Citation:

Blake, B., I. Druwe, AND X. Arzuaga. Synthesis of mechanistic evidence for male reproductive toxicity of benzo[a]pyrene using the key characteristics approach in concert with the mode of action framework. The Society of Toxicology Annual Meeting, San Diego, CA, March 27 - 31, 2022.

Impact/Purpose:

This abstract will be presented as a poster at the annual Society of Toxicology meeting. This project utilizes the eight key characteristics of male reproductive toxicants to evaluate the mechanistic evidence base for male reproductive toxicity of benzo[a]pyrene. This work serves as a case study to demonstrate the utility of applying the key characteristics to identifying, organizing, and evaluating mechanistic evidence of male reproductive toxicants.

Description:

Hazard identification is the first step in human health risk assessment and includes the synthesis of mechanistic evidence across the literature, however such synthesis is challenging due to differences across studies in experimental methods, models, and scope. To address these challenges, we applied the Key Characteristics (KCs) approach in combination with the mode of action (MOA) framework to identify, organize, and synthesize the mechanistic evidence for male reproductive effects induced by the male reproductive toxicant, benzo[a]pyrene (B[a]P). A literature search was performed and 2,172 studies were identified and then screened using SWIFT-Active Screener and DistillerSR by at least two independent reviewers based on predefined inclusion criteria for full text review. The full text review resulted in 64 in vitro and in vivo studies that met the inclusion criteria. An evidence inventory was compiled through manual extraction of study information, which underwent quality control by a second reviewer. The KCs of male reproductive toxicants were used to organize mechanistic evidence at the molecular, cellular, organ, and organism levels in the evidence inventory. Application of the KCs approach, in combination with the MOA framework, to the evidence inventory facilitated the identification of key events and relevant pathways in the MOA for B[a]P-induced male reproductive toxicity. Given the importance of mechanistic evidence in establishing biological plausibility and human relevance of effects observed in experimental models, this work demonstrates the KCs approach is a systematic, efficient, and transparent qualitative method for identifying, organizing, and summarizing mechanistic data for male reproductive hazard identification that can be expanded to other toxicants of interest.

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