| 1. |
- Bennike, Niels H., et al.
(författare)
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Allergic contact dermatitis caused by hydroperoxides of limonene and dose-response relationship-A repeated open application test (ROAT) study
- 2019
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 80:4, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- Background: Contact allergy to oxidized limonene, with hydroperoxides of limonene (Lim-OOHs) as the main allergens, is common. However, high proportions of weak positive and doubtful patch test reactions have been reported. Objectives: To determine the clinical relevance, elicitation threshold and dose-response relationship of Lim-OOHs in individuals with a positive or doubtful patch test reaction to standard Lim-OOHs 0.3% pet. Methods: A multicentre 3-week double-blind vehicle-controlled repeated open application test (ROAT) study with a simulated fine fragrance containing Lim-OOHs at 1260, 420 and 140 ppm, equal to a dose/area per application of Lim-OOHs of 3.0, 0.99 and 0.33 mu g/cm(2), was performed. Results: Among 11 subjects allergic to Lim-OOHs, 11 (100%), 7 (64%), and 3 (27%), respectively, reacted to the applied doses. No reactions were seen in 17 healthy controls exposed to the highest dose. This difference in reactivity was statistically significant (P < 0.0001). Among 13 subjects with doubtful patch test reactions to Lim-OOHs, two (15%) had positive ROAT reactions to the highest Lim-OOH dose applied (P = 0.36 as compared with controls). Conclusions: Contact allergy to Lim-OOHs is of clinical relevance in patients with positive patch test reactions. A doubtful patch test reaction to Lim-OOHs 0.3% pet. can be of clinical relevance.
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| 2. |
- Bråred Christensson, Johanna, 1965, et al.
(författare)
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Limonene hydroperoxide analogues differ in allergenic activity
- 2008
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 59:6, s. 344-352
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Tidskriftsartikel (refereegranskat)abstract
- Background: The fragrance terpene R-limonene is a very weak sensitizer but forms allergenic oxidation products upon contact with air. Oxidized (ox.) limonene is a frequent cause of contact allergy in clinical testing. Objectives: This study investigates the sensitizing potencies of ox. and non-ox. limonene and of structurally closely related limonene hydroperoxides. The clinical importance of the difference in sensitizing potency of two hydroperoxides in autoxidized limonene was studied. Patients/Methods: Ox. and non-ox. limonene were investigated in the murine local lymph node assay (LLNA). Limonene hydroperoxides were investigated using a modified LLNA involving non-pooled lymph nodes and statistical calculations; patch testing of patients with known contact allergy to ox. limonene was performed. Results: A marked increase in the sensitizing potency of ox. limonene compared with that of pure limonene was observed in the LLNA. One analogue, limonene-1-hydroperoxide, was a significantly more potent sensitizer than the other hydroperoxides and gave more positive test reactions in the allergic patients. Conclusions: The results support that hydroperoxides have a specific reactivity indicating that oxygen-centred radicals are important in hapten–protein complex formation of hydroperoxides. The primary oxidation products of ox. limonene, the hydroperoxides, have an important impact on the sensitizing capacity of the oxidation mixture.
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| 3. |
- Andernord, D., et al.
(författare)
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Contact allergy to haptens in the Swedish baseline series: Results from the Swedish Patch Test Register (2010 to 2017)
- 2022
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 86:3, s. 175-188
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Tidskriftsartikel (refereegranskat)abstract
- Background Allergic contact dermatitis has considerable public health impact and causative haptens vary over time. Objectives To report the prevalence of contact allergy to allergens in the Swedish baseline series 2010 to 2017, as registered in the Swedish Patch Test Register. Methods Results and demographic information for patients tested with the Swedish baseline series in 2010 to 2017 were analysed. Results Data for 21 663 individuals (females 69%) were included. Females had significantly more positive patch tests (54% vs 40%). The reaction prevalence rates were highest for nickel sulfate (20.7%), fragrance mix I (7.1%), Myroxylon pereirae (6.9%), potassium dichromate (6.9%), cobalt chloride (6.8%), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; 6.4%), MI (3.7%), colophonium (3.5%), fragrance mix II (3.2%), and formaldehyde (3.2%). Myroxylon pereirae reaction prevalence increased from 5% in 2010 to 9% in 2017 and that for methyldibromo glutaronitrile from 3.1% to 4.6%. MCI/MI and MI reactions decreased in prevalence after 2014. Nickel reaction prevalence decreased among females aged 10 to 19 years. Conclusions Nickel remains the most common sensitizing agent, with reaction prevalence decreasing among females younger than 20 years. The changes in MCI/MI and MI reaction prevalence mirrored those in Europe. The register can reveal changes in contact allergy prevalence over time among patients patch tested in Sweden.
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| 4. |
- Andersch-Björkman, Ylva, et al.
(författare)
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Air-oxidized linalool elicits eczema in allergic patients-a repeated open application test study.
- 2014
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Ingår i: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 70:3, s. 129-38
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Tidskriftsartikel (refereegranskat)abstract
- Linalool is a commonly used fragrance terpene that forms potent sensitizers upon oxidation. In a recent multicentre study, we found that 7% of 2900 patients showed positive patch test reactions to oxidized linalool at 6.0%. No elicitation studies have been performed.
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| 5. |
- Bråred Christensson, Johanna, 1965, et al.
(författare)
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Fragrance Allergens, Overview with a Focus on Recent Developments and Understanding of Abiotic and Biotic Activation
- 2016
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Ingår i: Cosmetics. - : MDPI AG. - 2079-9284. ; 3:2, s. 19-37
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Bäcktorp, Carina, 1964, et al.
(författare)
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Mechanism of Air Oxidation of the Fragrance Terpene Geraniol
- 2008
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Ingår i: J.Chem.Theory Comput.. - : American Chemical Society (ACS). ; 4, s. 101-106
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Tidskriftsartikel (refereegranskat)abstract
- The fragrance terpene geraniol autoxidizes upon air exposure and forms a mixture of oxidation products, some of which are skin sensitizers. Reactions of geraniol with O2 have been studied with DFT (B3LYP) and the computational results compared to experimentally observed product ratios. The oxidation is initiated by hydrogen abstraction, forming an allylic radical which combines with an O2 molecule to yield an intermediate peroxyl radical. In the subsequent step, geraniol differs from previously studied cases, in which the radical chain reaction is propagated through intermolecular hydrogen abstraction. The hydroxy-substituted allylic peroxyl radical prefers an intramolecular rearrangement, producing observable aldehydes and the hydroperoxyl radical, which in turn can propagate the radical reaction. Secondary oxidation products like epoxides and formates were also considered, and plausible reaction pathways for formation are proposed.
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| 7. |
- Delaine, Tamara, 1981, et al.
