Group Safety, Health, and Environmental Protection, F.Hoffmann-La Roche, Basle, Switzerland.
Department of Environmental Science, Radboud University Nijmegen, Nijmegen, The Netherlands.
Environ Toxicol Chem. 2019 Oct;38(10):2259-2278. doi: 10.1002/etc.4524. Epub 2019 Sep 19.
An environmental risk assessment is presented for mycophenolic acid (MPA), an immunosuppressive pharmaceutical used for prevention of organ rejection, and its prodrug mycophenolate mofetil (MPM). Mycophenolic acid will not significantly adsorb to activated sludge. In activated sludge, C-MPA attained >80% degradation, supporting an older environmental fate test with the same compound. Based on n-octanol/water distribution coefficient (log D ) values of 2.28, 0.48, and ≤-1.54 at pH 5, 7, and 9, respectively, MPA is not expected to bioaccumulate. Sales amounts of MPA+MPM in Europe were used to derive predicted environmental concentrations (PECs) in surface waters; PECs were refined by including expected biodegradation in sewage treatment, average drinking water use, and average dilution of the effluents in the receiving waters per country. In addition, the exposure to pharmaceuticals in the environment (ePiE) model was run for 4 European catchments. The PECs were complemented with 110 measured environmental concentrations (MECs), ranging from below the limit of quantitation (<0.001 µg/L) to 0.656 µg/L. Predicted no-effect concentrations (PNECs) were derived from chronic tests with cyanobacteria, green algae, daphnids, and fish. The comparison of PECs and MECs with the PNECs resulted in a differentiated environmental risk assessment in which the risk ratio of PEC/PNEC or MEC/PNEC was <1 in most cases (mostly >90%), meaning no significant risk, but a potential risk to aquatic organisms in generally <10% of instances. Because this assessment reveals a partial risk, the following questions must be asked: How much risk is acceptable? and Through which measures can this risk be reduced? These questions are all the more important in view of limited alternatives for MPM and MPA and the serious consequences of not using them. Environ Toxicol Chem 2019;38:2259-2278. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
本文对霉酚酸（MPA）及其前体药物吗替麦考酚酯（MPM）进行了环境风险评估。MPA 不会被活性污泥显著吸附。在活性污泥中，C-MPA 的降解率超过 80%，这支持了对同一化合物进行的一项较早期的环境归宿测试。基于在 pH 值为 5、7 和 9 时分别为 2.28、0.48 和≤-1.54 的正辛醇/水分配系数（log D）值，MPA 预计不会发生生物累积。利用欧洲 MPA+MPM 的销售量，推导出地表水的预测环境浓度（PEC）；通过包括污水处理厂的预期生物降解、平均饮用水用量和每个国家受纳水体中废水的平均稀释度，对 PEC 进行了细化。此外，还针对 4 个欧洲集水区运行了暴露于环境中的药物（ePiE）模型。PEC 与 110 个实测环境浓度（MEC）进行了补充，MEC 的范围从低于定量限（<0.001µg/L）至 0.656µg/L。通过对蓝藻、绿藻、水蚤和鱼类进行慢性试验，推导出无影响浓度（PNEC）。将 PEC 和 MEC 与 PNEC 进行比较，得出了一种差异化的环境风险评估结果，在大多数情况下（大部分>90%），PEC/PNEC 或 MEC/PNEC 的风险比<1，这意味着没有显著风险，但在<10%的情况下对水生生物存在潜在风险。由于这种评估显示存在部分风险，因此必须提出以下问题：可以接受多少风险？以及可以通过哪些措施降低这种风险？鉴于 MPM 和 MPA 的替代方案有限，以及不使用它们可能带来的严重后果，这些问题更加重要。环境毒理化学 2019；38：2259-2278。©2019 作者。环境毒理化学由 Wiley 期刊出版公司代表 SETAC 出版。
