Pyrethroid pesticides are extensively applied in agriculture and public health, leading to considerable environmental contamination and human exposure. D-tetramethrin is a widely used household insecticide frequently encountered by humans. Although considered low-toxicity, its potential to induce neurotoxicity and motor dysfunction remains poorly defined. Here, we evaluated the developmental neurotoxicity of D-tetramethrin using zebrafish embryos and human SH-SY5Y neuroblastoma cells. In vivo, exposure caused impaired development with increased malformations and reduced locomotor activity. Neurobehavioral testing revealed weakened touch and light–dark responses, anxiety-like behavior, and neuronal abnormalities, indicative of developmental neurotoxicity. Biochemical analyses demonstrated decreased ATPase and AChE activities, reduced GABA levels, compromised antioxidant defenses (SOD, CAT, GSH), and elevated ROS and MDA, consistent with oxidative stress. Transcriptomic profiling identified differentially expressed genes enriched in pathways related to neurodevelopment, neurotransmission, apoptosis, and oxidative stress. To further validate these findings, SH-SY5Y cells were exposed to D-tetramethrin and showed concentration-dependent cytotoxicity, ROS accumulation, and apoptosis, consistent with transcriptomic predictions. In summary, D-tetramethrin disrupts neurodevelopment, neurotransmitter balance, and antioxidant defenses while promoting oxidative stress and apoptosis, leading to neurotoxicity and locomotor dysfunction in zebrafish embryos, further supported by in vitro validation.
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