Schapaugh Adam W, McFadden Lisa G, Zorrilla Leah M, Geter David R, Stuchal Leah D, Sunger Neha, Borgert Christopher J
Monsanto Company, St. Louis, MO, USA.
The Dow Chemical Company, Midland, MI, USA.
Regul Toxicol Pharmacol. 2015 Aug;72(3):552-61. doi: 10.1016/j.yrtph.2015.05.028. Epub 2015 Jun 2.
EPA's Endocrine Disruptor Screening Program Tier 1 battery consists of eleven assays intended to identify the potential of a chemical to interact with the estrogen, androgen, thyroid, or steroidogenesis systems. We have collected control data from a subset of test order recipients from the first round of screening. The analysis undertaken herein demonstrates that the EPA should review all testing methods prior to issuing further test orders. Given the frequency with which certain performance criteria were violated, a primary focus of that review should consider adjustments to these standards to better reflect biological variability. A second focus should be to provide detailed, assay-specific direction on when results should be discarded; no clear guidance exists on the degree to which assays need to be re-run for failing to meet performance criteria. A third focus should be to identify permissible differences in study design and execution that have a large influence on endpoint variance. Experimental guidelines could then be re-defined such that endpoint variances are reduced and performance criteria are violated less frequently. It must be emphasized that because we were restricted to a subset (approximately half) of the control data, our analyses serve only as examples to underscore the importance of a detailed, rigorous, and comprehensive evaluation of the performance of the battery.
美国环境保护局（EPA）的内分泌干扰物筛查计划第一阶段检测组合包括十一项检测，旨在确定一种化学物质与雌激素、雄激素、甲状腺或类固醇生成系统相互作用的可能性。我们从第一轮筛查的部分检测订单接收者那里收集了对照数据。本文所进行的分析表明，EPA在发布进一步的检测订单之前应审查所有检测方法。鉴于某些性能标准被违反的频率，该审查的一个主要重点应考虑调整这些标准，以更好地反映生物变异性。第二个重点应是针对何时应舍弃结果提供详细的、针对具体检测的指导；对于因未达到性能标准而需要重新运行检测的程度，目前尚无明确的指导。第三个重点应是确定对终点差异有重大影响的研究设计和实施中允许存在的差异。然后可以重新定义实验指南，以便减少终点差异并减少违反性能标准的频率。必须强调的是，由于我们仅限于对照数据的一个子集（约一半），我们的分析仅作为示例，以强调对该检测组合的性能进行详细、严格和全面评估的重要性。