(författare)
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A structure activity relationship study of geranial derivatives
- 2012
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Ingår i: Contact Dermatitis 11th congress of the European society of contact dermatitis (ESCD) 13-16 june 2012, Malmö, Sweden. - : Wiley. ; 66:Suppl. 2
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Konferensbidrag (refereegranskat)abstract
- Background: Fragrances are common causes of contact allergy. Skin exposure to geranial is frequent since citral (mixture of geranial and neral) is commonly used in fragrances and flavors and is considered as a moderate allergen. Previous studies according to the local lymphnodeassay (LLNA)in micehaverevealed large variations in the sensitizing capacity of different geranial derivatives. Objectives: For a better understanding of these variations, a structure-activity relationship (SAR) study on a series of derivatives of geranial was carried out. Methods: The chemical reactivity of the compounds towards a model peptide was investigated using LC-MS. The adduct formation and the non-reacted peptide depletion were monitored. Adducts formed with model amino acids were investigated and structural determination was performed. Additional derivatives were synthesized and their sensitization potencies were evaluated in relation to their physicochemical and reactivity properties. Results: Most of the derivatives were shown to bind covalently to the cysteine residue of the model peptide. The percentage of depletion of the non-reacted peptide ranged from 0% to 100% after 24 hr, constant rate of depletion revealed a large difference between the fastest and lowest reacting derivatives. These resultswere congruent with the skin sensitization potencies obtained with the LLNA. Conclusions: A good correlation between the reactivity and the sensitizing potency was observed. Small changes in the chemical structure of geranial result in significant differences in sensitizing capacity and chemical reactivity. Conflicts of interest: The authors have declared no conflicts.
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| 8. |
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| 9. |
- Delaine, Tamara, 1981, et al.
(författare)
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Epoxyalcohols: bioactivation and conjugation required for skin sensitization.
- 2014
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Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 27:10, s. 1860-70
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Tidskriftsartikel (refereegranskat)abstract
- Allylic alcohols, such as geraniol 1, are easily oxidized by varying mechanisms, including the formation of both 2,3-epoxides and/or aldehydes. These epoxides, aldehydes, and epoxy-aldehydes can be interconverted to each other, and the reactivity of them all must be considered when considering the sensitization potential of the parent allylic alcohol. An in-depth study of the possible metabolites and autoxidation products of allylic alcohols is described, covering the formation, interconversion, reactivity, and sensitizing potential thereof, using a combination of in vivo, in vitro, in chemico, and in silico methods. This multimodal study, using the integration of diverse techniques to investigate the sensitization potential of a molecule, allows the identification of potential candidate(s) for the true culprit(s) in allergic responses to allylic alcohols. Overall, the sensitization potential of the investigated epoxyalcohols and unsaturated alcohols was found to derive from metabolic oxidation to the more potent aldehyde where possible. Where this is less likely, the compound remains weakly or nonsensitizing. Metabolic activation of a double bond to form a nonconjugated, nonterminal epoxide moiety is not enough to turn a nonsensitizing alcohol into a sensitizer, as such epoxides have low reactivity and low sensitizing potency. In addition, even an allylic 2,3-epoxide moiety is not necessarily a potent sensitizer, as shown for 2, where formation of the epoxide weakens the sensitization potential.
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| 10. |
- Delaine, Tamara, 1981, et al.
(författare)
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Skin Sensitization of Epoxyaldehydes: Importance of Conjugation.
- 2013
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Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 26:5, s. 674-684
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Tidskriftsartikel (refereegranskat)abstract
- Structure-activity relationship (SAR) models are important tools for predicting the skin sensitization potential of new compounds without animal testing. In compounds possessing a structural alert (aldehyde) and an activation alert (double bond), it is important to consider bioactivation/autoxidation (e.g., epoxidation). In the present study, we have explored a series of aldehydes with regard to contact allergy. The chemical reactivity of these 6 aldehydes toward a model hexapeptide was investigated, and their skin sensitization potencies were evaluated using the local lymph node assay (LLNA). Overall, we observed a similar trend for the in vitro reactivity and the in vivo sensitization potency for the structural analogues in this study. The highly reactive conjugated aldehydes (α,β-unsaturated aldehydes and 2,3-epoxyaldehydes) are sensitizing moieties, while nonconjugated aldehydes and nonterminal aliphatic epoxides show low reactivity and low sensitization potency. Our data show the importance of not only double bond conjugation to aldehyde but also epoxide-aldehyde conjugation. The observations indicate that the formation of nonconjugated epoxides by bioactivation or autoxidation is not sufficient to significantly increase the sensitization potency of weakly sensitizing parent compounds.
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| 11. |
- Engfeldt, Malin, et al.
(författare)
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Can patch testing with methylchloroisothiazolinone/methylisothiazolinone be optimized using a new diagnostic mix? - A multicenter study from the Swedish Contact Dermatitis Research Group
- 2020
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 82:5, s. 283-289
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 12. |
- Engfeldt, Malin, et al.
(författare)
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Patch Testing with a New Composition of Mercapto Mix: A Multi-centre Study by the Swedish Contact Dermatitis Research Group
- 2019
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 99:11, s. 960-963
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated whether more patients with contact allergies were detected by patch testing with mercapto mix with a higher concentration of 2-mercaptobenzothiazolinone (MBT) than the commonly used mercapto mix. A total of 3,143 dermatitis patients in 5 Swedish dermatology departments were patch-tested with 3 mercapto test preparations: MBT 2.0% petrolatum (pet.); mercapto mix 2.0% pet.; and mercapto mix 3.5% pet. Positive reactions to these mercapto mixes varied between 0-0.50%, 0-0.93%, and 0-1.4%, respectively, in the 5 centres. Numerically, mercapto mix 3.5% pet. detected all positive patients and more patch-test positive patients than did the 2 other substances, but the difference was not statistically significant. The authors recommend replacing mercapto mix 2.0% pet. in the Swedish baseline series with mercapto mix 3.5% pet., since the latter also detected those patients who would have been missed because MBT 2.0% is not included in the Swedish baseline series.
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| 13. |
- Hagvall, Lina, 1978, et al.
(författare)
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Air-oxidized linalyl acetate - an emerging fragrance allergen?
- 2015
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Ingår i: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 72:4, s. 216-23
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Tidskriftsartikel (refereegranskat)abstract
- Linalyl acetate is a fragrance chemical that is prone to autoxidation. Exposure to linalyl acetate occurs through cosmetic products and essential oils, but is difficult to assess, as linalyl acetate is not labelled in the EU.
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| 14. |
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| 15. |
- Hagvall, Lina, 1978, et al.
