Triage of mechanistic information for vanadium compounds using systematic evidence mapping
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Background and Purpose: The incorporation of mechanistic information into human health hazard assessments is challenging due to the large number of studies and wide variety of study designs that are often available for chemicals of interest. Solutions to this challenge are offered in this presentation, which will demonstrate a streamlined and transparent tiered workflow for the literature inventory of mechanistic information for vanadium compounds. This workflow is based on the principle of systematic evidence mapping, in which systematic review methods are used to organize the amount and type of available evidence in a user-friendly format. The goal is to identify mechanistic data that can be potentially used to inform mode of action (MOA) and strengthen the association between chemical exposure and health effects.
Methods: Publications on the health effects of vanadium compounds were identified from a broad key word search of the literature. Studies reporting any type of “mechanistic” data (e.g., oxidative stress, receptor activation, enzyme activity, gene or protein expression) were initially tagged as supplemental information during title/abstract screening. Of these, studies reporting mechanisms for vanadium compounds of interest (e.g., vanadium salts and oxides) were selected for systematic evidence mapping. These studies were tagged according to study type (i.e., human, animal, in vitro, ex vivo), route of exposure, form of vanadium, and health system or endpoint category (i.e., organ system or general category such as genotoxicity) based on full text review using customized forms enabled in DistillerSR software. Quality control was performed by toxicologists with subject matter expertise. More granular subtagging and synthesis of mechanistic evidence (e.g., by mechanistic event within an organ system) will be undertaken if warranted to support hazard identification.
Results: Two hundred and ninety-eight publications were included in the mechanistic literature inventory, with many reporting multiple experiments. In vitro studies in primary or immortalized cell lines were the most common source of mechanistic information, followed by mammalian animal studies (oral, inhalation, or injection exposure). The health systems/endpoint categories with the most information were respiratory, genotoxicity, hepatic, reproductive, and hematologic effects, which are all areas of interest for hazard identification for vanadium compounds. The literature inventory can be easily filtered to allow toxicologists to view the available mechanistic studies for health systems of interest and focus on the assay types that may be most informative for hazard identification.
Conclusions: This literature inventory was relatively rapid to assemble and provides a high-level snapshot of the available mechanistic data for vanadium compounds. The tagging structure reduces the workload for the toxicologists conducting the hazard assessment as it allows them to focus their review on the studies most pertinent to their health effects of interest. The tiered approach allows for expert judgement in determining the types of mechanistic events that warrant more detailed analysis to support MOA and hazard identification, and the tagging structure can be tailored to evaluate chemical-specific issues and potentially relevant toxicity pathways. The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.