The Systematic Review of Mechanistic Data in IRIS Assessments (Presentation)
EPA’s Integrated Risk Information System (IRIS) Program evaluates mechanistic data to inform hazard identification determinations regarding the biological plausibility of human and animal data, to identify susceptible populations or lifestages, and to inform low-dose-response relationships. Mechanistic studies, which include a variety of designs (i.e., in vitro, in vivo using various routes of exposure, ex vivo, and in silico), report measurements related to a health outcome that inform the biological or chemical events associated with phenotypic effects in both mammalian and non-mammalian model systems. Despite the importance of considering mechanistic data, incorporation of these studies within a systematic review framework remains challenging.
Challenges include: screening large numbers of diverse studies efficiently; developing transparent and reproducible criteria for identifying the most informative mechanistic studies; the lack of well-developed systematic review tools to assess internal validity of in vitro and in silico studies; and underdeveloped structured frameworks to guide integration of mechanistic information with human and animal health effects evidence. This presentation will provide an overview of the current approach for the systematic review and integration of mechanistic information in IRIS assessments. [The views expressed in this abstract are those of the author’s and do not necessarily represent the views or policies of the US Environmental Protection Agency or other affiliations.]
Challenges include: screening large numbers of diverse studies efficiently; developing transparent and reproducible criteria for identifying the most informative mechanistic studies; the lack of well-developed systematic review tools to assess internal validity of in vitro and in silico studies; and underdeveloped structured frameworks to guide integration of mechanistic information with human and animal health effects evidence. This presentation will provide an overview of the current approach for the systematic review and integration of mechanistic information in IRIS assessments. [The views expressed in this abstract are those of the author’s and do not necessarily represent the views or policies of the US Environmental Protection Agency or other affiliations.]