A. Raza1, K. Chaudhry2, J. Dong1, K. Wolf3, J. Pregenzer3, J. Brown1, J. Olson1, S. Al Janabi1, S. Kellum1, D. Poursina2, X. Sopko2, P. Gallant3, E. LeCluyse3, J. LaRocca2, R. Settivari1, and S. M. Catalano1.
1. Corteva Agriscience, Newark, DE; 2. Corteva Agriscience, Indianapolis, IN; and 3. LifeNet Health LifeSciences, Research Triangle Park, NC.
Background and Purpose:
Increased hepatic thyroid hormone (TH) metabolism due to induction of glucuronidation via Uridine 5'-diphospho-glucuronosyltransferase (UGTs) is the main key event in the TH perturbation mode of action (MoA).
Previously, Corteva collaborated with LifeNet Health to optimize a new approach methodology (NAM) utilizing TruVivo, an in vitro hepatic system, to compare liver-mediated TH perturbation in response to known AhR/CAR/PXR agonists.
Currently there are no guidelines and no acceptance criteria for an assay that evaluates the in vitro comparative quantitative analysis of liver mediated TH disruption among rats and humans.
The current study is focused to evaluate the quantitative variance of T4G among the two species (rat and human) in a set of nine primary hepatocytes lots after exposing to previously used reference compounds. The data was statistically evaluated after three independent repeats with the objective to generate a minimal historical database that can determine the range of variation and provides an acceptance criteria for the assay.