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Implementation of the Key Characteristics to Optimize Mechanistic Evidence Extraction and Organization
Citation:
Druwe, I., T. Anderson, P. Reinhart, R. Shaffer, Suryanarayana Vulimiri, AND L. Dishaw. Implementation of the Key Characteristics to Optimize Mechanistic Evidence Extraction and Organization. Society of Toxicology Annual Meeting, Nashville, TN, March 20 - 23, 2023.
Impact/Purpose:
To present at Society of Toxicology meeting the method for organizing mechanistic data on ethylbenzene
Description:
Since the last U.S. Environmental Protection Agency’s Integrated Risk Information System (IRIS) Toxicological Review of Ethylbenzene (EB) in 1991, hundreds of new mechanistic studies have been published on EB. Mechanistic studies report measurements related to health outcomes that inform biological or chemical events associated with phenotypic effects in both mammalian and non-mammalian model systems. They use a variety of model systems, including in vitro, in vivo, ex vivo and in silico models. Goal: To employ a method that would efficiently organize and extract the available mechanistic evidence associated with EB-induced human health outcomes. Methods: Create a preliminary mechanistic inventory in order to help with the identification, organization, and synthesize of such the mechanistic evidence base to help inform mode(s) of action and support risk assessment decisions through providing evidence for chemical-induced health hazards. A literature search was performed to identify all the available studies up to the date of the search (January 2022). The literature search identified 113 mechanistic EB studies. Studies were categorized by health outcome and details were extracted based on study type (e.g., human, animal, in vitro, in silico, or other), human relevance, and study design. We also used the “Key Characteristics (KCs) approach” to further categorized or map the studies in DistillerSR to specific published KCs (e.g., hepatic, endocrine, and cancer effects). This last step was not able to be performed for health outcomes for which KCs are still under development or unavailable (i.e., nervous, hematological, metabolic, nervous, respiratory, renal, and systemic effects). The available EB mechanistic evidence is being mapped to ten health effects and further subcategorized, when applicable, into their respective KCs under cancer, hepatic, endocrine health categories. Results: At present, 96 of the 113 mechanistic studies have been fully inventoried. Most were not organ system-specific; 29 related to mechanisms of cancer and 84 informed non-cancer mechanisms. The hepatic organ system had the most organ-specific studies (7 of 96), while the endocrine/exocrine and hematological systems had the least (1 of 96). Additionally, 14 studies were excluded from the inventory because they were not informative to the assessment. This case study demonstrated utility in identifying an approach to organize and extract mechanistic data that may be employed for use in other chemical risk evaluations. The resulting mechanistic systematic evidence map may help inform human health effects associated with EB exposure, identify data gaps in the literature, and assist in identifying studies that inform biological plausibility and MOA(s).