The Use of Adverse Outcome Pathways (AOPs) to Support Chemical Safety Decisions Within the Context of Integrated Approaches to Testing and Assessment (IATA)

Catherine Willett

doi:10.1007/978-981-13-2447-5_11

Abstract

New streamlined approaches that use fewer resources and animals are needed for the safety assessment of chemicals. Data gathering should be streamlined to fit regulatory need and the specific properties of the chemicals being assessed. Toward this goal, the Organization for Economic Cooperation and Development (OECD) has introduced the concept of integrated approaches to testing and assessment (IATA) to inform hazard or risk assessment. An IATA is designed to address a specific question, and may include exposure or regulatory considerations, depending on the context. IATA can be informed by mechanistic information about the chemical and related biology. OECD’s of Adverse Outcome Pathways (AOPs) framework is designed to gather biological information related to adverse outcomes of regulatory significance. An AOP is the collected chemical and biological information about a particular biological pathway. The OECD has developed guidance for building and assessing AOPs, and is coordinating development of the AOP Knowledge-base (AOP-KB) for collecting and using this information. The AOP-KB also accepts information about the perturbations of these pathways caused by chemical exposure – information can be used to design prediction models. AOPs can form the logical basis for the integration of information and the design of integrated testing strategies (ITS), within the context of an (IATA), to more effectively and efficiently inform hazard or risk determination.

Highlights

There are scientific, social, economic, practical and regulatory pressures stimulating the development and use of streamlined chemical testing and assessment approaches, including increased reliance on non-animal approaches [ called new approach methodologies (NAM)]
There are more than 200 Adverse Outcome Pathways (AOPs) and more than 1000 Key Events (KE) and KERs described in the wiki linked to 340 different stressors
AOPs can: support WoE evaluations; form the basis for integrated approaches to testing and assessment; provide the basis for biological hypothesis to identify what information would be most helpful for decreasing uncertainty in a given situation; provide transparent communication of the information and uncertainty that underlie decisions; form the basis for development of predictive models

Summary

Introduction

There are scientific, social, economic, practical and regulatory pressures stimulating the development and use of streamlined chemical testing and assessment approaches, including increased reliance on non-animal approaches [ called new approach methodologies (NAM)]. There are perhaps tens of thousands of industrial chemicals already in use and in the environment about which there is little toxicological information, and many new chemicals are developed each year, necessitating implementation of a new approach that can broadly assess a large number of chemicals relatively quickly Another driver comes from the personal care product sector where consumers and regional laws are increasing pressure to develop products without testing on animals. The AOP wiki is designed to capture all of the information about AOP elements in text form, via standardized drop-down menus (to keep a standard format and consistent ontology) and free text fields (to accommodate data, explanations and references) As of this writing, there are more than 200 AOPs and more than 1000 KEs and KERs described in the wiki linked to 340 different stressors (metrics available on the AOP Wiki). Once the authors and reviewers are satisfied, a “snapshot” of the AOP at that time is published on the OECD website and is considered the current state of knowledge about that pathway

The Use of AOPs to Support Hazard and Risk Assessment

Summary