(författare)
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Assessment of cross-reactivity of new less sensitizing epoxy resin monomers in epoxy resin-allergic individuals
- 2016
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873. ; 75:3, s. 144-150
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMeasures to prevent occupational exposure to epoxy resins, including education, medical examination, and voluntary agreements between employers and workers, have not been effective enough to protect against skin sensitization. Therefore, alternatives to the major epoxy resin haptens that have been found to be less sensitizing in the local lymph node assay have been developed. ObjectivesTo study the cross-reactivity of two newly designed epoxy resin monomers, with decreased skin-sensitizing potency and good technical properties as compared with diglycidyl ether of bisphenol A (DGEBA), in subjects with known contact allergy to epoxy resin of DGEBA type. Patients and MethodsEleven individuals with previous positive patch test reactions to epoxy resin of DGEBA participated in the study. The two alternative epoxy resin monomers were synthesized and patch tested in dilution series in parallel with epoxy resin of DGEBA from the baseline series (containing 92% DGEBA). ResultsAll participants reacted to epoxy resin of DGEBA on retesting. Three participants reacted to monomer 1. No reactions were seen to monomer 2. ConclusionsThe alternative monomers studied showed little or no cross-reactivity with epoxy resin of DGEBA. Decreasing the risk of sensitization by using less sensitizing compounds is important, as contact allergy to epoxy resins is common in spite of thorough preventive measures.
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| 16. |
- Hagvall, Lina, 1978, et al.
(författare)
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Can the epoxides of cinnamyl alcohol and cinnamal show new cases of contact allergy?
- 2018
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Ingår i: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 78:6, s. 399-405
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Tidskriftsartikel (refereegranskat)abstract
- Cinnamyl alcohol is considered to be a prohapten and prehapten with cinnamal as the main metabolite. However, many individuals who are allergic to cinnamyl alcohol do not react to cinnamal. Sensitizing epoxides of cinnamyl alcohol and cinnamal have been identified as metabolites and autoxidation products of cinnamyl alcohol.To investigate the clinical relevance of contact allergy to epoxycinnamyl alcohol and epoxycinnamal.Irritative effects of the epoxides were investigated in 12 dermatitis patients. Epoxycinnamyl alcohol and epoxycinnamal were patch tested in 393 and 390 consecutive patients, respectively. In parallel, cinnamyl alcohol and cinnamal were patch tested in 607 and 616 patients, respectively.Both epoxides were irritants, but no more positive reactions were detected than when testing was performed with cinnamyl alcohol and cinnamal. Late allergic reactions to epoxycinnamyl alcohol were observed. In general, patients with late reactions showed doubtful or positive reactions to cinnamal and fragrance mix I at regular patch testing.The investigated epoxides are not important haptens in contact allergy to cinnamon fragrance. The high frequency of fragrance allergy among patients included in the irritancy study showed the difficulty of suspecting fragrance allergy on the basis of history; patch testing broadly with fragrance compounds is therefore important.
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| 17. |
- Hagvall, Lina, 1978, et al.
(författare)
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Concomitant reactions to geraniol and citral – due to cross reactivity?
- 2012
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Ingår i: Contact Dermatitis. - 1600-0536. ; 66:s2, s. 66-87
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Konferensbidrag (refereegranskat)abstract
- Background: Fragrance allergy is estimated as the second most common contact allergy in the western world, based on test results using the fragrance markers in the baseline series. One of these markers, fragrance mix (FM), contains geraniol at a concentration of 1%. Although about 10% of tested consecutive dermatitis patients react to FM, geraniol is responsible for only 5% of positive patch test reactions to the individual components of FM. However, we have shown that geraniol forms sensitizing compounds via autoxidation and skin metabolism. Geranial and neral, the two isomers in citral, are the major haptens formed in both of these activation pathways. Objectives: To investigate whether testing with oxidized (ox) geraniol detects more cases of contact allergy than testing with pure geraniol. The pattern of reactions to pure and ox geraniol, and the metabolites/autoxidation products geranial and neral was studied to investigate the importance of autoxidation or cutaneous metabolism in contact allergy to geraniol. Patients and methods: Pure and ox geraniol were tested at 2.0% pet in 2227 and 2179 consecutive patients, respectively. In parallel, geranial, neral and citral were tested in 2152, 1626, and 1055 consecutive patients, respectively. Results: Pure and ox geraniol detected positive patch test reactions in 0.13% and 0.55% of the patients, respectively. Eight of 11 patients with positive patch test reactions to ox geraniol also reacted to citral or its components. Relevance for the positive patch test reactions in relation to the patients´ dermatitis was found in 11 of 14 cases. Conclusions: Testing with ox geraniol could detect more cases of contact allergy to geraniol. The reaction pattern of the 14 cases presented indicates that both autoxidation and metabolism could be important in sensitization to geraniol. Concomitant reactions for geraniol and citral could be due to cross reactivity.
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| 18. |
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| 19. |
- Hagvall, Lina, 1978, et al.
(författare)
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Contact allergy to citral and its constituents geranial and neral, coupled with reactions to the prehapten and prohapten geraniol
- 2020
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 82:1, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Background Citral is commonly used as a fragrance and flavor material and consists of the aldehydes geranial and neral. Citral is included in fragrance mix (FM) II. Geranial and neral have also been identified in autoxidation of geraniol, a fragrance compound present in FM I. Objectives To study contact allergy to citral, geranial, and neral, and concomitant reactivity to oxidized geraniol and fragrance markers of the baseline series. Methods A total of 1476 dermatitis patients with suspected allergic contact dermatitis were patch tested using geranial, neral, and citral, all 3.5% petrolatum (pet.) as well as geraniol 6.0% and oxidized geraniol 11% pet. in addition to the Swedish baseline series. Results Frequencies of positive reactions to citral, geranial, and neral were 2.9%, 3.4% and 1.9%, respectively. Together, citral and geranial gave 4.2% positive patch test reactions in consecutive dermatitis patients. In patients with positive reactions to citral or its components, 25% to 34% reacted to FM II and 61% reacted to oxidized geraniol. Conclusions Patch testing with citral, its components, or oxidized geraniol detects contact allergic reactions not detected using the baseline series. Patch testing with pure geraniol was shown to be of little value. Geranial and neral, although closely chemically related, are concluded to be separate haptens.
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| 20. |
- Hagvall, Lina, 1978, et al.
