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Fragrance chemicals are ubiquitous in cosmetics; however, they have been linked to allergic contact dermatitis. Allergy prevention involves two main strategies. Firstly, consumers are protected by limiting the maximum concentration of fragrance in a given product to avoid inducing allergies. Secondly, consumers who are already sensitized are protected by having the presence of such fragrance communicated to them. In this study, a validated GC-MS method was employed to quantify 26 allergens in 108 products marketed in Saudi Arabia.Additionally, a quantitative risk assessment (QRA) was performed on the studied cosmetics to determine the risk of inducing allergies. The results indicated that most allergens were present at acceptable concentrations, while 19 products carried a risk of inducing allergies. Furthermore, Lilial and Lyral, two prohibited fragrances, were detected in 97 products. It should be emphasized that this is the first study conducted in Saudi Arabia to evaluate the safety of the well-known 26 fragrance allergens. Hence, this study can potentially serve as a regional standard for future research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Considering consumer trends toward the use of "clean" personal care products and increasing recognition of childhood allergic contact dermatitis, we sought to characterize the allergen profile of such children's products., Methods: Ingredients of baby washes/shampoos, bubble baths, and moisturizers identified using the "Clean Baby" filter on Target®'s online marketplace were analyzed for relevant pediatric contact allergens., Results: Product compositions declared fragrance in 82% of products, Compositae in 46%, cocamidopropyl betaine in 45%, glucosides in 37%, propylene glycol in 12%, lanolin in 1%, and no allergens in 9%-methylisothiazolinone and formaldehyde were not found., Conclusion: Children are greatly impacted by atopic dermatitis and skin barrier dysfunction, which underscores a need for greater public awareness of sensitizing and irritating ingredients, particularly regarding pediatric personal care products., (© 2024 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Proteins in food and personal care products can pose a risk for an immediate immunoglobulin E (IgE)-mediated allergic response. Bioinformatic tools can assist to predict and investigate the allergenic potential of proteins. Here we present AllerCatPro 2.0, a web server that can be used to predict protein allergenicity potential with better accuracy than other computational methods and new features that help assessors making informed decisions. AllerCatPro 2.0 predicts the similarity between input proteins using both their amino acid sequences and predicted 3D structures towards the most comprehensive datasets of reliable proteins associated with allergenicity. These datasets currently include 4979 protein allergens, 162 low allergenic proteins, and 165 autoimmune allergens with manual expert curation from the databases of WHO/International Union of Immunological Societies (IUIS), Comprehensive Protein Allergen Resource (COMPARE), Food Allergy Research and Resource Program (FARRP), UniProtKB and Allergome. Various examples of profilins, autoimmune allergens, low allergenic proteins, very large proteins, and nucleotide input sequences showcase the utility of AllerCatPro 2.0 for predicting protein allergenicity potential. The AllerCatPro 2.0 web server is freely accessible at https://allercatpro.bii.a-star.edu.sg., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Common recommendations for tattoo aftercare to ensure proper healing include application of topical products. Little is known about tattoo aftercare products., Methods: Tattoo aftercare products were identified from a previous study and a search on Amazon.com using the phrase "tattoo aftercare." Duplicates and products without complete ingredient lists were excluded. Marketing claims were tabulated. All ingredients were entered in Excel and grouped according to Contact Allergen Management Program categories. Comparison of ingredients to North American Contact Dermatitis Group (NACDG) screening and American Contact Dermatitis Society (ACDS) Core allergens was conducted., Results: A total of 84 tattoo aftercare products from 52 distinct brands were found. Forty-eight distinctive market claims were identified; the use of "natural ingredient(s)" (42.9%) was most common. There were 4 to 28 ingredients per product (mean = 11.8 ± 5.5) with a total of 369 distinct ingredients listed. Products contained an average of 7.9 ± 3.9 ACDS Core allergens per product and 7.0 ± 3.7 NACDG allergens per product. Most common allergens included fragrance/botanicals (n = 529), vitamin E derivatives (n = 43), and vitamin B5 derivatives (n = 11)., Conclusions: This review of 84 products found that tattoo aftercare products contain an average of 8 ACDS Core and 7 NACDG allergens. Clinicians should be aware of potential allergens in tattoo aftercare products., Competing Interests: The authors have no funding or conflicts of interest to declare. This material is the result of work supported with resources and the use of facilities at the Minneapolis Veterans Affairs Medical Center. The contents do not represent the views of the US Department of Veterans Affairs or the US Government., (Copyright © 2020 American Contact Dermatitis Society. All Rights Reserved.)

Competing Interests: The authors have no conflicts of interest to declare.

Background: The usefulness of using patient's own products in patch tests for the diagnosis of allergic contact eczema is well known. However, most of the literature is based on case series published decades ago, and they are focused on cosmetics and fragrances., Objective: The aim of the study was to evaluate the usefulness of using patient's own products in patch tests for the diagnosis of contact eczema in a contact dermatitis unit, describing the most frequently positive own products, as well as the most frequently responsible allergens., Methods: In a 17-year period, 3514 patients were patch tested in our department. In 2429 patients, patch testing with the patients' own products was performed., Results: We found that 363 patients (10.33%) reacted to their own products. In 131 cases (3.81%), reacting to their own product was the only clue for detecting the responsible allergen for allergic contact eczema. Most reactions were found for topical medications, moisturizers, and adhesives. Fragrance mix I, methylchloroisothiazolinone/methylisothiazolinone, ketoprofen, and colophony were found to be the allergens most often responsible., Conclusions: It is essential to include patient's own products in the study of allergic contact eczema to make a correct diagnosis. In our series, 3.81% of the patients would not have been correctly diagnosed if their own products had not been included in patch tests., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2020 American Contact Dermatitis Society. All Rights Reserved.)

