Abstract：
Identification of Endocrine-Disrupting Chemicals (EDCs) in a regulatory context requires a high level of evidence. However, lines of evidence (e.g. human, in vivo, in vitro or in silico) are heterogeneous and incomplete for quantifying evidence of the adverse effects and mechanisms involved. To date, for the regulatory appraisal of metabolism-disrupting chemicals (MDCs), no harmonised guidance to assess the weight of evidence has been developed at the EU or international level. To explore how to develop this, we applied a formal Expert Knowledge Elicitation (EKE) approach within the European GOLIATH project. EKE captures expert judgment in a quantitative manner and provides an estimate of uncertainty of the final opinion. As a proof of principle, we selected one suspected MDC -triphenyl phosphate (TPP) - based on its related adverse endpoints (obesity/adipogenicity) relevant to metabolic disruption and a putative Molecular Initiating Event (MIE): activation of peroxisome proliferator activated receptor gamma (PPARγ). We conducted a systematic literature review and assessed the quality of the lines of evidence with two independent groups of experts within GOLIATH, with the objective of categorising the metabolic disruption properties of TPP, by applying an EKE approach. Having followed the entire process separately, both groups arrived at the same conclusion, designating TPP as a \"suspected MDC\" with an overall quantitative agreement exceeding 85%, indicating robust reproducibility. The EKE method provides to be an important way to bring together scientists with diverse expertise and is recommended for future work in this area.
摘要：
在监管环境中鉴定内分泌干扰化学物质（EDC）需要高水平的证据。然而,证据线(例如，人类，在体内，在体外或计算机模拟中）是异质的，并且对于量化所涉及的不良反应和机制的证据不完整。迄今为止,用于代谢干扰化学物质(MDC)的监管评估，在欧盟或国际一级，尚未制定评估证据权重的统一指南。为了探索如何发展这一点，我们在欧洲GOLIATH项目中应用了正式的专家知识获取(EKE)方法。EKE以定量方式捕获专家判断，并提供对最终意见不确定性的估计。作为原则的证明，我们选择了一个疑似MDC-磷酸三苯酯(TPP)-基于其与代谢破坏相关的不良终点(肥胖/脂肪形成性)和一个推定的分子起始事件(MIE):过氧化物酶体增殖物激活受体γ(PPARγ)的激活.我们进行了系统的文献综述，并与GOLIATH内部的两个独立专家组一起评估了证据的质量，为了对TPP的代谢破坏特性进行分类，通过应用EKE方法。单独跟踪了整个过程，两个小组得出了相同的结论，将TPP指定为“可疑MDC”，总体定量协议超过85%，表明稳健的再现性。EKE方法提供了将具有不同专业知识的科学家聚集在一起的重要途径，并推荐用于该领域的未来工作。
