Chapter 6.2 - The Current Situation and Prospects for Tomorrow: Toward the Achievement of Historical Ambitions

Abstract

Regulatory toxicology has begun to embrace new hazard characterisation approaches, which can be integrated into regulatory safety assessments. The vision is to fundamentally change the way the safety of chemicals is assessed, by replacing or reducing the use of traditional animal experiments with a predictive toxicology that is based on a comprehensive understanding of how chemicals can cause adverse effects in humans (MoA and AOP), or adversely impact on the environment, and a ‘renewed’ awareness of the importance of the fate of the chemical in the body (kinetics) for the induction of adverse effects. Integrated Approaches to Testing and Assessment (IATA) will help evaluators to assess data from such novel methods consistently, and to understand their relevance for specific endpoints, to obtain reproducible, understandable and statistically-sound results. To position toxicity data generated by alternative methods in a regulatory context, the need for reliable methods has to be combined with a strategy for how to best integrate the resulting data with computational modelling and existing knowledge and information, in order to provide a prediction with sufficient confidence for acceptance in a safety assessment. The new concept proposed by the US Food and Drug Administration to replace formal validation with qualification for a specific context of use, seems to be the most promising way forward. Once a new model or assay is considered to be qualified for a specific context of use, industry and other stakeholders can use it for its qualified purpose during product development, and regulators should then be confident in applying it without needing to re-review the underlying data supporting validation and acceptance for specific purposes.