A Feasibility Study Developing an Integrated Testing Strategy Assessing Skin Irritation Potential of Chemicals

Regulatory safety assessment of chemicals is still driven by hazard testing in animals. In light of the REACH legislation and new technologies becoming available, a shift in the way in which safety assessments are conducted is required. Integrated testing strategies (ITS) help in providing such a framework. Many of the ITS building blocks are already in use, but the concepts for their integration and application in a regulatory setting have yet to be fully implemented. This paper describes a feasibility study investigating how a combination of in silico, in vitro, and in vivo information could be applied in the assessment of skin irritation hazard. Therefore, a database of 100 existing and new chemicals was compiled. A number of strategies, both animal-free and inclusive of animal data were constructed and subsequently evaluated considering predictive capacities, severity of misclassifications and testing costs. Comparison of ITS based on these assessment parameters identified best performing strategies for chemical classification. However, defining the in vivo test as the reference test limited the evaluation of reduced ITS. This study demonstrated that ITS can be constructed, evaluated and compared in a systematic fashion. To promote ITS, further guidance on construction and multi-parameter evaluation needs to be developed.

HOFFMANN Sebastian;  GALLEGOS SALINER Ana;  TIER Grace;  ESKES Chantra;  ZUANG Valerie;  WORTH Andrew; 

2008-07-31

ELSEVIER IRELAND LTD

JRC41760

0378-4274,   

http://dx.doi.org/10.1016/j.toxlet.2008.05.004,    https://publications.jrc.ec.europa.eu/repository/handle/JRC41760,   

10.1016/j.toxlet.2008.05.004,