Exposure to 2-chlorohydroquinone induces systemic vascular disorders and increases the risk of cerebral hemorrhage in zebrafish larvae.

2-Chlorohydroquinone (2-CHQ), a chlorinated phenolic compound widely used in industrial processes, poses potential ecological risks due to its persistence and bioaccumulation. This study investigated the developmental toxicity of 2-CHQ in zebrafish larvae following 72-hour exposure. Results demonstrated that 2-CHQ induced severe systemic vascular malformations and dose-dependent cerebral hemorrhage, accompanied by blood-brain barrier disruption, neuroinflammation, and apoptosis. QRT-PCR analysis revealed dysregulation of vascular development genes (e.g., VEGFR2, pdgfrb) and tight junction proteins. Network pharmacology and molecular docking identified MAPK/ERK pathway as a core pathway, and pharmacological inhibition of the MAPK/ERK pathway with PD98059 ameliorated vascular defects and hemorrhage. These findings reveal that 2-CHQ impairs vascular integrity via MAPK/ERK activation, providing critical insights into its mechanistic toxicity and potential environmental health risks.