| 1. |
- Reisinger, Kerstin, et al.
(author)
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Systematic evaluation of non-animal test methods for skin sensitisation safety assessment.
- 2015
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In: Toxicology in Vitro. - : Elsevier BV. - 1879-3177 .- 0887-2333. ; 29:1, s. 259-270
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Journal article (peer-reviewed)abstract
- The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitisation potency prediction. The results of the first phase - systematic evaluation of 16 test methods - are presented here. This evaluation involved generation of data on a common set of ten substances in all methods and systematic collation of information including the level of standardisation, existing test data, potential for throughput, transferability and accessibility in cooperation with the test method developers. A workshop was held with the test method developers to review the outcome of this evaluation and to discuss the results. The evaluation informed the prioritisation of test methods for the next phase of the non-animal testing strategy development framework. Ultimately, the testing strategy - combined with bioavailability and skin metabolism data and exposure consideration - is envisaged to allow establishment of a data integration approach for skin sensitisation safety assessment of cosmetic ingredients.
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| 2. |
- Delaine, Tamara, 1981, et al.
(author)
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Epoxyalcohols: bioactivation and conjugation required for skin sensitization.
- 2014
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In: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 27:10, s. 1860-70
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Journal article (peer-reviewed)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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| 3. |
- Delaine, Tamara, 1981, et al.
(author)
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Structure-Activity Relationship between the in Vivo Skin Sensitizing Potency of Analogues of Phenyl Glycidyl Ether and the Induction of Nrf2-Dependent Luciferase Activity in the KeratinoSens in Vitro Assay.
- 2011
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In: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 24:8, s. 1312-8
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Journal article (peer-reviewed)abstract
- Because of regulatory constraints and ethical considerations, research on alternatives to animal testing to predict the skin sensitization potential of novel chemicals has become a high priority. Ideally, these alternatives should not only predict the hazard of novel chemicals but also rate the potency of skin sensitizers. Currently, no alternative method gives reliable potency estimations for a wide range of chemicals in differing structural classes. Performing potency estimations within specific structural classes has thus been proposed. Detailed structure-activity studies for the in vivo sensitization capacity of a series of analogues of phenyl glycidyl ether (PGE) were recently published. These studies are part of an investigation regarding the allergenic activity of epoxy-resin monomers. Here we report data on the same chemicals in the KeratinoSens in vitro assay, which is based on a stable transgenic keratinocyte cell line with a luciferase gene under the control of an antioxidant response element. A strong correlation between the EC3 values in the local lymph node assay (LLNA) and both the luciferase-inducing concentrations and the cytotoxicity in the cell-based assay was established for six analogues of PGE. This correlation allowed the potency in the LLNA of two novel structurally closely related derivatives to be predicted by read-across with errors of 1.4- and 2.6-fold. However, the LLNA EC3 values of two structurally different bifunctional monomers were overpredicted on the basis of this data set, indicating that accurate potency estimation by read-across based on in vitro data might be restricted to a relatively narrow applicability domain.
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| 4. |
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| 5. |
- Natsch, Andreas, et al.
(author)
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Interlaboratory evaluation of methods to quantify skin sensitizing hydroperoxides potentially formed from linalool and limonene in perfumes
- 2017
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In: Flavour and fragrance journal. - : Wiley. - 0882-5734 .- 1099-1026. ; 32:4, s. 277-285
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Journal article (peer-reviewed)abstract
- The fragrant terpenes limonene and linalool can form skin sensitizing hydroperoxides upon prolonged exposure to air. Recently, high frequencies of positive patch tests to oxidized linalool and limonene were reported from multiple dermatological centres. However, there is a lack of data indicating potential sources of consumer exposure to sensitizing doses of terpene hydroperoxides which explains this frequent contact allergy. Within the IDEA project ( International Dialogue for the Evaluation of Allergens; http://ideaproject.info/), a taskforce was formed to drive analytical method development and evaluation. In an inter-laboratory study in five laboratories, a method based on hydroperoxide reduction combined with GC-MS was tested for reproducibility. Blinded samples of commercial fine fragrances were spiked with four different hydroperoxides. In samples spiked with 100-200 mu g/ml, an average recovery of 86-105% with a relative standard deviation between laboratories of 7.4-22% was found. In samples spiked with 2050 mu g/ml, the recovery was 85-91%. The reduction approach offers a transferable and reproducible method to indirectly detect low levels of hydroperoxides, at least in fine fragrances. Ideally, one would prefer to directly detect the parent hydroperoxide. Therefore the same samples were further tested with three LC-based methods directly detecting the parent hydroperoxide. LC coupled to chemiluminescence, LC-Q-TOF-MS or LC-orbitrap-MS were used. Results indicate that with specific gradients a separation of the four analytes and quantification in the fragrance matrix can be achieved. Results of this method evaluation study present a toolbox of methods to detect terpene hydroperoxides to further investigate consumer exposure.
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| 6. |
- O'Boyle, Niamh M, et al.
(author)
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Analogues of the epoxy resin monomer diglycidyl ether of Bisphenol F: effects on contact allergenic potency and cytotoxicity
- 2012
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In: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 25:11, s. 2469-2478
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Journal article (peer-reviewed)abstract
- Diglycidyl ethers of bisphenol A (DGEBA) and bisphenol F (DGEBF) are widely used as components in epoxy resin thermosetting products. They are known to cause occupational and nonoccupational allergic contact dermatitis. The aim of this study is to investigate analogues of DGEBF with regard to contact allergy and cytotoxicity. A comprehensive knowledge of the structural features that contribute to the allergenic and cytotoxic effects of DGEBF will guide the development of future novel epoxy resin systems with reduced health hazards for those coming into contact with them. It was found that the allergenic effects of DGEBF were dependent on its terminal epoxide groups. In contrast, it was found that the cytotoxicity in monolayer cell culture was dependent not only on the presence of epoxide groups but also on other structural features.
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| 7. |
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