[Show abstract][Hide abstract] ABSTRACT: Background
In recent years, the prevalence of contact allergy to the preservative methylisothiazolinone (MI) has increased dramatically. Cosmetic products are one of the major sources of exposure.Objectives
To examine whether allowed concentrations of MI in cosmetic rinse-off products have the potential to cause allergic contact dermatitis.Materials/methods19 MI-allergic subjects and 19 controls without MI allergy applied 2 liquid hand soaps five times per day on areas of 5*10 cm2 on the ventral side of their forearms. One soap contained 100 ppm MI, the maximum allowed concentration in cosmetics, and was used by 10 allergic subjects and all controls. Another liquid soap with 50 ppm MI was used by 9 allergic subjects. As the negative control, all subjects used a similar soap that did not contain MI. The repeated open applications (ROAT) proceeded until a positive reaction occurred or up to 21 days. The study was conducted in a randomized and blinded fashion.Results10 out of 10 MI-allergic subjects developed positive reactions to the soap with 100 ppm and 7 out of 9 reacted to the 50 ppm soap, while none of the 19 controls had a positive reaction during 21 days of application. No reactivity was seen to the soap without MI. The difference in reactivity to MI between MI-allergic subjects and controls was statistically significant (Fisher's exact test, p˂0.0001).Conclusions
Rinse-off products preserved with 50 ppm MI or more are not safe for consumers. No safe level has yet been identified.This article is protected by copyright. All rights reserved.
British Journal of Dermatology 02/2015; 173(1). DOI:10.1111/bjd.13751 · 4.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Contact allergy prevalence rates change over time as a result of variations in allergen exposure. Data from patch test clinics are often used as markers for allergy trends.Objectives
The aim of the present retrospective study was to describe trends in rates of sensitization to allergens in the Swedish baseline series.Patients/materials/methodsPrevalence rates are described by comparing consecutive patch test data from 1992, 2000 and 2009 in Swedish patch test clinics. In total, 3680 patients were included in 1992, 3825 in 2000, and 3112 in 2009.ResultsAmong test substances with a sensitization rate above 2% in 2009, significant decreases were noted for nickel sulfate, cobalt chloride, colophonium, and methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI), and a significant increase for p-phenylenediamine, as compared with 1992. Potassium dichromate reactions had increased among younger women, whereas reactions to nickel and cobalt had decreased in this group. Sensitization to chromium, cobalt and fragrance mix I had decreased among older men, and sensitization to nickel had decreased among younger men.Conclusions
It is probable that these changes in 1992–2009 reflect both changes in regulations for nickel, lower levels of chromium in cement and of MCI/MI in cosmetics, and increasing use of hair dyes.
[Show abstract][Hide abstract] ABSTRACT: The preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) is a well-known sensitiser and present in the Swedish baseline series since the 1980s. The proportions of MCI/MI are 3:1. MI alone has been used as a preservative since less than 10 years. This study was conducted on behalf of the Swedish Contact Dermatitis Research Group to evaluate inclusion of MI in the Swedish baseline series since the preparation of MCI/MI might fail to detect contact-allergic reactions to MI alone. Patients with suspected allergic contact dermatitis at 5 Swedish dermatology departments were consecutively patch tested with MI 2,000 ppm aq and MCI/MI 200 ppm aq. The number of cases with exclusive contact allergy to MI varied between 0.8-4.2%. In total, 1.9% reacted exclusively to MI and not to MCI/MI. Due to the considerable frequency of contact allergy to MI not traced by MCI/MI, MI 2,000 ppm aq is included in the Swedish baseline series from January 2014. This corresponds to a dose of 60 μg/cm2.