Contact dermatitis linked to cosmetic products is a very common reason for visits to the dermatologist, and in more than half the cases, it is due to an allergic reaction. Fragrances are most often the culprit. The aim of the study was to describe the common fragrance allergens in different categories of cosmetic products available on the European market. We wanted to assess the influence of cosmetic type and distribution channel on the presence of fragrance allergens. There are the allergens whose concentration exceeds 0.001% in leave-on products and 0.01% in rinse-off products. A total of 2044 commercial hygiene, care, and makeup cosmetic products were analyzed to specifically study regulated fragrance allergens. The influence that the product category and its distribution channel (retail stores and specialized stores such as beauty institutes or hairdressers and pharmacy) have on the prevalence of these allergens was evaluated. The Kruskal-Wallis test has been used for statistical data analysis. There is a wide range of fragrance allergens, the most common being limonene (found in about 30% of products tested), linalool (just over a quarter of the products tested), and benzyl alcohol (approximately 16% of the products tested). The average number of allergens found and their nature varies depending on the type of product in question (maximum number for shampoos and oral care with about 70 allergens and minimum number for nail polish and makeup for eyes with fewer than 10 allergens). In the area of hygiene, deodorants and oral hygiene products are particularly noteworthy, the former for their significantly high number of allergens and the latter for their low number. There is also a significant difference between the number of allergens found in eye makeup and foundations. Our results indicate that the number of regulated fragrance allergens is particularly influenced by the type of products.

Background: Patients with allergic contact dermatitis rely on ingredient lists published in databases and by online retailers to find safe skincare products., Objective: The aim of this study was to determine the accuracy of product ingredient labeling by comparing drugstore product labels to ingredient lists published online., Methods: Amazon was queried for best-selling items in several categories of skincare, generating a list of 93 products. These products were then found at a local Target and Walgreens and online on Contact Allergen Management Program, SkinSAFE, and Consumer Product Information Database. Drugstore product labels were compared with online ingredient lists and analyzed for discrepancies., Results: There were 31 occurrences in which an allergen listed in the 2017 American Contact Dermatitis Society Core Allergen Series was omitted (present on the in-store label but missing from an online list.) Seven omissions occurred on Contact Allergen Management Program, 11 occurred on SkinSAFE, 5 occurred on Consumer Product Information Database, and 8 occurred on Amazon., Conclusions: Definitive treatment of allergic contact dermatitis is avoidance of allergens found on patch testing. These data suggest that patients may be at risk of inadvertent exposure to allergens from products, which are supposedly deemed safe according to online ingredient lists.

Background: Allergic contact dermatitis (ACD) has become more frequent in children. The prevalence of contact sensitization varies with respect to age, sex, and geographic localization., Objective: The aim of the study was to investigate the experience of a tertiary health center regarding the patch test results of contact sensitization in children without atopic dermatitis., Methods: This is a retrospective review of 89 children (30 boys and 59 girls) who were aged between 3 and 18 years and who were diagnosed with ACD between July 2013 and July 2017. Children with a known history of atopic dermatitis were excluded. All patients were tested with the TRUE (Thin-layer Rapid Use Epicutaneous) test series., Results: The most frequently determined allergens by TRUE test were methylchloroisothiazolinone (n = 7 [16.3%]), disperse blue 106 (n = 5 [11.6%]), and bacitracin (n = 5 [11.6%]). Formaldehyde-related allergens produced 15 positives., Conclusions: Preservatives, such as methylchloroisothiazolinone, formaldehyde, and formaldehyde releasers, emerge as the most frequent allergens in children who undergo patch testing because of ACD. This finding might be attributed to the increase in the utilization of these chemical compounds in personal hygiene products for children.

Background: There is currently no agreed cosmetic series for use across Europe., Objectives: To establish allergens currently tested in local and national cosmetic series., Method: Members of the European Surveillance System on Contact Allergy and the European Cooperation in Science and Technology project TD1206 ("StanDerm") were surveyed to establish their current practice., Results: A wide range of allergens was tested but there was significant variation between centres on the allergens considered to be important in screening for allergy to cosmetics. The number of allergens tested in addition to the baseline series varied between 2 and 50., Conclusions: There is a need for further investigation to establish the frequency and relevance of reactions to cosmetic allergens to enable an agreed evidence-based cosmetic series to be produced. Criteria for inclusion need to be established., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Limonene is a fragrance widely used in cosmetics and household products. Until recently, contact allergy to limonene was considered rare because positive patch tests to it were infrequently observed. In recent years, however, it has been demonstrated that exposure of limonene to oxygen (air) results in the formation of a number of oxidation products, of which the hydroperoxides have a far stronger sensitizing potency than the pure compound. By routine testing of patients suspected of contact dermatitis with hydroperoxides of limonene, high frequencies of positive reactions were found, indicating that these chemicals are important fragrance allergens. It should be realized, however, that a number of "positive" reactions may well be false-positive, irritant responses.

Background: (Meth)acrylates are potent sensitizers and a common cause of allergic contact dermatitis (ACD). The frequency of (meth)acrylate ACD has increased with soaring demand for acrylic nails. A preliminary audit has suggested a significant rate of positive patch tests to (meth)acrylates using aimed testing in patients providing a clear history of exposure. To date, (meth)acrylates have not been routinely tested in the baseline patch test series in the U.K. and Europe., Objectives: To determine whether inclusion of 2-hydroxyethyl methacrylate (2-HEMA) 2% in petrolatum (pet.) in the baseline series detects cases of treatable (meth)acrylate ACD., Methods: During 2016-2017, 15 U.K. dermatology centres included 2-HEMA in the extended baseline patch test series. Patients with a history of (meth)acrylate exposure, or who tested positive to 2-HEMA, were selectively tested with a short series of eight (meth)acrylate allergens., Results: In total 5920 patients were consecutively patch tested with the baseline series, of whom 669 were also tested with the (meth)acrylate series. Overall, 102 of 5920 (1·7%) tested positive to 2-HEMA and 140 (2·4%) to at least one (meth)acrylate. Had 2-HEMA been excluded from the baseline series, (meth)acrylate allergy would have been missed in 36 of 5920 (0·6% of all patients). The top (meth)acrylates eliciting a positive reaction were 2-HEMA (n = 102, 1·7%), 2-hydroxypropyl methacrylate (n = 61, 1·0%) and 2-hydroxyethyl acrylate (n = 57, 1·0%)., Conclusions: We recommend that 2-HEMA 2% pet. be added to the British baseline patch test series. We also suggest a standardized short (meth)acrylate series, which is likely to detect most cases of (meth)acrylate allergy., (© 2019 British Association of Dermatologists.)

