Neurotoxic effects of 2-ethylhexyl diphenyl phosphate exposure on zebrafish larvae: Insight into inflammation-driven changes in early motor behavior

The extensive utilization and potential adverse impacts of the replacement flame-retardant 2-Ethylhexyl Diphenyl Phosphate (EHDPP) have raised concerns. Currently, there is limited knowledge regarding the developmental, neurological, and immunotoxic consequences of EHDPP exposure, as well as its potential behavioral outcomes. In this study, we undertook a comprehensive examination and characterization of the toxic effects over the EHDPP concentration range of 14-1400 nM. Our findings unveiled that EHDPP, even at an environmentally relevant concentration of 14 nM, exhibited excitatory neurotoxicity, eliciting a 13.5 % increase in the swimming speed of zebrafish larvae. This effect might be attributed to the potential influence of EHDPP on the release of neurotransmitters like serotonin and dopamine, which, in turn, mediated anxiety-like behavior in the zebrafish larvae. Conversely, sublethal dose EHDPP (1400 nM) exposure significantly suppressed the swimming vigor of zebrafish larvae, accompanied by morphological changes, abnormal behaviors, and alterations in intracerebral molecules. Transcriptomics revealed the underlying mechanism. The utilization of pathway inhibitors reshaped the inflammatory homeostasis and alleviated the toxicity induced by EHDPP exposure, anchoring the pivotal role played by the TLR4/NF-kappa B signaling pathway in EHDPP-induced adverse changes in zebrafish behavior and neurophysiology. This study observed the detrimental effects of EHDPP on fish sustainability at environmentally relevant concentrations, highlighting the practical significance for EHDPP risk management. Elucidating the toxic mechanisms of EHDPP will contribute to a deeper comprehension of how environmental pollutants can intricately influence human health.