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Sensitizing Potency (sensitizing + potency)
Selected AbstractsAutoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergensCONTACT DERMATITIS, Issue 1 2008Maria Sköld 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. Objective:, The aim of the present study was to investigate the autoxidation of linalyl acetate and the influence of oxidation on its sensitizing potency. Methods:, Analyses were performed using gas chromatography, nuclear magnetic resonance spectrometry and mass spectrometry. Sensitizing potencies of compounds were determined using the local lymph node assay (LLNA) in mice. Results:, Analyses showed that the content of linalyl acetate decreased over time on air exposure and other compounds were formed. Hydroperoxides, an epoxide and an alcohol were identified as oxidation products from linalyl acetate. In the LLNA, linalyl acetate of high purity showed a weak sensitizing potency (EC3 25%). Autoxidation increased the sensitizing potency of linalyl acetate, and a 10 weeks oxidized sample gave an EC3 value of 3.6%. As for linalool, the hydroperoxides were shown to be the oxidation products with the highest sensitizing potency. Conclusion:, It is concluded that autoxidation of the weakly allergenic linalyl acetate leads to formation of allergenic oxidation products. [source] The local lymph node assay and the assessment of relative potency: status of validationCONTACT DERMATITIS, Issue 2 2007David A. Basketter For the prediction of skin sensitization potential, the local lymph node assay (LLNA) is a fully validated alternative to guinea-pig tests. More recently, information from LLNA dose,response analyses has been used to assess the relative potency of skin sensitizing chemicals. These data are then deployed for risk assessment and risk management. In this commentary, the utility and validity of these relative potency measurements are reviewed. It is concluded that the LLNA does provide a valuable assessment of relative sensitizing potency in the form of the estimated concentration of a chemical required to produce a threefold stimulation of draining lymph node cell proliferation compared with concurrent controls (EC3 value) and that all reasonable validation requirements have been addressed successfully. EC3 measurements are reproducible in both intra- and interlaboratory evaluations and are stable over time. It has been shown also, by several independent groups, that EC3 values correlate closely with data on relative human skin sensitization potency. Consequently, the recommendation made here is that LLNA EC3 measurements should now be regarded as a validated method for the determination of the relative potency of skin sensitizing chemicals, a conclusion that has already been reached by a number of independent expert groups. [source] Predictive identification of human skin sensitization thresholdsCONTACT DERMATITIS, Issue 5 2005David A. Basketter For years, methods have been available for the predictive identification of chemicals that possess the intrinsic potential to cause skin sensitization. However, many have proven less suitable for the determination of relative sensitizing potency. In this respect, the local lymph node assay (LLNA) has been shown to have a number of important advantages. Through interpolation of LLNA dose,response data, the concentration of a chemical required to produce a threshold positive response (a 3-fold increase in activity compared with concurrent vehicle controls, the EC3 value) can be measured. The robustness of this parameter has been demonstrated rigorously in terms of inter- and intralaboratory reproducibility. Additionally, the relationship between potency estimates from the LLNA and an appreciation of human potency based on clinical experience has been reported previously. In the present investigations, we have sought to consolidate further our understanding of the association between EC3 values and human skin-sensitization potency by undertaking a thorough and extensive analysis of existing human predictive assays, particularly where dose,response information is available, from historical human repeated insult patch tests (HRIPTs). From these human data, information on the approximate threshold for the induction of skin sensitization in the HRIPT was determined for 26 skin-sensitizing chemicals. These data were then compared with LLNA-derived EC3 values. The results from each assay, expressed as dose per unit area (,g/cm2), revealed a clear linear relationship between the 2 values, thereby substantiating further the utility of LLNA EC3 values for prediction of the relative human sensitizing potency of newly identified skin sensitizers. [source] Evaluation of the skin sensitizing potency of chemicals by using the existing methods and considerations of relevance for elicitationCONTACT DERMATITIS, Issue 1 2005David A. Basketter The Technical Committee of Classification and Labelling dealing with harmonized classification of substances and classification criteria under Directive 67/548/EEC on behalf of the European Commission nominated an expert group on skin sensitization in order to investigate further the possibility for potency consideration of skin sensitizers for future development of the classification criteria. All substances and preparations should be classified on the basis of their intrinsic properties and should be labelled accordingly with the rules