Background: Nail polish is known to contain potentially hazardous chemicals that have been linked to adverse health effects after overexposure. Formaldehyde is used as an antimicrobial, preservative, and nail hardener in select nail products, yet it is a recognized carcinogen and potent allergen in allergic contact dermatitis., Objective: The aim of this study was to investigate whether formaldehyde is present in nail polishes marketed as formaldehyde-free., Methods: Twenty-nine cosmetic nail polishes were purchased for analysis; of these, 28 were advertised as formaldehyde-free and/or did not declare formaldehyde in their ingredient lists. Initial testing was pursued using the chromotropic acid method, which uses a red-purple color change to indicate the presence of formaldehyde. Products were subsequently analyzed at least twice using high-performance liquid chromatography, quantifying formaldehyde amount above the detection limit of 2 ppm., Conclusions: High-performance liquid chromatography analysis found 5 of 29 products containing formaldehyde, 4 of which were advertised as formaldehyde-free. All other products were negative for formaldehyde (<2 ppm). Further investigation is warranted among brands testing positive and whether multiple products within the same line contain formaldehyde. Nail products must be labeled appropriately to avoid adverse reactions among individuals with cutaneous sensitivities.

Introduction: Cosmetic products contain a wide range of chemicals to which we are exposed every day. The aim of the study was to determine the presence of potential dangerous substances which can cause adverse health effects by examining product labels., Materials and Methods: A total of 283 products were collected from various shops in Lecce (Italy) and divided into 3 categories: rinse-off, leave-on and make-up. The label of every product was examined and a list including fragrances, preservatives and other chemicals of concern was created., Results: Fragrances were present in 52.3% of the examined products, mostly limonene (76.9%) and linalool (64.6%) but also citronellol (34.1%), geraniol (31.5%), coumarin (30%) and hexyl cinnamal (29.2%). Preservatives showed a rate of 60% and the most frequently identified were phenoxyethanol (48.7%), sodium benzoate (35.6%), potassium sorbate (22%), methylparaben (15.2%) and MI/MCI (9.9%). The other chemicals of concern were detected in 58% of products; included PEGs (62.3%), acrylate copolymer (34%), petrolatum (17.2%), polysorbates (14,8%), BHT (14.7%), ethylhextyl methoxycinnamate (13.6%), benzophenone-1 (3.7%), benzophenone-3 (4.9%), BHA (1.6%), cocamide DEA and toluene (1.2%)., Conclusions: The use of many of these substances is allowed within certain limits, due to their toxicity at higher concentrations. Other important aspects should be considered as, for instance, the possibility of long-term effects. On the other hand, other substances may induce several acute adverse side-effects, i.e. contact dermatitis and allergic reactions. For these reasons, an enhancement of the criteria used for cosmetics formulation is required since many chemicals used singularly or combined are potentially unsafe.

Consumer products and topical medications today contain many allergens that can cause a reaction on the skin known as allergic contact dermatitis. This review looks at various allergens in these products and reports current allergic contact dermatitis incidence and trends in North America, Europe, and Asia. First, medication contact allergy to corticosteroids will be discussed along with its five structural classes (A, B, C, D1, D2) and their steroid test compounds (tixocortol-21-pivalate, triamcinolone acetonide, budesonide, clobetasol-17-propionate, hydrocortisone-17-butyrate). Cross-reactivities between the steroid classes will also be examined. Next, estrogen and testosterone transdermal therapeutic systems, local anesthetic (benzocaine, lidocaine, pramoxine, dyclonine) antihistamines (piperazine, ethanolamine, propylamine, phenothiazine, piperidine, and pyrrolidine), topical antibiotics (neomycin, spectinomycin, bacitracin, mupirocin), and sunscreen are evaluated for their potential to cause contact dermatitis and cross-reactivities. Finally, we examine the ingredients in the excipients of these products, such as the formaldehyde releasers (quaternium-15, 2-bromo-2-nitropropane-1,3 diol, diazolidinyl urea, imidazolidinyl urea, DMDM hydantoin), the non-formaldehyde releasers (isothiazolinones, parabens, methyldibromo glutaronitrile, iodopropynyl butylcarbamate, and thimerosal), fragrance mixes, and Myroxylon pereirae (Balsam of Peru) for contact allergy incidence and prevalence. Furthermore, strategies, recommendations, and two online tools (SkinSAFE and the Contact Allergen Management Program) on how to avoid these allergens in commercial skin care products will be discussed at the end.

Purpose of Review: The purpose of this review was to explore recent developments in the study of ocular cosmetics, as they pertain to adverse reactions that can be attributed to them., Recent Findings: Immunologically mediated adverse reactions to cosmetics are most commonly the result of sensitization to preservatives, fragrances and dyes used in these products. Metals such as nickel, cobalt, chromium and lead are used in products such as eye shadows and eye liners as well as toy makeup sets in amounts greater than the recommended amount of 1 ppm. Cosmetics make up the majority of fragrance-induced contact dermatitis. Recently, a free smartphone app was developed by American Contact Dermatitis Society that holds promise in better enabling patients to utilize their patch test data while shopping for cosmetics., Summary: Both immediate and delayed hypersensitivity reactions linked to cosmetics are often the result of sensitization to preservatives, fragrances and additives in the products themselves. Despite significant advances in our understanding of these reactions, further research will be necessary to elucidate the mechanisms behind these reactions and bring this knowledge to the bedside as to improve patient care with potential cosmetic-based related allergic disorders.

