The eight key characteristics of male reproductive toxicants: an approach for screening and evaluating mechanistic evidence.-Poster
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Systematic review approaches in human health assessment includes the integration of evidence from experimental, epidemiological, and mechanistic studies. The process of screening and evaluating evidence can be challenging due to the diversity of research models, methods, outcomes, and the variety of known mechanistic pathways resulting in chemical-induced toxicity. The goal of the current project was to identify a set of key characteristics that can be used to analyze mechanistic evidence which may inform the potential pathways/networks associated with chemical-induced male reproductive toxicity. This approach is motivated by the outcome of the Ten Key Characteristics of Carcinogens (Smith et al 2016), now recognized as a useful method for searching and screening mechanistic information on chemical-induced carcinogenesis (NASEM 2017). The proposed key characteristics for male reproductive toxicity were identified through a review of established mechanisms for chemical-induced male reproductive toxicity. An expert workgroup was convened in March 2018 at the University of California-Berkeley to determine whether the key characteristics approach can also be applied to non-cancer effects including male reproductive toxicity. Eight key characteristics were identified and include alterations in: 1) germ cell functions, 2) somatic cell functions, 3) reproductive hormone levels/production, 4) hormone receptors, 5) DNA damage, 6) epigenetic modifications, 7) oxidative stress, and 8) inflammation. As a proof of principle, the key characteristics were used to evaluate evidence from mechanistic studies on the PCB mixture Aroclor 1254. A database was developed to capture experimental design information and mechanistic outcomes from the available studies. The resulting database can be used to qualitatively evaluate mechanistic and toxicological evidence as part of a hazard characterization analysis.