A Multi-Life-Stage Zebrafish Study on Neurobehavioral Effects of Captan and Its Metabolite at Environmentally Relevant Concentrations

The widely used phthalimide fungicide captan and its major metabolite tetrahydrop- hthalimide (THPI) are frequently detected in aquatic environments; however, their neurotoxic effects remain unclear. In this study, a multiple-life-stage Danio rerio (zebrafish) model was used to assess the developmental and neurobehavioral toxicity of captan and THPI. Zebrafish embryos were exposed to captan (1, 10, and 100 µg/L) and THPI (100 µg/L); developmental endpoints and spontaneous locomotor activity were subsequently evaluated. Although exposure to concentrations ≤100 µg/L did not significantly affect early development, it significantly inhibited locomotor activity (p < 0.05). Behavioral assays revealed that captan produced a biphasic dose-response effect on anxiety-like behavior and an adaptive response in memory. Captan exposure also significantly altered the expression of neurodevelopment-related genes, including mbpa, shha, and gap43. These findings reveal nonmonotonic dose‒response effects of captan on zebrafish and demonstrate that THPI exerts independent neurotoxic effects. This study provides a scientific basis for improving aquatic ecological risk and environmental safety assessments of captan and highlights the need to consider the independent neurotoxicity of its metabolite THPI.