(författare)
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Contact allergy to oxidized geraniol among Swedish dermatitis patients-A multicentre study by the Swedish Contact Dermatitis Research Group
- 2018
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 79:4, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- Background: Geraniol is a widely used fragrance terpene, and is included in fragrance mix I. Geraniol is prone to autoxidation, forming the skin sensitizers geranial, neral, and geraniol-7-hydroperoxide. Oxidized geraniol has previously been patch tested in 1 clinic, giving 1% to 4.6% positive reactions in consecutive patients when tested at 2% to 11%. Aim: To compare test reactions to pure and oxidized geraniol, to compare 2 different test concentrations of oxidized geraniol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series in a multicentre setting. Methods: One thousand four hundred and seventy-six consecutive patients referred for patch testing were patch tested with geraniol 6% pet. and oxidized geraniol 6% and 11% pet. Results: Pure geraniol 6% pet., oxidized geraniol 6% pet. and oxidized geraniol 11% pet. gave 1%, 3% and 8% positive patch test reactions and 0.7%, 3% and 5% doubtful reactions, respectively. Approximately 50% of the patients with doubtful reactions to oxidized geraniol 6% pet. had positive reactions to oxidized geraniol 11% pet. Conclusions: Oxidized geraniol 11% pet. provides better detection than oxidized geraniol 6% pet. As most patients reacted only to oxidized geraniol, it is important to explore further whether oxidized geraniol should be included in a baseline patch test series.
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| 21. |
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| 22. |
- Hagvall, Lina, 1978, et al.
(författare)
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Cross-reactivity between citral and geraniol-can it be attributed to oxidized geraniol?
- 2014
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Ingår i: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 71:5, s. 280-8
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Tidskriftsartikel (refereegranskat)abstract
- The fragrance compound geraniol is susceptible to autoxidation when in contact with air, and to cutaneous metabolism. In both processes, the isomeric aldehydes geranial and neral are formed. Citral consists of geranial and neral. Among patients with positive reactions to citral, we have previously detected concomitant reactions to geraniol in 85% of cases and to oxidized geraniol in 73% of cases.
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| 23. |
- Hagvall, Lina, 1978, et al.
(författare)
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Cytochrome P450-mediated activation of the fragrance compound geraniol forms potent contact allergens.
- 2008
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Ingår i: Toxicology and applied pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 233:2, s. 308-13
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Tidskriftsartikel (refereegranskat)abstract
- Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered to be a weak allergen, although its chemical structure does not indicate it to be a contact sensitizer. We have shown that geraniol autoxidizes and forms allergenic oxidation products. In the literature, it is suggested but not shown that geraniol could be metabolically activated to geranial. Previously, a skin-like CYP cocktail consisting of cutaneous CYP isoenzymes, was developed as a model system to study cutaneous metabolism. In the present study, we used this system to investigate CYP-mediated activation of geraniol. In incubations with the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed followed by 6,7-epoxygeraniol. The allergenic activities of the identified metabolites were determined in the murine local lymph node assay (LLNA). Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and 6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1 and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly responsible for the metabolic activation of geraniol in the skin, as they are expressed constitutively at significantly higher levels than CYP2B6. Thus, geraniol is activated through both autoxidation and metabolism. The allergens geranial and neral are formed via both oxidation mechanisms, thereby playing a large role in the sensitization to geraniol.
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| 24. |
- Hagvall, Lina, 1978, et al.
(författare)
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Experimental and Theoretical Investigations of the Autoxidation of Geranial: A Dioxolane Hydroperoxide Identified as a Skin Sensitizer.
- 2011
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Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X.
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Tidskriftsartikel (refereegranskat)abstract
- The autoxidation of geranial with O(2) was studied both experimentally and using density functional theory. Computational results were used to interpret experimentally observed product ratios. Geranial was found to autoxidize, forming 6,7-epoxygeranial as the main oxidation product. Hydroperoxides corresponding to those identified as important skin sensitizers in previous studies of fragrance terpenes could not be detected. Instead, a dioxolan derivative and its corresponding hydroperoxide were identified and detected in high concentrations. The distribution of products in autoxidation generally depends on the stabilities of the intermediate peroxyl radicals. In this study, the formation of a peracyl radical was found to be highly favored. This radical forms peracid which epoxidizes geranial. The epoxide thus produced can react with acyl radical to yield the dioxolan hydroperoxide. The dioxolan derivative is believed to form in an acid catalyzed closed shell reaction between 6,7-epoxygeranial and geranial. The dioxolan hydroperoxide and 6,7-epoxygeranial are strong sensitizers and are considered to be the compounds mainly responsible for the skin sensitization potency of air-exposed geranial.
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| 25. |
- Hagvall, Lina, 1978, et al.
(författare)
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Finding the optimal patch test material and test concentration to detect contact allergy to geraniol.
- 2013
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Ingår i: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 68:4, s. 224-31
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Tidskriftsartikel (refereegranskat)abstract
- Background. Geraniol is a commonly used fragrance terpene, and is tested in the baseline series in fragrance mix I. Geraniol is a pro-hapten and a pre-hapten, and sensitizers are formed in the autoxidation and skin metabolism of geraniol. Previous patch testing with air-exposed (oxidized) geraniol has suggested that oxidized geraniol could be a better marker for contact allergy to geraniol than pure geraniol. Objectives. To find the optimal patch test substance and concentration for detecting contact allergy to geraniol. Patients and methods. Six hundred and fifty-five patients were patch tested with pure and oxidized geraniol at 4.0%, 6.0% and 11.0% in petrolatum. Before patch testing, the irritant properties of pure and oxidized geraniol were studied in 27 patients at 2.5%, 5.0%, 10.0% and 20.0% pet. Results. Pure geraniol detected positive reactions in 0.15–1.1% of the patients, and oxidized geraniol detected positive reactions in 0.92–4.6% of the patients. Reactions to pure geraniol in patients not reacting to oxidized geraniol indicated metabolic activation of geraniol. Neither pure nor oxidized geraniol gave significant irritant reactions. Conclusions. Increasing the test concentrations of pure and oxidized geraniol enables the detection of more cases of contact allergy. Oxidized geraniol detects more patients than pure geraniol, but patch testing with only oxidized geraniol does not detect all cases of contact allergy to geraniol.
