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|Title:||The Local Lymph Node Assay and Skin Sensitisation - A Cut-Down Screen to Reduce Animal Requirements|
|Authors:||KIMBER Ian; DEARMAN Rebecca; BETTS Catherine; GERBERICK Frank; RYAN Cindy; KERN Petra; TIER GRACE; BASKETTER David|
|Citation:||CONTACT DERMATITIS vol. 54 p. 181-185|
|Type:||Articles in Journals|
|Abstract:||Skin sensitisation is an important occupational and environmental health problem and there is a continuing need to identify potential contact allergens. In recent years there has become available the local lymph node assay (LLNA), an alternative approach to skin sensitising testing that offers scientific advantages compared with the guinea pig methods that were used previously. The LLNA is viewed as having made a significant contribution to animal welfare, achieved through a requirement for fewer experimental animals, coupled with a reduction in the trauma to which animals are potentially subject. Nevertheless there is clearly an aspiration to improve further animal welfare in the context of skin sensitisation testing, and in the long-term to seek ways to eliminate altogether the need for the use of animals. However, although this latter objective is laudable, and the subject of intensive research, it is appropriate also to consider other opportunities for refinement and reduction of animal use. To this end we have here explored the possibility of using a modified version of the LLNA for screening purposes when there is a need to evaluate the sensitising activity of a large number of chemicals, as will be the case under the auspices of REACH (Registration, Evaluation and Authorisation of Chemicals). Specifically we have examined, using an existing LLNA database of 211 chemicals, whether a cut-down assay comprising only a single high dose group, together with a concurrent vehicle control, would provide a realistic approach (either alone, or as part of an integrated testing strategy) for screening chemicals for sensitising potential. The analyses reported here suggest this is the case. Such an approach offers significant animal welfare benefits and we speculate here that these may be enhanced further by considering also a reduction in the number of animals required in each experimental group. However, it is emphasised that currently this remains speculation only and clearly a detailed evaluation will be necessary to provide reassurance that a reduction in group size would provide adequate sensitivity across a range of skin sensitisation potencies. This article provides recommendations for achieving additional animal welfare benefits with respect to screening for skin sensitising activity using a reduced LLNA approach.|
|JRC Institute:||Institute for Health and Consumer Protection|
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