Background: Personal care products marketed for babies and children are often regarded as "safe" or "gentle." However, little is known about the prevalence of contact allergens in these types of products., Objective: This study assessed the prevalence of important sensitizers in personal care products marketed for babies and children. A secondary objective of this study was to determine whether a product's cost correlates with content of sensitizing ingredients., Methods: The ingredient lists of 533 unique personal care products were analyzed for presence of fragrance, betaines, propylene glycol, methylchloroisothiazolinone, methylisothiazolinone, formaldehyde, lanolin, and neomycin. Price per ounce was determined for each product as well., Conclusions: Most personal care products for babies and children contain 1 or more sensitizers. Products containing more sensitizers tend to cost less than those without any sensitizing ingredients.

Background: Allergic contact dermatitis commonly occurs on the face. Facial cleansing wipes may be an underrecognized source of allergens., Objective: The aim of this study was to determine the frequency of potentially allergenic ingredients in facial wet wipes., Methods: Ingredient lists from name brand and generic facial wipes from 4 large retailers were analyzed., Results: In the 178 facial wipes examined, a total of 485 ingredients were identified (average, 16.7 ingredients per wipe). Excluding botanicals, the top 15 potentially allergenic ingredients were glycerin (64.0%), fragrance (63.5%), phenoxyethanol (53.9%), citric acid (51.1%), disodium EDTA (44.4%), sorbic acid derivatives (39.3%), tocopherol derivatives (38.8%), polyethylene glycol derivatives (32.6%), glyceryl stearate (31.5%), sodium citrate (29.8%), glucosides (27.5%), cetearyl alcohol (25.8%), propylene glycol (25.3%), sodium benzoate (24.2%), and ceteareth-20 (23.6%)/parabens (23.6%). Of note, methylisothiazolinone (2.2%) and methylchloroisothiazolinone (1.1%) were uncommon. The top potential allergens of botanical origin included Aloe barbadensis (41.0%), chamomile extracts (27.0%), tea extracts (21.3%), Cucumis sativus (20.2%), and Hamamelis virginiana (10.7%)., Conclusions: Many potential allergens are present in facial wet wipes, including fragrances, preservatives, botanicals, glucosides, and propylene glycol.

An interspecies sensitization assessment factor (SAF) is used in the quantitative risk assessment (QRA) for skin sensitization when a murine-based NESIL (No Expected Sensitization Induction Level) is taken as point of departure. Several studies showed that, on average, the murine sensitization threshold is in good correspondence with that determined in humans. However, on an individual level, the murine and human sensitization thresholds may differ considerably. In this study, the interspecies SAF was quantified by using a probabilistic approach, to be able to take these cases into account. As expected, the geometric means of the probability distributions of murine and human sensitization threshold ratios were close to one, but taking the 95 th percentile of these distributions resulted in an interspecies SAF of 15. By using this value, one is sure that with 95% probability, the sensitization threshold determined in mice does not underestimate the human threshold. It can be concluded that a murine-based NESIL requires the use of an interspecies SAF (of 15) in the QRA for skin sensitization, to correct for the differences between mice and humans. This empirically derived interspecies SAF contributes to refinement of the risk assessment methodology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The in vitro sensitization assay LCSA (Loose-fit Coculture-based Sensitization Assay) has proved reliable for the detection of contact sensitizers in the past. However, the coculture of human monocyte-derived dendritic cells (DCs) with primary human keratinocytes (KCs) in serum-free medium is relatively complex compared to other sensitization assays which use continuous cell lines. To facilitate high-throughput screening of chemicals, we replaced KCs with the HaCaT cell line under various culture conditions. Coculture of HaCaT with peripheral blood mononuclear cells in serum-supplemented medium leads to generation of CD1a + /CD1c + DCs after addition of GM-CSF, IL-4, and TGF-β1 (as opposed to CD1a - /CD1c - DCs which arise in the "classic" LCSA coculture). These cells resemble monocyte-derived DCs generated in monoculture, but, unlike those, they show a marked upregulation CD86 after treatment with contact allergens. All of the nine sensitizers in this study were correctly identified by CD1a + /CD1c + DCs in coculture with HaCaT. Among the substances were weak contact allergens such as propylparaben (which is false negative in the local lymph node assay in mice) and resorcinol (which was not detected by CD1a - /CD1c - DCs in the "classic" LCSA). The level of CD86 upregulation on CD1a + /CD1c + DCs was higher for most allergens compared to CD1a - /CD1c - DCs, thus improving the assay's discriminatory power. Three out of four non-sensitizers were also correctly assessed by the coculture assay. A false-positive reaction to caprylic (octanoic) acid confirms earlier results that some fatty acids are able to induce CD86 on DC in vitro. In conclusion, change of the LCSA protocol led to reduction of time and cost while even increasing the assay's sensitivity and discriminatory power.

