Approaching Chemical Safety Assessment Through Application of Integrated Approaches to Testing and Assessment: Combining Mechanistic Information Derived from Adverse Outcome Pathways and Alternative Methods

Abstract

Data derived from animal testing are challenging to interpret and sometimes insufficient to enable regulators to reach conclusions related to the safety of a chemical. Animal data most often rely on the observation of the final adverse effects caused by chemicals. Recent advances in cell culture techniques, coupled with the ability to use sophisticated technologies, have enabled the start of a paradigm shift in the evaluation of chemical hazards that draws upon other types of information, such as those from in vitro or in silico systems, rather than from in vivo studies. These complementary types of information are then integrated. An additional key driver in this shift is an effort to capture and store toxicological mechanistic knowledge in a structured way using Adverse Outcome Pathways (AOPs), which is supported by a program started by the Organization for Economic Co-operation and Development (OECD) in 2012. To facilitate the exploration of the use of new approaches that apply information from new technologies and AOPs and to increase confidence in their potential regulatory applications, the OECD launched a number of activities related to the development of Integrated Approaches to Testing and Assessment (IATA). These activities encourage the combining of information from various methods and tools while increasing the transparency and understanding of their use in chemical safety assessment. In this article, the literature relevant to IATA and AOPs are examined and related OECD and research activities are discussed. There is an increasing understanding of the concept of AOP-informed IATA, and the use of new methods and technologies in the arena of regulatory toxicology. Collectively, these novel models and mechanistic understanding can be used under the umbrella of IATA to answer fundamental regulatory questions by strengthening the knowledge base underpinning decision-making and at the same time gradually replace animal testing.