Two-Compartmental Toxicokinetic Model Predicts Interspecies Sensitivity Variation of Imidacloprid to Aquatic Invertebrates

Interspecies sensitivity to the same chemical can be several orders of magnitude different. Quantifying toxicologically internal levels and toxicokinetic (TK) parameters is critical in elucidating the interspecies sensitivity. Herein, a two-compartmental TK model was constructed to characterize the uptake, distribution, and elimination kinetics toward interspecies sensitivity to an insecticide, imidacloprid. Imidacloprid exhibited the highest lethality to the insect Chironomus dilutus, followed by Lumbriculus variegatus, Hyalella azteca, and Daphnia magna. Interspecies sensitivity of imidacloprid to these invertebrates varied by ∼1000 folds based on water concentrations (LC50). Remarkably, the sensitivity variation decreased to ∼50 folds based on the internal residues (LR50), highlighting the critical role of TK in interspecies sensitivity. A one-compartmental TK model failed to simulate the bioaccumulation of imidacloprid in these invertebrates except for D. magna. Instead, a two-compartmental model successfully simulated the slow elimination of imidacloprid in the remaining three species by internally distinguishing the highly dynamic (C₁) and toxicologically available (C₂) fractions. We further showed that the species sensitivity of the invertebrates to imidacloprid was significantly related to C₂, demonstrating that C₂ was toxicologically available and responsible for the toxicity of imidacloprid. This mechanistic-based model bridged the internal distribution of organic contaminants in small invertebrates and the associated toxic potency. © 2023 American Chemical Society