A QSAR-ICE-SSD model prediction of the PNECs for alkylphenol substances and application in ecological risk assessment for rivers of a megacity

Abstract

Alkylphenols (APs) are ubiquitous and generally present in higher residue levels in the environment. The present work focuses on the development of a set of in silico models to predict the aquatic toxicity of APs with incomplete/unknown toxicity data in aquatic environments. To achieve this, a QSAR-ICE-SSD model was constructed for aquatic organisms by combining quantitative structure-activity relationship (QSAR), interspecies correlation estimation (ICE), and species sensitivity distribution (SSD) models in order to obtain the hazardous concentrations (HCs) of selected APs. The research indicated that the keywords "alkylphenol" and "nonylphenol" were most commonly studied. The selected ICE models were robust (R²: 0.70-0.99; p-value < 0.01). All models had a high reliability cross- validation success rates (>75%), and the HC₅ predicted with the QSAR-ICE-SSD model was 2-fold than that derived with measured experimental data. The HC₅ values demonstrated nearly linear decreasing trend from 2-MP to 4-HTP, while the decreasing trend from 4-HTP to 4-DP became shallower, indicates that the toxicity of APs to aquatic organisms increases with the addition of alkyl carbon chain lengths. The ecological risks assessment (ERA) of APs revealed that aquatic organisms were at risk from exposure to 4-NP at most river stations (the highest risk quotient (RQ) = 1.51), with the highest relative risk associated with 2.9% of 4-NP detected in 82.9% of the sampling sites. The targeted APs posed potential ecological risks in the Yongding and Beiyun River according to the mixture ERA. The potential application of QSAR-ICE-SSD models could satisfy the immediate needs for HC₅ derivations without the need for additional in vivo testing.

Keywords: Endocrine disrupting chemicals; HC(5); In silico models; Surface water; Toxicity threshold.