Handy Richard D, Galloway Tamara S, Depledge Michael H
Plymouth Environmental Research Centre, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK.
Ecotoxicology. 2003 Feb-Aug;12(1-4):331-43. doi: 10.1023/a:1022527432252.
Despite a wealth of information on biomarkers, they are not routinely used for regulatory purposes, even though the potential benefits of biomarkers to rationalise complex exposure-response relationships are clear. Biomarkers can be inappropriately applied or misinterpreted, because the fundamental assumptions in exposure-response relations have not been considered. Factors causing temporal and spatial variability in biomarker responses are reviewed. These include numerous geochemical and biotic variables. The variation can be minimised by appropriate study site selection, experimental replication, multivariate epidemiological approaches, normalised controls, and temporal calibration of responses; so that the regulatory use of biomarkers for biomonitoring and tracking pollution events, including chronic or multiple exposures to complex mixtures is possible. We propose and define the characteristics of biomarkers of chronic exposure or effect, which must measure changes in pollution/effect against long-term changes in other general stresses (disease, nutrition, environmental quality), relate to cumulative injury, and remain responsive over months or years. Neuroendocrine, immunological, and histological biomarkers are suggested for chronic pollution. We propose a regulatory framework for biomarkers based on a weight of evidence approach that can integrate biomarkers in risk assessment and long-term monitoring programmes.
尽管有大量关于生物标志物的信息，但它们并未常规用于监管目的，尽管生物标志物在合理化复杂的暴露-反应关系方面的潜在益处是显而易见的。生物标志物可能会被不恰当地应用或误解，因为暴露-反应关系中的基本假设未得到考虑。本文综述了导致生物标志物反应出现时空变异性的因素。这些因素包括众多地球化学和生物变量。通过适当选择研究地点、进行实验重复、采用多变量流行病学方法、设置标准化对照以及对反应进行时间校准，这种变异性可以降至最低；从而使生物标志物能够用于监管目的，进行生物监测和追踪污染事件，包括对复杂混合物的慢性或多重暴露。我们提出并定义了慢性暴露或效应生物标志物的特征，这些生物标志物必须衡量污染/效应相对于其他一般应激（疾病、营养、环境质量）长期变化的变化情况，与累积损伤相关，并在数月或数年时间内保持反应性。建议将神经内分泌、免疫和组织学生物标志物用于慢性污染研究。我们基于证据权重法提出了一个生物标志物监管框架，该框架可以将生物标志物纳入风险评估和长期监测计划。
