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Skin Sensitization (skin + sensitization)
Selected AbstractsSkin sensitization, false positives and false negatives: experience with guinea pig assaysJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2010David A. Basketter Abstract The advent of the local lymph node assay (LLNA), and efforts to develop in vitro alternatives for the identification of skin sensitizing chemicals has focused attention on the issue of false positive and false negative results. In essence, the question becomes ,what is the gold standard?' In this context, attention has focused primarily on the LLNA as this is now the preferred assay for skin sensitization testing. However, for many years prior to introduction of the LLNA, the guinea pig maximization test and the occluded patch test of Buehler were the methods of choice. In order to encourage a more informed dialogue about the relative performance, accuracy and applicability of the LLNA and guinea pig tests, we have here considered the extent to which guinea pig methods were themselves subject to false positives and negative results. We describe and discuss here well-characterized examples of instances where both false negatives (including abietic acid and eugenol) or false positives (including vanillin and sulfanilic acid) have been recorded in guinea pig tests. These and other examples are discussed with particular reference to the fabrication of a gold standard dataset that is required for the validation of in vitro alternatives. Copyright © 2010 John Wiley & Sons, Ltd. [source] Sensitization, asthma and allergic disease in young soccer playersALLERGY, Issue 4 2009M. T. Ventura Background:, The aim of this study was to identify the prevalence of allergic disease in young soccer players compared to age-matched students and to evaluate if this prevalence changes as the intensity of training increases. Methods:, A modified ECRHS questionnaire was administered to 194 soccer players divided by age as Beginners (8,11 years), Juniors (12,16 years) and Under 21 (17,20 years) to evaluate the prevalence of allergic diseases and symptoms as well as drug consumption. Subjects with a positive personal history of allergic diseases underwent skin prick and/or patch tests. Age-matched students (n = 136) were used as a control group. Results:, The prevalence of allergic diseases was 34.5% in soccer players and 31.6% in control subjects (n.s.). Skin sensitization to inhalant allergens was detected in 14.4% of symptomatic soccer players and in 19.2% of control students (n.s.). Patch tests were positive in 35.7% of soccer players and 23.0% of controls with allergic dermatitis (n.s.). The prevalence of allergic diseases did not significantly change in relation to the intensity of training. Although the relative prevalence of sensitization to perennial allergens and asthma was less frequent in soccer players than in controls, and the occurrence of exercise-induced bronchoconstriction was similar in the two groups, soccer players used twice as many anti-allergic and anti-asthmatic drugs as control students. Conclusions:, An increasingly intensive training programme is not associated with greater risk of allergic disease in soccer players. Therapy regimens of allergic athletes and exercisers should be monitored more closely to guarantee adequate treatment yet avoid inappropriate drug use and doping practices. [source] Identification and classification of skin sensitizers: identifying false positives and false negativesCONTACT DERMATITIS, Issue 5 2006David A. Basketter The first step in regulatory evaluation of substances involves the identification of their intrinsic hazards, including the potential for skin sensitization. This is, quite properly, entirely different from assessment of the risks to human health, which might arise from incorporation of substances in products. EU guidance on regulations concerning the classification of skin sensitizers suggests a range of sources of information be deployed in the hazard identification process. These include chemical structure, predictive animal tests, and various types of human data. Where the information is clear-cut, then uncertainties rarely arise. However, for some materials, discordant information arises, perhaps because the substance is on the borderline of test sensitivity and classification (sensitizing materials of insufficient potency do not classified according to the EU scheme), due to conflicting results in predictive tests or for other reasons. In this study, we review data on a number of substances where a classification decision is complicated by such discordances and seek to use these examples to demonstrate how best to make a weight of evidence decision on whether a substance should, or should not, be classified as a skin sensitizer. [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] Hapten,protein binding: from theory to practical application in the in vitro prediction of skin sensitizationCONTACT DERMATITIS, Issue 4 2005Maja Divkovic In view of the forthcoming European Union ban on in vivo testing of cosmetic and toiletry ingredients, following the publication of the 7th amendment to the Cosmetics Directive, the search for practical, alternative, non-animal approaches is gathering pace. For the end-point of skin sensitization, the ultimate goal, i.e. the development and validation of alternative in vitro/in silico assays by 2013, may be achieved through a better understanding of the skin sensitization process on the cellular and molecular levels. One of the key molecular events in skin sensitization is protein haptenation, i.e. the chemical modification of self-skin protein(s) thus forming macromolecular immunogens. This concept is widely accepted and in theory can be used to explain the sensitizing capacity of many known skin sensitizers. Thus, the principle of protein or peptide haptenation could be used in in vitro assays to predict the sensitization potential of a new chemical entity. In this review, we consider some of the theoretical aspects of protein haptenation, how mechanisms of protein haptenation can be investigated experimentally and how we can use such knowledge in the development of