Proposed key characteristics of male reproductive toxicants as an approach for organizing and evaluating mechanistic evidence in human health hazard assessments
Assessing chemicals for their potential to cause male reproductive toxicity involves the evaluation of evidence obtained from experimental, epidemiological, and mechanistic studies. Although mechanistic evidence plays an important role in hazard identification and evidence integration, the process of sorting and analyzing mechanistic studies and outcomes is a challenging exercise due to the diversity of research models, methods and the variety of known and proposed pathways for chemical-induced toxicity. The ten key characteristics of carcinogens provide a valuable tool for organizing and assessing chemical-specific data by potential mechanisms for cancer-causing agents. However, such an approach has not yet been developed for non-cancer adverse outcomes. The objective in this study was to identify a set of key characteristics that could be applied for organizing mechanistic evidence related to chemical-induced male reproductive toxicity. The identification of eight key characteristics of male reproductive toxicants was based on a survey of known male reproductive toxicants and established mechanisms and pathways of toxicity. The key characteristics is a useful framework that can facilitate the systematic, transparent, and objective organization of mechanistic evidence relevant to chemical-induced effects on the male reproductive system. Disclaimer: The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA or CalEPA.