Estrogen-mediated outcomes for alkylphenols via an adverse outcome pathway (AOP) construct

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Description: The overall objective of this project is to create a systematic map in order to catalogue studies evaluating possible key events (KEs) associated with estrogen receptor interactions by alkylphenols, as a class of chemicals. Ultimately, this systematic map will facilitate the evaluation of KEs as they relate to possible adverse outcomes (AOs) associated with estrogen receptor mediation (both agonism and antagonism) in the construct of an adverse outcome pathway (AOP) or AOP network(s). Recognizing that this group of chemicals contains hundreds of individual chemicals which may have similar, overlapping activity, as well as dissimilar activity, as it relates to ER binding and subsequent events, a comprehensive literature review and synthesis of available data will provide a landscape of evidence. This "map” will provide a tool to enhance the understanding of estrogen-mediated downstream biological effects and/or adverse outcomes that are associated with alkylphenols. The resulting map is anticipated to inform the hypothesis that the estrogenicity of alkylphenols can be predicted using an integrated computational toxicology approach. As such, the evidence map can be used to identify and prioritize data strengths and data gaps as well as potential research needs for the group of chemicals to further understand or inform a possible computational approach for evaluating estrogenicity and related adverse outcomes.

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