Acute triclosan exposure induces multidimensional toxicity in zebrafish larvae: Disruption of development, behavior,...

Triclosan (TCS), a widely used antibacterial agent, is frequently detected in aquatic environments, raising concerns about its ecological toxicity. However, the mechanisms underlying TCS-induced developmental toxicity, neurobehavioral impairment, immune dysfunction, and cell death pathways remain insufficiently understood. In this study, zebrafish larvae were exposed to TCS at 2.3, 23, and 230 μg/L to systematically evaluate its effects on development, behavior, oxidative stress, immune responses, and cell death-related pathways. The results showed that TCS exposure induced developmental abnormalities, including shortened body length, delayed yolk sac absorption, and eye malformations. Behavioral assays further revealed reduced locomotor activity and impaired responses to light-dark transitions, suggesting neurobehavioral toxicity. At the cellular and biochemical levels, TCS exposure caused ROS accumulation, GSH depletion, increased MDA content, iron accumulation, mitochondrial dysfunction, and enhanced apoptosis, indicating the involvement of oxidative stress, ferroptosis, and apoptosis in TCS-induced toxicity. In addition, TCS exposure significantly increased macrophage and neutrophil abundance and caused intestinal and hepatic injury, suggesting broader systemic toxicity. Gene expression analysis indicated that TCS exposure at 2.3 and 23 μg/L mainly affected necroptosis- and pyroptosis-related signaling pathways, whereas exposure to 230 μg/L TCS was associated with ferroptosis induction and alterations in autophagy. Molecular docking analysis suggested that TCS may interact with key proteins, including Jak2a, Stat3, and Ptgs2a, thereby contributing to the regulation of multiple cell death pathways. Overall, these findings demonstrate that acute TCS exposure induces multidimensional toxicity in zebrafish larvae through developmental disruption, oxidative stress, ferroptosis, apoptosis, immune disturbance, and related molecular signaling pathways.