Quantification of uncertainties in extrapolating from in vitro androgen receptor (AR) antagonism to in vivo Hershberger Assay endpoints and adverse reproductive development in rats#

Multiple molecular initiating events exist that disrupt male sexual differentiation in utero including AR antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of androgen signaling by AR antagonists in utero reduces anogenital distance (AGD) and induces malformations in F1 male rat offspring.

Impact/Purpose

Our objective was to determine how accurately the in vitro potency for AR predicts the dose of a chemical that reduces androgen dependent tissue growth in the Hershberger assay (HA) or the dose level that reduces Anogenital Distance (AGD) in male rat offspring exposed to AR antagonists during sexual differentiation.

Citation

Gray, E. Quantification of uncertainties in extrapolating from in vitro androgen receptor (AR) antagonism to in vivo Hershberger Assay endpoints and adverse reproductive development in rats#. Virtual - NC Society of Toxicology Meeting, Research Triangle Park, North Carolina, September 21, 2020.