Structure-Dependent Neurodevelopmental Toxicity of Priority Liquid Crystal Monomers in Early-Life-Stage Zebrafish

Abstract Liquid crystal monomers (LCMs) are persistent, bioaccumulative, and toxic contaminants released from flat-screen displays and have been detected in human blood, urine, placenta, and breast milk. Recent studies indicate that LCMs can cross biological barriers and accumulate in animal brains. However, their neurodevelopmental toxicity and structure-dependent toxicological responses remain poorly characterized. We aimed to evaluate the structure-dependent neurotoxicity of seven priority LCMs and to explore their associated putative toxicological mechanisms in early-life-stage zebrafish. Zebrafish embryos were exposed to environmentally relevant and bioaccumulation-equivalent concentrations of LCMs from 10 to 500 ng/mL from 2 h postfertilization through 14 days postfertilization. Transcriptomic responses were compared using integrated GO–KEGG functional similarity analysis and validated by RT-qPCR. LCMs showed structure-dependent bioaccumulation, with marked compound-specific differences in internal accumulation. Developmental toxic effects included reduced heart rate, delayed hatching, and compound-specific malformations, with 5OCB causing the most severe effects and mortality. LCMs altered locomotor activity, with compound-specific hyperactivity or hypoactivity. 5OCB and EDFPPB altered cholinergic biomarkers, whereas several alkyl-cyclohexyl LCMs showed oxidative stress responses. Whole-larva transcriptomic profiling revealed compound-specific enrichment of neurodevelopmental, cardiotoxicity-related, and proteostasis-associated responses. Integrated GO–KEGG analysis identified shared and distinct transcriptional patterns, with the greatest similarity between EDFPPB and 5OCB. LCMs induce structure-associated neurodevelopmental toxicity accompanied by multiple toxicological response patterns, supporting structure-informed risk assessment. Risk assessment for LCMs needs to adopt structure-based strategies to capture the full spectrum of developmental neurotoxicity.