Xingang Liu

Combined pesticide applications are ubiquitous in agricultural production, yet the joint toxic effects and associated molecular mechanisms of such mixtures remain largely elusive. Herein, we assessed the acute and chronic toxicities of dinotefuran (DNT) and pymetrozine (PMZ) to Daphnia magna under single-compound and binary-mixture exposures, quantified mixture interaction patterns via the MIXTOX model with Independent Action (IA) model, and elucidated the underlying molecular mechanisms by computational toxicology approaches. Results showed PMZ was ~274-fold more acutely toxic than DNT, and mixture toxicity was strictly additive, consistent with IA predictions. Chronic co-exposure to PMZ and DNT induced severe additive reproductive toxicity: total offspring dropped from 497 ± 20 (control) to 27 ± 11, first brood was delayed to day 11, and brood number reduced to 3–5. Acetylcholinesterase (AChE) was their common target, with binding free energies of DNT-AChE (-14.62 ± 1.74 kcal/mol) and PMZ-AChE (-18.34 ± 2.82 kcal/mol); DFT calculations revealed electronic differences explaining their binding discrepancies. This study addresses the critical data gap in understanding the joint toxicity of DNT and PMZ mixtures, and provides robust experimental and theoretical support for the ecological risk assessment of pesticide co-exposures in aquatic environments

The intergenerational effects on behavior following parental imidacloprid (IMI) exposure were detected in zebrafish F1 offspring at different stages. At 4 dpf, F1 larvae exhibited detectable IMI residues, accompanied by significant behavioral impairments, altered expression levels of opsin and circadian rhythm genes, and reduced levels of retinol-related metabolites. At 2 and 4 months, no statistical variations were detected in the behavioral end points and the levels of retinol-related metabolites. The changes in the mRNA/protein levels of opsins and circadian rhythm were reduced in the number and/or the tested time points. The reduction in changes in gene/protein expression and metabolites might partially explain the recovery of behavioral abnormalities, which occurred concurrently with the elimination of IMI and the development of zebrafish F1 offspring. These results emphasize that circadian photoentrainment orchestrates diverse behaviors, highlight the importance of critical developmental windows in toxicology, and suggest the potential resilience of zebrafish to recover from parental exposure.