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| 26. |
- Hagvall, Lina, 1978
(författare)
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Formation of Skin Sensitizers from Fragrance Terpenes via Oxidative Activation Routes. Chemical analysis, Structure Elucidation and Experimental Sensitization Studies
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The work presented in this thesis emphasizes the importance of considering oxidative activation in the toxicity assessment of fragrance chemicals. Compounds without contact allergenic properties can be activated either via autoxidation in contact with air or via cutaneous metabolism to reactive products which can cause contact allergy. It is important to prevent sensitization as the immunological memory formed in the development of contact allergy persists throughout life. The investigation of compounds susceptible to oxidative activation, thereby forming sensitizing compounds is important in the work of prevention of contact allergy. The overall aim of this thesis was to investigate mechanisms of activation via autoxidation and metabolism of single fragrance compounds and essential oils, and to study the impact of this activation on the contact allergenic activity. The oxidative activation via autoxidation and cutaneous metabolism of the fragrance compounds geraniol and geranial was studied. It was shown that both compounds were susceptible to autoxidation, forming oxidation products with increased sensitizing capacity compared to the original compound. The oxidation products of geraniol were formed by two separate pathways, corresponding to autoxidation of each of the two double bonds in geraniol, respectively. Hydroperoxides, which previously have been identified as the most important sensitizers in the oxidation mixtures of air-exposed fragrance compounds could not be detected in air-exposed geranial. Instead, a sensitizing epoxide was detected. Geraniol and geranial were also activated metabolically. Many of the metabolites identified were also present in the autoxidation mixtures. The autoxidation of lavender oil was studied in order to investigate if essential oils possess a natural protection against autoxidation. The results were compared to the results from the autoxidation studies of linalyl acetate and linalool, the main components of lavender oil. It was found that the autoxidation proceeded in the same way in both the pure samples and the lavender oil, and that sensitizing oxidation products were formed in both cases. The most important sensitizers formed were hydroperoxides of linalool and linalyl acetate. This thesis adds important information on routes of autoxidation as well as on the relationship between metabolic and air induced activation of non- or weakly sensitizing compounds to sensitizers. The results presented here indicate that other fragrance terpenes could be susceptible to oxidative activation via autoxidation or cutaneous metabolism. This should be considered in the risk assessment of fragrance chemicals.
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| 27. |
- Hagvall, Lina, 1978, et al.
(författare)
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Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization
- 2007
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 20:5, s. 807-814
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Tidskriftsartikel (refereegranskat)abstract
- Fragrances are common causes of contact allergy. Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an important fragrance terpene. It is considered a weak contact allergen and is used for fragrance allergy screening among consecutive dermatitis patients. Analogous to other monoterpenes studied, such as limonene and linalool, geraniol has the potential to autoxidize on air exposure and form highly allergenic compounds. The aim of the present study was to investigate and propose a mechanism for the autoxidation of geraniol at room temperature. To investigate whether allergenic compounds are formed, the sensitizing potency of geraniol itself, air-exposed geraniol, and its oxidation products was determined using the local lymph node assay in mice. The results obtained show that the allylic alcohol geraniol follows an oxidation pattern different from those of linalool and limonene, which autoxidize forming hydroperoxides as the only primary oxidation products. The autoxidation of geraniol follows two paths, originating from allylic hydrogen abstraction near the two double bonds. From geraniol, hydrogen peroxide is primarily formed together with aldehydes geranial and neral from a hydroxyhydroperoxide. In addition, small amounts of a hydroperoxide are formed, analogous to the formation of the major linalool hydroperoxide. The autoxidation of geraniol greatly influenced the sensitizing effect of geraniol. The oxidized samples had moderate sensitizing capacity, quite different from that of pure geraniol. The hydroperoxide formed is believed to be the major contributor to allergenic activity, together with the aldehydes geranial and neral. On the basis of the present study and previous experience, we recommend that the possibility of autoxidation and the subsequent formation of contact allergenic oxidation products are considered in risk assessments performed on fragrance terpenes.
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| 28. |
- Hagvall, Lina, 1978, et al.
(författare)
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Lavender oil lacks natural protection against autoxidation, forming strong contact allergens on air exposure
- 2008
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 59:3, s. 143-150
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Tidskriftsartikel (refereegranskat)abstract
- Lavender oil is an essential oil frequently used as a fragrance ingredient and in traditional herbal medicine. We have previously studied the effect of air oxidation on the skin sensitizing potency of the monoterpenes linalyl acetate, linalool and β-caryophyllene, the main constituents of lavender oil.
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| 29. |
- Hagvall, Lina, 1978, et al.
(författare)
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Patch-testing with Main Sensitizers Does Not Detect All Cases of Contact Allergy to Oxidized Lavender Oil.
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 96:5, s. 679-683
-
Tidskriftsartikel (refereegranskat)abstract
- Lavender oil is an essential oil obtained from lavender (Lavendula angustifolia). The main components linalool and linalyl acetate have been shown to autoxidize in contact with oxygen in the air, forming sensitizing hydroperoxides. Patients with suspected allergic contact dermatitis were consecutively patch-tested with oxidized lavender oil 6% pet., oxidized linalyl acetate 6% pet., and oxidized linalool 6% pet. to investigate the frequency of contact allergy to oxidized lavender oil, and the pattern of concomitant reactions to oxidized linalool and oxidized linalyl acetate. Positive reactions to oxidized lavender oil were found in 2.8% of the patients. Among those, 56% reacted to oxidized linalool and/or oxidized linalyl acetate, while 52% reacted to the fragrance markers of the baseline series. Oxidized lavender oil showed among the highest frequencies of contact allergy to studied essential oils. A well-standardized preparation of oxidized lavender oil could be a useful tool for diagnosis of contact allergy to fragrances.
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| 30. |
- Hagvall, Lina, 1978, et al.
(författare)
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Patch testing with purified and oxidized citronellol
- 2020
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 83:5, s. 372-379
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Tidskriftsartikel (refereegranskat)abstract
- Background Citronellol is a commonly used fragrance terpene included in fragrance mix II. As with many other fragrance terpenes, citronellol is susceptible to autoxidation. Citronellol hydroperoxides are formed in large amounts and are the only oxidation products identified as sensitizers in oxidized citronellol. Aim To compare frequencies of contact allergy to purified and oxidized citronellol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series, oxidized linalool, and oxidized limonene. Methods A total of 658 dermatitis patients were patch tested with purified and oxidized citronellol at 2.0%, 4.0%, 6.0%, and 1.0%, 2.0%, 4.0%, 6.0% petrolatum, respectively. The irritant properties of purified and oxidized citronellol were studied before patch testing. Results Few irritant reactions were observed in the pretest. Purified citronellol detected positive reactions in 0.15%-0.31% of patients, while oxidized citronellol detected positive reactions in 0.61%-4.5%. Among patients reacting to oxidized citronellol, 34%-50% showed concomitant reactions to fragrance markers of the baseline series and 75%-91% to oxidized linalool or oxidized limonene. Conclusion Oxidized citronellol detects more cases of contact allergy than purified citronellol, and these cases are not all detected using fragrance mix II. Patch testing with oxidized citronellol will add to the tools in the diagnosis of fragrance allergy.
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| 31. |
- Hagvall, Lina, 1978, et al.
