New approach methodologies: moving beyond animal testing
Chemical risk assessment has relied for over half a century almost exclusively on the data generated by animal testing. Yet, the approach of testing chemicals in rodents (and other animal species) for human safety purposes has been questioned repeatedly. In addition to ethical issues, the transferability of animal data across species is often problematic because of differences in physiology, metabolism and chemical susceptibilities. In this thematic session, we intend to explore the opportunities provided by new approach methodologies to shift the current paradigm from regulatory chemical risk assessment based on in vivo animal testing towards new generation risk assessment. This alternative will be supported by adverse outcome pathways and informed by mechanisms using integrated approaches based on in vitro testing in human-relevant cell models, alternative animal models (e.g., zebra fish, Caenorhabditis elegans) and in silico technologies.
The science of toxicology has advanced significantly as regards its ability to model complex toxicological processes in simpler systems, and in identifying modes of action that lead to adverse events. New Approach Methodology (NAM) performance-based models are therefore expected to replace animal tests, and alternative mechanistic assays can be used to integrate the in vivo, in vitro and modelling information into one organizational construct (Adverse Outcome Pathway).
During the ONE – Health, Environment, Society – Conference 2022, we will explore how the current paradigm based on in vivo testing can be shifted towards a mechanistic understanding using NAMs.
Background – Challenges and opportunities
Chemical risk assessment has relied for over half a century almost exclusively on the data generated by animal testing. Yet, the approach of testing chemicals in rodents (and other animal species) for human safety purposes has been questioned repeatedly. In addition to the ethical issues that arise from this, the transferability of animal data across species is often problematic because of differences in physiology, metabolism and chemical susceptibilities. Another issue is the sheer number of individual chemicals and mixture permutations on the European market. The result is that a full complement of in vivo toxicity data cannot be generated for many of the chemicals, to which humans or the environment are exposed.
Overall, the huge investment made in toxicity testing has provided us with a vast amount of publicly available data that can be used for broad in vitro and in silico profiling of bioactivities across large inventories of chemicals. Coupling this mechanistic data with an understanding of pathways of toxicity lays the groundwork for new approach methodologies (NAMs) to be used to evaluate chemical toxicity and change the regulatory toxicology paradigm. Mode of action-based High Throughput Screening (HTS) methods like ToxCast and toxicogenomics can already detect biological activity known to adversely affect human health endpoints, and these methods are already being applied in prioritizing the large number of chemicals to which humans may be exposed. These methods, put into an AOP framework, could be a valuable adjunct to, and potential replacement for, in vivo testing. However, to make this a reality, more work needs to improve how the mode-of-action or AOP landscape is catalogued, and to develop case studies where a hypothesis-driven selection of models is used to investigate the potential of agents to cause harm. The results can be compared, both qualitatively and quantitatively, to existing data that underpin regulatory decisions. Obstacles often exist at several levels blocking full engagement in the paradigm shift to NGRA.
While some success has been achieved in areas such as skin irritation and skin sensitisation, many of the NAM approaches dealing with other endpoints are often viewed critically as not being standardised or validated. Moreover, the available in vitro and in silico approaches are often considered only as complementary to the existing in vivo tests, with the assumption that in vitro and in silico tests are not able to fully address complex endpoints. The interpretation of NAMs and their integration and acceptance into the regulatory risk assessment process represents an additional hurdle.
The ONE conference provides a unique occasion to bring together the EU’s scientific agencies that work in the remit of the Environment, Public Health and Food Safety (ENVI), the scientific community developing NAMs and EU risk managers to evaluate the current state of knowledge on NAMs and their use in regulatory risk assessment. The aim is to build the synergies necessary for a clear commitment and a holistic roadmap to enable a paradigm shift to NGRA.
Scope and objectives
This session aims to showcase the added value NAMs bring to chemical risk assessment and to explore the synergies necessary to draw up a holistic roadmap to enable a shift in the current risk assessment paradigm to NGRA. The session will discuss the EFSA 2027 roadmap for NAMs, currently under development through the SPIDO initiative, contributing to its finalisation. Moreover, it will also explore the current status quo of NAM approaches for regulatory use and identify challenges and opportunities as well as how EU agencies, the wider risk assessment community and the research community can make a clear commitment to and draw up a holistic roadmap for shifting the paradigm to NGRA.
Opening and welcome
Maurice Whelan, Joint Research Centre (JRC)
Part I - Framing of issues
NAMs in regulatory risk assessment: the REACH experience
Katrin Schutte, European Commission
Experience of ECHA in developing and applying NAMs for regulatory applications
Tomasz Sobanski, European Chemicals Agency (ECHA)
Developing NAMs for regulatory risk assessment at US EPA: experience, state-of-the-art, lessons learnt
Russell Thomas, U.S. Environmental Protection Agency (US EPA)
Developing NAMs for regulatory risk assessment: academia’s experience
Bob Van De Water, Leiden University
Development and Implementation of NAMs at the OECD
Bob Diderich, Organisation for Economic Co-operation and Development (OECD)
General discussion with all speakers moderated by Maurice Whelan
Part II - EFSA Roadmap and round-the-table discussion
Presentation of EFSA Roadmap
Sylvia Escher, Fraunhofer ITEM
Panel discussion moderated by Maurice Whelan
Suzanne Fitzpatrick, U.S. Food and Drug Administration (US FDA) | Michael Empl, European Medicines Agency (EMA) | Marcel Leist, University of Konstanz | Carl Westmoreland, Unilever | Julia Baines, PETA Science Consortium International | Anna Lennquist, ChemSec