The oral acute toxicity of per- and polyfluoroalkyl compounds (PFASs) to Rat and Mouse: A mechanistic interpretation and prioritization analysis of untested PFASs by QSAR, q-RASAR and interspecies modelling methods.

Per- and polyfluoroalkyl substances (PFASs) are widely used in modern industry, causing many adverse effects on both the environment and human health. In this study, for the first time, we followed OECD guidelines to systematically investigate the quantitative structure-activity relationship (QSAR) of the oral acute toxicity of PFASs to Rat and Mouse using simple 2D descriptors. The Read-Across similarity descriptors and 2D descriptors were also combined to develop the quantitative read-across structure-activity relationship (q-RASAR) models. Interspecies toxicity (iST) correlation was also explored between the two rodent species. All developed QSAR, q-RASAR and iST models met the state-of-the-art validation criteria and were applied for toxicity predictions of hundreds of untested PFASs in true external sets. Subsequently, we performed the priority ranking of the untested PFASs based on the model predictions, with the mechanistic interpretation of the top 20 most toxic PFASs predicted by both QSAR and q-RASAR models. The two univariate iST models were also used for filling the interspecies toxicity data gap. Overall, the developed QSAR, q-RASAR and iST models can be used as effective tools for predicting the oral acute toxicity of untested PFASs to Rat and Mouse , thus being important for risk assessment of PFASs in ecological environment. [Display omitted] • QSAR and q-RASAR models for PFASs toxicity to Rat and Mouse were built first time. • The correlation between descriptors and toxicity was interpreted in detail. • Interspecies toxicity modelling was firstly explored for PFASs between Rat and Mouse. • All models were applied to predict true PFASs for the first time. • Untested PFASs with top 20 predicted toxicity by both models were ranked and analyzed. [ABSTRACT FROM AUTHOR]