Overall goal/objectives:
New approach methodologies (NAMs) for toxicology have resulted in the availability of in vitro bioactivity data across multiple pathways and endpoints for chemicals that often have no other data. HTTK allows for in vitro-in vivo extrapolation (IVIVE) so that bioactivity data (such as µM concentrations) can be placed in a human exposure context (such as mg/kg bodyweight/day intake rates). We aim to demonstrate that HTTK, with appropriately propagated uncertainty, enhances NAM-based prediction of in vivo points of departure to inform regulatory decision making. A framework will be developed for decision makers to make use of toxicokinetic (TK) new approach methods that take into consideration chemical space and the decision-making context. Quantitative uncertainty in HTTK-based predictions of toxicokinetics will be reviewed. A gap analysis will be performed by identifying, for example, areas of chemical space and routes of exposure in need of further research.
Case Study Leader:
US EPA (John Wambaugh)
Collaborators:
US EPA (ORD), Health Canada, EFSA, NTP, JRC
Status: In progress
- Working on a plan to synthesize comments from the initial kick-off meeting
- Planning to develop a framework for identifying the decision making context(s) where one might use HTTK and delineating the differences in data needs between HTTK and bespoke PBPK modeling.
Presentations or publications that have been publicly released:
NA
