Organophosphate esters (OPEs) are increasingly recognized as pervasive environmental contaminants, primarily from their extensive application in flame retardants and plasticizers. Despite their widespread presence, the intricacies of OPE bioaccumulation within aquatic ecosystems remain poorly understood, particularly the environmental determinants influencing their distribution and the bioaccumulation dynamics across aquatic food chains. Here we show that water temperature plays a crucial role in modulating the dispersion of OPE in the aquatic environment of Poyang Lake. We quantified OPE concentrations across various matrices, uncovering levels ranging from 0.198 to 912.622 ng L⁻¹ in water, 0.013–493.36 ng per g dry weight (dw) in sediment, 0.026–41.92 ng per g wet weight (ww) in plankton, 0.13–2100.72 ng per g dw in benthic invertebrates, and 0.31–3956.49 ng per g dw in wild fish, highlighting a pronounced bioaccumulation gradient. Notably, the intestines emerged as the principal site for OPE absorption, displaying the highest concentrations among the seven tissues examined. Among the various OPEs, tris(chloroethyl) phosphate was distinguished by its significant bioaccumulation potential within the aquatic food web, suggesting a need for heightened scrutiny. The propensity for OPE accumulation was markedly higher in benthic invertebrates than wild fish, indicating a differential vulnerability within aquatic biota. This study lays a foundational basis for the risk assessment of OPEs as emerging contaminants and underscores the imperative to prioritize the examination of bioaccumulation effects, particularly in benthic invertebrates, to inform future environmental safeguarding strategies.

Organophosphate esters (OPEs) are widespread in various environmental media, and can disrupt thyroid endocrine signaling pathways. Mechanisms by which OPEs disrupt thyroid hormone (TH) signal transduction are not fully understood. Here, we present in vivo-in vitro-in silico evidence establishing OPEs as environmental THs competitively entering the brain to inhibit growth of zebrafish via multiple signaling pathways. OPEs can bind to transthyretin (TTR) and thyroxine-binding globulin, thereby affecting the transport of TH in the blood, and to the brain by TTR through the blood–brain barrier. When GH3 cells were exposed to OPEs, cell proliferation was significantly inhibited given that OPEs are competitive inhibitors of TH. Cresyl diphenyl phosphate was shown to be an effective antagonist of TH. Chronic exposure to OPEs significantly inhibited the growth of zebrafish by interfering with thyroperoxidase and thyroglobulin to inhibit TH synthesis. Based on comparisons of modulations of gene expression with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, signaling pathways related to thyroid endocrine functions, such as receptor–ligand binding and regulation of hormone levels, were identified as being affected by exposure to OPEs. Effects were also associated with the biosynthesis and metabolism of lipids, and neuroactive ligand–receptor interactions. These findings provide a comprehensive understanding of the mechanisms by which OPEs disrupt thyroid pathways in zebrafish.