Chloroxylenol impairs the visual system, induces visually-mediated behavioral abnormalities and circadian rhythm...

p-Chloro-m-xylenol (PCMX) is a widely used broad-spectrum antimicrobial agent. Its extensive production, utilization and discharge have led to frequent detection in aquatic environments and biological samples, posing potential ecological risks. However, its toxic effects on the visual system and visual-related behaviors of aquatic organisms remain poorly understood. Here, zebrafish larvae were exposed to 0.4, 1.2, 2 and 2.8 mg/L PCMX to investigate impacts on ocular morphology, retinal development, visual-mediated behaviors and circadian rhythms. The results demonstrated that PCMX at ≥0.4 mg/L induced ocular malformations. Specifically, PCMX suppressed the expression of key genes regulating photoreceptor proliferation and differentiation and disrupted thyroid hormone signaling, inhibiting photoreceptor development and causing retinal pathology. At concentrations of 2 and 2.8 mg/L, these impairments further impaired image-forming (IF) vision and visuomotor responses to light-dark transitions. Concurrently, PCMX disrupted the rhythmic expression of melanopsin family genes in the non-image-forming (NIF) visual system. Furthermore, at higher concentrations (≥1.2 mg/L), PCMX disturbed the circadian rhythmic expression of core clock genes, ultimately induced abnormal sleep/wake behaviors featuring daytime hyperactivity and insomnia-like sleep fragmentation at night. Melatonin (MT) intervention effectively alleviated the sleep/wake behavioral deficits. In conclusion, PCMX damages IF vision by inhibiting photoreceptor development, leading to visual-mediated behavioral abnormalities, while also disrupting the NIF visual system through altered rhythmic expression of melanopsin genes. PCMX-induced circadian and sleep/wake behavioral disorders can be ameliorated by exogenous MT. This study provides novel molecular targets for PCMX ecological risk assessment and support MT as a potential intervention strategy for pollutant-induced toxicities.