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Skin sensitization in chemical risk assessment: Report of aWHO/IPCS international workshop focusing on dose–responseassessment
Citation:
Van Loveren, H., A. Cockshott, T. Gebel, U. Gundert-Remy, W. H. De Jong, J. Matheson, H. McGarry, L. Musset, M. K. SELGRADE, AND C. Vickers. Skin sensitization in chemical risk assessment: Report of aWHO/IPCS international workshop focusing on dose–responseassessment. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, 50(2):155-99, (2008).
Impact/Purpose:
Based on newer testing approaches there is a desire to expand skin sensitization testing from merely hazard identification to more quantitative assessment. The workshop focused on whether it is possible to distinguish between chemicals with a high and low potency to elicit allergic skin reactions. In addition, emerging approaches, such as structure–activity relationships (SARs), were explored. The meeting also explored whether experimental approaches used in identifying skin sensitization could inform approaches to identify chemicals with the potential for respiratory tract sensitization.
Description:
An international workshop was held in 2006 to evaluate experimental techniques for hazard identification and hazard characterization of sensitizing agents in terms of their ability to produce data, including dose–response information, to inform risk assessment. Human testing to identify skin sensitizers is discouraged for ethical reasons. Animal-free alternatives, such as quantitative structure–activity relationships and in vitro testing approaches, have not been sufficiently developed for such application. Guinea pig tests do not generally include dose–response assessment and are therefore not designed for the assessment of potency, defined as the relative ability of a chemical to induce sensitization in a previously naive individual. In contrast, the mouse local lymph node assay does include dose–response assessment and is appropriate for this purpose. Epidemiological evidence can be used only under certain circumstances for the evaluation of the sensitizing potency of chemicals, as it reflects degree of exposure as well as intrinsic potency. Nevertheless, human diagnostic patch test data and quantitative elicitation data have provided very important information in reducing allergic contact dermatitis risk and sensitization in the general population. It is therefore recommended that clinical data, particularly dose–response data derived from sensitized patients, be included in risk assessment.
