Evaluation of the Mechanistic and Toxicological Evidence on Benzo[a]Pyrene-Induced Male Reproductive Effects Using the Key Characteristics Approach
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The hazard evaluation of potential chemical-induced adverse effects in the male reproductive system involves the analysis and synthesis of epidemiological toxicological and mechanistic evidence. Mechanistic evidence can inform biological plausibility and thus plays an important role in hazard identification and evidence integration. However, the diversity of research models, methods, and the variety of known and proposed pathways for chemical-induced toxicity can make the process of identifying, screening, and analyzing mechanistic studies and outcomes a challenging exercise. The ten key characteristics of carcinogens has been shown to provide a valuable tool for organizing and assessing chemical-specific data. Here we apply the recently published eight key characteristics of male reproductive toxicants to evaluate the mechanistic and toxicological evidence on benzo[a]pyrene (B[a]P)-induced male reproductive toxicity. Studies were identified from the U.S. Environmental Protection Agency Integrated Risk Information System (IRIS) Toxicological Review of B[a]P. Additional literature searches were performed to capture studies published since the completion of the Toxicological Review, plus any additional studies that may have been missed. Literature inventories were developed to facilitate the qualitative review of the available evidence. Preliminary analysis of the available evidence suggests that potential key characteristics involved in B[a]P-induced male reproductive toxicity include: (1) Alters germ cell development, function, or death; (2) Alters somatic cell development, functions, or death; (3) Alters production and levels of reproductive hormones; (4) Alters hormone receptor levels/functions; (5) Is genotoxic; and (7) Induces oxidative stress. This case study demonstrates that the key characteristics approach provides an objective tool for organizing and evaluating complex mechanistic evidence on chemical-induced male reproductive toxicity. Disclaimer: The views expressed are those of the authors and do not necessarily represent the views or policies of the US EPA.