Use of adverse outcome pathways in human risk assessment and toxicology

Abstract

Mechanistic information has been used for many years to inform chemical hazard and risk assessments. NRC reports and several agency strategic plans in recent years promote the large-scale use of mechanistic information, organized in the form of pathways at different levels of biological organization as a basis to underpin a dramatic change in the way chemical assessment is performed. As a result, there now exist international collaborations to develop the data and knowledge bases, guidance and principles for development and use of "Adverse Outcome Pathways" (AOPs). Many of the principles for developing and using pathways are based on experience with Mode of Action frameworks for human health risk assessment. Expert groups within the Organization for Economic Cooperation and Development (OECD) are publishing guidance and partnering with the US EPA and European Commissions Joint Research Centre (JRC) to develop a public knowledge base for building AOPs on a large scale. Although this direction is fairly new, there are many pathways already in development. In addition, pathway-based approaches are increasingly being applied to a variety of assessments of hazard in a number of sectors. This chapter describes the genesis of the AOP concept, the development of the necessary tools based on international collaborations, and provides some examples of the use of AOPs in human health risk assessment.