The DEMETRA acute toxicity model toward the water flea (Daphnia magna)was used as a case studyto outline a validation method compatible with regulatory use. Reliability, predictive power, uncertainty, and applicability were verified with an external test set of pesticides. Predictions for this external set using the DEMETRA model, developed ad hoc for pesticides, were compared with the results using ECOSAR and TOPKAT as benchmarks. The evaluation considered statistical parameters and the presence of errors, with their size and sign. DEMETRA gave good statistical predictions, and the maximum error of the outliers was lower than that with the other two models. DEMETRA gave a limited number of false negatives, and the use of defined rules indicated the level of uncertainty was acceptable.