Application of US EPA IRIS systematic review methods to the health effects of phthalates: Lessons learned and path forward
The work described in this Special Issue was designed to characterize the range of health outcomes associated with exposure to phthalates, including emerging health outcomes that were not covered by recent reports, and consists of six systematic review papers and three methodology papers. Systematic reviews of epidemiology studies were conducted for six phthalates (DEHP, DBP, BBP, DINP, DIBP, DEP) and are reported in four papers that describe associations of these chemicals with male reproductive effects (Radke et al., 2018), female reproductive and developmental effects (Radke et al., 2019a), metabolic effects (Radke et al., 2019b), and neurodevelopmental effects (Radke et al., 2020). Systematic reviews of experimental animal studies were conducted for DIBP (Yost et. al., 2018) and DEP (Weaver et al., 2020), with each paper describing the evidence for six major health outcome categories: male reproductive, female reproductive, developmental, liver, kidney, and cancer. Methodology papers address issues encountered during the course of conducting these reviews that will be of broad applicability to practitioners of systematic review in environmental health, including the evaluation of epidemiological studies with development of outcome-specific evaluation criteria (Radke et al. 2019c) and evaluation of animal studies for reporting quality, risk of bias, and sensitivity (Dishaw et al., 2020). Lastly, Blessinger et al. (2020) presents an ordinal dose-response model that addresses the challenges of modeling the collection of endpoints that characterize “phthalate syndrome” in experimental animal studies. We believe our experience in applying systematic review methods to a large, complex evidence base will be informative for others in the field. Systematic review is being increasingly recognized by research and regulatory organizations as the gold standard for chemical risk assessment. The benefits of systematic review, as well as the major advances and challenges facing researchers in this field, are illustrated in the July 2016 Environment International special issue, “Systematic Review Methods for Advancing Chemical Risk Assessment” (Whaley and Halsall 2016). Advantages of this approach include transparency and objectivity. However, challenges remain, including how to make systematic review pragmatic when applied to the broad topic areas encountered in environmental health.