The Registration, Evaluation, Authorisation and Restriction of Chemical substance (REACH) is the new European Community Regulation on chemicals and their safe use. Estimates indicate that as much as 30,000 single chemicals may be required to be registered with a potentially risk assessment requirement based on substance-specific data for the persistence, bioaccumulation and toxic (PBT) properties for several thousand chemicals. This introduce a challenge for industry, the regulatory agencies and the toxic ological research community to develop and validate alternative high-throughput testing strategies and limit the testing with animals by implementing the reduction, refinement and replacement (the 3Rs) principle in ecotoxicological testing. This applies i n particular to the use of aquatic vertebrates such as fish, which under the legislation . This proposal seeks to provide theoretical and experimental data to develop and evaluate alternative ecotoxicological test methods for fish in risk assessment and to provide input to risk regulators, industry and academia on the applicability of the different approaches to assess the PBT properties of chemicals. The proposed work will be performed through use of a combination between computational (in silico) and experimental (in vitro, in vivo screening) investigations with comparison with existing in vivo testing data. The project is multi-disciplinary and highly integrated with partners from key environmental institutes in Germany, United Kingdom, Switzerlan d and Norway will and the project will be lead by the Norwegian Institute for Water Research (NIVA). The proposed project will support both research by established research groups as well as education of one PhD and 3 Ms. Sc. student to be working in the different collaborating laboratories.