Center for Marine Environmental Studies, Ehime University , 2-5 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan.
Graduate School of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto , 3-1-100 Tsukide, Kumamoto 862-8502, Japan.
Environ Sci Technol. 2015 Oct 6;49(19):11649-58. doi: 10.1021/acs.est.5b02478. Epub 2015 Sep 17.
A fish plasma model (FPM) has been proposed as a screening technique to prioritize potential hazardous pharmaceuticals to wild fish. However, this approach does not account for inter- or intraspecies variability of pharmacokinetic and pharmacodynamic parameters. The present study elucidated the uptake potency (from ambient water), tissue distribution, and biological risk of 20 pharmaceutical and personal care product (PPCP) residues in wild cyprinoid fish inhabiting treated-wastewater-impacted streams. In order to clarify the uncertainty of the FPM for PPCPs, we compared the plasma bioaccumulation factor in the field (BAFplasma = measured fish plasma/ambient water concentration ratio) with the predicted plasma bioconcentration factor (BCFplasma = fish plasma predicted by use of theoretical partition coefficients/ambient water concentration ratio) in the actual environment. As a result, the measured maximum BAFplasma of inflammatory agents was up to 17 times higher than theoretical BCFplasma values, leading to possible underestimation of toxicological risk on wild fish. When the tissue-blood partition coefficients (tissue/blood concentration ratios) of PPCPs were estimated, higher transportability into tissues, especially the brain, was found for psychotropic agents, but brain/plasma ratios widely varied among individual fish (up to 28-fold). In the present study, we provide a valuable data set on the intraspecies variability of PPCP pharmacokinetics, and our results emphasize the importance of determining PPCP concentrations in possible target organs as well as in the blood to assess the risk of PPCPs on wild fish.
已经提出了一种鱼类血浆模型(FPM)作为筛选技术,以优先考虑对野生鱼类有潜在危害的药物。然而,这种方法没有考虑到药代动力学和药效学参数的种间或种内变异性。本研究阐明了栖息在受处理废水影响的溪流中的野生鲤科鱼类中 20 种药物和个人护理产品(PPCP)残留的摄取能力(从环境水中)、组织分布和生物风险。为了阐明 FPM 对 PPCP 的不确定性,我们比较了野外的血浆生物累积因子(BAFplasma = 实测鱼类血浆/环境水浓度比)与实际环境中预测的血浆生物浓缩因子(BCFplasma = 用理论分配系数预测的鱼类血浆/环境水浓度比)。结果表明,炎症药物的实测最大 BAFplasma 比理论 BCFplasma 值高 17 倍,这可能导致对野生鱼类的毒理学风险被低估。当估计 PPCP 的组织-血液分配系数(组织/血液浓度比)时,发现精神药物在组织中的迁移能力更高,特别是大脑,但大脑/血浆比在个体鱼类之间差异很大(高达 28 倍)。在本研究中,我们提供了关于 PPCP 药代动力学种内变异性的有价值的数据集,我们的结果强调了在可能的靶器官以及血液中确定 PPCP 浓度以评估 PPCP 对野生鱼类的风险的重要性。