A Mechanism-based QSTR Model for Acute to Chronic Toxicity Extrapolation: A Case Study of Antibiotics on Luminous Bacteria

Abstract

The determination of the chronic toxicity is time-consumed and costly, so it's of great interest to predict the chronic toxicity based on acute data. Current methods include the acute to chronic ratios (ACRs) and the QSTR models, both of which have some usage limitations. In this paper, the acute and chronic mixture toxicity of three types of antibiotics, namely sulfonamides, sulfonamide potentiators and tetracyclines, were determined by a bioluminescence inhibition test. A novel QSTR model was developed for predicting the chronic mixture toxicity using the acute data and docking-based descriptors. This model revealed a complex relationship between the acute and chronic toxicity, i.e. a linear correlation between the acute and chronic lg(-lgEC50)s, rather than the simple EC50s or-lgEC50s. In particular, the interaction energies (Ebind) of the chemicals with luciferase and LitR in the bacterial quorum sensing systems were introduced to represent their acute and chronic actions, respectively, regardless of their defined toxic mechanisms. Therefore, the present QSTR model can apply to the chemicals with distinct toxic mechanisms, as well as those with undefined mechanism. This study provides a novel idea for the acute to chronic toxicity extrapolation, which may benefit the environmental risk assessment on the pollutants.