Abstract
High-throughput (HT) in vitro to in vivo extrapolation (IVIVE) is an integral component in new approach method (NAM)-based risk assessment paradigms, for rapidly translating in vitro toxicity assay results into the context of in vivo exposure. When coupled with rapid exposure predictions, HT-IVIVE supports the use of HT in vitro assays for risk-based chemical prioritization. However, the reliability of prioritization based on HT bioactivity data and HT-IVIVE can be limited as the domain of applicability of current HT-IVIVE is generally restricted to intrinsic clearance measured primarily in pharmaceutical compounds. Further, current approaches only consider parent chemical toxicity. These limitations occur because current state-of-the-art HT prediction tools for clearance and metabolite kinetics do not provide reliable data to support HT-IVIVE. This paper discusses current challenges in implementation of IVIVE for prioritization and risk assessment and recommends a path forward for addressing the most pressing needs and expanding the utility of IVIVE.
Original language | English (US) |
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Article number | 894569 |
Journal | Frontiers in Toxicology |
Volume | 4 |
DOIs | |
State | Published - 2022 |
Keywords
- HT-IVIVE
- in vitro
- IVIVE
- metabolism
- QSAR
- risk assessment
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
- Toxicology