(författare)
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Skin permeation of nickel, cobalt and chromium salts in ex vivo human skin, visualized using mass spectrometry imaging
- 2021
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Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 76
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Tidskriftsartikel (refereegranskat)abstract
- Skin permeation and distribution of three of the most common skin sensitizers was investigated using a previously developed animal-free exposure method combined with imaging mass spectrometry. Nickel, cobalt, and chromium (III) salts were dissolved in a buffer and exposed to human skin ex vivo, to be analyzed using time of flight secondary ion mass spectrometry (ToF-SIMS). Our findings demonstrate that metal haptens mainly accumulated in the stratum corneum, however all three metal sensitizers could also be detected in the epidermis. Cobalt and chromium (III) species penetrated into the epidermis to a larger extent than nickel species. The degree of penetration into the epidermis is suggested to be affected by the sensitization potency of the metal salts, as well as their speciation, i.e. the amount of the respective metal present in the solution as bioaccessible and solubilised ions. Our method provided permeation profiles in human skin for known sensitizers, on a level of detail that is not possible to achieve by other means. The findings show that the permeation profiles are different, despite these sensitizers being all metal ions and common causes of contact allergy. Studying skin uptake by only considering penetration through the skin might therefore not give accurate results.
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| 32. |
- Hagvall, Lina, 1978, et al.
(författare)
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Skin permeation studies of chromium species-Evaluation of a reconstructed human epidermis model
- 2023
-
Ingår i: Toxicology in Vitro. - 0887-2333 .- 1879-3177. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- A reconstructed human epidermis (RHE) model, the EpiDerm, was investigated and compared to human skin ex vivo regarding tissue penetration and distribution of two chromium species, relevant in both occupational and general exposure in the population. Imaging mass spectrometry was used in analysis of the sectioned tissue. The RHE model gave similar results compared to human skin ex vivo for skin penetration of CrVI. However, the penetration of CrIII into the tissue of the RHE model compared to human skin ex vivo differed markedly, such that in the RHE model the CrIII species accumulated in the tissue layer corresponding to stratum corneum whereas in human skin ex vivo, the CrIII species penetrated evenly through the skin tissue. Further, skin lipids such as cholesterol were less abundant in the RHE model compared to the human skin tissue. Results presented here indicate that the RHE models do not possess the same fundamental properties as human skin tissue. As the RHE models appear to be able to give false negative results, experiments using RHE models for the study of skin penetration should be evaluated with caution.
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| 33. |
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| 34. |
- Isaksson, Marléne, et al.
(författare)
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Exclusion of Disperse Orange 3 is possible from the textile dye mix present in the Swedish baseline patch test series. A study by the Swedish Contact Dermatitis Research Group
- 2022
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 88:1, s. 54-59
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Tidskriftsartikel (refereegranskat)abstract
- Background The textile dye mix (TDM) 6.6% in petrolatum contains Disperse Blue (DB) 35, Disperse Yellow 3, Disperse Orange (DO) 1 and 3, Disperse Red 1 and 17, and DB 106 and 124. The most frequent allergen in TDM-positive patients is DO 3. Around 85% of para-phenylenediamine (PPD)-allergic dermatitis patients have been positive to DO 3. There has been a discussion to exclude DO 3 from TDM 6.6% because of strong simultaneous reactions to TDM and PPD. Objectives To study if DO 3 can be excluded from TDM 6.6%. Methods Patch tests were performed on 1481 dermatitis patients with TDM 6.6%, TDM 7.0% (without DO 3 but the other disperse dyes at 1.0% each), DO 3 1.0%, and PPD 1.0% pet. Results Contact allergy to TDM 6.6% was 3.6% and to TDM 7.0% was 3.0%. All 26 DO 3-positive patients were positive to PPD. The 44 patients positive to TDM 7.0% plus the 13 positive to PPD and TDM 6.6% but negative to TDM 7.0% were 57, outnumbering the 53 positive to TDM 6.6%. Conclusion TDM 7.0% can replace TDM 6.6% in the Swedish baseline series, since TDM 7.0% together with PPD 1.0% will detect patients with textile dye allergy.
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| 35. |
- Isaksson, Marléne, et al.
(författare)
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Suitable test concentration of cobalt and concomitant reactivity to nickel and chromium. A multicentre study from the Swedish Contact Dermatitis Research Group
- 2021
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 84:3, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Background In Sweden, cobalt chloride 0.5% has been included in the baseline series since the mid-1980s. A recent study from Stockholm showed that cobalt chloride 1% petrolatum (pet.) was more suitable than 0.5%. Cobalt chloride at 1.0% has been patch tested for decades in many European countries and around the world. Objectives To study the suitability of patch testing to cobalt 1.0% vs 0.5% and to analyze the co-occurrence of allergy to cobalt, chromium, and nickel. Results Contact allergy to cobalt was shown in 90 patients (6.6%). Eighty (5.9%) patients tested positive to cobalt 1.0%. Thirty-seven of the 90 patients (41.1%) with cobalt allergy were missed by cobalt 0.5% and 10 (0.7%) were missed by cobalt 1.0% (P < .001). No case of patch test sensitization was reported. Allergy to chromium was seen in 2.6% and allergy to nickel in 13.3%. Solitary allergy to cobalt without nickel allergy was shown in 61.1% of cobalt-positive individuals. Female patients had larger proportions of positive reactions to cobalt (P = .036) and nickel (P < .001) than males. Conclusion The results speak in favor of replacing cobalt chloride 0.5% with cobalt chloride 1.0% pet. in the Swedish baseline series, which will be done 2021.
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| 36. |
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| 37. |
- Knox, S., et al.
(författare)
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Topical Application of Metal Allergens Induces Changes to Lipid Composition of Human Skin
- 2022
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Ingår i: Frontiers in Toxicology. - : Frontiers Media SA. - 2673-3080. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Lipids are an important constituent of skin and are known to be modified in many skin diseases including psoriasis and atopic dermatitis. The direct effects of common metallic contact allergens on the lipid composition of skin has never been investigated, to the best of our knowledge. We describe skin lipid profiles in the stratum corneum and viable epidermis of ex vivo human skin from a female donor upon exposure to three metal allergens (nickel, cobalt and chromium) visualised using time-of-flight secondary ion mass spectrometry (ToF-SIMS), which allows for simultaneous visualisation of both the allergen and skin components such as lipids. Multivariate analysis using partial least squares discriminant analysis (PLS-DA) indicated that the lipid profile of metal-treated skin was different to non-treated skin. Analysis of individual ions led to the discovery that cobalt and chromium induced increases in the content of diacylglycerols (DAG) in stratum corneum. Cobalt also induced increases in cholesterol in both the stratum corneum and viable epidermis, as well as monoacylglycerols (MAG) in the viable epidermis. Chromium caused an increase in DAG in viable epidermis in addition to the stratum corneum. In contrast, nickel decreased MAG and DAG levels in viable epidermis. Our results indicate that skin lipid content is likely to be altered upon topical exposure to metals. This discovery has potential implications for the molecular mechanisms by which contact allergens cause skin sensitization.
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| 38. |
- Linauskiene, K., et al.
