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

Abstract

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 (C 1 ) and toxicologically available (C 2 ) fractions. We further showed that the species sensitivity of the invertebrates to imidacloprid was significantly related to C 2 , demonstrating that C 2 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.

Toxicokinetics Explain Differential Freshwater Ecotoxicity of Nanoencapsulated Imidacloprid Compared to Its Conventional Active Ingredient

“…Among the three organisms, C. kiinensis displayed the highest sensitivity toward IMI (Figure S6), which was consistent with previous studies. 8 The 96-h LC50 values of nano-IMI and IMI for C. kiinensis were 3.35 (3.18−3.53) and 3.00 (2.83−3.19) μg/L, respectively, showing no significant difference in toxicity between nano-IMI and IMI to this species. Similarly, no discernible difference was observed for the toxicity of nano-IMI and IMI to D. magna (28.9 and 29.0 mg/L, respectively), which was approximately 4 orders of magnitude less sensitive to IMI than C. kiinensis.…”

“…The f ss2 of Nano-IMI and IMI were 0.96 and 0.99 in C. kiinensis, respectively, suggesting that the majority of both pesticides were retained in the C 2 , which is the toxicologically available site for C. kiinensis. 8 The difference in the BCFs between nano-IMI and IMI (4.51 and 2.35 mL/g, respectively) was largely narrowed based on the two-compartmental model compared to the BCFs calculated by the one-compartmental TK model (20.8 and 105 mL/g, respectively), possibly explaining the similar toxicity of nano-IMI and IMI to C. kiinensis.…”

“…The species sensitivity variation of IMI reached 3 orders of magnitude among invertebrates based on external exposures, and the variation, however, reduced to less than 10 folds when thresholds based on toxicologically available fractions were used for evaluation. 8 It is hypothesized that thresholds based on toxicologically available concentrations of IMI might exhibit cross-species similarity, a notion supported by the insignificant binding affinity of IMI to nAChRs of insecta, chondrichthyes, and mammalia (Table S10). As aforementioned, the external exposure-based threshold of IMI for insecta (C. kiinensi) was 5 orders of magnitude lower than zebrafish embryos, implying a substantially higher toxicologically available fraction of IMI in insecta.…”

“…where C 1 is the concentration in compartment one, which is highly dynamic and considered nontoxic due to not binding to the target sites, and C 2 is the concentration in compartment two, which is slow exchanging and considered to be toxicologically available by binding with target sites. 8 k e1 is the elimination rate constant (1/h) from compartment one, and k 12 and k 21 are the transfer rate constants from compartment one to compartment two and vice versa (1/h), respectively. The fraction of nano-IMI and IMI distributed in C 2 when the steady state is reached (f ss2 ) can be calculated using eq 8.…”

“…Ecotoxicological responses to nanoencapsulated pesticides significantly vary depending on the active ingredients and the test species, emphasizing the necessity for interspecies assessments and indepth understanding of toxic mechanisms. Toxicokinetics (TK) play a significant role in understanding pesticide toxicity and risks, 8,9 yet limited TK works have been performed for nanopesticides. 10 Hypothetically, the controlled release and prolonged residence time of nanoencapsulated pesticides in the environment could enhance ingestion by organisms and extend exposure duration, 11 which, in turn, poses more severe threats to aquatic ecosystems through elevated bioaccumulation and trophic transfer.…”