Exposure to 4-hydroxy-4'-isopropoxydiphenylsulfone causes retinal structural damage and visual impairment in zebrafish.

4-Hydroxy-4'-isopropoxydiphenylsulfone (BPSIP), an emerging substitute for bisphenol A (BPA), has been increasingly detected in the environment, yet its toxicological profile remains poorly understood. In this study, zebrafish larvae were exposed to BPSIP at various concentrations, including an environmentally relevant level (50 μg/L), for 5 days. Transcriptomic analysis indicated that BPSIP predominantly disrupted biological processes associated with optic nerve development, including oxidative stress and energy metabolism. Corresponding biochemical assays confirmed metabolic disturbance, marked by altered levels of adenosine triphosphate (ATP), pyruvate, and lactate. Oxidative stress was further demonstrated by elevated superoxide dismutase (SOD) activity, coupled with reduced catalase (CAT) activity, total antioxidant capacity (T-AOC), and glutathione (GSH) content. Multi-level toxicological endpoints confirmed optic nerve dysfunction: locomotor behavior assays revealed impaired photoresponse, which was consistent with systemic downregulation of key phototransduction-related genes and histopathological damage in the retina and lens. Additionally, increased thyroid hormone levels and altered expression of hypothalamic-pituitary-thyroid (HPT) axis-related genes indicated thyroid disruption. Together, these results demonstrate that BPSIP exposure disrupts visual function in zebrafish larvae, likely mediated by interference in phototransduction, oxidative homeostasis, energy metabolism, and thyroid signaling. This study provides new insights into the toxicity of BPSIP and underscores its potential ecological and health risks.