[Show abstract][Hide abstract] ABSTRACT: Background
Omeprazole is a proton pump inhibitor for the treatment of gastric acid-related disorders. In recent years, reports of dermatitis upon exposure to omeprazole during manufacture have been noted.Objective
To present diagnostic findings in workers who reported suspected hypersensitivity reactions resulting from occupational exposure to omeprazole.Methods
Ninety-six workers exposed to omeprazole during the manufacturing process underwent investigation by the AstraZeneca Occupational Health Centre (Södertälje, Sweden) for suspected allergy. All subjects underwent a lymphocyte transformation test (LTT) and a skin test within 6 months of the clinical reaction. Predictive tests on guinea-pigs were conducted to establish omeprazole's sensitizing potential.ResultsThirty-one subjects with clinical symptoms had a positive LTT result. Twenty-eight subjects had positive patch test results; of these, 23 also had a positive LTT result (sensitivity of the LTT: 82%). Fifty-six subjects had negative patch test results; 46 of these had a negative LTT result (specificity: 82%). All subjects who underwent prick testing (n = 18) had negative results. Delayed contact hypersensitivity was observed in 18 of 20 test animals.Conclusions
These findings confirm the risk of sensitization to omeprazole from occupational exposure. They are of importance for the development of new formulations of omeprazole, or its enantiomers, in light of the potential for inducing skin allergy.
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Disperse dyes, which are used for colouring synthetic textile fibres, are well-known contact sensitisers. To investigate the outcome of patch-testing with a textile dye mix (TDM) at 7 dermatology clinics in Sweden, a TDM tested at 2 concentrations was included into the baseline series during one year. The mix consisted of Disperse (D) Blue 35, D Yellow 3, D Orange 1 and 3, D Red 1 and 17, all 1.0%, and D Blue 106 and D Blue 124, each 0.3% in the mix 6.6% and 1.0% each in the mix 8.0%. In 2,122 tested patients, contact allergy to the TDM at the concentration 8.0% was found in 2.8% and to the TDM at 6.6% in 2.5% of the patients. The contact allergy to the TDM could explain or contribute to the dermatitis in about 35% of the patients.
contact allergy to the TDM is common and inclusion into the Swedish baseline series should be considered.
[Show abstract][Hide abstract] ABSTRACT: In a multicentre study consecutively patch-tested dermatitis patients were tested simultaneously with 1.0% and 2.0% (w/v) formaldehyde in aqua applied with a micropipette (15 µl) to the filter paper disc in Finn Chambers (0.30 mg/cm2 and 0.60 mg/cm2, respectively). A total of 2,122 dermatitis patients were patch-tested. In all, 77 (3.6%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 35 reacted to both concentrations and 5 patients reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde with 2.0% compared to 1.0% (p < 0.001) without causing more irritant reactions. The detected number of isolated allergic reactions to the 2 formaldehyde-releasers in the Swedish baseline series and not to formaldehyde itself raises the question whether quaternium-15 1.0% and diazolidinyl urea 2.0% should be present in the Swedish baseline series.
[Show abstract][Hide abstract] ABSTRACT: According to EU legislation, 26 fragrance substance allergens must be labelled on cosmetic products. For 12 of them, the optimal patch test concentration/dose has not been evaluated.
To establish the optimal patch test doses in mg/cm2 for the 12 fragrance substances that are not included in fragrance mix I or II in the European baseline patch test series.
Patch testing with the 12 fragrance substances was performed in a stepwise manner encompassing up to five rounds in at least 100 dermatitis patients for each round. Before patch testing, an individual maximum concentration/dose was determined for each fragrance substance.
The predetermined maximum patch test concentrations/doses could be tested for all 12 fragrance substances, with no observable adverse reactions being noted.
For each fragrance substance investigated, it is recommended that half of the maximum patch test dose (mg/cm2) be used for aimed and screening patch testing.
[Show abstract][Hide abstract] ABSTRACT: Contact allergy to phenol-formaldehyde resins (PFRs) based on phenol and formaldehyde is not detected by a p-tertiary-butylphenol-formaldehyde resin (PTBP-FR) included in most baseline patch test series.
To investigate the rate of contact allergy to PFR-2 (a mixture of monomers and dimers from a resol resin based on phenol and formaldehyde) in a Swedish population, and to investigate associated simultaneous allergic reactions.
Five centres representing the Swedish Contact Dermatitis Research Group included PFR-2 in their patch test baseline series for a period of 1.5 years.
Of 2504 patients tested, 27 (1.1%) reacted to PFR-2. Of those 27 individuals, 2 had a positive reaction to formaldehyde and 2 to PTBP-FR. Simultaneous allergic reactions were noted to colophonium in 6, to Myroxylon pereirae in 14, and to fragrance mix I in 15.
The contact allergy frequency in the tested population (1.1%) merits its inclusion in the Swedish baseline series and possibly also in other baseline series. Simultaneous allergic reactions were noted to colophonium, M. pereirae, and fragrance mix I.