Background: Essential oils are fragrance substances that are labelled on cosmetic products by their INCI names, potentially confusing consumers., Objectives: To establish whether contact allergy to essential oils might be missed if not specifically tested for., Methods: We tested 471 patients with 14 essential oils and 2104 patients with Melaleuca alternifolia oil between January 2008 and June 2014. All patients were tested with fragrance mix I, fragrance mix II, hydroxyisohexyl 3-cyclohexene carboxaldehyde, and Myroxylon pereirae. Three hundred and twenty-six patients were tested with hydroperoxides of limonene and linalool., Results: Thirty-four patients had a +/++/+++ reaction to at least one essential oil. Eleven had no reaction to any of the six marker fragrance substances. Thus, 4 of 11 positive reactions to M. alternifolia oil, 2 of 7 reactions to Cymbopogon flexuosus oil, 1 of 5 reactions to Cananga odorata oil, 3 of 4 reactions to Santalum album oil and 2 of 3 reactions to Mentha piperita oil would have been missed without individual testing., Conclusion: A small number of patients who are allergic to essential oils could be missed if these are not specifically tested. Labelling by INCI names means that exposure may not be obvious. Careful inspection of so-called 'natural' products and targeted testing is recommended., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A new β-cyclodextrin/graphene oxide hybrid material prepared via a chemical covalent interaction and layer-to-layer assembly was developed as a sorbent for the solid-phase microextraction of fragrance allergens. As a result of its ultra-large surface area, large delocalized π-electron system and abundant hydroxyls, the β-cyclodextrin/graphene oxide-coated fiber could be used to extract particular compounds via strong π-π interactions, van der Waals forces and hydrogen bonding interactions. β-Cyclodextrin with a hydrophobic interior cavity and hydrophilic peripheral face was conducive in extracting the fragrances with hydrophobic and hydrophilic groups. Under the optimized extraction and desorption conditions, the β-cyclodextrin/graphene oxide-coated fiber showed acceptable extraction efficiency for hydrophilic and hydrogen-bonding-donating alcohols. Compared with other methods based on different coating fibers, the proposed fiber obtained wide linear ranges for fragrances with correlation coefficients ranging from 0.9921 to 0.9970, and low limits of detection in the range of 0.050-0.150 μg L(-1). The obtained results indicated that the newly developed fiber was a selective, feasible and cost-effective microextraction medium and could be successfully applied for the determination of several fragrances in personal products.

Background: Atopic dermatitis (AD) is the most common inflammatory disease. The prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher in patients with AD, despite a trend toward weaker clinical allergic contact dermatitis reactions. The role of the AD skin phenotype in modulating allergic sensitization to common sensitizers has not been evaluated., Objective: We sought to investigate whether patients with AD have altered tissue immune responses on allergen challenge., Methods: Gene expression and immunohistochemistry studies were performed on biopsy specimens from 10 patients with AD and 14 patients without AD patch tested with common contact allergens (nickel, fragrance, and rubber)., Results: Although 1085 differentially expressed genes (DEGs) were commonly modulated in patch-tested skin from patients with AD and patients without AD versus control skin, 1185 DEGs were uniquely altered in skin from patients without AD, and only 246 DEGs were altered in skin from patients with AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude changes and upregulation of interferon responses were evident only in the non-AD group. Stratification by allergen showed decreased expression of immune, TH1-subset, and TH2-subset genes in nickel-related AD responses, with increased TH17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude. Negative regulators showed higher expression in patients with AD., Conclusions: Through contact sensitization, our study offers new insights into AD. Allergic immune reactions were globally attenuated and differentially polarized in patients with AD, with significant decreases in levels of TH1 products, some increases in levels of TH17 products, and inconsistent upregulation in levels of TH2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased TH2, TH17, and negative regulator levels compared with those seen in non-AD skin., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Most animal experiments on cosmetics safety are prohibited and since March 2013, this obligation includes sensitization tests. However, until now there has been no validated alternative in vitro method. In this work, 400 compounds used in the cosmetic industry were selected to cover the greatest diversity of structures, biological activities and sensitizing potential. These molecules were submitted to a series of tests aimed at reproducing essential steps in sensitization and to distinguish between sensitization and irritations, i.e., transcutaneous permeation (factor A), haptenation (factor B), sensitization cytokines production (factor C) and acute toxicity (factor D). The transcutaneous diffusion was measured on human skin explants using Franz cells. Haptenation was tested in solution on human serum albumin. Sensitization cytokine production was investigated by measurement of interleukin-18 release by keratinocytes. Acute toxicity was determined using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(75) cell viability test. As only sufficiently stable, soluble and detectable compounds are usable, 33, 72, 68 and 68 molecules were finally tested on factors A, B, C and D, respectively, and 32 were completely screened by the four factors. The individual correlation of the four factors with the reference in vivo tests was limited but the combination of these factors led to a correlation between in vivo and in vitro assays of 81.2% and the safety of the test (risk of false negative) reached 96.8%. The techniques employed are simple and inexpensive and this model of four tests appears as a promising technique to evaluate in vitro the skin sensitization potential of unknown molecules., (Copyright © 2014 John Wiley & Sons, Ltd.)

