PRINCETON, NJ — An international consortium of 39 partner organizations will be funded by the European Commission to work on the integration of new concepts for regulatory chemical safety assessment. These new concepts involve cutting-edge human-relevant in vitro non-animal methods and in silico computational technologies to translate molecular mechanistic understanding of toxicity into safety testing strategies. The ultimate goal is to deliver reliable, animal-free hazard and risk assessment of chemicals.

Coordinated by Bob van de Water, Professor of Toxicology at Leiden University (The Netherlands), EU-ToxRisk intends to become the European flagship for animal-free chemical safety assessment. The project will integrate advancements in cell biology, omics technologies, systems biology and computational modeling to define the complex chains of events that link chemical exposure to toxic outcome. The consortium will provide proof of concept for a new mechanism-based chemical safety testing strategy with a focus on repeated-dose systemic toxicity as well as developmental and reproductive toxicity. Importantly, novel mechanism-based test methods will be integrated in fit-for-purpose testing batteries that are in line with the regulatory framework and will meet industrial implementation. EU-ToxRisk will develop new quantitative risk assessment approaches based on understanding of so-called “Adverse Outcome Pathways” incorporating all mechanistic toxicity data available in the public domain. It will also achieve a rapid improvement of so-called “read across” approaches as the most important data-gap filling and hence animal-saving alternative method at present. Thus, the project strives towards faster safety evaluation of the many chemicals used by industry and society.

“Certara is proud to participate in this international effort to develop reliable, efficient, animal-free toxicology tests for agrochemicals, industrial chemicals, and cosmetics,” said Certara Chief Executive Officer Edmundo Muniz, MD, PhD. “We plan to demonstrate the pivotal role that physiologically-based pharmacokinetic modeling and simulation can play in improving toxicology testing.”

Dr. Susanne Hougaard Bennekou from the Danish Environmental Protection Agency explained: “Safety evaluation is largely based on animal testing. This is the best we have today. However, there are widely recognized limitations, these being that the sensitivity and specificity of animal-based safety testing could lead to wrong predictions of chemical-induced human adversities. Whilst false-negative results compromise human safety, false-positive animal tests and use of unnecessarily large safety factors may lead to the loss of beneficial and safe chemicals and drugs.” Professor Marcel Leist, head of the Center for Alternatives to Animal Testing in Europe (CAAT-Europe) in Konstanz, Germany, added: “Ethical issues related to the use of experimental animals as well as economic considerations (high costs, time delay by testing) demand a paradigm shift, away from ‘black box’ animal testing towards a toxicological assessment based on responses observed in human cells and a comprehensive mechanistic understanding of cause-consequence relationships of adverse chemical effects.”

EU-ToxRisk builds on testing strategies and knowledge developed in previous national and European projects, including the SEURAT-1 program, a cluster of seven projects in the field of animal-free safety assessment: 2010-2015 (https://www.seurat-1.eu). The EU-ToxRisk consortium includes many of Europe’s leading toxicologists and experts in related fields such as cell and developmental biology, genomics, computational biology, cheminformatics, bioinformatics, biostatistics, regulatory sciences, as well as management and dissemination, from a range of organizational backgrounds and covering several industry sectors. This breadth of expertise will allow EU-ToxRisk to develop efficient and innovative safety testing strategies, covering the whole range of stakeholders, to ensure fit-for-purpose solutions, practical routine applicability and quick uptake of results. EU-ToxRisk will establish strong ties with the European Union Reference Laboratory for alternatives to animal testing (EURL-ECVAM), hosted by the Joint Research Centre (JRC), Institute for Health and Consumer Protection, to establish novel alternative testing strategies that are fit for regulatory purposes. In addition, the project will strongly collaborate with ongoing safety and risk assessment initiatives across the globe, including the Tox21 initiative in the United States.

Dr. Rob Taalman, Science and Research Director at Cosmetics Europe, the Brussels-based Personal Care Association, which co-funded the SEURAT-1 cluster with the European Commission, said: “We are thrilled to be part of this strategic EU project. This joint action restates our long-held commitment to be at the forefront of research into alternatives to animal testing. For more than 20 years, the industry has been pushing the boundaries of cutting-edge science to develop technologies that would feed into novel, sustainable safety testing strategies in line with the European regulatory framework. Since the ban on animal testing within the cosmetics industry, there is the wish and the scientific capabilities to improve safety assessment approaches based on alternatives.”

Overall, EU-ToxRisk intends to evolve a new era for European safety sciences. At the end of the project the novel risk assessment strategies should find wide application in various regulatory contexts, across industry sectors, and for different population groups, such as patients, workers, consumers, and the society at large. Altogether, EU-ToxRisk expects to have a strong impact on the future regulatory chemical safety and risk assessment in Europe as well as the rest of world.

The EU-ToxRisk project will kick-off in January 2016 in Leiden, The Netherlands, and will run for six years.

Project Partners

Universities

Leiden University, The Netherlands

Leiden University Medical Centre, The Netherlands

Konstanz University, Germany

Katholieke Universiteit Leuven, Belgium

Maastricht University, The Netherlands

Medical University of Innsbruck, Austria

Ruprecht-Karls-Universität Heidelberg, Germany

University of Copenhagen, Denmark

Universitat Pompeu Fabra, Spain

University of Vienna, Austria

Research Institutions

Center for Alternatives to Animal Testing in the Johns Hopkins Bloomberg School of Public Health, United States of America

EMBL/European Bioinformatics Institute, United Kingdom

Forschungsgesellschaft für Arbeitsphysiologie und Arbeitsschutz (IFADO), Germany

Fraunhofer Society – Fraunhofer ITEM, Germany

Fundación para la Investigación del Hospital Universitario La Fe de la Comunidad Valenciana, Spain

Institut National de l’Environnement et des Risques, France

Istituto di Ricerche Farmacologiche Mario Negri, Italy

Karolinska Institutet/Swedish Toxicology Sciences Research Center, Sweden

TNO, The Netherlands

Large industry

BASF, Germany

Cosmetics Europe, Belgium

F. Hoffmann – La Roche, Switzerland

L’Oreal, France

Simcyp, a Certara company, United Kingdom

Steinbeis CAAT-Europe at the University of Konstanz, Germany

Unilever, Safety and Environmental Assurance Centre, United Kingdom

SMEs

ARTTIC, France

BioDetectionSystems, The Netherlands

BioTalentum, Hungary

Cyprotex Discovery Ltd, United Kingdom

Douglas Connect, Switzerland

InSphero AG, Switzerland

Lhasa Limited, United Kingdom

Open PHACTS Foundation, United Kingdom

TissUse, Germany

Regulatory bodies

Federal Institute for Occupational Safety and Health, Germany

Istituto Superiore di Sanità, Italy

The Danish Environmental Protection Agency, Denmark

Research funder

National Centre for the Replacement, Refinement & Reduction of Animals in Research, United Kingdom