Triphenylphosphine oxide (TPPO) as a new organophosphorus flame retardant is extensively used in the industrial and pharmaceutical fields due to its chemical stability and abundance. In marine environments, TPPO accumulates as a result of natural ecological processes. This study aimed to evaluate the accumulation process and toxicological effects of TPPO utilizing mussels (Mytilus coruscus), a species traditionally employed in marine monitoring and commonly cultivated in offshore aquaculture. GC–MS/MS was employed to quantify the accumulation of TPPO in the gill, gonad, muscle, and digestive gland tissues of mussels exposed to three sublethal concentrations (20.0, 100.0, and 500.0 μg/L) over durations of 3, 7, 14, and 28 days, as well as the examining of the chemical and molecular parameters. Results showed that the accumulation of TPPO (100.0 and 500.0 μg/L) increased throughout the 28 d of exposure, and the peak accumulation of 20.0 μg/L TPPO was detected on 14 d. Short-term TPPO exposure did not cause oxidative stress in mussels. Chronic exposure for 28 days resulted in significant oxidative damage and oxidative stress in mussels, as evidenced by elevated expression and activity of SOD, increased levels of glutathione and malondialdehyde, and upregulation of HSP70 and HSP90, metallothionein, and CYP4Y1, alongside the initiation of apoptotic cell death. TPPO exposure activated natural immune genes and disrupted lipid metabolism in mussels. This study demonstrated the persistent accumulation of TPPO in mussels, highlighting its ecotoxicological hazards and underscoring the necessity to predict the risks associated with widespread environmental exposure to TPPO.
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