A systematic review on the evaluation of endocrine-disrupting chemicals as potential neurotoxins during zebrafish development

Endocrine-disrupting chemicals (EDCs) are well known for their ability to interfere with endocrine function; however, growing evidence indicates that they can also cause profound neurotoxic effects. These substances can affect both the central and peripheral nervous systems of aquatic organisms, including fish, and can disrupt neurobehavioral development, posing a potential threat to aquatic species. In this systematic review, we examine the neurotoxic effects of EDCs on zebrafish ( Danio rerio ), a widely utilized model organism for investigating vertebrate nervous system development. A comprehensive bibliographic search was conducted in PubMed using the terms “developmental neurotoxicity” and “fish,” which yielded 603 articles. The search was refined by incorporating the terms “endocrine disruptors” and “zebrafish,” resulting in 15 relevant studies. Of these, three were excluded—two due to irrelevance to the topic and one for being a review on strobilurin, a fungicide. The remaining 12 studies provided insights into the neurotoxic effects of 14 chemicals, including 6-OH-BDE-47 (2,2´,4,4´-tetrabromodiphenyl ether), atrazine, BDE-209, bisphenol (BPA), bisphenol S (BPS), Cd, estrone, OBS, Pb, tributyltin (TBT), tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), Thifluzamide (THM), and Ti. These compounds, encompassing biocides, heavy metals, hormones, brominated compounds, plastic components, and flame retardants, were identified as potential EDCs that disrupt nervous system development and behavior in zebrafish during embryonic, larval, and adult stages. Studies have also investigated co-exposure effects of binary mixtures like BDE-209 with Pb, BPA with Ti, and TBT with Cd. We identified significant neurodevelopmental endpoints, including alterations in thyroid/sex steroid hormone levels; neurotransmitter contents, including dopamine, serotonin, and GABA; AChE activity; locomotor behavior; and expression of sensitive genes and proteins. Notably, these neurotoxic effects were shown to have intergenerational/transgenerational/epigenetic consequences. Overall, this review provides comprehensive evidence of the neurotoxic potential of EDCs on zebrafish, emphasizing their relevance to vertebrate neurodevelopment and the potential implications for human health.