(författare)
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Solvent Orange 60 is a potent contact sensitizer in occupational and everyday life
- 2018
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873. ; 79:3, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSolvent Orange (SO) 60 is a perinone-type dye that is often used in plastic materials such as spectacle frames and has been shown to cause contact allergy. The first case of SO 60 allergic contact dermatitis caused by spectacle frames was reported in 1999, and the second in 2011. We have recently seen 10 patients, of whom 6 developed dermatitis in the retroauricular/temporal area after wearing plastic spectacles. ObjectivesTo report the cause of the dermatitis in the 10 patients and to describe our first case with occupational SO 60 contact allergy. MethodsIn this retrospective study, patch test results of 10 patients, tested with the Swedish baseline series and our specific spectacle and/or plastic series, including SO 60 1.0% pet., in 2011-2017 were analysed. ResultsTen patients, 2 males and 8 females, aged 43 to 71years, reacted positively to SO 60 1.0% pet., namely, 4 pensioners, 2 nurses, 1 office worker, 1 teacher, 1 shop assistant, and 1 unemployed person. Four of the patients had an atopic history. Patch test reactions varied from + to +++; some had spread >20cm outside the test area in terms of erythematous, infiltrated skin with papules. Retesting of patient no. 1 with serial dilutions of SO 60 in acetone showed positive reactions down to 1 ppm. Three patients reacted to the extracts of their earpieces. Gas chromatography-mass spectrometry was used to confirm the presence of SO 60 in 2 earpieces. ConclusionsSO 60 should be included in any spectacle patch test series that may be used. If there is a strong suspicion of contact allergy to SO 60 before patch testing, lowering the test concentration from 1.0% to 0.01% should be considered.
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| 39. |
- Malmberg, Per, 1974, et al.
(författare)
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Imaging mass spectrometry for novel insights into contact allergy - a proof-of-concept study on nickel
- 2018
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 78:2, s. 109-116
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Tidskriftsartikel (refereegranskat)abstract
- Background. In spite of extensive regulation to limit exposure, nickel remains the main cause of contact allergy in the general population. More detailed knowledge on the skin uptake of haptens is required. So far, no method exists for the visualization of this clinically relevant hapten and its distribution in the skin. Objectives. To show, in terms of a proof of concept, that imaging mass spectrometry [time of flight secondary ion mass spectrometry (ToF-SIMS)] can be applied for investigation of the penetration and distribution of nickel in human skin. Method. Full-thickness human skin obtained from breast reduction surgery was exposed to nickel sulfate (5% in deionized water) for 24 h in Franz-type diffusion cells. Biopsies were obtained from nickel-treated samples and control (deionized water). The tissue was sliced, and analysed with ToF-SIMS, generating high-resolution images of ion distribution in the epidermis and upper dermis. Results. The skin layers could be discerned from the ToF-SIMS data, particularly on the basis of the collagen signal. Nickel ions were localized to the stratum corneum and upper epidermis. Conclusions. This is the first time that ToF-SIMS has been applied to trace the distribution of a hapten in human skin. Proof of principle was shown for nickel, and the technique can, in the future, be expanded for investigation of the skin distribution of clinically relevant sensitizers in general.
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| 40. |
- Munem, Marwa, 1986, et al.
(författare)
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Animal- free skin permeation analysis using mass spectrometry imaging
- 2021
-
Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 71
-
Tidskriftsartikel (refereegranskat)abstract
- Here we demonstrate an animal-free skin permeation analytical approach suitable for testing pharmaceuticals, cosmetics, occupational skin hazards and skin allergens. The method aims to replace or significantly reduce existing in-vivo models and improve on already established in-vitro models. This by offering a more sensitive and flexible analytical approach that can replace and/or complement existing methods in the OECD guidelines for skin adsorption (no 427 and no 428) and measure multiple compounds simultaneously in the skin while being able to also trace endogenous effects in cells. We demonstrate this here by studying how active ingredients in sunscreen permeate through left-over human skin, from routine surgery, in a in a Franz-cell permeation model. Two common sunscreens were therefore applied to the human skin and Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to trace the molecules through the skin. We show that that ToF-SIMS imaging can be applied in visualizing the distribution of Avobenzone, Bemotrizinol, Biscotrizole and Ethyl hexyl triazine at subcellular resolution in the skin. The UV-blockers could be visualized at the same time in one single experiment without any probes or antibodies used. The UV-blockers mostly remained in the stratum corneum. However, in certain features of the skin, such as sebaceous glands, the penetration of the UV-blockers was more prominent, and the compounds reached deeper into the epidermis.
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| 41. |
- Nyman, Gunnar, 1954, et al.
(författare)
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Contact Allergy in Western Sweden to Propolis of Four Different Origins
- 2020
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- Propolis, which is produced by honeybees and is used in "natural" products, can cause contact allergy. The composition of propolis varies between regions, but little is known about how this variation affects contact allergenicity. The aims of this study were to investi-gate the frequency of propolis contact allergy in western Sweden, and whether the frequency varies according to the origin of the propolis. Patch-testing was performed using propolis from China, Lithuania, North America, and Sweden in 722 consecutive patients with dermatitis in western Sweden. Frequencies of positive patch-test reactions ranged from 2.4% to 3.6%. There were some, not statistically significant, differences in frequency of contact allergy to the 4 samples of propolis of different origins, with the highest frequency to the sample from China and the lowest frequency to the sample from Sweden. Concomitant positive patch test reactions to plant and fragrance substances in the baseline series were common, most frequently to Myroxylon pereirae resin and colophonium.
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| 42. |
- Nyman, Gunnar, 1954, et al.
(författare)
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Contact allergy to beeswax and propolis among patients with cheilitis or facial dermatitis
- 2019
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 81:2, s. 110-116
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Tidskriftsartikel (refereegranskat)abstract
- Background: Beeswax, both white and yellow, has many uses, such as in lip balm. This material can cause contact allergy, although not many cases have been described. Methods: Ninety-five patients with contact cheilitis, facial eczema or a suspicion of contact allergy to beeswax were patch tested with yellow and white beeswax and with propolis, in addition to the Swedish baseline series. Patients who reacted positively to beeswax were additionally tested with caffeic acid, and two derivatives thereof that are believed to be important haptens in propolis. Results: Seventeen patients had positive reactions to beeswax. Fourteen of these patients had been tested with both yellow and white beeswax. Among those 14, eight had positive reactions to both types of wax, five only to yellow wax, and one only to white wax. Of the 10 wax-positive patients tested with caffeic acid derivatives, three reacted positively. Fourteen beeswax-positive patients also had positive reactions to propolis. Conclusion: Patch testing cheilitis patients is important, as contact allergy is common. Our suggestion is to patch test, apart from the baseline series and the patient's own products, also with beeswax and propolis. Many beeswax-allergic cheilitis patients would not have been diagnosed with a relevant contact allergy if only the Swedish baseline series had been used.
