Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg, Germany; Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg, Germany.
Water Res. 2014 Feb 1;49:11-22. doi: 10.1016/j.watres.2013.11.014. Epub 2013 Nov 20.
The fate of thalidomide (TD) was investigated after irradiation with a medium-pressure Hg-lamp. The primary elimination of TD was monitored and structures of phototransformation products (PTPs) were assessed by LC-UV-FL-MS/MS. Environmentally relevant properties of TD and its PTPs as well as hydrolysis products (HTPs) were predicted using in silico QSAR models. Mutagenicity of TD and its PTPs was investigated in the Ames microplate format (MPF) aqua assay (Xenometrix, AG). Furthermore, a modified luminescent bacteria test (kinetic luminescent bacteria test (kinetic LBT)), using the luminescent bacteria species Vibrio fischeri, was applied for the initial screening of environmental toxicity. Additionally, toxicity of phthalimide, one of the identified PTPs, was investigated separately in the kinetic LBT. The UV irradiation eliminated TD itself without complete mineralization and led to the formation of several PTPs. TD and its PTPs did not exhibit mutagenic response in the Salmonella typhimurium strains TA 98, and TA 100 with and without metabolic activation. In contrast, QSAR analysis of PTPs and HTPs provided evidence for mutagenicity, genotoxicity and carcinogenicity using additional endpoints in silico software. QSAR analysis of different ecotoxicological endpoints, such as acute toxicity towards V. fischeri, provided positive alerts for several identified PTPs and HTPs. This was partially confirmed by the results of the kinetic LBT, in which a steady increase of acute and chronic toxicity during the UV-treatment procedure was observed for the photolytic mixtures at the highest tested concentration. Moreover, the number of PTPs within the reaction mixture that might be responsible for the toxification of TD during UV-treatment was successfully narrowed down by correlating the formation kinetics of PTPs with QSAR predictions and experimental toxicity data. Beyond that, further analysis of the commercially available PTP phthalimide indicated that transformation of TD into phthalimide was not the cause for the toxification of TD during UV-treatment. These results provide a path for toxicological assessment of complex chemical mixtures and in detail show the toxic potential of TD and its PTPs as well as its HTPs. This deserves further attention as UV irradiation might not always be a green technology, because it might pose a toxicological risk for the environment in general and specifically for water compartments.
将沙利度胺（TD）用中压汞灯照射，研究其命运。通过 LC-UV-FL-MS/MS 监测 TD 的主要消除情况，并评估光转化产物（PTPs）的结构。使用计算机 QSAR 模型预测 TD 及其 PTPs 以及水解产物（HTPs）的环境相关性质。采用 Ames 微板格式（MPF）水相测定法（Xenometrix，AG）研究 TD 及其 PTPs 的致突变性。此外，还应用改良发光细菌测试（动力学发光细菌测试（kinetic LBT）），使用发光细菌物种费氏弧菌，对环境毒性进行初步筛选。此外，还分别在动力学发光细菌测试中研究了鉴定出的 PTP 之一邻苯二甲酰亚胺的毒性。紫外线照射消除了 TD 本身，但没有完全矿化，并导致了几种 PTP 的形成。TD 及其 PTPs 在没有代谢激活的情况下，在鼠伤寒沙门氏菌 TA 98 和 TA 100 菌株中没有表现出致突变反应。相比之下，使用计算机软件中的其他终点对 PTPs 和 HTPs 的 QSAR 分析提供了致突变性、遗传毒性和致癌性的证据。不同生态毒理学终点的 QSAR 分析，如对费氏弧菌的急性毒性，为几种鉴定出的 PTPs 和 HTPs 提供了阳性警报。这部分被动力学发光细菌测试的结果所证实，在最高测试浓度下，光解混合物在 UV 处理过程中观察到急性和慢性毒性的持续增加。此外，通过将 PTPs 的形成动力学与 QSAR 预测和实验毒性数据相关联，成功地将反应混合物中可能导致 TD 在 UV 处理过程中中毒的 PTPs 数量缩小。此外，对市售 PTP 邻苯二甲酰亚胺的进一步分析表明，TD 转化为邻苯二甲酰亚胺不是 TD 在 UV 处理过程中中毒的原因。这些结果为复杂化学混合物的毒理学评估提供了一条途径，并详细显示了 TD 及其 PTPs 以及 HTPs 的毒性潜力。这值得进一步关注，因为紫外线照射不一定总是一种绿色技术，因为它可能对环境一般和特别是对水团产生毒理学风险。
