Aquatic toxicity information is essential in environmental risk assessment to determine the potential hazards and risks of new and existing chemicals. Prediction and modelling techniques, such as quantitative structure activity relationships (QSAR) and species sensitivity distributions (SSDs), are applied to fill data gaps and to predict, assess and extrapolate the toxicity of chemicals. In this study, both techniques (i.e. the ECOSAR programme as QSAR tool and SSDs) were assessed for a set of polar narcotic structural analogues that differ in their degree of chloro-substitution (aniline, 4-chloroaniline, 3,5-dichloroaniline and 2,3,4-chloroaniline). The acute toxicity of these compounds was tested in one prokaryote species (Escherichia coli) and three eukaryote aquatic species (Pseudokirchneriella subcapitata, Daphnia magna and Danio rerio). Consequently, the experimental acute toxicity data were compared to the QSAR predictions made by the ECOSAR programme and compared to the species sensitivity modelling results. Large interspecies differences in sensitivity were observed (D. magna > P. subcapitata > D. rerio > E. coli). 4-Chloroaniline acted as an outlier in P. subcapitata toxicity. Whereas in D. magna, toxicity decreased rather than increased with increasing log Kow of the test compounds. In general, large interchemical and interspecies differences in toxicity of these relatively simple chemical structures were observed. Moreover, this species variation could not entirely be characterized by the ECOSAR tool. SSD modelling is particularly focussed on species variations and emphasis is put on protecting those species that are most affected by chemical exposure. Compared to QSARs, SSDs offer broader perspectives regarding species sensitivity ranking, however, in this study they could only be applied for aniline and 4-chloroaniline.