Kümmerer Klaus, Haiß Annette, Schuster Armin, Hein Arne, Ebert Ina
Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststraße1, 21335, Lüneburg, Germany.
Department of Environmental Health Sciences, University Medical Centre Freiburg, Breisacher Str. 115B, 79106, Freiburg, Germany.
Environ Sci Pollut Res Int. 2016 Aug;23(15):14791-804. doi: 10.1007/s11356-014-3902-8. Epub 2014 Dec 6.
Antineoplastic drugs are important in the treatment of cancer. Some interact directly with the deoxyribonucleic acid (DNA) and are of utmost importance in terms of risk. As highly active compounds, antineoplastics and their metabolites are largely excreted into wastewater and are found in the aquatic environment up to the lower μg/L range. Their predicted environmental concentrations are often below the action limit set in the European Medicines Agency (EMA) guideline. An in-depth risk assessment regarding their presence and effects in the aquatic environment is often not performed, and there is a lack of knowledge. This study considered whether there is an underestimation of possible risks associated with the presence of antineoplastic drugs with regard to trigger value stated in the EMA and FDA guidelines. In a balance, we identified a total of 102 active pharmaceutical ingredients of the ATC-group L01 (antineoplastic agents), which are environmentally relevant. In Germany, 20.7 t of antineoplastic agents was consumed in 2012. The share of drugs with DNA-damaging properties increased within the last 6 years from 24 up to 67 %. Solely, capecitabine and 5-fluorouracil amount together 8 t-which corresponds to 39 % of the total antineoplastic consumption. Around 80 % of the total mass consumed could be attributed to prescriptions issued by office-based practitioners and is mostly excreted at home. Based on the different mode of actions, a case-by-case evaluation of the risk connected to their presence in the environment is recommended. DNA-damaging drugs should be assessed independently as no action limit can be assumed.
抗肿瘤药物在癌症治疗中至关重要。一些药物直接与脱氧核糖核酸（DNA）相互作用，在风险方面极为重要。作为高活性化合物，抗肿瘤药物及其代谢产物大量排入废水，并在水生环境中被发现，浓度可达较低的μg/L范围。它们预测的环境浓度通常低于欧洲药品管理局（EMA）指南设定的行动限值。关于它们在水生环境中的存在和影响的深入风险评估往往没有进行，并且缺乏相关知识。本研究考虑了对于EMA和FDA指南中规定的触发值，与抗肿瘤药物存在相关的潜在风险是否被低估。综合来看，我们总共确定了102种ATC分类L01组（抗肿瘤药）中与环境相关的活性药物成分。2012年，德国消耗了20.7吨抗肿瘤药。具有DNA损伤特性的药物所占份额在过去6年中从24%增至67%。仅卡培他滨和5-氟尿嘧啶总量就达8吨，占抗肿瘤药总消耗量的39%。消耗总量的约80%可归因于门诊医生开出的处方，且大多在家中排出。基于不同的作用方式，建议对其在环境中存在所关联的风险进行逐案评估。具有DNA损伤作用的药物应独立评估，因为无法假定有行动限值。
