This article is part of our special report The way forward to an animal-free science.
Over the past 15 years, the European Partnership for Alternative Approaches to Animal Testing has helped facilitate coordination and cooperation via the 3R principles to successfully Replace animal testing with innovative methods, Reduce the number of animals in established methods, and to Refine procedures where no alternative exists to ensure safety. While much progress has been achieved in lessening the need for animal testing, we have more work ahead.
Patrick Masscheleyn is Senior Vice President of Research & Development and Global Product Stewardship for the Procter & Gamble Company.
During the past 5 years, regulatory mandated testing accounted for millions of animals in the Member States of the EU alone. These numbers are simply too large to be ignored and warrant integration of 3Rs approaches. Regulatory mandated animal testing is likely to further increase as the EU chemicals management policy develops under the EU Green Deal toxic-free environmental strategy. How can we address both challenges, a better protection of people and our planet and less animal testing, at once?
Our Opportunity – Improving Predictions of Health Risks While Reducing Reliance on Animal Testing
The range of animal alternative tests has evolved over time. They generally involve the evaluation of local and systemic effects and the dose response associated with those effects. This has formed the basis for safety assessments that are predictive of risks and protective of people and our planet. Yet replacement of animal models to those with greater precision and predictive power is a complex problem for endpoints like systemic toxicity, reproductive toxicity, and carcinogenicity where harmful effects can occur beyond a chemical’s entry point can be the result of complex interactions among biological processes and may take time to manifest.
The connections between toxicants and their initial molecular targets is increasingly well understood, but the cellular responses that must occur before these initial interactions lead to adverse outcomes are not. Alternative methods for these systemic endpoints have advanced by understanding the initiating factors of toxicity. The current best approaches for predicting toxicity from initiating events involve read across, based on either the chemical structure or the biological response.
These approaches are enabled by large databases of animal toxicity data and the understanding of biological responses at a molecular level – from gene expression studies and High Throughput Screening. While these methods and approaches exist and can be successfully applied in some cases, there are many others for which further research is needed. A continued effort is needed to catalogue the complex adverse outcome pathways associated with systemic effects and link them to existing animal data via computational modeling, because the non-linear aspects of downstream events render it difficult to determine safety from initiating events alone.
Now is the time to act
It will take additional research and innovation to develop a robust understanding of the human biological ‘system’, i.e. all the events in all adverse outcome pathways. Computational models (virtual tissues) that predict emergent properties can increase, together with state-of-the-art in vitro methods to confirm the results in an iterative fashion.
These advances in systems biology are already demonstrating the ability to make safety assessment of chemicals more predictive of human health, at lower costs, and in quicker time than classical endpoint-focused animal testing. As the knowledge in systems biology and toxicology increases, then provision of computational modelling and the like could be advanced.
If we want to support a toxic free environment based on better prediction of human and environmental risks, then it is time for the EPAA and other partners to advocate for a fourth “R” principle – a systems biology “Revolution”.
The case for investment.
The potential positive impacts to human and planetary health make new approaches to hazard and risk evaluation ripe for investment. Importantly there is a critical need to unlock finance to validate the hypothesis that systems biology and toxicology can bring about a safer world, and one without animal testing.
With a coordinated and collaborative approach and strong European leadership there is a unique opportunity to unleash historic change. Creating and promoting non-animal methods through systems biology is not just the best way to end animal testing; it’s also a game-changing innovation that advances safety science as a whole that will contribute to a toxic-free environment that allows for sustainable innovation for EU competitiveness.