Ecotoxicological QSAR modelling of the acute toxicity of fused and non-fused polycyclic aromatic hydrocarbons (FNFPAHs) against two aquatic organisms: Consensus modelling and comparison with ECOSAR

Fused and non-fused polycyclic aromatic hydrocarbons (FNFPAHs) are a type of organic compounds widely occurring in the environment that pose a potential hazard to ecosystem and public health, and thus receive extensive attention from various regulatory agencies. Here, quantitative structure-activity relationship (QSAR) models were constructed to model the ecotoxicity of FNFPAHs against two aquatic species, Daphnia magna and Oncorhynchus mykiss. According to the stringent OECD guidelines, we used genetic algorithm (GA) plus multiple linear regression (MLR) approach to establish QSAR models of the two aquatic toxicity endpoints: D. magna (48 h LC50) and O. mykiss (96 h LC50). The models were established using simple 2D descriptors with explicit physicochemical significance and evaluated using various internal/external validation metrics. The results clearly show that both models are statistically robust (QLOO2 = 0.7834 for D. magna and QLOO2 = 0.8162 for O. mykiss), have good internal fitness (R2 = 0.8159 for D. magna and R2 = 0.8626 for O. mykiss and external predictive ability (D. magna: Rtest2 = 0.8259, QFn2 = 0.7640∼0.8140, CCCtest = 0.8972; O. mykiss:Rtest2 = 0.8077, QFn2 = 0.7615∼0.7722, CCCtest = 0.8910). To prove the predictive performance of the developed models, an additional comparison with the standard ECOSAR tool obviously shows that our models have lower RMSE values. Subsequently, we utilized the best models to predict the true external set compounds collected from the PPDB database to further fill the toxicity data gap. In addition, consensus models (CMs) that integrate all validated individual models (IMs) were more externally predictive than IMs, of which CM2 has the best prediction performance towards the two aquatic species. Overall, the models presented here could be used to evaluate unknown FNFPAHs inside the domain of applicability (AD), thus being very important for environmental risk assessment under current regulatory frameworks.