Use of acute and chronic ecotoxicity data in environmental risk assessment of pharmaceuticals
Use of acute and chronic ecotoxicity data in environmental risk assessment of pharmaceuticals
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急性和慢性生态毒性数据在药品环境风险评估中的应用
DOI：
10.1002/etc.3260
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发表时间：
2016
影响因子：
4.1
通讯作者：
Peter Wilson
中科院分区：
文献类型：
--
作者：
Jessica Vestel;D. J. Caldwell;L. Constantine;V. D'Aco;T. Davidson;D. Dolan;S. Millard;R. Murray;N. Parke;Jim J. Ryan;J. Straub;Peter Wilson
对于许多较老的药物，慢性水生毒性数据有限。为了评估开发、规模化和生产过程中的风险，需要利用急性数据和物理化学特性来减少对环境的潜在长期影响。从水蚤、鱼类和藻类研究中收集了102种活性药物成分（api）的水生毒性数据，以评估急性和慢性试验中预测的无效应浓度（PNECs）之间的关系。研究了急性和慢性水生毒性与正辛醇/水分配系数（DOW）之间的关系。在毒性和对数DOW之间观察到统计学上显著但微弱的相关性，表明DOW不是毒性的唯一贡献者。102种原料药中60种的急性和慢性PNEC值均可计算。对于大多数化合物，急性数据得出的pnec低于慢性数据得出的pnec，但类固醇雌激素除外。来自急性数据的7%的pnec低于欧盟行动限值0.01 μg/L，并且都是影响藻类物种的抗感染药物。从长期数据中得出的可获得的pnec中有8%低于欧盟行动限值，鱼类是除1种API外对所有API最敏感的物种。这些分析表明，如果没有慢性数据，使用急性数据是可以接受的，除非具体的行动方式另有建议。环境科学与技术，2016;35(5):1212 - 1212。©2015作者。环境毒理学与化学由Wiley期刊公司代表SETAC出版。
For many older pharmaceuticals, chronic aquatic toxicity data are limited. To assess risk during development, scale‐up, and manufacturing processes, acute data and physicochemical properties need to be leveraged to reduce potential long‐term impacts to the environment. Aquatic toxicity data were pooled from daphnid, fish, and algae studies for 102 active pharmaceutical ingredients (APIs) to evaluate the relationship between predicted no‐effect concentrations (PNECs) derived from acute and chronic tests. The relationships between acute and chronic aquatic toxicity and the n‐octanol/water distribution coefficient (DOW) were also characterized. Statistically significant but weak correlations were observed between toxicity and log DOW, indicating that DOW is not the only contributor to toxicity. Both acute and chronic PNEC values could be calculated for 60 of the 102 APIs. For most compounds, PNECs derived from acute data were lower than PNECs derived from chronic data, with the exception of steroid estrogens. Seven percent of the PNECs derived from acute data were below the European Union action limit of 0.01 μg/L and all were anti‐infectives affecting algal species. Eight percent of available PNECs derived from chronic data were below the European Union action limit, and fish were the most sensitive species for all but 1 API. These analyses suggest that the use of acute data may be acceptable if chronic data are unavailable, unless specific mode of action concerns suggest otherwise. Environ Toxicol Chem 2016;35:1201–1212. © 2015 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.