Home About us Contact
|
Home About us Contact | ||
|
|
||
Skin Sensitizers (skin + sensitizer)
Selected AbstractsIdentification 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] Allergenicity evaluation of Bioban CS-1135 in experimental animalsCONTACT DERMATITIS, Issue 6 2004Tetsuo Yamano An industrial preservative, Bioban CS-1135, was evaluated for its contact allergenicity by means of multiple-dose guinea-pig maximization test and non-radioactive murine local lymph node assay. In the guinea-pig test, an induction dose of 0.5% Bioban CS-1135 sensitized all animals of the group. The dose,response study of the elicitation phase determined a minimum elicitation dose of 5% for positive skin reactions. In the murine assay, Bioban CS-1135 at doses of 10% and more exerted significant effects on lymphoid cell proliferation. Although the data clearly designated Bioban CS-1135 as a skin sensitizer, its relative potency was ranked lowest among skin-sensitizing biocides previously evaluated in this laboratory. [source] Strong irritants masquerading as skin allergens: the case of benzalkonium chlorideCONTACT DERMATITIS, Issue 4 2004David A. Basketter Chemicals may possess a number of hazards to human health including the ability to cause skin irritation and contact allergy. Identification and characterization of these properties should fall within predictive toxicology, but information derived from human exposure, including clinical experience, is also of importance. In this context, it is of interest to review the case of benzalkonium chloride, a cationic surfactant. This chemical is a well-known skin irritant, but on occasions it has also been reported to have allergenic properties, typically on the basis of positive diagnostic patch test data. Because the accumulated knowledge concerning the properties of a chemical is employed as the basis for its regulatory classification (e.g. in Europe), as well as for informing the clinical community with respect to the diagnosis of irritant versus allergic contact dermatitis (ACD), it is important to distinguish properly which chemicals are simply irritants from those which are both irritant and allergenic on skin. A review of the information on benzalkonium chloride confirms that it is a significant skin irritant. However, both predictive test results and clinical data lead to the conclusion that benzalkonium chloride is, at most, an extremely rare allergen, except perhaps in the eye, but with many supposed cases of ACD being likely to arise from the misinterpretation of patch test data. As a consequence, this substance should not normally be regarded as, or classified as, a significant skin sensitizer. [source] Analysis of allergens in metalworking fluidsCONTACT DERMATITIS, Issue 5 2008Maj-Len Henriks-Eckerman Background:, Metalworking fluids (MWFs) are well-known causes of occupational contact dermatitis in machinists. Objective:, To gain information about skin sensitizers in MWFs and to compare it with the information in safety data sheets (SDSs). Methods:, A total of 17 samples of MWF concentrates were analysed for skin sensitizers known or suspected to be used in MWF. Alkanolamines, formaldehyde, isothiazolinones, methyldibromo glutaronitrile (MDBGN), and iodopropynyl butylcarbamate (IPBC) were separated by liquid chromatography. Resin acids of colophonium (colophony) were separated by gas chromatography. The substances were identified with mass spectrometric detection and ultraviolet detection. Results:, Of the MWFs, 15 contained 6,39% of alkanolamines, mostly monoethanolamine and triethanolamine. Formaldehyde was detected in all MWFs: the concentrations of total formaldehyde ranged between 0.002% and 1.3%. Benzisothiazolinone and octylisothiazolinone were detected in one fluid each. IPBC was detected in nine MWFs, and the highest concentration was 0.09%. Methylisothiazolinone and MDBGN were not detected in any of the fluids. Resin acids of colophonium were detected in seven MWFs in concentrations ranging from 0.41% to 3.8%. On the whole, the allergens analysed were poorly declared in the SDSs. Conclusions:, The content of total formaldehyde was not declared in any SDS. IPBC, a relatively new allergen, seems to be common in MWFs. Isothiazolinones may be relevant allergens of machinists, and they should be analysed in MWFs in case other sources are not identified. The occupational relevance of positive patch test results to MWF ingredients in machinists is difficult to determine if information in the SDSs is relied upon. [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] Quantitation of suspected allergens in fragrances (Part I): evaluation of comprehensive two-dimensional gas chromatography for quality controlFLAVOUR AND FRAGRANCE JOURNAL, Issue 2 2004Robert Shellie Abstract An evaluation of comprehensive two-dimensional (2D) gas chromatography (GC×GC) was performed to assess its suitability for the analysis of volatile fragrance components, recognized by the European Commission's Scienti,c Committee on Cosmetics and other Non-food Products (SCCNFP) as possible skin sensitizers. The 24 volatile components listed by the SCCNFP were baseline-resolved or better within one 30 min analysis. High-quality calibration data for standard mixtures were obtained, with R2 > 0.998 over the concentration range 2,1000 mg/l. However, the analysis of small spiked amounts of target compounds in truly complex fragrances was problematic, due to uncertainty in component assignment. The bene,ts and limitations of GC×GC are reported, and a discussion of the proposed directions for the solution of this analysis is provided. Copyright © 2004 John Wiley & Sons, Ltd. [source] Advantage of using CBA/N strain mice in a non-radioisotopic modification of the local lymph node assayJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2006Masahiro Takeyoshi Abstract The murine local lymph node assay (LLNA) is currently recognized as a stand-alone test method for determining the skin sensitizing potential of chemicals. It has been incorporated into the official test guidelines published by some authorities, including the OECD. To avoid the use of radioisotopes, efforts have been made recently to develop non-radioisotopic modifications of the LLNA. A non-radioisotopic modification of the LLNA was developed previously using 5-bromo-2,-deoxyuridine (BrdU) incorporation (non-RI LLNA). However, the non-RI LLNA was found to be somewhat less sensitive than the standard assay. This study reports the advantage of using mice of the CBA/N strain in the non-RI LLNA to improve the sensitivity of this method. The non-RI LLNA was performed using CBA/JN and CBA/N mice exposed to one of four confirmed skin sensitizers, 2,4-dinitrochlorobenzene (DNCB), eugenol (EG), isoeugenol (IEG) or , -hexylcinnamic aldehyde (HCA), and to one non-sensitizer, propylene glycol (PG). The EC3 values for DNCB, IEG, EG, HCA and PG were calculated to be 0.1%, 9.6%, 40.6%, 45.5% and >50% in CBA/JN mice and 0.08%, 1.9%, 10.7%, 20.3% and >50% in CBA/N mice, respectively. The EC3 values for DNCB, IEG, EG, HCA and PG in the standard LLNA using CBA/Ca mice and radioisotopes were reported elsewhere as being 0.08%, 1.3%, 13.0%, 8.0% and >50%, respectively. The EC3 values derived from the CBA/N mice in the non-RI LLNA were nearly equivalent to the EC3 values obtained using the standard radioisotopic LLNA with CBA/Ca mice. These data suggest that the use of CBA/N mice may provide a realistic opportunity to develop a version of the LLNA that does not have a requirement for the use of radioisotopes, but which nevertheless has sensitivity approaching, or comparable to, the standard method. Copyright © 2005 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] Gene expression studies in cultured dendritic cells: new indicators for the discrimination of skin sensitizers and irritants in vitroCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2009S. Szameit Summary Background The replacement of animal tests for the detection of the sensitizing potential of chemicals is of great importance due to current legislation. One promising approach for the development of an in vitro assay is the exposure of immature dendritic cells (iDCs) to contact sensitizers and irritants, followed by an analysis of the maturation status of the cells. Objective The aim of this study was to further investigate the performance of our previously developed targeted microarray, the immune toxicity chip. In addition, we aimed to identify new marker genes for the discrimination of allergens and irritants using whole-genome microarrays. Methods Monocyte-derived iDCs were exposed to contact sensitizers and irritants in concentrations resulting in 10,20% cytotoxicity, as determined by dose,response curves. Changes in gene expression were analysed using the immune toxicity chip and a commercially available whole-genome microarray. Results Using the immune toxicity chip, we could identify a panel of marker genes suitable to discriminate strong allergens and irritants. Analysis with the whole-genome array revealed additional genes that are differentially expressed after allergen exposure, but not after irritant exposure. Hierarchical clustering of these genes showed distinct groups representing the different chemicals. Conclusion Here we show that our test system based on an immune-specific microarray is suitable for the discrimination of strong allergens and irritants. Genes detected as differentially expressed with the whole-genome array and previously not connected to the maturation process of DCs might be suitable candidate genes for the identification of weaker sensitizers. [source] | |||||||||||||