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Applying the Key Characteristics Approach for Qualitative and Quantitative Evaluation of the Toxicological and Mechanistic Evidence on Benzo[a]Pyrene-Induced Male Reproductive Toxicity.
Citation:
Druwe, I., B. Blake, AND X. Arzuaga. Applying the Key Characteristics Approach for Qualitative and Quantitative Evaluation of the Toxicological and Mechanistic Evidence on Benzo[a]Pyrene-Induced Male Reproductive Toxicity. Society for Risk Analysis, NA, Virtual, December 13 - 17, 2020.
Impact/Purpose:
To share and have an interchange with other in the field of quantification of AOPs
Description:
The analysis of chemical-induced effects in the male reproductive system involves a qualitative evaluation and integration of toxicological, epidemiological, and mechanistic evidence. Consideration of mechanistic studies in this process may inform biological plausibility and the human relevance of effects observed in experimental animal models, identify database uncertainties, and facilitate decision-making that impacts quantitative assessment. However, the diverse array of known and proposed pathways causally associated with chemical-induced male reproductive toxicity, and the diversity of research methods and models, can present an additional challenge for screening and analyzing mechanistic evidence. Here we integrate the eight key characteristics of male reproductive toxicants with established pathways for loss of reproductive function to identify and analyze the mechanistic evidence on benzo[a]pyrene (B[a]P)-induced male reproductive effects. Qualitative and quantitative evaluations of mechanistic studies are underway to identify potential causal pathways of B[a]P-induced male reproductive toxicity, inform biological plausibility, and facilitate dose response interpretation and assessment. The B[a]P case study demonstrates that the key characteristics approach serves as a practical and objective tool for identifying and organizing mechanistic evidence as well as quantitative information along key event continuums in male reproductive toxicity in support of human health risk assessment. Disclaimer: The views expressed are those of the authors and do not necessarily represent the views or policies of the US EPA