Integrated Approaches to Testing and Assessment: OECD Activities on the Development and Use of Adverse Outcome Pathways and Case Studies

Abstract

The Organisation for Economic Co-operation and Development (OECD) works with member countries and other stakeholders to improve and harmonize chemical assessment methods. In 2012, the OECD Adverse Outcome Pathways (AOPs) Development Programme started. The Programme has published six AOPs thus far and more than 60 AOPs are under various stages of development under the Programme. This article reviews recent OECD activities on the use of AOPs in developing Integrated Approaches to Testing and Assessments (IATAs). The guidance document for the use of AOPs in developing IATA, published in 2016, provides a framework for developing and using IATA and describes how IATA can be based on an AOP. The guidance document on the reporting of defined approaches to be used within IATA, also published in 2016, provides a set of principles for reporting defined approaches to testing and assessment to facilitate their evaluation. In the guidance documents, the AOP concept plays an important role for building IATA approaches in a science-based and transparent way. In 2015, the IATA Case Studies Project was launched to increase experience with the use of IATA and novel hazard methodologies by developing case studies, which constitute examples of predictions that are fit-for-regulatory use. This activity highlights the importance of international collaboration for harmonizing and improving chemical safety assessment methods.

In silico toxicology: From structure–activity relationships towards deep learning and adverse outcome pathways

“…This assessment could be used for gap filling as well as the prediction of potential mechanisms to guide further investigations. A useful guideline on how AOPs can be integrated into risk assessment was published by Sakuratani and coworkers . Arzuaga and coworkers showed that the AOP framework can be used to identify and describe possible species‐specific effects .…”

Toxicology Meets Pharmacodynamics and Pharmacokinetics – New Concepts, Models and In Vitro Approaches and Tools

“…Integrated Approaches to Testing and Assessment (IATA) is a novel procedure outlining science‐based approaches for toxicological decision‐making based on the integration of multiple information sources from in vivo , in vitro and in silico . The IATA concept is a tool to promote risk assessment by non‐animal testing methods, and it is already used for some end‐points such as skin corrosion/irritation and skin sensitization, where validated in vitro tests are available and in conjunction with other relevant information .…”

“…The most important element in applying IATA is Adverse Outcome Pathway (AOP) concept where the toxicologically critical, molecular, biochemical and biological pathways or networks of pathways with key events are identified and in vitro assays developed to cover these pathways. OECD has published guidance documents on how to use AOPs in developing IATA . Six AOPs have been published so far .…”

“…OECD has published guidance documents on how to use AOPs in developing IATA . Six AOPs have been published so far . For wider application of IATA in regulatory toxicology, more validated in vitro tests are needed.…”

Generation of a Triple-Transgenic Zebrafish Line for Assessment of Developmental Neurotoxicity during Neuronal Differentiation

“…Thus, alternative test systems, such as human stem/progenitor cell and zebrafish models, have the potential to enable testing of large chemical libraries while reducing expense and minimizing rodent use [4,[20][21][22][23][24][25].In human stem/progenitor cell models, various endpoints have been used to assess DNT, including viability, apoptosis, proliferation, migration, differentiation, and neuronal network formation [24,26,27]. These endpoints facilitate the identification of adverse outcome pathways and the development of integrated approaches to test and assess chemical-induced DNT [22,28]. Differentiation of neural stem/progenitor cells into neurons, astrocytes, and oligodendrocytes has been analyzed by immunohistochemical staining with antibodies against cell-specific proteins such as NeuN/RNA-binding Fox3 (Rbfox3) for neurons, glial fibrillary acidic protein (GFAP) for astrocytes, and myelin basic protein (MBP) for oligodendrocytes [26,29].…”