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Notes: 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 have collected a large 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, in particular for the development of in silico methods. Prerequisite for the development of in silico models is always the availability of a large high quality data set, suitable for modeling. This dataset encompasses both the chemical and biological diversity of known chemical allergens, and provides also examples of negative controls. The data are a collection of published and non-proprietary industry data. All materials were tested in standard vehicules following the standard LLNA protocol. It is hoped that this dataset will accelerate the development, evaluation and eventual validation of new approaches to skin sensitization testing.

Notes: For new chemicals introduced into the workplace or marketplace, and which come into contact with the skin, it is necessary, to conduct a thorough skin safety testing and risk assessment program to be certain that the exposures will be well tolerated. One vital risk assessment process involves the determination of allergic skin reactions, referred to as skin sensitization, the clinical manifestation of which is allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization is dependent on many factors including the ability of the chemical to penetrate the skin, react with protein, and trigger a cell-mediated immune response. Based on our chemical, cellular and molecular understanding of allergic contact dermatitis, it is possible to carry out a quantitative risk assessment. It has been well known for years that chemical allergens display dose-response characteristics regardless of whether the sensitization is induced in an experimental system or in humans. Moreover, it is well known that the critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. The skin sensitization testing and risk assessment process for new ingredients and consumer products generally follows a step-wise approach that may involve structure-activity evaluations, analytical assessments, preclinical skin sensitization testing (e.g., the mouse local lymph node assay), confirmatory clinical testing (e.g., the human repeat insult patch test), and benchmarking of resulting data against similar ingredients and product types. Essential elements for conducting a sound risk assessment involve the development of an understanding of the sensitization potential of the contact allergen and the likely dose, nature, extent and duration of exposure. With an understanding of the exposure and potency of the chemical one can assess whether the chemical, under the specific conditions of exposure, ould pose an acceptable or unacceptable risk of induction of skin sensitization. As with any test method or risk assessment approach, it is critical to understand the strengths and limitations so that one can conduct the best assessment possible and assure the skin safety of the chemical under evaluation.

Notes: The successful acquisition of skin sensitisation requires orchestrated cellular and molecular interactions that collectively result in the induction of a cutaneous immune response of the required quality and vigour. Pivotal roles are played by epidermal Langerhans cells (LC), and by the mature immunostimulatory dendritic cells (DC) into which they mature. LC serve as sentinels of the adaptive immune system with responsibility for surveying changes in the local microenvironment and for processing antigen (and chemical allergens) encountered at skin surfaces. Following such encounters LC are mobilised and stimulated to migrate, via afferent lymphatics, to regional lymph nodes. While in transit they lose the properties of antigen processing cells and acquire instead the characteristics of mature DC that are able to interact effectively with, and present antigen to, T lymphocytes. To gain a greater understanding of the molecular events that induce and regulate cutaneous immune responses to chemical allergens, we have used microarray transcript profiling and related experimental approaches to characterise changes in gene expression and protein production associated with the development of skin sensitisation. Our attention has focused particularly on changes in the expression of mRNA and protein resulting from the interaction of chemical allergens with DC, and associated with the presentation of antigen to T lymphocytes.