[Show abstract][Hide abstract] ABSTRACT: Sesquiterpene lactone mix detects contact allergy to these compounds present in the plant family Asteraceae. This marker is present in many baseline series. An additional marker is Compositae mix, which is not present in many baseline series. To investigate whether this allergen should be inserted into the Swedish baseline series, six dermatology centres representing the Swedish Contact Dermatitis Research Group included Compositae mix into their baseline series for 1.5 years. Of 2818 patients tested, 31 (1.1%) reacted to Compositae mix and 26 (0.9%) to Sesquiterpene lactone mix. Active sensitization to Compositae mix was noted in two cases. Only 0.4% of Asteraceae contact allergy cases would have been missed if Compositae mix had not been tested, a frequency too low to merit its inclusion in the baseline series. Due to obvious geographical differences in frequency in frequency of simultaneous allergic reactions to Compositae mix and Sesquiterpene lactone mix, the question as to whether specific baseline series (including Compositae mix or not as a "tail" substance) should be used in the different centres must be addressed. Another option could be to remove Sesquiterpene lactone mix from the baseline series and substitute it with Compositae mix.
[Show abstract][Hide abstract] ABSTRACT: The technique of patch testing is well established for diagnosing contact allergy. New allergens are continously identified,
and the method itself is constantly developing. The outcome of patch testing depends on several factors including the knowledge
and skill of the testing dermatologist. In the present chapter, we discuss the different aspects of patch testing ranging
from test systems, allergens, evaluation, and relevance to strategies for including new allergens in baseline series and for
the clinical investigation of patients.
[Show abstract][Hide abstract] ABSTRACT: Linalool is a widely used fragrance terpene. Pure linalool is not allergenic or a very weak allergen, but autoxidizes on air exposure and the oxidation products can cause contact allergy. Oxidized (ox.) linalool has previously been patch tested at a concentration of 2.0% in petrolatum (pet.) in 1511 patients, and 1.3% positive patch test reactions were observed. Objective: To investigate the optimal patch test concentration for detection of contact allergy to ox. linalool.
Four concentrations of ox. linalool (2.0%, 4.0%, 6.0%, 11.0% pet.) were tested in 3418 consecutive dermatitis patients.
Ox. linalool 2.0%, 4.0%, 6.0%, and 11.0% pet. detected positive patch test reactions in 0.83%, 3.2%, 5.3%, and 7.2% of the tested patients, respectively. The doubtful reactions increased with rising concentrations but relatively less, giving 5.1%, 6.4%, and 7.3% doubtful reactions, respectively, for ox. linalool 4.0%, 6.0%, and 11.0% pet. Few irritative reactions were seen.
Raising the patch test concentration for ox. linalool gave a better detection of contact allergy, as many as 5-7% positive patch test reactions were detected. We suggest a patch test concentration of ox. linalool 6.0% pet. for future patch testing, giving a dose per unit area of 2.4 mg/cm(2) when 20 mg test substance is tested in small Finn Chambers.
[Show abstract][Hide abstract] ABSTRACT: Linalool and limonene are common fragrance terpenes that autoxidize on air exposure. The pure compounds are not allergenic but their oxidation products can cause contact allergy. Little has been investigated regarding the irritancy of oxidized terpenes.
The aim of this study was to investigate the irritating effect of pure and oxidized R-limonene and linalool in concentration series and to study the MNIC (Maximum Non Irritant Concentration) of autoxidized linalool and limonene.
Patch testing was performed in dermatitis patients and controls with sequentially diluted concentrations of oxidized and non-oxidized linalool, and oxidized and non-oxidized R-limonene. Readings were made with visual assessment and using laser Doppler imaging.
The non-oxidized terpenes were non-irritating in all tested concentrations. Both linalool and especially R-limonene were more irritating after oxidation compared with the pure compounds. No difference in response was seen between dermatitis patients and controls.
Autoxidation of the fragrance terpenes linalool and R-limonene increases irritation. Oxidized linalool is less irritating than oxidized R-limonene. In this study, we found no advantages in using laser Doppler technique compared with visual assessment.