Potential allergenic fragrances are part of the Cosmetic Regulation with labelling and concentration restrictions. This means that they have to be declared on the ingredients list, when their concentration exceeds the labelling limit of 10 ppm or 100 ppm for leave-on or rinse-off cosmetics, respectively. Labelling is important regarding consumer safety. In this way, sensitised people towards fragrances might select their products based on the ingredients list to prevent elicitation of an allergic reaction. It is therefore important to quantify potential allergenic ingredients in cosmetic products. An easy to perform liquid extraction was developed, combined with a new headspace GC-MS method. The latter was capable of analysing 24 volatile allergenic fragrances in complex cosmetic formulations, such as hydrophilic (O/W) and lipophilic (W/O) creams, lotions and gels. This method was successfully validated using the total error approach. The trueness deviations for all components were smaller than 8%, and the expectation tolerance limits did not exceed the acceptance limits of ± 20% at the labelling limit. The current methodology was used to analyse 18 cosmetic samples that were already identified as being illegal on the EU market for containing forbidden skin whitening substances. Our results showed that these cosmetic products also contained undeclared fragrances above the limit value for labelling, which imposes an additional health risk for the consumer., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The use of cosmetics exposes consumers to mixtures of ingredients, many of which are potential allergens. Ultraviolet (UV) filters are used not just in sunscreens, but also in other products. Many UV filters are known contact allergens and photoallergens., Objective: To examine the pattern of co-exposure to UV filters in cosmetics., Methods: A survey of products marketed in Germany, conducted in 2006-2009 by the Chemical and Veterinary Investigation Office in Karlsruhe, identified 4447 products (of all 5667 cosmetic products examined) (i) that were categorizable according to Annex I to the Cosmetics Directive, and (ii) with information on the presence of UV filters or zinc oxide. The occurrence and co-occurrence of UV filters were analysed and presented in tabular and graphical format., Results: UV filters or zinc oxide were present in 22.5% of all 4447 products, ranging from almost 100% in sunscreens to a few per cent in, for example, some hair products; they were absent in two product categories. Frequently, several different UV filters were included in one product, for example in sunscreens (median 4) and in perfumes (median 3). The overall most frequent UV filters were butyl methoxydibenzoylmethane and titanium dioxide, combined mostly with octocrylene in sunscreens and with ethylhexyl methoxycinnamate in creams., Conclusions: The frequent co-occurrence of UV filters in cosmetic products possibly facilitates sensitization, and may explain why patients often react to chemically unrelated UV filters., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The use of cosmetics exposes consumers to mixtures of ingredients, many of which are potential allergens. Many cosmetics contain one or several preservatives, some being important contact allergens., Objective: To examine the pattern of co-exposure to preservatives in different categories of cosmetics., Methods: A survey of products marketed in Germany, conducted in 2006-2009 by the Chemical and Veterinary Investigation Office in Karlsruhe, identified 4680 products categorizable according to Annex I to the Cosmetics Directive with information on the presence of preservatives. The occurrence and co-occurrence of preservatives were analysed and presented in tabular and graphical format., Results: Thirty per cent of all products were not declared to contain any preservatives; for 8%, no INCI labelling was present. For the remainder, the number of preservatives used tended to be higher in leave-on than in rinse-off products. Most often, combinations of (up to all five) parabens were used (39% of all products). Combinations with phenoxyethanol were also frequent. Formaldehyde releasers were found in 8% of products overall., Conclusions: The pattern of co-exposure to preservatives in important categories of cosmetic products illustrates the 'cocktail' of allergens that may facilitate sensitization, although, conversely, the combination of preservatives allows individual use levels to be kept lower, thereby possibly reducing sensitization risk., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A micellar electrokinetic chromatography method was developed for determination of 15 suspected fragrance allergens and preservatives. The target compounds are widely used as ingredients in many personal care products, and all of them are included in the European Regulation concerning cosmetic products. The method was optimized by using a central composite experimental design and response surface methodology. A modified chromatographic response function was defined to weigh the terms in the response function adequately. After optimization of experimental conditions, a background electrolyte of 100 mM sodium dodecyl sulphate and 24 mM sodium tetraborate and pH 9.0 was selected for the separation of the analytes. The developed methodology was evaluated in terms of linearity, limits of detection and quantification, precision and accuracy, showing appropriate values (i.e., R (2) = ≥0.99 and accuracy of 89-115 %). Finally, applicability of the micellar electrokinetic chromatography method was assessed by successfully quantifying fragrance allergens and preservatives in commercial personal care products. The most commonly found analyte was linalool (48.3 % of samples) followed by benzoic acid (37.6 %). All samples contained at least one of the target compounds, thus confirming the ubiquity of fragrance allergens and preservatives in personal care products.

In Japan, two patients who had been primary sensitized to hydrolyzed wheat protein (HWP) present in facial soap and subsequently experienced wheat-dependent exercise-induced anaphylaxis (WDEIA) after the ingestion of normal wheat products were reported in 2009 as first cases. Since that report, more than 1900 patients with such an allergy have been reported (through June 20, 2013) from various institutes all around Japan. Importantly, the majority of the patients used the same facial soap (Cha no Shizuku(®)) containing acid-hydrolyzed wheat protein (acid-HWP). The commercial acid-HWP contained in the facial soap (Glupearl 19S(®), average molecular weight of 30-50 kDa) was produced from gluten after partial hydrolysis with hydrogen chloride at 95℃ for 40 minutes. In this presentation, I would like to summarize the mechanism of the induction of immediate hypersensitivity by HWP which has been reported by us and other European groups.

Suspected fragrance allergens were determined in cosmetic products using a combination of full evaporation-dynamic headspace (FEDHS) with selectable one-dimensional/two-dimensional GC-MS. The full evaporation dynamic headspace approach allows the non-discriminating extraction and injection of both apolar and polar fragrance compounds, without contamination of the analytical system by high molecular weight non-volatile matrix compounds. The method can be applied to all classes of cosmetic samples, including water containing matrices such as shower gels or body creams. In combination with selectable (1)D/(2)D GC-MS, consisting of a dedicated heart-cutting GC-MS configuration using capillary flow technology (CFT) and low thermal mass GC (LTM-GC), a highly flexible and easy-to-use analytical solution is offered. Depending on the complexity of the perfume fraction, analyses can be performed in one-dimensional GC-MS mode or in heart-cutting two-dimensional GC-MS mode, without the need of hardware reconfiguration. The two-dimensional mode with independent temperature control of the first and second dimension column is especially useful to confirm the presence of detected allergen compounds when mass spectral deconvolution is not possible., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The preservative methylchloroisothiazolinone (MCI)/methylisothiazo- linone (MI) is an important allergen, and has thus been subject to regulation in some areas of exposure, mainly in cosmetics., Objectives: To examine whether a decline in sensitization prevalence and intensity of elicitation (by the patch test) can be observed, either overall, or in certain subgroups defined by causative exposures., Methods: On the basis of long-term contact allergy surveillance data collected by the Information Network of Departments of Dermatology (www.ivkd.org), 1992-2010, in the course of 171 883 consultations, the time trend of (different grades of) positive patch test reactions to MCI/MI (0.01% aqua) was examined in an age-stratified analysis., Results: The overall frequency of positive patch test reactions was 2.33% (95% confidence interval 2.26-2.4%). No significant overall trend of positive reactions or of the distribution of +, ++ and + + + reactions (p > 0.05) was observed, similarly to what was found for patients in whom cosmetics were recorded as causative exposure (p = 0.55). In contrast, in patients with occupational contact dermatitis who were < 40 years of age, a significant increase in prevalence, by 0.87 percentage points per decade, was identified (p = 0.018)., Conclusions: Both applications of MCI/MI, cosmetic and industrial, should be the target of further preventive efforts., (© 2012 John Wiley & Sons A/S.)

