The toxicity of 17 active pharmaceutical ingredients (APIs) was investigated using standardized acute and chronic tests with Daphnia magna and 2 algae species. Chronic toxicity was generally greater for Daphnia than for algae. Compilation of additional data resulted in 100 APIs for which the acute-to-chronic ratio (ACR) was determined for Daphnia. The frequency of high ACRs (~20% with ACRs > 100) indicates that specific receptor-mediated toxicity toward D. magna is rather common among APIs. The 11 APIs with ACRs > 1000 included lipid-modifying agents, immunosuppressants, antibiotics, antineoplastics, antiobesics, antivirals, and antihistamines. There was no consistent association between ACR and chronic toxicity, ionization status, or lipophilicity. High ACRs were not exclusively associated with the presence of orthologs of the pharmacological target in Daphnia. Statins, acetylcholinesterase inhibitors, and antihistamines are discussed in more detail regarding the link between targets and toxic mode of action. For acetylcholinesterase inhibitors, receptor-mediated toxicity was already apparent after acute exposure, whereas the high ACR and chronic toxicity of some antihistamines probably related to interaction with a secondary rather than the primary pharmacological target. Acute or modeled chronic toxicity estimates have often been used for prioritizing pharmaceuticals. This may be seriously misleading because chronic effects are currently not predictable for APIs with specific receptor-mediated toxicity. However, it is exactly these APIs that are the most relevant in terms of environmental risks. Environ Toxicol Chem 2022;41:601–613. © 2021 SETAC

中文翻译：

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来自急性和慢性标准终点的水生生物中特定受体介导的药物毒性的证据

使用大型水蚤和 2 种藻类的标准化急性和慢性试验研究了 17 种活性药物成分 (API) 的毒性。水蚤的慢性毒性通常大于藻类。对其他数据的汇编产生了 100 种 API，确定了水蚤的急慢性比 (ACR) 。高 ACR 的频率（约 20%，ACR > 100）表明特定受体介导的对D. magna的毒性在 API 中相当普遍。ACR > 1000 的 11 种 API 包括脂质调节剂、免疫抑制剂、抗生素、抗肿瘤药、抗肥胖药、抗病毒药和抗组胺药。ACR 与慢性毒性、电离状态或亲脂性之间没有一致的关联。高 ACR 并不完全与水蚤中药理学靶标的直系同源物的存在相关. 他汀类药物、乙酰胆碱酯酶抑制剂和抗组胺药在靶点和毒性作用模式之间的联系方面进行了更详细的讨论。对于乙酰胆碱酯酶抑制剂，受体介导的毒性在急性暴露后已经很明显，而一些抗组胺药的高 ACR 和慢性毒性可能与与次要而非主要药理学靶点的相互作用有关。急性或模拟的慢性毒性估计经常被用于优先考虑药物。这可能会严重误导，因为目前无法预测具有特定受体介导毒性的 API 的慢性影响。然而，就环境风险而言，正是这些 API 最为相关。环境毒物化学2022；41：601–613。© 2021 SETAC