State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China.
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China.
Environ Pollut. 2021 Apr 1;274:116586. doi: 10.1016/j.envpol.2021.116586. Epub 2021 Jan 23.
Cresyl diphenyl phosphate (CDP), as a kind of aryl substituted organophosphate esters (OPEs), is commonly used as emerging flame retardants and plasticizers detected in environmental media. Due to the accumulation of CDP in organisms, it is very important to discover the toxicological mechanism and metabolic process of CDP. Hence, liver microsomes of crucian carps (Carassius carassius) were prepared for in vitro metabolism kinetics assay to estimate metabolism rates of CDP. After 140 min incubation, the depletion of CDP accounted for 58.1%-77.1% (expect 0.5 and 2 μM) of the administrated concentrations. The depletion rates were best fitted to the Michaelis-Menten model (R = 0.995), where maximum velocity (V) and Michaelis-Menten constant (K) were 12,700 ± 2120 pmol min·mg protein and 1030 ± 212 μM, respectively. Moreover, the in vitro hepatic clearance (C) of CDP was 12.3 μL min·mg protein. Log K and bioconcentration factor (BCF) of aryl-OPEs were both higher than those of alkyl- and chlorinated-OPEs, indicating that CDP may easily accumulate in aquatic organisms. The results made clear that the metabolism rate of CDP was greater than those of other OPEs detected in liver microsomes in previous research. This paper was first of its kind to comprehensively investigate the in vitro metabolic kinetics of CDP in fish liver microsomes. The present study might provide useful information to understand the environmental fate and metabolic processes of these kinds of substances, and also provide a theoretical basis for the ecological risk assessment of emerging contaminants.
Cresyl diphenyl phosphate (CDP)，作为一种芳基取代的有机磷酸酯（OPEs），通常被用作环境介质中新兴的阻燃剂和增塑剂。由于 CDP 在生物体中的积累，发现其毒理学机制和代谢过程非常重要。因此，本研究采用鲤鱼（Carassius carassius）肝微粒体进行体外代谢动力学研究，以评估 CDP 的代谢速率。孵育 140 分钟后，CDP 的耗竭率占给药浓度的 58.1%-77.1%（除 0.5 和 2 μM 外）。耗竭率与米氏方程拟合最好（R=0.995），其中最大速度（V）和米氏常数（K）分别为 12700±2120 pmol min·mg protein 和 1030±212 μM。此外，CDP 的体外肝清除率（C）为 12.3 μL min·mg protein。芳基-OPEs 的 log K 和生物浓缩因子（BCF）均高于烷基-OPEs 和氯化-OPEs，表明 CDP 可能容易在水生生物体内积累。研究结果表明，与之前在肝微粒体中检测到的其他 OPEs 相比，CDP 的代谢速率更大。这是首次全面研究鱼肝微粒体中 CDP 的体外代谢动力学。本研究可为了解此类物质的环境归宿和代谢过程提供有用信息，也可为新兴污染物的生态风险评估提供理论依据。
