Combined Developmental Toxicity of the Pesticides Difenoconazole and Dimethomorph on Embryonic Zebrafish

Difenoconazole (DIF) and dimethomorph (DIM) are widely used pesticides frequently detected together in environmental samples, so the deleterious effects of combined exposure warrant detailed examination. In this study, the individual and combined effects of DIM and DIF on conventional developmental parameters (hatching rate, deformity rate, lethality) and gene expression were measured in embryonic zebrafish. Both DIF and DIM interfered with normal zebrafish embryo development, and the most sensitive toxicity index for both was 96 h post-fertilization (hpf) deformity rate (BMDL10 values of 0.30 and 1.10 mg/L, respectively). The combination of DIF and DIM had mainly synergistic deleterious effects on 96 hpf deformity and mortality rates. Transcriptome analysis showed that these compounds markedly downregulated expression of mcm family genes, cdk1, and cdc20, thereby potentially disrupting DNA replication and cell cycle progression. Enhanced surveillance for this pesticide combination is recommended as simultaneous environmental exposure may be substantially more harmful than exposure to either compound alone.

Automated summary

The study found that Difenoconazole (DIF) and dimethomorph (DIM) had negative effects on the development of embryonic zebrafish, especially showing synergistic deleterious effects on deformity and mortality rates. Transcriptome analysis revealed that these compounds may disrupt DNA replication and cell cycle progression by downregulating certain genes. Enhanced surveillance is recommended for this pesticide combination due to the potentially more harmful effects of simultaneous environmental exposure.