Vandenberg Laura N, Ågerstrand Marlene, Beronius Anna, Beausoleil Claire, Bergman Åke, Bero Lisa A, Bornehag Carl-Gustaf, Boyer C Scott, Cooper Glinda S, Cotgreave Ian, Gee David, Grandjean Philippe, Guyton Kathryn Z, Hass Ulla, Heindel Jerrold J, Jobling Susan, Kidd Karen A, Kortenkamp Andreas, Macleod Malcolm R, Martin Olwenn V, Norinder Ulf, Scheringer Martin, Thayer Kristina A, Toppari Jorma, Whaley Paul, Woodruff Tracey J, Rudén Christina
Department of Environmental Health Sciences, University of Massachusetts Amherst School of Public Health & Health Sciences, Amherst, MA, USA.
Department of Environmental Science and Analytical Chemistry, Stockholm University, Stockholm, Sweden.
Environ Health. 2016 Jul 14;15(1):74. doi: 10.1186/s12940-016-0156-6.
The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs.
We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity.
Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs.
When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.
内分泌干扰化学物质（EDC）问题正受到科学界和监管界的广泛关注。近期对EDC文献的分析因未能采用透明且客观的方法来得出关于EDC暴露与不良健康或环境结果之间证据强度的结论而受到批评。系统评价方法是解决这一问题的理想选择，因为它们为研究选择和评估提供了透明且一致的方法。需要客观的方法来整合在评估EDC时相关的多种证据流（流行病学、野生动物、实验动物、体外和计算机数据）。
我们开发了一个用于EDC研究的系统评价和综合评估（SYRINA）框架。该框架旨在与国际化学品安全规划署（IPCS）和世界卫生组织（WHO）对EDC的定义一起使用，这需要评估关于以下方面的证据：1）暴露与不良效应之间的关联；2）暴露与内分泌干扰活性之间的关联；3）不良效应与内分泌干扰活性之间的合理联系。
基于现有的评估和综合证据的方法，SYRINA框架包括七个步骤：1）明确问题；2）制定综述方案；3）识别相关证据；4）评估单个研究的证据；5）总结和评估每条证据流；6）整合所有证据流的证据；7）得出结论、提出建议并评估不确定性。所提出的方法是根据IPCS/WHO对EDC的定义量身定制的，但在其他EDC定义的背景下使用时具有灵活性。
使用SYRINA框架时，总体目标是提供支持决策所需的证据基础，包括任何避免/最小化暴露潜在不良影响的行动。该框架允许对来自多个证据流的证据进行评估和综合。最后，关于监管行动的决策不仅取决于证据的强度，还取决于行动/不行动的后果，例如，如果后果严重或不可逆转，有限或薄弱的证据可能足以证明采取行动是合理的。
