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首页> 美国卫生研究院文献>Environmental Health Perspectives >Screening and Testing for Endocrine Disruption in Fish—Biomarkers As Signposts Not Traffic Lights in Risk Assessment
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Screening and Testing for Endocrine Disruption in Fish—Biomarkers As Signposts Not Traffic Lights in Risk Assessment

机译：鱼类内分泌干扰的筛选和测试-在风险评估中将生物标志物标记为路标而非交通灯

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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.
机译：目前，在破坏内分泌的化学物质（EDC）的环境风险评估中，生物标记物最好用作机械“路标”，而不是“交通灯”。在现场研究中，暴露的生物标志物（例如雄鱼中的卵黄蛋白原（VTG）诱导）是追踪所关注的单一物质和混合物的有力工具。生物标记物还提供了田间和实验室数据之间的联系，从而在指导对EDC进行鱼类慢性检验的需求和设计中发挥了重要作用。这些测试的不良反应终点（例如，发育，生长和/或繁殖改变）对于计算不良 NOEC（无观察到的效应集中）或不良< / sup> EC10（10％反应的有效浓度），随后推算出无作用预测浓度（PNEC）。在当前不确定性的情况下，不应单独使用 biomarker NOEC或 biomarker EC10数据来导出PNEC。但是，如果可以在组织的各个层次之间建立合理的联系，从而可以设想相对于生物标志物反应的不良结果，那么将来在环境决策中可能会越来越多地使用生物标志物数据。为了使生物标记物发挥其潜力，它们应在机械上相关且可复制（通过同一方案的实验室间比较来衡量）。 VTG是此类生物标记物的一个很好的例子，因为它可以洞察对于鱼类生殖健康至关重要的作用方式（雌激素）。 VTG的实验室间可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法）提供的变异系数（CV）为38-55％（与法规测试指南中所使用的鱼类存活率和生长终点的公布CV相比为19-58％）。尽管人们对环境中的异雌激素的关注导致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起作用，因此对EDC的环境风险评估是一个广泛而复杂的问题。同样，诸如第二性征，性腺机能指数，血浆类固醇和性腺组织学等生物标志物在指导EDC的种间评估和设计鱼类慢性试验方面具有巨大潜力。为了增强EDC生物标记物在鱼类中的效用，我们需要建立一个历史对照数据库（还要考虑自然变异性），以帮助区分统计学上可检测的响应和生物学上重要的响应。总而言之，随着研究不断开发出一系列有用的EDC生物标记，环境决策需要向前发展，并且提出“生物标记作为路标”方法是当前EDC风险评估中的一种务实方法。

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