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| 43. |
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| 44. |
- Nyman, Gunnar, 1954, et al.
(författare)
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Patch Testing with Propolis of Different Geographical Origins in a Baseline Series.
- 2021
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 101:11
-
Tidskriftsartikel (refereegranskat)abstract
- The chemical composition of propolis varies with geographical origin; however, it is not known whether this affects the frequency of contact allergy to propolis. In order to study the frequency of contact allergy to propolis of different geographical origins and concomitant reactions, 1,470 consecutive patients with dermatitis from Denmark, Lithuania and Spain were patch tested with propolis from China, Lithuania, North America and Sweden, and with a baseline series. Patch test reactions to any type of propolis ranged from 1.3% to 5.8%. There were no statistically significant differences in the frequency of positive reactions between the 4 types of propolis in the respective countries. Testing with a single commercially available type of propolis detects only approximately half of propolis-allergic patients. In patients allergic to propolis, concomitant reactions to Myroxylon pereirae resin, colophonium and Fragrance mix I were common, ranging from 12.5% to 50.0%.
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| 45. |
- Peter, N., et al.
(författare)
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Common fragrance chemicals activate dendritic cells in coculture with keratinocytes
- 2023
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Ingår i: Contact Dermatitis. - 0105-1873. ; 89:1, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fragrances are important contact allergens; however, investigation of their skin sensitization potency has been challenging in new approach methods (NAMs). Many fragrance chemicals are susceptible to autoxidation or can be metabolized by enzymes constitutively expressed in skin keratinocytes. Strong sensitizers can be formed in both of these processes. Further, keratinocytes can modulate the dendritic cell (DC) activation and maturation potential, a key event in the acquisition of contact allergy. Objectives: To evaluate the 2D coculture model consisting of keratinocytes and DCs using different weak to moderate sensitizing fragrance chemicals. Further, to investigate fragrances and related oxidation products in the in vitro model and compare to in vivo data. Methods: Chemicals were tested in the coculture activation test (COCAT), consisting of HaCaT keratinocytes and THP-1 cells. THP-1 cell surface expression of costimulatory and adhesion molecules (CD86 and CD54) collected after 24 h incubation with the chemicals was analysed using flow cytometry. Results: Twenty-four molecules were tested positive, three were negative (n = 27). Four pairs were evaluated, with aldehydes showing a 6- to 13-fold stronger responses compared to their corresponding alcohols. Conclusions: Results provide insight into the activation of DC in their natural environment of keratinocytes. alpha,beta-Unsaturated alcohols were classified as weaker sensitizers compared to their corresponding aldehydes. In sum, testing of fragrances retrieved results in good agreement with in vivo data.
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| 46. |
- Ramzy, Ahmad G., et al.
(författare)
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Investigation of diethylthiourea and ethyl isothiocyanate as potent skin allergens in chloroprene rubber
- 2015
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 72:3, s. 139-146
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundExposure to chloroprene rubber has resulted in numerous cases of allergic contact dermatitis, attributed to organic thiourea compounds used as vulcanization accelerators. However, thiourea compounds are not considered to be strong haptens.ObjectivesTo analyse common commercial chloroprene materials for their contents of diethylthiourea (DETU), dibutylthiourea (DBTU), diphenylthiourea (DPTU), and their degradation products, isothiocyanates; and to investigate the sensitization potencies of possible degradation products of the mentioned thiourea compounds.MethodsLiquid chromatography/mass spectrometry (MS) was used for quantification of organic thiourea compounds in chloroprene products, such as medical, sports and diving gear; isothiocyanates were measured by solid-phase microextraction/gas chromatography/MS. Sensitization potencies were determined with the murine local lymph node assay (LLNA).ResultsDETU was identified at concentrations of 2.7-9.4 mu g/cm(2) in all samples, whereas neither DBTU nor DPTU was detected. At 37 degrees C, degradation of DETU in the materials to ethyl isothiocyanate (EITC) was detected. EITC and ethyl isocyanate showed extreme and strong sensitization potencies, respectively, in the LLNA.ConclusionsDETU can act as a prehapten, being degraded to EITC when subjected to body temperature upon skin contact. EITC could thus be the culprit behind allergic contact dermatitis caused by chloroprene rubber.
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| 47. |
- Ramzy, Ahmad G., et al.
(författare)
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Isothiocyanates are important as haptens in contact allergy to chloroprene rubber
- 2017
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 177:2, s. 522-530
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Tidskriftsartikel (refereegranskat)abstract
- Background Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate. Objectives To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates. Methods Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates. Results All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2-1200 nmol cm(-2). At 35 degrees C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission. Conclusions Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.
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| 48. |
- Rudbäck, Johanna, 1984, et al.
(författare)
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Characterization of skin sensitizers from autoxidized citronellol - impact of the terpene structure on the autoxidation process
- 2014
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 70:6, s. 329-339
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Tidskriftsartikel (refereegranskat)abstract
- Background. Citronellol is a frequently used fragrance compound in consumer products. It is present in fragrance mix II, which is used for screening of contact allergy to fragrances. Because of its chemical structure, citronellol could be susceptible to autoxidation. Objectives. To compare the behaviour of citronellol with that of the structurally similar compounds linalool and geraniol, in terms of ability to autoxidize, the products formed, and the sensitization potencies of these. Methods. Citronellol was exposed to air, and autoxidation was followed by gas chromatography-mass spectrometry (GC-MS) analysis after derivatization of thermolabile compounds. The sensitizing potencies of the oxidation mixture and its major oxidation compounds were examined with the local lymph node assay. Results. The concentration of citronellol decreased while the sensitization potency increased in air-exposed samples over time, with hydroperoxides being identified as the major oxidation products and main skin sensitizers. Conclusions. The present study shows the impact of the absence of the 2,3-double bond in the citronellol structure on the oxidation pathways for formation of oxidation products. The study also shows the usefulness of our new GC-MS method for quantification of the citronellol oxidation products, especially the hydroperoxides. The investigated citronellol hydroperoxides could be important allergens, owing to the high concentrations detected and frequent exposure to citronellol in the population.
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| 49. |
- Sköld, Maria, 1976, et al.
(författare)
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Autoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergens
- 2008
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873. ; 58:1, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fragrances are among the most common causes of allergic contact dermatitis. We have in previous studies shown that linalool, present in lavender oil, autoxidizes on air exposure, forming allergenic oxidation products. Oxidized linalool was found to be a frequent cause of contact allergy in a patch test study on consecutive dermatitis patients. Linalyl acetate, the main component of lavender oil is commonly used as a fragrance chemical in scented products. Because of structural similarities, linalyl acetate should also be susceptible to oxidation on air exposure, forming similar oxidation products as linalool.
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| 50. |
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