The adverse outcome pathway concept: A basis for developing regulatory decision-making tools.

The Adverse Outcome Pathway (AOP) concept is expected to guide risk assessors in their work to use all existing information on the effects of chemicals on humans and wildlife, and to target the generation of additional information to the regulatory objective. AOPs will therefore be used in the Organisation for Economic Co-operation and Development (OECD) chemical safety programme, as underlying scientific rationales for the development of alternative methods for hazard assessment, such as read-across, in vitro test methods or the development of integrated testing strategies that have the potential to replace animal tests. As a proof-of-concept, the OECD has developed an AOP for skin sensitisation, and as a follow-up has: a) implemented the AOP into the OECD QSAR Toolbox, so that information related to the Key Events (KEs) in the AOP can be used to group chemicals that are expected to act by the same mechanism and hence have the same skin sensitisation potential; b) developed alternative test methods for the KEs, so that ultimately chemicals can be tested for skin sensitisation without the use of animal tests. The development of integrated testing strategies based on the AOP is ongoing. Building on this proof-of-concept, the OECD has launched an AOP development programme with a first batch of AOPs published in 2016. A number of IT tools, which together form an AOP Knowledge Base, are at various stages of development, and support the construction of AOPs and their use in the development of integrated approaches for testing and assessment. Following the publication of the first batch of AOPs, OECD member countries will decide on priorities for their use in supporting the development of tools for regulatory use.

The OECD QSAR Toolbox Starts Its Second Decade.

The OECD QSAR Toolbox is a computer software designed to make pragmatic qualitative and quantitative structure-activity relationship methods-based predictions of toxicity, including read-across, available to the user in a comprehensible and transparent manner. The Toolbox, provide information on chemicals in structure-searchable, standardized files that are associated with chemical and toxicity data to ensure that proper structural analogs can be identified. This chapter describes the advantages of the Toolbox, the aims, approach, and workflow of it, as well as reviews its history. Additionally, key functional elements of it use are explained and features new to Version 4.1 are reported. Lastly, the further development of the Toolbox, likely needed to transform it into a more comprehensive Chemical Management System, is considered.