Journal
REPRODUCTIVE TOXICOLOGY
Volume 81, Issue -, Pages 272-280Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2018.08.017
Keywords
Androgen receptor; In vitro; High-throughput screening; ToxCast/Tox21; Hershberger; Androgenic; Anti-androgenic; Endocrine disruptor
Categories
Funding
- Intramural EPA [EPA999999] Funding Source: Medline
Ask authors/readers for more resources
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 vivo extrapolation to estimate equivalent administered doses. The AR model had 100% positive predictive value for the in vivo response, 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 vivo Hershberger 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available