2-Hydroxy-4-n-octyloxybenzophenone induces developmental neurotoxicity and multiple sclerosis-like symptoms through cacna1a regulated Ca

Summary

Using zebrafish exposed to environmentally relevant UV-531 concentrations, the study found significant neurotoxicity without overt developmental defects. Multi-modal assays implicated dopaminergic neuron alterations, BBB/vascular changes, and cacna1a-regulated calcium dysregulation as mechanistic drivers.

Key Findings

• Environmentally relevant UV-531 (0.1–1.6 μg/L) caused significant neurotoxicity in zebrafish without overt developmental toxicity.
• Dopaminergic neuron alterations and changes in cerebral vessels/BBB were observed in transgenic lines.
• Transcriptomic/qPCR data and calcium assays implicated cacna1a-regulated Ca2+ dysregulation as a mechanistic pathway.

Clinical Implications

Dermatologists and formulators should be aware of potential systemic neurotoxic risks from UV-531 exposure; risk assessors may consider substituting or limiting UV-531 in cosmetic products pending confirmatory mammalian data.

Limitations

• Findings are limited to zebrafish; mammalian in vivo confirmation is needed
• Real-world co-exposures and long-term outcomes were not assessed

Future Directions

Conduct mammalian neurotoxicity and pharmacokinetic studies of UV-531, compare with alternative UV filters, and evaluate dose–response and human exposure relevance.