A tiered toxicity testing strategy for assessing early life stage toxicity in estuarine fish (Mugilogobius chulae): A case study on tris (1-chloro-2-propyl) phosphate ester

• Published in: Journal of hazardous materials 2024-12, Vol.480, p.136108, Article 136108
• Main Authors: Ren, Jinzhi, Peng, Ying, She, Luhang, Yan, Lu, Li, Jianjun, Gao, Caixia, Wang, Chao, Wang, Yimeng, Nie, Xiangping, Zhang, Xiaowei
• Format: Article
• Language: English
• Subjects: Animals; case studies; cognition; Concentration-dependent transcriptome; developmental stages; Embryo, Nonmammalian - drug effects; environmental assessment; Estuaries; Estuarine ecological risk; estuarine fish; Glutamatergic signaling pathway; memory; molecular dynamics; Mugilogobius; Neurodevelopmental toxicity; neurotransmitters; New approach methodologies; Organophosphates - toxicity; phosphates; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; risk; Smegmamorpha; synapse; toxicity; Toxicity Tests; transcriptomics; Water Pollutants, Chemical - toxicity
• ISSN: 0304-3894; 1873-3336; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.136108

The estuarine ecological environment faces significant threats from contaminants of emerging concern (CECs); yet, the risk posed by CECs to resident organisms remains poorly understood. Here, we employed tiered toxicity testing to investigate the adverse effects and potential mechanisms of tris (1-chloro-2-propyl) phosphate (TCPP) on the early life stages of an estuarine fish, Mugilogobius chulae. TCPP affected the development of M. chulae embryos, including survival, morphology, hatching, and behavior. A concentration-dependent transcriptomic analysis showed that TCPP disrupted 12 neurodevelopment-related KEGG pathways in M. chulae embryos, with five of the 30 % top-ranked pathways related to neurotransmitter signaling. Besides the cholinergic synapse signaling pathway, the glutamatergic signaling pathway (including NMDAR and AMPAR subtypes) may also mediate TCPP-induced neurodevelopmental toxicity. The NMDAR subtype GRIN2B was downregulated at high concentrations. Molecular dynamics simulations revealed a strong interaction between TCPP and GRIN2B, with TCPP binding to the residues Ile153 and Ile188. The results suggest that NMDARs play a crucial role in TCPP-induced neurodevelopmental toxicity toward M. chulae. AOP network analysis predicted that TCPP may impact cognitive functions and memory. Our study provides a novel testing strategy for identifying the mechanisms of toxicity of CECs, a crucial component of ecological risk assessment. [Display omitted] •TCPP exposure induced behavior change of embryos and larvae of M. chulae.•TCPP interfered with cholinergic and glutaminergic pathways in M. chulae.•GRIN2B may play a key role in TCPP-induced neurodevelopmental toxicity in M. chulae.•TCPP may eventually affect the learning and memory abilities of M. chulae.