novel, alternative approaches for predicting skin sensitization potential in the future. [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] A chemical dataset for evaluation of alternative approaches to skin-sensitization testingCONTACT DERMATITIS, Issue 5 2004G. Frank Gerberick Allergic contact dermatitis resulting from skin sensitization is a common occupational and environmental health problem. In recent years, the local lymph node assay (LLNA) has emerged as a practical option for assessing the skin-sensitization potential of chemicals. In addition to accurate identification of skin sensitizers, the LLNA can also provide a reliable measure of relative sensitization potency, information that is pivotal in successful management of human health risks. However, even with the significant animal welfare benefits provided by the LLNA, there is interest still in the development of non-animal test methods for skin sensitization. Here, we provide a dataset of chemicals that have been tested in the LLNA and the activity of which correspond with what is known of their potential to cause skin sensitization in humans. It is anticipated that this will be of value to other investigators in the evaluation and calibration of novel approaches to skin-sensitization testing. The materials that comprise this dataset encompass both the chemical and biological diversity of known chemical allergens and provide also examples of negative controls. It is hoped that this dataset will accelerate the development, evaluation and eventual validation of new approaches to skin-sensitization testing. [source] The importance of exposure estimation in the assessment of skin sensitization riskCONTACT DERMATITIS, Issue 5 2000Michael K. Robinson The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) as a case study. [source] Predicting the development of early skin test sensitization in offspring of parents with asthmaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2007Y. Jin Abstract Background, The direct causal relationship between skin sensitization and asthma are controversial until now and remains to be further researched. Our aim is to analyse the role of parental asthma in the development of skin sensitization in offspring. Materials and methods, This study was performed among nuclear families (determined by index of asthma patients), and subjects included parents and offspring. Parents were subdivided into four phenotypes on the basis of skin sensitization (SPT+ or SPT,) and asthma status (AST+ or AST,) and offspring were subdivided into three age groups: 3,8, 9,14 and 15,20 years. The main tests included a standard questionnaire and skin prick tests. Results, Offspring's skin sensitization differed among parental phenotypes at all ages (P < 0·05). In the SPT+/AST,, SPT,/AST+ and SPT+/AST+ groups, offspring were significantly more likely to be allergic than the ones in SPT,/AST, group at 3,8 years. Offspring with at least one parent with asthma were significantly more likely to have positive skin prick test response than those with non-asthmatic parents at age 3,8 years and 9,14 years, but not at 15,20 years among offspring with allergic parents. Results were independent of asthma in the children and of the characteristics of atopy in the parents. Conclusion, Parent asthma history is an independent risk factor for allergic sensitization in their offspring in a Chinese population. [source] Skin sensitization potency of isoeugenol and its dimers evaluated by a non-radioisotopic modification of the local lymph node assay and guinea pig maximization testJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2008Masahiro Takeyoshi Abstract Allergic contact dermatitis is the serious unwanted effect arising from the use of consumer products such as cosmetics. Isoeugenol is a fragrance chemical with spicy, carnation-like scent, is used in many kinds of cosmetics and is a well-known moderate human sensitizer. It was previously reported that the dimerization of eugenol yielded two types of dimer possessing different sensitization potencies. This study reports the differences in skin sensitization potencies for isoeugenol and two types of dimer, , -O-4-dilignol and dehydrodiisoeugenol (DIEG), as evaluated by the non-radioisotopic local lymph node assay (non-RI LLNA) and guinea pig maximization test. In the guinea pig maximization test, isoeugenol, , -O-4-dilignol and DIEG were classified as extreme, weak and moderate sensitizers, respectively. As for the results of non-RI LLNA, the EC3 for isoeugenol, , -O-4-dilignol and DIEG were calculated as 12.7%, >30% and 9.4%, respectively. The two types of isoeugenol dimer showed different sensitizing activities similar to the case for eugenol dimers. A reduction of sensitization potency achieved by dimerization may lead to developing safer cosmetic ingredients. Isoeugenol dimers are not currently used for fragrance chemicals. However, the dimerization of isoeugenol may yield a promising candidate as a cosmetic ingredient with low sensitization risk. The data may also provide useful information for the structure-activity relationship (SAR) in skin sensitization. Copyright © 2007 John Wiley & Sons, Ltd. [source] QSARs for the skin sensitization potential of aldehydes and related compoundsMOLECULAR INFORMATICS, Issue 2 2003Grace Patlewicz Abstract Although not all aldehydes are skin sensitizers, many of them, covering a diverse range of structures, show varying degrees of sensitization potential. Based on consideration of their reaction chemistry, it is possible to identify structural features associated with sensitization potential or the lack of it. Many aldehydes, including several fragrance allergens, can sensitize by Schiff base formation. A QSAR based on reactivity and hydrophobicity parameters has been developed for these aldehydes. The QSAR can be extended to include 1,2-diketones, which can also react by Schiff base formation. The findings indicate that for skin sensitization, as for several other areas of toxicology, chemicals are better classified in terms of their reaction chemistry rather than in terms of their functional groups, i.e., based on mechanisms of action as opposed to chemical class. [source] |