Evaluation of androgen assay results using a curated Hershberger database
2018
Abstract A set of 39 reference chemicals with reproducible androgen pathway effects in
vivo, identified in the companion manuscript [ 1 ], were used to interrogate the performance of the ToxCast/Tox 21
androgen receptor(AR) model based on 11 high throughput assays. Cytotoxicity data and specificity confirmation assays were used to distinguish assay loss-of-function from true antagonistic signaling suppression. Overall agreement was 66% (19/29), with ten additional inconclusive chemicals. Most discrepancies were explained using in vitro to in
vivoextrapolation to estimate equivalent administered doses. The AR model had 100% positive predictive value for the in
vivoresponse, i.e. there were no false positives, and chemicals with conclusive AR model results (agonist or antagonist) were consistently positive in
vivo. Considering the lack of reproducibility of the in
vivoHershberger assay, the in vitro AR model may better predict specific AR interaction and can rapidly and cost-effectively screen thousands of chemicals without using animals.
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