Bogers Rinus, De Vries-Buitenweg Selinda, Van Gils Mariëlle, Baltussen Erik, Hargreaves Adam, van de Waart Beppy, De Roode Daphne, Legler Juliette, Murk Albertinka
NOTOX Safety and Environmental Research, Hambakenwetering 7, 5231 DD's-Hertogenbosch, The Netherlands.
Aquat Toxicol. 2006 Nov 16;80(2):119-30. doi: 10.1016/j.aquatox.2006.07.020. Epub 2006 Aug 5.
The Endocrine Modulators Study Group (EMSG) of the European Chemical Industry has proposed an extended fish early-life stage (ELS) test based on OECD test guideline 210 in combination with a fish pair-breeding reproduction study as a possible alternative for fish full life cycle testing. In this paper the androgen methyldihydrotestosterone (MDHT) was tested in an extended ELS test with fathead minnow supplementary to such a test with the weak estrogen 4-tert-pentylphenol (4TPP). Main endpoints were secondary sexual characteristics (SSC), plasma vitellogenin (VTG) induction and gonadal development. Early blastula embryos were exposed to 0, 0.10, 0.32 and 1.0 microgMDHTl(-1) for up to 114 days post-hatch (dph). A batch of fish exposed to 1.0 microg l(-1) was transferred to clean water after 30 or 63 dph for the remainder of the study. Ethinylestradiol (EE2) was included as estrogenic reference substance at 0.01 microg l(-1). Exposure to MDHT had no significant effect on hatching success or survival, but significantly increased the condition factor of fish exposed for 63 and 114 dph (up to 150% of the control). At 63 dph MDHT exposure induced appearance of tubercles on the snout (a male SSC) of more than 80% of fish. Compared to the controls, plasma VTG was not detectable or significantly lower in fish exposed to MDHT at 0.10 microg/l, but not significantly affected at higher MDHT concentrations. Both lower levels of MDHT significantly inhibited the development of female gonads as of 30 dph. Fish exposed to MDHT at 0.32 and 1.0 microg l(-1) showed higher incidences of mixed sex gonads (10-25%) and smaller testes or dysplasia of gonadal tissue. Dysplasia was present in 80% of the fish continuously exposed to 1.0 microg l(-1) up to 114 dph, but reversible when fish were transferred to dilution water. Results indicate that suppression of ovarian development was the most sensitive endpoint for MDHT exposure after 30 dph. Other endpoints (e.g., growth and SSC) required exposure during at least up to 63 dph to yield a significant effect. Androgenic effects on VTG production required even longer exposure, i.e., until sufficient number of females had matured.
欧洲化学工业内分泌调节剂研究小组（EMSG）提出了一项基于经合组织测试指南210的扩展鱼类早期生活阶段（ELS）测试，并结合鱼类配对繁殖研究，作为鱼类全生命周期测试的一种可能替代方案。在本文中，雄激素甲基二氢睾酮（MDHT）在扩展的ELS测试中用黑头呆鱼进行了测试，并辅以用弱雌激素4-叔戊基苯酚（4TPP）进行的此类测试。主要终点是第二性征（SSC）、血浆卵黄蛋白原（VTG）诱导和性腺发育。早期囊胚胚胎在孵化后长达114天（dph）暴露于0、0.10、0.32和1.0微克MDHT/升。一批暴露于1.0微克/升的鱼在30或63 dph后转移到清洁水中进行剩余的研究。乙炔雌二醇（EE2）作为雌激素参考物质以0.01微克/升的浓度包含在内。暴露于MDHT对孵化成功率或存活率没有显著影响，但显著增加了暴露63和114 dph的鱼的条件因子（高达对照组的150%）。在63 dph时，MDHT暴露导致超过80%的鱼在吻部出现瘤（雄性SSC）。与对照组相比，暴露于0.10微克/升MDHT的鱼中血浆VTG不可检测或显著降低，但在较高MDHT浓度下没有显著影响。两种较低水平的MDHT从30 dph开始均显著抑制雌性性腺的发育。暴露于0.32和1.0微克/升MDHT的鱼显示出更高的混合性性腺发生率（10 - 25%）以及较小的睾丸或性腺组织发育异常。在持续暴露于1.0微克/升直至114 dph的鱼中，80%存在发育异常，但当鱼转移到稀释水中时是可逆的。结果表明，在30 dph后，抑制卵巢发育是MDHT暴露最敏感的终点。其他终点（如生长和SSC）至少需要暴露至63 dph才能产生显著影响。雄激素对VTG产生的影响需要更长时间的暴露，即直到足够数量的雌性成熟。
