Cemagref, UR Milieux Aquatiques Ecologie et Pollution (MAEP), Laboratoire d'écotoxicologie/Laboratoire d'analyses physico-chimiques des milieux aquatiques, 3 bis quai Chauveau, CP 220, F-69226 Lyon, France.
Environ Int. 2012 Feb;39(1):73-86. doi: 10.1016/j.envint.2011.10.002. Epub 2011 Nov 8.
This study considers the implications and research needs arising from anticancer (also referred to as antineoplastic) drugs being released into the aquatic environment, for the entire therapeutic classes used: cytotoxic, cytostatic and endocrine therapy drugs. A categorization approach, based on French consumption amounts, allowed to highlight parent molecules and several metabolites on which further occurrence and ecotoxicological studies should be conducted. Investigations of consumption trends at a national and a local scale show an increase in the use of anticancer drugs between 2004 and 2008, thus leading to increased levels released in the environment. It therefore appears necessary to continue surveying their presence in surface waters and in wastewater treatment plant (WWTP) effluents. Furthermore, due to the rise of anticancer home treatments, most of the prescribed molecules are now available in town pharmacies. Consequently, hospital effluents are no longer the main expected entry route of anticancer drugs into the aquatic environment. Concerning ecotoxicological risks, current knowledge remains insufficient to support a definitive conclusion. Risk posed by cytotoxic molecules is still not well documented and it is not possible to conclude on their long-term effects on non-target organisms. To date, ecotoxicological effects have been assessed using standardized or in vitro assays. Such tests however may not be suitable for anticancer drugs, and further work should focus on full-life cycle or even multigenerational tests. Environmental significance (i.e. occurrence and effects) of cytostatics (protein kinases inhibitors and monoclonal antibodies), if any, is not documented. Protein kinases inhibitors, in particular, deserve further investigation due to their universal mode of action. Finally, concerning endocrine therapy drugs, molecules such as antiestrogen Tamoxifen and its active metabolites, could be of concern. Overall, to accurately assess the ecotoxicological risk of anticancer drugs, we discuss the need to break away from tests on isolated molecules and to test effects of mixtures at the low ng.l(-1) range.
本研究考虑了将抗癌（也称为抗肿瘤）药物释放到水生环境中对整个治疗类别（细胞毒性、细胞抑制和内分泌治疗药物）的影响和研究需求。一种基于法国消费数据的分类方法，突出了需要进一步研究其存在和生态毒性的母体分子和几种代谢物。在国家和地方范围内对消费趋势的调查表明，2004 年至 2008 年间，抗癌药物的使用有所增加，因此导致环境中释放的水平增加。因此，有必要继续调查它们在地表水和污水处理厂（WWTP）废水中的存在情况。此外，由于抗癌家庭治疗的兴起，现在大多数规定的分子都可以在城镇药店买到。因此，医院废水不再是抗癌药物进入水生环境的主要预期进入途径。关于生态毒性风险，目前的知识仍然不足以支持明确的结论。细胞毒性分子的风险仍然没有得到很好的记录，也无法确定它们对非目标生物的长期影响。迄今为止，使用标准化或体外测定法评估了抗癌药物的生态毒性。然而，这些测试可能不适合抗癌药物，进一步的工作应集中在全生命周期甚至多代测试上。环境意义（即存在和影响）的细胞抑制剂（蛋白激酶抑制剂和单克隆抗体），如果有的话，没有记录。蛋白激酶抑制剂，特别是由于其普遍的作用模式，值得进一步研究。最后，关于内分泌治疗药物，如抗雌激素他莫昔芬及其活性代谢物等分子可能值得关注。总的来说，为了准确评估抗癌药物的生态毒性风险，我们讨论了需要打破对孤立分子的测试，在低 ng.l(-1) 范围内测试混合物的效果。