[Show abstract][Hide abstract] ABSTRACT: Terpenes are among the most widely used fragrances, found not only in fine fragrances but most often incorporated in domestic and occupational products. Terpenes oxidize easily at air-exposure. Our previous studies have proved that limonene, linalool and caryophyllene are not allergenic in themselves but easily form allergenic products due to autoxidation. The aim of this study was to study the frequency and characteristics of allergic reactions in Europe to some oxidized fragrance terpenes.Method: Consecutive dermatitis patients in six European dermatological centers were patch tested with oxidized terpenes. Questionnaires, standard and additional fragrance patch test materials were used in the diagnosis of fragrance allergy.Results: Oxidized limonene was tested in 2411, while oxidized linalool, linalool hydroperoxide, oxidized caryophyllene, caryophyllene oxide and oxidized myrcene in additional 1511 patients. Of the patients tested 2.6% showed positive reaction to oxidized limonene, 1.3% to oxidized linalool, 0.5% to oxidized caryophyllene and 1 patient to oxidized myrcene. 1.1% of the patients reacted to linalool hydroperoxide, while testing with caryophyllene oxide resulted in few positive Results: 60% of the patients reacting to oxidized terpenes had fragrance related contact allergy and/or positive history for fragrance related dermatitis.Conclusion: Oxidized limonene and linalool are common allergens in dermatitis patients tested consecutively in Europe. Our results indicate that autoxidation of fragrance terpenes contributes to fragrance allergy to a great extent. This observation emphasises the need of testing with chemicals that patients actually come in contact with and not only ingredients that were originally applied in the commercial formulations.
[Show abstract][Hide abstract] ABSTRACT: This is part of an ongoing effort to investigate how autoxidation affects the sensitzing potential of terpene-based fragrances. We have previously shown that terpenes such as abeitic acid (diterpene), limonene and linalool (monoterpenes) form stable hydroperoxides when oxidized. These hydroperoxides have proved to be strong allergens. Its therefore of special interest to study the connection between formation of hydroperoxides caused by autoxidation of fragrance chemicals during handling and storage and an increased allergenic effect.
Objective: To investigate the autoxidation of caryophyllene (sesquiterpene) and study its effect on the sensitizing capacity.
Methods: Caryophyllene was exposed to air and the autoxidation was monitored by GC and HPLC. The major oxidation products were isolated and their structure determined. The allergenic activity of pure caryophyllene and its oxidation products was investigated in animal assays and clinical testing.
Result: Only 10% of the staring material remained after 20 weeks of air exposure. The major oxidation product was caryophyllene oxide. Substantial amounts of formaldehyde were found in the oxidation mixture. Little or no hydroperoxides were detected in the total oxidation mixture. Caryophyllene oxide and oxidized caryophyllene showed a low sensitizing capacity in animals and very few positive reactions at patch testing.
Conclusion: Caryophyllene is easily oxidized at air exposure. A low allergenic effect is observed in both sensitization studies and clinical testing. This is consistent with our earlier findings that the amount of hydroperoxides is important for the allergenic activity of autoxidized terpenes.
[Show abstract][Hide abstract] ABSTRACT: Linalool is one of the most frequently used fragrance chemicals in scented products and a large population is exposed to it. It is therefore important to study the allergenic properties of linalool, and the effect of autoxidation.
Objectives: To study the autoxidation of linalool and identify formed oxidation products, to investigate the impact of autoxidation on the sensitizing capacity and to study the frequency of contact allergy to oxidized linalool among consecutive dermatitis patients.
Methods: Linalool was air-exposed and the degradation followed with GC. Oxidation products were identified with GC-MS and NMR. Pure linalool, 2 different states of oxidized linalool and 3 oxidation products were tested for their sensitizing capacity in the local lymph node assay (LLNA). Consecutive dermatitis patients were patch-tested with oxidized linalool and a fraction of oxidized linalool.
Results: Linalool started to decompose immediately when air-exposed. Several oxidation products were identified among which 3 (2 hydroperoxides and an alpha, beta-unsaturated aldehyde) contain structural features that make them potential allergens. LLNA showed that the 3 oxidation products were moderate allergens, and that the sensitizing potential of linalool increased with longer air-exposure times. In the patch-test study positive reactions were observed to oxidized linalool in 1.65% of the patients.
Conclusions: The extensively used fragrance chemical linalool is not allergenic in itself. The autoxidation process that takes place at air-exposure leads to the formation of sensitizing oxidation products. The frequency of consecutive patients reacting to oxidized linalool shows that the experimental findings are clinically important.