Learning by Doing: Gaining confidence in new approaches for regulatory decision-making and risk assessment

抄録

The use of toxicological test methods that do not use animals, but rather rely on computational predictions or in vitro methods, is becoming more common worldwide. Most are familiar with straightforward in vitro testing strategies for genotoxicity or irritation, or the combination of in silico and in vitro approaches for skin sensitization. Many more tools are available, including high-content and high-throughput assay batteries, assessment of absorption, distribution, metabolism, and excretion (ADME) behavior, physiologically-based kinetic modeling, mechanstically-driven testing strategies, and similar Integrated Approaches to Testing and Assessment (IATA). With an increase of available tools and approaches, standardization and guidance on how to combine these tools to provide information for weight-of-evidence decision-making is needed.

A modernized, flexible approach to validation is also needed. National and international efforts are ongoing to update guidance to test method developers and users to ensure robust non-animal approaches that meet the needs of industry and decision-makers and maintain human health and environmental protection. This presentation will review recent case examples of applying non-animal approaches for decision-making and risk assessment. Some key concepts related to how users are gaining confidence in applying new approaches, including evaluation of method relevance and reliability, describing use contexts for new methods, and standardization and documentation to help harmonize use and evaluation of data from new methods, will be discussed.