Evaluation of OASIS QSAR Models Using ToxCast in Vitro Estrogen and Androgen Receptor Binding Data and Application in an Integrated Endocrine Screening Approach

Conclusions: We used the extensive ToxCast HTS binding data set to show that OASIS ER and AR QSAR models had high sensitivity and specificity when compounds were in-domain of the models. Based on this research, we recommend a tiered screening approach wherein (1) QSAR is used to identify compounds in-domain of the ER or AR binding models and predicted to bind; (2) those compounds are screened in vitro to assess binding potency; and (3) the stronger binders (AC50 < 1 µM) are screened in vivo. This scheme prioritizes compounds for integrative testing and risk assessment. Importantly, compounds not in-domain, predicted either not to bind or to bind weakly, not active in in vitro, that require metabolism to manifest activity or for which in vivo AR testing is in order, need to be assessed differently. This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process. Citation: Bhhatarai B, Wilson DM, Price PS, Marty S, Parks AK, Carney E. Evaluation of OASIS QSAR Models Using ToxCast in Vitro Estrogen and Androgen Receptor...
Source: EHP Research - Category: Environmental Health Authors: Tags: Research Article Source Type: research