Institute of Earth Surface Dynamics, University of Lausanne, Switzerland.
Protein Analysis Facility, Center for Integrative Genomics, University of Lausanne, Switzerland.
Sci Total Environ. 2016 Mar 1;545-546:21-9. doi: 10.1016/j.scitotenv.2015.11.155. Epub 2015 Dec 30.
Tamoxifen and its metabolite 4-hydroxy-tamoxifen (4OHTam) are two potent molecules that have anticancer properties on breast cancers. Their medical use is expected to increase with the increasing global cancer rate. After consumption, patients excrete tamoxifen and the 4OHTam metabolite into wastewaters, and tamoxifen has been already detected in wastewaters and natural waters. The concentrations of 4OHTam in waters have never been reported. A single study reported 4OHTam effects on the microcrustacean Daphnia pulex. The effects of tamoxifen and 4OHTam over more than two generations are unknown in aquatic invertebrates. The main goal of this study was to assess the long-term sensitivity of the microcrustacean D. pulex over four generations, based on size, reproduction, viability and the intrinsic rate of natural increase (r). Additional experiments were carried out to observe whether the effects of tamoxifen and 4OHTam were reversible in the next generation after descendants were withdrawn from chemical stress (i.e., recovery experiment), and whether the lowest test concentration of each chemical induced toxic effects when both concentrations were combined (i.e., mixture experiments). Our results showed that tamoxifen and 4OHTam induced the adverse effects at environmentally relevant concentrations. Tamoxifen and 4OHTam impaired size, viability, reproduction and the r in four generations of treated D. pulex, but these effects were not clearly magnified over generations. Tamoxifen was more potent than 4OHTam on D. pulex. When used in a mixture, the combination of tamoxifen and 4OHTam induced effects in offspring, whereas no effects were observed when these chemicals were tested individually. In the recovery experiment, the reproduction and size were reduced in offspring withdrawn from chemical exposures. Our results suggested that tamoxifen and its metabolite may be a relevant pharmaceutical to consider in risk assessment.
他莫昔芬及其代谢产物 4-羟基他莫昔芬（4OHTam）是两种具有抗癌特性的有效分子，可用于治疗乳腺癌。随着全球癌症发病率的上升，预计它们的医疗用途将会增加。患者在服用后会将他莫昔芬及其代谢产物 4OHTam 排泄到废水中，而他莫昔芬已经在废水中和天然水中被检测到。水中 4OHTam 的浓度从未被报道过。一项单独的研究报告了 4OHTam 对小型甲壳类动物 Daphnia pulex 的影响。在水生无脊椎动物中，尚不清楚他莫昔芬和 4OHTam 对两代以上的影响。本研究的主要目标是在四代的基础上评估小型甲壳类动物 D. pulex 的长期敏感性，评估指标为大小、繁殖、生存能力和自然增长率（r）。还进行了额外的实验，以观察在后代从化学胁迫中撤出后（即恢复实验），他莫昔芬和 4OHTam 的影响是否可以在下一代中逆转，以及当两种浓度同时存在时，每种化学物质的最低测试浓度是否会引起毒性作用（即混合物实验）。我们的研究结果表明，他莫昔芬和 4OHTam 在环境相关浓度下诱导了不良影响。他莫昔芬和 4OHTam 损害了四代处理过的 D. pulex 的大小、生存能力、繁殖能力和 r，但这些影响在几代之间并没有明显放大。他莫昔芬对 D. pulex 的作用比 4OHTam 更强。当混合物使用时，他莫昔芬和 4OHTam 的组合会对后代产生影响，而当这些化学物质单独测试时，没有观察到影响。在恢复实验中，从化学暴露中撤出的后代的繁殖和大小都减少了。我们的研究结果表明，他莫昔芬及其代谢物可能是在风险评估中需要考虑的相关药物。
