Prioritization of the ecotoxicological hazard of PAHs towards aquatic species spanning three trophic levels using 2D-QSTR, read-across and machine learning-driven modelling approaches

Polycyclic aromatic hydrocarbons (PAHs) represent a common group of environmental pollutants that endanger various aquatic organisms via various pathways. To better prioritize the ecotoxicological hazard of PAHs to aquatic environment, we used 2D descriptors-based quantitative structure-toxicity relationship (QSTR) to assess the toxicity of PAHs toward six aquatic model organisms spanning three trophic levels. According to strict OECD guideline, six easily interpretable, transferable and reproducible 2D-QSTR models were constructed with high robustness and reliability. A mechanistic interpretation unveiled the key structural factors primarily responsible for controlling the aquatic ecotoxicity of PAHs. Furthermore, quantitative read-across and different machine learning approaches were employed to validate and optimize the modelling approach. Importantly, the optimum QSTR models were further applied for predicting the ecotoxicity of hundreds of untested/unknown PAHs gathered from Pesticide Properties Database (PPDB). Especially, we provided a priority list in terms of the toxicity of unknown PAHs to six aquatic species, along with the corresponding mechanistic interpretation. In summary, the models can serve as valuable tools for aquatic risk assessment and prioritization of untested or completely new PAHs chemicals, providing essential guidance for formulating regulatory policies.