A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals
Background: Endocrine disrupting chemicals (EDCs) have received wide attention from both the scientific and regulatory communities. A number of 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 a transparent and consistent approach to study evaluation and are therefore needed to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Methods: 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 observed adverse effect and the endocrine disrupting activity. Results: 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 (observational human and wildlife, laboratory mammal and non-mammal, in vitro, in silico); 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 an EDC. Conclusions: The SYRINA framework we have developed allows for the evaluation and synthesis of evidence from multiple study streams including human epidemiology, wildlife, in vivo laboratory animal, in vitro, and in silico data. Finally, a decision about the strength of evidence is independent of making a decision, which may be made based on limited, adequate or strong evidence depending on the circumstances of the decision.