In this study we propose an alternative strategy for chemical prioritization on the example of acute aquatic toxicity, where the QSAR-based activity prediction step is skipped. Our direct classification model directly converts molecular descriptors into chemical categories, avoiding the errors inherent to the activity prediction step. As a proof of concept, this strategy was tested with experimentally determined 96h lethal concentration (LC50) values for fish, for 907 organic chemicals. We compared the results of our direct classification strategy with the conventional QSAR approach. Additionally, our modeling strategy was expanded to 32000 chemicals from Norman SusDat. Finally, we performed a critical evaluation of applicability domains for all the models in this study.