Zhang_2025_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__110293

N, N-Diethyl-meta-toluamide (DEET) is a widely used insect repellent that can be detected in water and soil worldwide. Although adverse reactions have been reported following the use of DEET - containing products, there are few toxicity studies. In this study, zebrafish were exposed to 0, 0.2 mg/mL, 0.25 mg/mL, and 0.3 mg/mL of DEET. With increasing exposure concentrations, zebrafish mortality increased and body length development was reduced. At 72 hours post fertilization (hpf), zebrafish exhibited pericardial edema, decreased heart rate, and yolk sac edema. Significant abnormalities in the looping morphology of the heart were observed, with the atrium and ventricle positioned along the midline, resulting in cardiac linearization. The expression levels of genes related to cardiac development (myh6, nppa, nkx2.5, gata4, tbx5a, vmhc) increased. On the other hand, the quantity of neutrophils and macrophages exhibited a decrease, and the expression level of genes related to mediating inflammatory response (myd88, ifn-gamma, tlr4) and inflammatory factor genes (il-6, il-8, il-10) increased. In addition, DEET exposure caused a reduction in newly generated neurons at 24 hpf. At 72 hpf, the activity of acetylcholinesterase (AChE) was inhibited, and motor behavior show that the total distance and average speed were significantly reduced. Further research found that oxidative stress was activated, and reactive oxygen species (ROS) content increased significantly. In summary, DEET cause multiple toxicities to the heart, immune system, and nervous system during early developmental stages of zebrafish embryos, and these toxicities may be induced by oxidative stress.