High Throughput In Vitro-In Vivo Extrapolation is Critical to Next Generation Risk Assessment

抄録

Next generation chemical risk assessment (NGRA) aims to replace and enhance traditional toxicity testing via in vitro new approach methodologies (NAMs). Translating in vitro points of departure (PODs) to more traditional contexts requires in vitro-in vivo extrapolation (IVIVE) based upon toxicokinetics (TK). Information needed for risk assessment – characterization of chemical hazard, exposure, and TK – are often unavailable for non-pharmaceutical chemicals. Single chemical methods for IVIVE have been thoroughly developed by the pharmaceutical industry, but higher throughput toxicokinetic (HTTK) methods are needed to accelerate the pace of chemical risk assessment via higher throughput IVIVE. While HTTK is unlikely to produce better predictions than single chemical (“bespoke”) models developed with detailed chemical-specific data, we expect HTTK to be more reproducible and more throughly statistically evaluated, with more accurately quantified uncertainty. Because of throughput and transparency, HTTK may, in some cases, be suitable to decision-making contexts. Chemical prioritization efforts based upon HTTK are under consideration at U.S. EPA, Health Canada, and the European Food Safety Authority. There are thousands of chemicals are in need of triage, prioritization, and, potentially, full assessment. HTTK is a key technology supporting next generation approaches to chemical decision making. The views expressed in this presentation are those of the authors and do not necessarily reflect the views or policies of the U.S. EPA.