Octocrylene is an organic UV filter, commonly used in sunscreens and cosmetics, which can give rise to both contact and photocontact allergy. Our aim was to investigate octocrylene's interaction with amino acid analogs in the presence of UV radiation to better understand the reason for octocrylene's photoallergenic capacity. The amino acid analogs were photolysed in presence and absence of octocrylene for 1 h in cyclohexane. The rate of degradation was considerably slower for all amino acid analogs when octocrylene was present in the mixture. Benzylamine, the lysine analog, did react with octocrylene during the photolysis and the corresponding amide was formed in an acylation reaction. By varying the benzylamine concentration and keeping the octocrylene concentration fixed the reaction rate was shown to be independent of the amine concentration. The same type of acylation reaction took place when octocrylene alone was photolysed in ethanol in which the ethyl ester was formed from octocrylene and ethanol. Our results suggest that octocrylene's ability to cause photocontact allergy could be due to its photoinduced reactivity toward primary amines and alcohols., (© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.)

Background: Contact dermatitis to cosmetics is a common dermatosis, especially in adults and professionals who handle them., Objective: The objective of this study was to evaluate the frequency of sensitization to cosmetics' components in patients with suspected allergic contact dermatitis and to identify the main sensitizers related to occupational contact dermatitis., Methods: During the period of January 2008 to June 2010, all the patients with a presumptive diagnosis of allergic contact dermatitis to cosmetics were selected. The patients were submitted to the patch tests of cosmetics series, composed by ten substances., Results: Among the 147 patients studied sensitization to cosmetics components occurred in 31,29% of the cases, 14 of those (19,18%) equally corresponding to BHT and triethanolamine substances, 13 (17,81%) to ammonium thioglycolate, 09 to sorbic acid (12,33%), 08 to tosilamida (10,95%), 06 to germall (8,22%). The other elements tested showed indices of 5% or less. A higher frequency of contact dermatitis to cosmetics was observed in women and the age most affected was concordant with the age range of greatest professional activity of the population., Conclusion: Allergic contact dermatitis was more frequently associated with Triethanolamine, BHT and ammonium thioglycolate, and the relation with occupational contact dermatitis was discreet.

Objectives: Reports about the nature of the ingredients responsible for allergic contact dermatitis caused by specific cosmetic products are scarce., Methods: Between January 2000 and December 2010, the specific cosmetic products having caused allergic contact dermatitis, as well as the individual allergenic cosmetic ingredients present in them, were recorded by use of a standardized form., Results: Among 11 different categories of cosmetic product, skin care products, followed by hair care and body-cleansing products, were most often involved. The presence of the allergenic ingredient(s) in a specific cosmetic product was confirmed according to the ingredient label in 959 of 1448 records. Six hundred and twenty-one of 959 concerned non-fragrance components, preservatives being responsible for 58% of them. Reactions to formaldehyde and formaldehyde-releasers were most often correlated with body-cleansing products, particularly 2-bromo-2-nitropropane-1,3-diol and skin care products. They were followed by the methylchloroisothiazolinone/methylisothiazolinone mixture, most frequently found as allergens in hair care and intimate hygiene products, and facial cleansers (in the last category together with diazolidinyl urea). Octocrylene was by far the most frequent (photo)allergen in sun care products., Conclusions: This study provides information on the presence and frequency of allergens in specific causal cosmetic products., (© 2011 John Wiley & Sons A/S.)

Previous publications investigated different data treatment strategies for quantification of volatile suspected allergens by GC/MS. This publication presents the validation results obtained on "ready to inject" samples under reproducibility conditions following inter-laboratory ring-testing. The approach is based on the monitoring of three selected ions per analyte using two different GC capillary columns. To aid the analysts a decisional tree is used for guidance during the interpretation of the analytical results. The method is evaluated using a fragrance oil concentrate spiked with all suspected allergens to mimic the difficulty of a real sample extract or perfume oil. At the concentrations of 10 and 100mg/kg, imposed by Directive 76/768/EEC for labeling of leave-on and rinse-off cosmetics, the mean bias is +14% and -4%, respectively. The method is linear for all analytes, and the prediction intervals for each analyte have been determined. To speed up the analyst's task, an automated data treatment is also proposed. The method mean bias is slightly shifted towards negative values, but the method prediction intervals are close to that resulting from the decisional tree., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC)-Lyral® is a widely used synthetic fragrance found in personal care and household products. It is an aldehyde, lipophilic enough to penetrate the skin and is a frequent cause of contact sensitization., Objective: Describe the frequency of contact allergy to HICC in a Contact Dermatitis Unit, after its inclusion in baseline patch test series., Methods: A retrospective study including all patients submitted to patch test, from January 2007 to December 2009., Results: Over a 3-year period, 629 consecutive patients were patch tested. The frequency of positive reactions to HICC was 2.7% (17/629). Of the positive patients, 35% (6/17) gave a history of atopy, 58.8% (10/17) had eczema on the face and neck, 23.5% (4/17) on the hands, 23.5% (4/17) in the axillae, 17.6% (3/17) on the trunk and 6% (3/17) had generalized eczema. All patients were patch positive for more than one allergen: all (17/17) positive to fragrance Mix 2 (FM2); 47% of the patients (8/17) positive to fragrance Mix 1 (FM1); and 23.5% of the patients (4/17) positive to Balsam of Peru. In 94% (16/17) of cases, the reaction was judged to be of current relevance., Discussion: The frequency of positive reactions to HICC of 2.7% found in our population is according to what is described in several European reports, where HICC is still widely used as a fragrance ingredient. In contrast, in North America, the prevalence is lower. All the patients were positive also to FM2. The association found between reactions to FM1 and HICC is also commonly reported and could represent a concomitant sensitization following increased exposure to fragrance allergens. These data confirm the importance of HICC introduction in the baseline patch test series.

