Citation:

Arzuaga, X., C. Gibbons, A. Hotchkiss, E. Yost, B. Beverly, L. Zeise, M. Smith, N. Skakebaek, G. Prins, R. Pagani, R. Hauser, AND S. Schrader. Key characteristics of male reproductive toxicants: an approach for screening and sorting mechanistic evidence -Poster. Strategies and Tools for Conducting Systematic Reviews, Washington, DC, December 10 - 11, 2018.

Impact/Purpose:

This poster is for the National Academies of Sciences workshop: Strategies and Tools for Conducting Systematic Reviews of Mechanistic Data to Support Chemical Assessments. Hazard identification as part of a human health risk assessment consists of an analysis of the available evidence on chemical-induced adverse health effects that are focused on cancer and non-cancer outcomes such as male reproductive toxicity. Evaluation of epidemiological, toxicological, and mechanistic studies for direct evidence of effects after chemical exposures plays a critical role in the hazard identification process. Analysis of mechanistic events that are precursors to apical endpoints seen in animals and humans support evidence of a hazard, identify potential susceptible populations and lifestages, and inform the human relevance of effects observed in animals, and identify data gaps.

Description:

Since the introduction of ten key characteristics of carcinogens as a basis for organizing mechanistic data on carcinogenesis, the National Academy of Sciences has recommended that key characteristics approaches also be developed for noncancer hazards. The aim of this project was to identify a set of key characteristics that can be used for searching, screening, and sorting mechanistic evidence on chemical-induced toxicological responses in the male reproductive system. An expert workgroup was convened at the University of California-Berkeley in March 2018 to review the key characteristics approach and determine whether it can be applied to endocrine disruptors and male and female reproductive toxicants. For male reproductive toxicants, eight key characteristics were identified based on survey of established mechanisms, 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, this set of key characteristics was used to organize mechanistic evidence from in vivo and in vitro studies on the PCB mixture Aroclor 1254 and effects in the male reproductive system. The proposed key characteristics of male reproductive toxicants facilitates the systematic screening and categorization of mechanistic data from diverse research methods, models, and endpoints, as well as from a variety of known pathways for chemical-induced toxicity that can support hazard characterization. Disclaimer: The views expressed are those of the authors and do not necessarily represent the views or policies of the US EPA.

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