Screening and testing for endocrine disruption in fish-biomarkers as "signposts," not "traffic lights," in risk assessment.
Screening and testing for endocrine disruption in fish-biomarkers as "signposts," not "traffic lights," in risk assessment.
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在风险评估中，对鱼类生物标志物中内分泌干扰的筛查和测试是“路标”，而不是“交通信号灯”。
DOI：
10.1289/ehp.8062
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发表时间：
2006-04
影响因子：
10.4
通讯作者：
Tyler, Charles R
中科院分区：
文献类型：
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作者：
Hutchinson, Thomas H;Ankley, Gerald T;Segner, Helmut;Tyler, Charles R
目前，在内分泌干扰物(EDCs)的环境风险评估中，生物标志物最好用作机械“路标”，而不是“红绿灯”。在实地研究中，暴露的生物标记物[例如，雄鱼体内诱导的卵黄蛋白原(VTG)]是追踪所关注的单一物质和混合物的有力工具。生物标记物还提供现场数据和实验室数据之间的联系，从而在指导对内分泌细胞的鱼类慢性测试的需求和设计方面发挥重要作用。这类测试的不良影响终点(例如，发育、生长和/或生殖的改变)对于计算不良NOEC(无观察到的浓度影响)或不良EC10(10%反应的有效浓度)以及随后得出预测的无效浓度(PNEC)是最有价值的。在目前的不确定性下，不应单独使用生物标记物NOEC或生物标记物EC10数据来得出PNEC。然而，未来可能会有更多地在环境决策中使用生物标记物数据的余地，如果能够在组织各级之间建立看似合理的联系，从而可能设想相对于生物标记物反应的不利结果。为了使生物标记物发挥其潜力，它们应具有机械相关性和可重复性(通过同一方案的实验室间比较来衡量)。VTG是这种生物标志物的一个很好的例子，因为它提供了对鱼类生殖健康至关重要的作用模式(雌激素活性)的洞察。VTG的实验室间重复性数据也令人鼓舞；最近的比较(使用相同的免疫分析方案)提供了38-55%的变异系数(CV)(与监管测试指南中使用的公布的鱼类存活和生长终点的变异系数19-58%相当)。虽然对环境异种雌激素的关注导致了对鱼类生殖生物标志物的评估，但必须记住，许多物质通过不同的作用机制发挥作用，因此对内源性雌激素的环境风险评估是一个广泛而复杂的问题。此外，第二性征、性腺指数、血浆类固醇和性腺组织学等生物标志物在指导内分泌细胞的物种间评估和设计鱼类慢性试验方面也具有重要的潜力。为了加强EDC生物标志物在鱼类中的效用，我们需要建立一个历史对照数据库(也考虑自然变异性)，以帮助区分统计上可检测到的反应和生物学上有意义的反应。总之，随着研究继续开发一系列有用的环境影响区生物标志物，环境决策需要向前推进，并建议在当前环境影响区风险评估中，“生物标志物作为路标”的方法是一个务实的前进方向。
Biomarkers are currently best used as mechanistic “signposts” rather than as “traffic lights” in the environmental risk assessment of endocrine-disrupting chemicals (EDCs). In field studies, biomarkers of exposure [e.g., vitellogenin (VTG) induction in male fish] are powerful tools for tracking single substances and mixtures of concern. Biomarkers also provide linkage between field and laboratory data, thereby playing an important role in directing the need for and design of fish chronic tests for EDCs. It is the adverse effect end points (e.g., altered development, growth, and/or reproduction) from such tests that are most valuable for calculating adverseNOEC (no observed effect oncentration) or adverseEC10 (effective concentration for a 10% response) and subsequently deriving predicted no effect concentrations (PNECs). With current uncertainties, biomarkerNOEC or biomarkerEC10 data should not be used in isolation to derive PNECs. In the future, however, there may be scope to increasingly use biomarker data in environmental decision making, if plausible linkages can be made across levels of organization such that adverse outcomes might be envisaged relative to biomarker responses. For biomarkers to fulfil their potential, they should be mechanistically relevant and reproducible (as measured by interlaboratory comparisons of the same protocol). VTG is a good example of such a biomarker in that it provides an insight to the mode of action (estrogenicity) that is vital to fish reproductive health. Interlaboratory reproducibility data for VTG are also encouraging; recent comparisons (using the same immunoassay protocol) have provided coefficients of variation (CVs) of 38–55% (comparable to published CVs of 19–58% for fish survival and growth end points used in regulatory test guidelines). While concern over environmental xenoestrogens has led to the evaluation of reproductive biomarkers in fish, it must be remembered that many substances act via diverse mechanisms of action such that the environmental risk assessment for EDCs is a broad and complex issue. Also, biomarkers such as secondary sexual characteristics, gonadosomatic indices, plasma steroids, and gonadal histology have significant potential for guiding interspecies assessments of EDCs and designing fish chronic tests. To strengthen the utility of EDC biomarkers in fish, we need to establish a historical control database (also considering natural variability) to help differentiate between statistically detectable versus biologically significant responses. In conclusion, as research continues to develop a range of useful EDC biomarkers, environmental decision-making needs to move forward, and it is proposed that the “biomarkers as signposts” approach is a pragmatic way forward in the current risk assessment of EDCs.