Applied Pharmacology & Toxicology, Inc., Gainesville, FL, USA.
Regul Toxicol Pharmacol. 2011 Nov;61(2):185-91. doi: 10.1016/j.yrtph.2011.07.007. Epub 2011 Jul 23.
"Weight of Evidence" (WoE) approaches are often used to critically examine, prioritize, and integrate results from different types of studies to reach general conclusions. For assessing hormonally active agents, WoE evaluations are necessary to assess screening assays that identify potential interactions with components of the endocrine system, long-term reproductive and developmental toxicity tests that define adverse effects, mode of action studies aimed at identifying toxicological pathways underlying adverse effects, and toxicity, exposure and pharmacokinetic data to characterize potential risks. We describe a hypothesis-driven WoE approach for hormonally active agents and illustrate the approach by constructing hypotheses for testing the premise that a substance interacts as an agonist or antagonist with components of estrogen, androgen, or thyroid pathways or with components of the aromatase or steroidogenic enzyme systems for evaluating data within the US EPA's Endocrine Disruptor Screening Program. Published recommendations are used to evaluate data validity for testing each hypothesis and quantitative weightings are proposed to reflect two data parameters. Relevance weightings should be derived for each endpoint to reflect the degree to which it probes each specific hypothesis. Response weightings should be derived based on assay results from the test substance compared to the range of responses produced in the assay by the appropriate prototype hormone and positive and negative controls. Overall WoE scores should be derived based on response and relevance weightings and a WoE narrative developed to clearly describe the final determinations.
“证据权重”（WoE）方法常用于批判性地检查、优先考虑和整合来自不同类型研究的结果，以得出总体结论。对于评估具有激素活性的物质，WoE 评估对于评估筛选检测方法是必要的，这些方法可以识别与内分泌系统成分的潜在相互作用、长期生殖和发育毒性测试，以确定不良反应、作用机制研究，旨在确定不良反应的毒理学途径，以及毒性、暴露和药代动力学数据，以表征潜在风险。我们描述了一种针对具有激素活性的物质的假设驱动的 WoE 方法，并通过构建假设来阐明该方法，这些假设用于测试以下前提：一种物质作为激动剂或拮抗剂与雌激素、雄激素或甲状腺途径的成分相互作用，或与芳香酶或甾体生成酶系统的成分相互作用，以评估美国环保署内分泌干扰物筛选计划中的数据。使用已发布的建议来评估每个假设的测试数据有效性，并提出定量权重，以反映两个数据参数。应针对每个终点得出相关性权重，以反映其对每个特定假设的探测程度。应根据测试物质与适当的原型激素和阳性对照和阴性对照在检测中产生的反应范围相比的检测结果得出反应权重。应根据反应和相关性权重得出总体 WoE 得分，并制定 WoE 叙述，以清楚地描述最终结论。
