marker of fragrance
sensitization. Objectives: This literature review aims to assess the prevalence of
fragrance sensitization in the general population, and to suggest how future populationbased studies and questionnaires should be constructed, better to assess the prevalence
and burden of fragrance sensitization. This is of relevance as it is often difficult to
establish causality in biological systems. Methods: A systematic review of the literature
was carried out by searching Pubmed-Medline, Biosis and contact dermatitis textbooks.
Results: Nineteen studies were identified, of which 13 were performed among adults.
Sample sizes varied between 82 and 2545 tested subjects, and 11,648 subjects were tested
in total. The median prevalence of FM and MP sensitization among adults was 2.3%
(women, 1.7%; men, 1.3%) and 1.% (women, 1.4%; men, 0%), respectively.
Conclusions: Based on the reliability of patch test data from the general population and
exposure data obtained from patients with dermatitis, the prevalence and burden of
fragrance sensitization in the general population is significant.
Ezendam J et al Immune effects of respiratory exposure to fragrance chemicals (the
Netherlands). RIVM Reports 2007 http://hdl.handle.net/10029/16464
Result: Inhalation of the fragrance chemicals, isoeugenol and cinnamal, by mice
resulted in immune reactions in the respiratory tract. RIVM investigated the effects of
inhalation of isoeugenol and cinnamal, fragrance chemicals that can cause skin allergy.
Mice were exposed to the fragrance chemicals via inhalation. Effects on the immune
system were measured using a respiratory lymph node assay, which measures cell
proliferation in lymph nodes of the respiratory tract. Inhalation of both isoeugenol
and cinnamal resulted in stimulation of the immune system of the respiratory tract. The
effects of isoeugenol were more pronounced than those of cinnamal. To obtain more
insight into the hazards of fragrance chemicals used in scented products, RIVM is
advising assessment of more fragrance chemicals in the respiratory lymph node assay.
Luckenbach, T & Epel, D Nitromusk and Polycyclic Musk Compounds as Long-Term
Inhibitors of Cellular Xenobiotic Defense Systems Mediated by Multidrug Transporters.
EHP 2005 113(1):17–24.
Response from Salvito, D, Synthetic Musk Compounds and Effects on Human Health?
Fragrance industry’s response Letter to the Editor EHP (2005) 113,(12) A802-A803.
28. Herbert M, Glick R, Black H. Olfactory precipitants of bronchial asthma. J Psychosomat Res
11:195–202 (1967).
29. Shim C, Williams MH. Effect of odors in asthma. Am J Med 80:18–22 (1986).
30. Kumar P, Caradonna-Graham VM, Gupta S, Cai X, Rao PN Thompson J. Inhalation
challenge effects of perfume scent strips in patients with asthma. Ann Allergy Asthma
Immunol 75:429–433 (1995).
31. Anderson RC, Anderson JH. Toxic effects of air freshener emissions. Arch Environ Health
52(6):433–441 (1997).
32. Anderson RC, Anderson JH. Acute toxic effects of fragrance products. Arch Environ Health
53(2):138–146 (1998).
33. Anderson RC, Anderson JH. Respiratory toxicity in mice exposed to mattress covers. Arch
Environ Health 54(3):202–209 (1999).
34. Anderson RC, Anderson JH. Acute respiratory effects of diaper emissions. Arch Environ
Health 54(5):353–358 (1999).
35. Shusterman D, Balmes J, Cone J. Behavioral sensitization to irritants/odorants after acute
overexposures. J Occup Med 30:565–567 (1988).
Report on the project at http://archive.leg.state.mn.us/docs/2008/mandated/080128.pdf
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