Toxic effects of octocrylene on zebrafish larvae and liver cell line (ZFL)

Highlights: • The toxic effects of octocrylene (OC) on zebrafish larvae and ZFL were studied. • OC had no obvious phenotypic toxicity to larvae, but it was very toxic to ZFL. • OC upregulated CYP1A, CYP3A65, ERα, ERβ1, CYP19A, and DMRT1 genes but downregulated 11β-HSD. • OC upregulated glutathione transferases. • OC is not a ligand of AhR1B and AhR2, but it can activate ERα and GPER. Octocrylene (OC) is a broad-spectrum ultraviolet-absorbing chemical used in sunscreen and other personal care products. Its health effects are a concern because it has been detected in water, fish, humans, and food chains. In vivo and in vitro investigations were performed in zebrafish (Danio rerio) larvae and a zebrafish liver cell line (ZFL), respectively, to understand the potential risks and molecular mechanisms of OC toxicity. The 96-h median lethal concentration (LC₅₀) of OC was determined to be 251.8 μM in larvae and 5.5 μM in ZFL cells. Quantitative real-time PCR (qRT-PCR) showed that OC induced the expression of genes for CYPs (CYP1A, CYP3A65), estrogen receptors (ERα, ERβ1, GPER), vitellogenin (VTG1), and sex determination (BRCA2, CYP19A, DMRT1, SOX9A), both in vitro and in vivo. A whole-transcriptome sequencing method was used to evaluate the gene expression profile of larvae exposed to OC. OC was found to mediate the biosynthesis of estrogens (such as estriol) and affect the antioxidant pathway (glutathione transferases and peroxisome). These findings clarify the toxic effects and molecular mechanisms of OC and support banning its use in cosmetics.