The adverse effect of TCIPP and TCEP on neurodevelopment of zebrafish embryos/larvae

Abstract Tris (1-chloro-2-propyl) phosphate (TCIPP) and tris (2-chloroethyl)phosphate (TCEP) are two widely used chlorinated organophosphate flame retardants (ClOPFRs), and have been frequently detected in various environmental media. Concern is now growing whether TCIPP and TCEP can cause neurotoxicity since they have similar chemical structure with organophosphorus pesticide. Therefore, in this study, zebrafish embryos (2–120 h post-fertilization [hpf]) were exposed to TCIPP or TCEP (0, 100, 500 or 2500 μg/L) or a model neurotoxicant, chlorpyrifos (CPF, 100 μg/L) to investigate the adverse effects and possible mechanisms of TCIPP and TCEP on neurodevelopment. Our results showed that CPF exposure resulted in developmental toxicity including decreased hatching, survival rates and increased malformation rates (e.g., spinal curvature) as well as behavior changes such as decreased locomotive activity in dark stimulation. In contrast, TCIPP and TCEP showed no significant effects on developmental parameters, but caused similar effects on locomotive activity at high concentration, indicating that although not as potent as CPF, TCIPP and TCEP may still cause adverse effects on neurodevelopment. Furthermore, our results suggest that TCIPP and TCEP showed no effects on acetylcholine content or AChE activity, which were considered as the main targets of CPF. However, TCIPP and TCEP exposure can significantly down-regulate the expression of selected genes and proteins related to neurodevelopment (e.g., mbp, syn2a, and α1-tubulin) similar as CPF did. Besides that, TCIPP and TCEP can also affect the transcription of shha and gap43 , which were not affected by CPF, pointing out a complex mechanism underlying TCIPP and TCEP's neurodevelopmental toxicity. Overall, our results demonstrated that TCEP and TCIPP may have adverse effect on the neurodevelopment of zebrafish embryos/larvae, but the underlying mechanism is not via the inhibition of acetyl cholinesterase activity.