When are Adverse Outcome Pathways and Associated Assays "Fit for Purpose" for Regulatory Decision-Making and Management of Chemicals?

There have been increasing demands for chemical hazard and risk assessments in recent years. Chemical companies have expanded internal product stewardship initiatives, and jurisdictions have increased the regulatory requirements for the manufacture and sale of chemicals. There has also been a shift in chemical toxicity evaluations within the same timeframe with new methodologies being developed to improve chemical safety assessments for both human health and the environment. With increased needs for chemical assessments coupled with more diverse data streams from new technologies, regulators and others tasked with chemical management activities are faced with increasing workloads and more diverse types of data to consider. The Adverse Outcome Pathway (AOP) framework can be applied in different scenarios to integrate data and guide chemical assessment and management activities. In this paper, scenarios of how AOPs can be used to guide chemical management decisions during research and development, chemical registration, and subsequent regulatory activities like prioritization and risk assessment are considered. Furthermore, specific criteria (e.g. the type and level of AOP complexity, confidence in the AOP, as well as external review and assay validation) are proposed to examine whether AOPs and associated tools are fit for purpose when applied in different contexts. Certain toxicity pathways are recommended as priority areas for AOP research and development, and the continued use of AOPs and defined approaches in regulatory activities are recommended. Furthermore, a call for increased outreach, education and enhanced use of AOP databases are proposed to increase their utility in chemicals management. This article is protected by copyright. All rights reserved

When are Adverse Outcome Pathways and Associated Assays "Fit for Purpose" for Regulatory Decision-Making and Management of Chemicals?

There have been increasing demands for chemical hazard and risk assessments in recent years. Chemical companies have expanded internal product stewardship initiatives, and jurisdictions have increased the regulatory requirements for the manufacture and sale of chemicals. There has also been a shift in chemical toxicity evaluations within the same timeframe with new methodologies being developed to improve chemical safety assessments for both human health and the environment. With increased needs for chemical assessments coupled with more diverse data streams from new technologies, regulators and others tasked with chemical management activities are faced with increasing workloads and more diverse types of data to consider. The Adverse Outcome Pathway (AOP) framework can be applied in different scenarios to integrate data and guide chemical assessment and management activities. In this paper, scenarios of how AOPs can be used to guide chemical management decisions during research and development, chemical registration, and subsequent regulatory activities like prioritization and risk assessment are considered. Furthermore, specific criteria (e.g. the type and level of AOP complexity, confidence in the AOP, as well as external review and assay validation) are proposed to examine whether AOPs and associated tools are fit for purpose when applied in different contexts. Certain toxicity pathways are recommended as priority areas for AOP research and development, and the continued use of AOPs and defined approaches in regulatory activities are recommended. Furthermore, a call for increased outreach, education and enhanced use of AOP databases are proposed to increase their utility in chemicals management. This article is protected by copyright. All rights reserved