Human skin is exposed to a large variety of cosmetic allergens. Most allergic contact dermatitis occurs after exposure to fragrance, preservatives, and hair dyes. Such reactions can often be occult. As a result, a high index of suspicion is needed in assessing the patient with facial or cosmetic dermatitis. This contribution looks at why such a large number of chemicals are in everyday usage, at how dermatologists monitor trends in allergy to cosmetics, and at a number of new and emerging allergens to consider in the assessment of suspected cosmetic allergy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Together with preservative agents, fragrance components are the most important sensitizing culprits in cosmetic products., Objectives: To identify the nature of the fragrance ingredients responsible for allergic contact dermatitis (ACD) from specific cosmetic products., Methods: Between 2000 and 2009, positive patch test reactions or positive usage tests with the patients' own cosmetic products, were recorded using a standardised form., Results: Of the 806 cosmetic records, corresponding to 485 patient files, 344 concerned reactions to fragrance ingredients that according to the label were present ('Presence Confirmed' [PC n = 301]) or suspected to be present ('Presence Not Confirmed' [PNC n = 376]) in the causal cosmetic products used, which belonged to 15 different categories, toilet waters/fine perfumes being the most frequent. Geraniol in fragrance mix I (FM I) and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) in FM II were the most frequent PC, and together with hydroxycitronellal and Evernia prunastri (oak moss) the most frequent PNC ingredients in the causal cosmetic products. Limonene was the most frequent PC confirmed fragrance allergen., Conclusions: This study not only underlines the usefulness of fragrance-ingredient labelling in order to identify the causal allergen(s) present in specific cosmetic products, but may also provide information on trends in the actual use of sensitizing fragrance ingredients in them., (© 2011 John Wiley & Sons A/S.)

Majantol is a synthetic fragrance with an intensely floral, slightly fruity, and amber scent used in perfumes, cosmetics, and personal hygiene products. It has recently been identified as yet another fragrance contact allergen, with relatively high rates of sensitization. Majantol is not included in fragrance mix I or fragrance mix II, which are common patch-test screening chemicals for fragrance allergy. Moreover, because it is only a supplement to the North American series, there is a paucity of published data on the prevalence of contact allergy to this substance. Patch testing with Majantol could be useful in patients with suspected or proven contact allergy to fragrances; however, avoidance would be challenging, given that Majantol is unlikely to be listed specifically on the product label.

A mixture of 18 neutral UV-active compounds with different characteristics of polarity was determined by capillary electrophoresis using a pseudostationary phase constituted by a microemulsion. The test analytes were volatile fragrance compounds, included in a list of 24 chemicals classified as suspected allergens according to Directive 2003/15/CE. The considered compounds were detected at 195 nm and p-anisaldehyde was chosen as internal standard. The background electrolyte consisted of a standard microemulsion made of 90.95% 10mM borax buffer, pH 9.2, 1.05% n-heptane, 8.00% SDS/n-butanol in 1:2 ratio, to which 40 mM methyl-β-cyclodextrin was added. Temperature and voltage were set at 20 °C and 25 kV, respectively. These experimental conditions allowed separation of the compounds to be obtained in about 20 min. The method was applied to real samples made up of rinse-off scented products. The results obtained using the standard microemulsion as pseudostationary phase showed its high resolution power, capable of effectively separating a complex mixture of analytes. Microemulsion electrokinetic chromatography was confirmed to have a great potential for different analytical challenges, holding up the possibility of using this technique as a good and complementary alternative to HPLC methods for routine analysis., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Some fragrance compounds are severe contact allergens. According to the so-called "26 allergens rule" (Article 1 (10) of Directive 2003/15/EC) (EC, 2003), 26 supposedly allergenic fragrances must be listed on the containers of cosmetics products if they are present above certain mass percentages in the product. This declaration is meant to inform the consumer of potential risks of skin sensitizers in the products., Objective: The objective of this paper is to validate whether "the 26 allergens rule" meets the expectations to improve consumer protection., Methods: The method used for this validation was on one hand a reflection on the elements of the approach used in "the 26 allergens rule" and on the other hand a product analysis of 742 products by 4 large producers of cosmetic products on the German market., Results: It was found that more than 50% of these cosmetic and washing and cleansing products contain at least one of the 26 substances above the thresholds for labelling and that there are 14% of all products which contain strong allergens. Many consumers apparently still buy these products. The indirect effect that producers reduce the amounts of these fragrances to avoid declaration seems to be small., Discussion and Recommendations: Several arguments were assembled which show that other instruments are needed to ensure consumer protection or protection of the environment. This paper recommends different approaches. The use of a list of single substances in such a directive is not in line with scientific standards. It is recommended to base decision making on comprehensive risk assessments or at least on valid and strong criteria. More parameters need to be involved, not only contact allergy. As illustrated in this article, the roles taken over by authorities and manufacturers in risk management of the "26 allergens" are relatively small compared with the responsibility carried by consumers. However, consumers are only able to take over their part properly if they are sufficiently trained and have the necessary infrastructure, capability and time to inform themselves. Regulations are not effective if they load the major responsibility for risk management on consumers, instead of on authorities and manufacturers. A successful risk management would include bans and restrictions of especially hazardous substances issued by governments, as well as efficient surveys to control the implementation of regulations by the responsible authorities. It would also include that producers meet the legal standards and take over voluntary action to make products safer. The evaluation of "the 26 allergens rule" is an example which can be transferred to other regulations and which could help to improve future regulatory approaches, with a focus on the roles authorities, manufacturers and consumers play in a promising risk management., (Copyright 2010 Elsevier GmbH. All rights reserved.)