set up in the Directive 67/548/EEC. The classification should be the same under their full life cycle and in the case that there is no harmonized classification the substance or preparation should be self-classified by the manufacturer in accordance with the same criteria. The Directive does not apply to certain preparations in the finished state, such as medical products, cosmetics, food and feeding stuffs, which are subject to specific community legislation. The main questions that are answered in this report are whether it would be possible to give detailed guidance on how to grade allergen potency based on the existing methods, whether such grading could be translated into practical thresholds and whether these could be set for both induction and elicitation. Examples are given for substances falling into various potency groups for skin sensitization relating to results from the local lymph node assay, the guinea pig maximization test, the Buehler method and human experience. [source] Vehicle effects on skin sensitizing potency of four chemicals: assessment using the local lymph node assayINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2001Z M Wright Synopsis The murine local lymph node assay (LLNA) can be used to determine the relative skin sensitizing potency of chemicals via interpolation of the quantitative dose response data generated. Using this approach we have demonstrated previously that the vehicle matrix in which a chemical allergen is encountered on the skin can have a significant influence on sensitizing potency. Estimates of relative potency are calculated from LLNA dose responses as a function of the mathematically derived EC3 value, this being the concentration estimated to induce a stimulation index (SI) of 3. To investigate further the influence of application vehicle on sensitizing potency, the LLNA has been used to examine the activity of four recognized human contact allergens: isoeugenol and cinnamic aldehyde, two fragrance chemicals; 3-dimethylaminopropylamine (a sensitizing impurity of cocamidopropyl betaine, a surfactant used in shower gel) and dibromodicyanobutane (the sensitizing component of Euxyl K 400, a preservative used in cosmetics). The four chemicals were applied in each of seven different vehicles (acetone: olive oil [4 : 1]; dimethylsulphoxide; methylethylketone; dimethyl formamide; propylene glycol; and both 50 : 50 and 90 : 10 mixtures of ethanol and water). It was found that the vehicle in which a chemical is presented to the epidermis can have a marked effect on sensitizing activity. EC3 values ranged from 0.9 to 4.9% for isoeugenol, from 0.5 to 1.7% for cinnamic aldehyde, from 1.7 to > 10% for dimethylaminopropylamine and from 0.4 to 6.4% for dibromodicyanobutane. These data confirm that the vehicle in which a chemical is encountered on the skin has an important influence on the relative skin sensitizing potency of chemicals and may have a significant impact on the acquisition of allergic contact dermatitis. The data also demonstrate the utility of the LLNA as a method for the prediction of these effects and thus for the development of more accurate risk assessments. Résumé Le test local des ganglions lymphatiques murins (LLNA) peut être utilisé pour déterminer le potentiel relatif de sensibilisation de la peau de produits chimiques, par interpolation des données quantitatives de dose/réponse obtenues. En utilisant cette approche, nous avions démontré précédemment que la matrice vecteur par laquelle un allergène chimique est mis en contact avec la peau peut avoir une influence significative sur le potentiel de sensibilisation. Des estimations d'activité relative sont calculées à partir des doses/réponses de LLNA en fonction de la valeur EC3 dérivée mathématiquement, celle-ci étant la concentration estimée comme induisant un indice de stimulation (IS) de 3. Pour examiner plus avant l'influence du vecteur d'application sur l'activité de sensibilisation, on a utilisé le LLNA pour déterminer l'activité de quatre allergènes de contact humains reconnus: isoeugénol et aldéhyde cinnamique, deux substances chimiques de parfumerie; la 3-diméthylaminopropylamine (une impureté sensibilisante de la cocamidopropyl bétaïne, un tensioactif utilisé dans les gels douches) et le dibromodicyanobutane (le composant sensibilisant de Euxyl K 400, un conservateur utilisé dans les cosmétiques). Les quatre produits chimiques ont été appliqués dans chacun de sept vecteurs différents (acétone: huile d'olive [4: 1]; diméthylsulfoxyde; méthyléthylcétone; diméthylformamide; propy- lène glycol; et deux mélanges 50: 50 et 90: 10 d'éthanol et d'eau). On observe que le vecteur dans lequel le produit chimique est présentéà l'épiderme peut avoir un effet marqué sur l'activité sensibilisatrice. Les valeurs EC3 vont de 0,9 à 4,9 % pour l'isoeugénol, de 0,5 à 1,7 % pour l'aldéhyde cinnamique, de 1,7 à > 10 % pour la diméthylaminopropylamine et de 0,4 à 6,4 % pour le dibromodicyanobutane. Ces données confirment que le vecteur dans lequel un produit chimique est mis en contact avec la peau a une influence importante sur le potentiel relatif de sensibilisation de la peau des produits chimiques, et peut avoir un impact significatif sur l'apparition de dermatite allergique par contact. Les données démontrent aussi l'utilité du LLNA comme méthode de prévision de ces effets et donc pour le développement d'évaluations plus précises des risques. [source] | ||||||||||