Application of TKTD models in predicting time-resolved bioaccumulation and toxicity of pesticides to aquatic organisms

Abstract

Pesticides play a crucial role in global food production, but their extensive use has led to increasing threats to aquatic ecosystems due to their ubiquitous occurrence in aquatic ecosystems and high toxic potency to non-target organisms. Conventional ecological risk assessment (ERA) approaches, which mainly rely on static external exposure thresholds (e.g., LC50s), are often inadequate for accurately predicting pesticide risks in environmentally realistic scenarios where pesticide exposures fluctuate dynamically due to intermittent pesticide applications and hydrological events. Recent advances advocate for a paradigm shift toward internal exposure-based metrics and mechanistic toxicokinetic-toxicodynamic (TKTD) modeling approaches to address these challenges. These models provide a robust framework for quantifying pesticide uptake, internal distribution, metabolism, and elimination processes in organisms (TK), and simultaneously characterize the time-dependent biological effects (TD). The present review synthesizes current applications of TKTD modeling in predicting bioaccumulation and toxicity of pesticides in aquatic organisms. The influences of chemical properties (e.g., hydrophobicity, metabolic potency) and biological traits (e.g., body size) on bioaccumulation potential of pesticides in aquatic organisms are evaluated. We further discuss the application of TD models in predicting time-resolved effects (e.g., delayed and carry-over effects) and species sensitivity. By integrating these mechanistic insights into aquatic risk assessment approaches and regulatory needs, a TKTD-based ERA framework is recommended for advancing pesticide risk assessments, particularly for addressing the challenges under realistic and fluctuating exposure conditions in natural aquatic ecosystems.