Clinical and experimental studies on oxidized fragrance terpenes as contact allergens

The work presented in this thesis aims to improve the possibilities for diagnosing contact allergy to oxidized limonene and linalool and to, in patients, study contact allergy from structurally closely related hydroperoxides with regard to their specificity, potency and cross-reactivity. The fragrance terpenes limonene (from citrus oil) and linalool (from lavender oil) are widely used in household and industrial products. For both limonene and linalool, exposure to air at normal handling results in autoxidation and thus formation of allergenic oxidation products among which the primary oxidation products, the hydroperoxides, are the most potent allergens. Concomitant positive patch test reactions to oxidation mixtures where the main allergens are hydroperoxides are recorded in specific patch test studies. However today, oxidized terpenes are not included in routine patch testing for contact allergy. An irritation study was performed for non-oxidized and oxidized limonene and linalool, showing that air oxidation increased irritation of both limonene and linalool and that oxidized limonene was more irritating than oxidized linalool at similar concentrations. Based on these results, a dose-response study was conducted in 3418 consecutive dermatitis patients investigating four patch test concentrations of oxidized linalool 2.0-11.0% in petrolatum (pet.). 5-7% of the patients showed positive patch test reactions to oxidized linalool. Oxidized linalool at 6.0% pet. concentration is suggested for future screening. Concomitant positive patch test reactions and cross-reactivity of hydroperoxides were investigated in clinical studies and experimental procedures. No evidence for general cross-reactivity or formation of non-specific antigens upon administration of the investigated hydroperoxides was found. Cross-reactivity was only seen between hydroperoxides with great similarity in structure. Furthermore, three limonene hydroperoxide analogues were investigated as to allergenic potential in a modified murine local lymph node assay (LLNA) calculating on lymph nodes from individual mice. A statistically significant difference between sensitizing capacities of the investigated limonene hydroperoxides was established. Two of the limonene hydroperoxide analogues were assessed in individuals allergic to oxidized limonene. The analogue with the highest sensitizing capacity in the modified LLNA (limonene-1-hydroperoxide) gave more reactions in the tested individuals. In conclusion, this thesis shows that it is important to study the contact allergenic potential of chemicals to which we are exposed. Seemingly harmless products may cause or worsen ACD. Such risks can only be detected by testing of relevant allergenic compounds in appropriate concentrations. The frequency of positive patch test reactions to autoxidized linalool observed among the dermatitis patients, places this material among the most common contact allergens tested today. In addition, a new main allergen in the oxidation mixture of limonene, limonene-1-hydroperoxide, is proposed. The thesis confirms the effect of air oxidation on the allergenicity of common fragrance terpenes. Furthermore, the studies show the great specificity of the contact allergens in vivo. Finally, the impact on the allergenic potency by the primary oxidations products, the hydroperoxides is re-established in humans

Fragrance Allergens, Overview with a Focus on Recent Developments and Understanding of Abiotic and Biotic Activation

Fragrances and fragranced formulated products are ubiquitous in society. Contact allergies to fragrance chemicals are among the most common findings when patch-testing patients with suspected allergic contact dermatitis, as well as in studies of contact allergy in the general population. The routine test materials for diagnosing fragrance allergy consist mainly of established mixes of fragrance compounds and natural extracts. The situation is more complex as several fragrance compounds have been shown to be transformed by activation inside or outside the skin via abiotic and/or biotic activation, thus increasing the risk of sensitization. For these fragrance chemicals, the parent compound is often non-allergenic or a very weak allergen, but potent sensitizers will be formed which can cause contact allergy. This review shows a series of fragrance chemicals with well-documented abiotic and/or biotic activation that are indicative and illustrative examples of the general problem. Other important aspects include new technologies such as ethosomes which may enhance both sensitization and elicitation, the effect on sensitization by the mixtures of fragrances found in commercial products and the effect of antioxidants. A contact allergy to fragrances may severely affect quality of life and many patients have multiple allergies which further impact their situation. Further experimental and clinical research is needed to increase the safety for the consumer

Разработка автоматизированной системы получения изображений микрорельефа поверхности с помощью оптического микроскопа

Научный руководитель: к.т.н., доцент Комраков В.В.Диссертация на соискание академической степени магистра технических наук по специальности 1– 40 80 04 «Математическое моделирование, численные методы и комплексы программ»

Swedish Experiences From Patch-testing Methylisothiazolinone Separately

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 mu g/cm(2)

Patch Testing with a Textile Dye Mix in Two Concentrations : A Multicentre Study by the Swedish Contact Dermatitis Research Group

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. Conclusion: contact allergy to the TDM is common and inclusion into the Swedish baseline series should be considered

Can patch testing with methylchloroisothiazolinone/methylisothiazolinone be optimized using a new diagnostic mix? – A multicenter study from the Swedish Contact Dermatitis Research Group

Background: Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and methylisothiazolinone (MI) are tested to detect contact allergy to these isothiazolinones. Objectives: To study if an aqueous patch test preparation with MCI and MI in a mix of 0.015% and 0.2%, respectively, detects more contact allergies than the commonly used preparations of MCI/MI in 0.02% aq. and MI in 0.2% aq. Methods: A total of 1555 patients with dermatitis in five Swedish dermatology departments were tested consecutively with MCI/MI 0.215% aq., MCI/MI 0.02% aq., and MI 0.2% aq. Results: The share of contact allergy to MCI/MI 0.215% aq., MCI/MI 0.02% aq., and MI 0.2% aq. varied in the test centers between 7.9% and 25.9%, 3.2% and 10.3%, and 5.8% and 12.3%, respectively. MCI/MI 0.215% aq. detected significantly more patch-test positive individuals than both MCI/MI 0.02% aq. (P <.001) and MI 0.2% aq. (P <.001), as well as either one of MCI/MI and MI (P <.001). In the patients only reacting to MCI/MI 0.215% aq., 57.7% were recorded as having a dermatitis that was explained or aggravated by exposure to either MCI/MI or MI. Conclusion: The results speak in favor of replacing the preparations MCI/MI 0.02% aq. and MI 0.2% aq. with MCI/MI 0.215% aq. as the screening substance in the Swedish baseline series, which has been implemented in 2020

Patch Testing with a Textile Dye Mix in Two Concentrations : A Multicentre Study by the Swedish Contact Dermatitis Research Group

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. Conclusion: contact allergy to the TDM is common and inclusion into the Swedish baseline series should be considered

Patch testing with formaldehyde 2.0% in parallel with 1.0% by the Swedish Contact Dermatitis Research Group

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 &lt; 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