Comparison of developmental toxicity of benzophenone-3 and its metabolite benzophenone-8 in zebrafish

Benzophenone-3 (BP-3) as one of frequently used organic UV filters has been considered an emerging pollutant due to its toxicities. Benzophenone-8 (BP-8) is one of the main metabolites of BP-3 in organisms. Current reports show that BP-8 may be more toxic than BP-3. However, difference of their toxicities on embryonic development has rarely been reported. In this study, zebrafish embryos were chosen as the target organism to explore the developmental toxicities of BP-3 and BP-8. Non-targeted metabolomic analysis was performed to compare their modes of action. Results showed that BP-8 exposures led to higher bioaccumulation and lower hatching rate of zebrafish larvae than BP-3. Both BP-8 and BP-3 exposures caused behavioral abnormalities of zebrafish larvae, but no significant difference was found between them. At the metabolome level, 1 μg/L BP-3 and 1 μg/L BP-8 exposures altered neuroactive ligand-receptor interaction pathway and FoxO signaling pathway, respectively, which might be involved in the abnormal behaviors in zebrafish larvae. For higher exposure groups (30 and 300 μg/L), both BP-3 and BP-8 exposures changed metabolism of cofactors and vitamins of zebrafish larvae. Exposure of BP-3 altered the metabolism by pantothenate and CoA biosynthesis pathway, while BP-8 exposure changed riboflavin metabolism and folate biosynthesis. The above results indicated different modes of action of BP-3 and BP-8 in zebrafish embryonic development. This study sheds new light to biological hazards of BP-3 due to its metabolism in aquatic organisms.