The combined use of (Q)SARs and in vitro testing methods for creating intelligent testing strategies for local effects - potential and current limitations.

In the EU, for both animal welfare and economical considerations, the future policy for the risk assessment of chemicals (REACH proposal) relies on the use of both (Q)SARs and in vitro testing methods.Consequently, so-called intelligent testing strategies that are based completely on non-animal testing and/or in silico prediction methods have lately received increasing attention. In the past 15 years, activities at the BfR in this field have focused on both the validation of in vitro methods at ZEBET and the development of valid (Q)SARs for the prediction of the presence or absence of substance-related adverse effects.The work of Ingrid Gerner and colleagues at the BfR to predict/exclude local effects such as skin/eye irritation and corrosion or skin sensitisation has led to a set of physico-chemical exclusion rules and structural alerts that have been submitted to the European Chemicals Bureau for external validation in early 2005.The potential and possible limitations of these rules and alerts in combination with well-established in vitro testing methods to be used in the frame of animal-free testing strategies for local effects are discussed. Both components could complement each other to close data gaps and extend the applicability domain of such a testing strategy. Future work needs are addressed.