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Toxicity assessment of verapamil and its photodegradation products.
Environmental Science and Pollution Research Pub Date : 2020-06-29 , DOI: 10.1007/s11356-020-09830-w
Šárka Klementová 1 , Martina Poncarová 1 , David Kahoun 1 , Michal Šorf 1, 2 , Eliška Dokoupilová 1 , Pavla Fojtíková 1
Affiliation  

Pathways of photochemical degradation of a cardiovascular drug verapamil under conditions relevant to natural waters and the toxicity of the photoproducts to Daphnia magna were investigated. Photodegradation was shown to proceed via photocatalysed mechanism. Two main photodegradation pathways were recognised: the first leading to hydroxylation at the methylamino position followed by splitting of verapamil molecule into two fragments, and the second providing the main active metabolite of verapamil, norverapamil, and a series of norverapamil isomers, followed again by their splitting at the amino group position. Twenty-two products of photodegradation were identified. Toxicity assays in sublethal concentrations of the parental drug, of the photoproduct mixture, and of norverapamil revealed no direct negative response in Daphnia magna to verapamil. On the other hand, photochemical products significantly lowered the number of juveniles, number of clutches, and body size of Daphnia. The exposition of Daphnia to norverapamil showed the same but even more pronounced effects than its exposition to the mixture of photoproducts, which leads to the conclusion that norverapamil is mainly responsible for the toxicity of photoproduct mixture and represents a noteworthy threat to aquatic invertebrates.



中文翻译:

维拉帕米及其光降解产物的毒性评估。

心血管药物维拉帕米在与天然水相关的条件下光化学降解的途径以及光产物对大的毒性被调查。显示光降解是通过光催化机制进行的。认识到了两种主要的光降解途径:第一个导致甲氨基位置的羟基化,然后维拉帕米分子分裂成两个片段,第二个提供维拉帕米、去甲维拉帕米和一系列去甲维拉帕米异构体的主要活性代谢物,然后再次是它们的在氨基位置分裂。鉴定了 22 种光降解产物。在母体药物、光产物混合物和去甲维拉帕米的亚致死浓度下的毒性测定显示,大型水蚤对维拉帕米没有直接的负面反应。另一方面,光化学产品显着降低了幼鱼的数量、离合器的数量和体型。水蚤水蚤暴露于去甲维拉帕米表现出与暴露于光产物混合物相同但更显着的影响,由此得出结论:去甲维拉帕米是光产物混合物毒性的主要原因,对水生无脊椎动物构成显着威胁。

更新日期:2020-06-29
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