Tributyl phosphate inhibits neurogenesis and motor functions during embryonic development in zebrafish

Abstract

Tributyl phosphate (TBP), an organophosphate ester (OPE), is heavily used as a solvent in chemical industries, a plasticizer, and to extract radioactive molecules. Thus, widespread uses of TBP in industrialized countries led to the release of TBP and its metabolites, dibutyl phosphate (DBP) and monobutyl phosphate (MBP), in the environment and were detected in human samples. Accumulating these OPEs over time in humans and aquatic animals may develop toxicological effects. The reports also say TBP passes through the mother-fetal transmission route and may affect embryonic development. However, the impact of TBP and its metabolites on vertebrate development has been poorly studied. Ex-utero development, high fecundity, and optical transparency make the zebrafish a preferred model for toxicological evaluation. Thus, we aim to explore the toxic effects of TBP and its metabolites on aquatic animals using zebrafish as a model organism. Embryos in the chorion were incubated in 10–60 µM test chemicals from 6 to 48 h post fertilization (hpf), and analyzed the adverse effects on embryos. Our study found that 10–20 µM TBP inhibits neural growth, resulting in decreased spontaneous movement frequency and locomotive behavior without altering the overall embryonic growth and muscle functions. In contrast, DBP-treated embryos showed increased spontaneous movement frequency without changing the motor neuron growth and locomotive behavior. Further, in higher concentrations, TBP is teratogenic, and DBP is lethal to the embryos. Altogether, we found that TBP inhibits neurogenesis and motor behavior; however, its metabolite DBP is neuroexcitatory in zebrafish embryos.