Teigeler Matthias, Schaudien Dirk, Böhmer Walter, Länge Reinhard, Schäfers Christoph
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Schmallenberg, Germany.
Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany.
Environ Toxicol Chem. 2022 Mar;41(3):580-591. doi: 10.1002/etc.5008. Epub 2021 Mar 29.
The amount of pharmaceuticals transferred to the aquatic environment via municipal and hospital waste water is steadily increasing. The progress in medical research has resulted in the manufacture of active substances of increased stability, specificity, and potency, which can trigger adverse effects in aquatic organisms. Moreover, advanced analytical methods allow the detection of pharmaceuticals in environmental matrices at very low concentrations, which increases the number of substances to be assessed. Levonorgestrel is a synthetic gestagen commonly used in medicinal products for contraception. Because progestogenic compounds could have an impact on fish maturation processes, a life cycle test was performed to assess the effects of levonorgestrel exposure of the embryonic to the adult stages of zebrafish (Danio rerio) at mean measured concentrations of 0.06, 0.16, 0.47, 1.64, and 5.45 ng/L. Apical endpoints were survival, growth, reproduction, and sex ratio. Determination of endocrine modulation was completed by measurement of vitellogenin and 11-keto testosterone in blood plasma, as well as by histopathological analysis of gonads. For all parameters, control values were within the recommended quality range. The most prominent levonorgestrel effect was a shift toward an increased number of male fish at 1.64 and especially 5.45 ng/L, at which point all fish were histologically determined to be males and no spawning occurred; 11-keto testosterone was significantly decreased. A no-observed-effect concentration (NOEC) of 0.47 ng levonorgestrel/L was confirmed by the fertilization capability of adult fish, the male maturation stages, and female gonad histopathology. Whereas hatch and juvenile growth were not affected, posthatch survival was significantly impeded at ≥0.47 ng levonorgestrel/L, although it was not clearly related to the test concentration. For male length and weight, the same NOEC of 0.16 ng/L was obtained at study termination. Environ Toxicol Chem 2022;41:580-591. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
通过城市和医院废水排入水生环境的药物数量正在稳步增加。医学研究的进展带来了稳定性、特异性和效力更高的活性物质的生产，这些物质可能会对水生生物产生不利影响。此外，先进的分析方法能够检测出环境基质中极低浓度的药物，这增加了需要评估的物质数量。左炔诺孕酮是一种常用于避孕药品的合成孕激素。由于孕激素化合物可能会影响鱼类的成熟过程，因此进行了一项生命周期试验，以评估斑马鱼（Danio rerio）从胚胎期到成年期暴露于平均测量浓度为0.06、0.16、0.47、1.64和5.45 ng/L的左炔诺孕酮的影响。关键终点包括生存、生长、繁殖和性别比例。通过测量血浆中的卵黄蛋白原和11-酮睾酮以及性腺的组织病理学分析来完成内分泌调节的测定。对于所有参数，对照值均在推荐的质量范围内。左炔诺孕酮最显著的影响是在1.64 ng/L尤其是5.45 ng/L时雄性鱼类数量增加，此时所有鱼类经组织学鉴定均为雄性且未发生产卵；11-酮睾酮显著降低。成年鱼的受精能力、雄性成熟阶段和雌性性腺组织病理学确定左炔诺孕酮的无观察效应浓度（NOEC）为0.47 ng/L。虽然孵化和幼鱼生长未受影响，但≥0.47 ng/L的左炔诺孕酮显著阻碍了孵化后存活，尽管这与试验浓度并无明显关联。在研究结束时，雄性体长和体重的NOEC同样为0.16 ng/L。《环境毒理学与化学》2022年；41:580 - 591。© 2021作者。《环境毒理学与化学》由威利期刊有限责任公司代表SETAC出版。
