AstraZeneca, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon TQ58BA, United Kingdom.
Aquat Toxicol. 2010 May 10;97(4):314-23. doi: 10.1016/j.aquatox.2009.12.019. Epub 2010 Jan 4.
A fish full life-cycle (FFLC) is the most comprehensive test to determine reproductive toxicity of chemicals to fish and this is likely to apply equally to endocrine active chemicals (EACs). However, FFLC tests use large numbers of animals, are expensive and time consuming. Alternative chronic tests, to the FFLC, potentially include sensitive life-stage windows of effect, such as sexual differentiation, early gonadal development and reproduction. In this paper, a fish pair-breeding study was applied to assess the biological effects of a weak environmental oestrogen, 4-tert-pentylphenol (4TPP), on reproduction and subsequent development of the F1 generation. The results of this study were then compared with the results for a published FFLC study, with this chemical. Fathead minnows (Pimephales promelas) were held in pairs and their reproductive performance assessed over two concurrent 21-day periods, the first without exposure to the test chemical, followed by the second with exposure to the test chemical, in a flow-through system at 25+/-1 degrees C. Embryos from two pairs, per treatment, were subsequently grown up in clean water until 90 days post-hatch to assess developmental effects of the parental exposure on the F1 generation. Nominal (measured geometric mean, time weighted) test concentrations of 4TPP were 56 (48), 180 (173) and 560 (570) microg l(-1). A significant decrease in fecundity was observed in all 4TPP exposed fish (mean number of eggs spawned per pair and number of spawns per pair) when compared to the solvent control. Vitellogenin (VTG) was significantly elevated in F0 males exposed to 560 microg 4TPPl(-1). Somatic endpoints, secondary sexual characteristics (SSC) and gonadosomatic index (GSI) were not affected by the 4TPP exposure. In the F1 generation, there were no treatment-related effects on hatching success, survival, growth, SSC or GSI. Histological examination of the gonads of the F1 fish revealed no treatment-related effects on sex ratio, sexual differentiation or sexual development. However, plasma VTG concentrations were significantly elevated in F1 male fish, derived from parents that had previously been exposed to 4TPP at concentrations of > or = 180 microg l(-1). These data show that the reproductive performance test is suitable for detecting weak environmental oestrogenic chemicals and that exposure of adult fish to oestrogens can result in altered biomarker expression (VTG) of the F1 generation. Our findings indicate that the reproductive performance test was as sensitive for detecting effects on reproduction when compared with a published FFLC test for 4TPP.
鱼类全生命周期(FFLC)是最全面的测试,用于确定化学物质对鱼类的生殖毒性,这可能同样适用于内分泌活性化学物质(EACs)。然而,FFLC 测试使用大量的动物,昂贵且耗时。替代慢性测试,对于 FFLC,可能包括敏感的生命阶段效应窗口,如性分化、早期性腺发育和繁殖。在本文中,应用鱼类配对繁殖研究来评估一种弱环境雌激素,4-叔戊基苯酚(4TPP)对繁殖的生物学效应,以及随后对 F1 代的发育。然后,将这项研究的结果与用这种化学物质进行的一项已发表的 FFLC 研究的结果进行比较。在 25+/-1 摄氏度的流动系统中,将黑头呆鱼(Pimephales promelas)成对饲养,并在两个同时进行的 21 天期间评估其繁殖性能,第一个期间没有接触测试化学物质,第二个期间接触测试化学物质。每对处理各有两个胚胎,随后在清洁水中生长至孵化后 90 天,以评估亲代暴露对 F1 代的发育影响。4TPP 的名义(测量几何平均值,时间加权)测试浓度为 56(48)、180(173)和 560(570)μg l(-1)。与溶剂对照相比,所有暴露于 4TPP 的鱼类(每对产卵的平均卵数和产卵次数)的繁殖力都显著降低。暴露于 560μg 4TPPl(-1)的 F0 雄性鱼类的卵黄蛋白原(VTG)显著升高。F0 鱼类的体轴终点、次要性征(SSC)和性腺体指数(GSI)不受 4TPP 暴露的影响。在 F1 代中,孵化成功率、存活率、生长、SSC 或 GSI 没有与处理相关的影响。对 F1 鱼性腺的组织学检查显示,性比、性分化或性发育没有与处理相关的影响。然而,来自先前暴露于 4TPP 浓度>或=180μg l(-1)的亲鱼的 F1 雄性鱼的血浆 VTG 浓度显著升高。这些数据表明,生殖性能测试适用于检测弱环境雌激素化学物质,并且暴露于鱼类的雌激素会导致 F1 代生物标志物表达(VTG)的改变。我们的研究结果表明,生殖性能测试在检测对繁殖的影响方面与 4TPP 的已发表 FFLC 测试一样敏感。