Analysis of oral and inhalation toxicity of per- and polyfluoroalkylated organic compounds in rats and mice using multivariate QSAR

Per- and polyfluoroalkylated organic compounds (PFAs) are versatile compounds extensively used in global industries. However, they are also persistent organic pollutants (POPs). This study aimed to develop new models for assessing oral and inhalation toxicity in rat and mice models. A set of 407 PFAs from the literature was divided into four groups based on the endpoints of interest. The models were constructed using only 2D structure descriptors derived from SMILES strings. The resulting models showed a strong statistical quality for all endpoints. They present an applicability domain (AD) that ensures good reliability, and provided meaningful interpretation, which are partially supported by existing literature. Consequently, these models are valuable for understanding how PFAs exert their toxic effect on mammals and for predicting the risk associated with these significant industrial chemical agents.