The aim of the project EU-ToxRisk is to drive the required paradigm shift in toxicological testing. EU-ToxRisk will integrate advancements in cell biology, systems biology and computational modeling to provide the proof of concept for a mechanism-based chemical safety testing strategy and define the complex chains of events that link chemical exposure to toxic outcome. The focus of this project is on two areas: repeated-dose systemic toxicity, using the lung, kidney, liver and nervous system as examples of potential target organs; and developmental and reproductive toxicity.
Fraunhofer ITEM scientists will test new approach methodologies
Scientists from Fraunhofer ITEM are contributing to this project in many ways. For example, they are leading three case studies in which groups of compounds are tested by new approach methodologies (NAMs). These groups are selected based on available preclinical in-vivo data, for example, from the Fraunhofer database RepDose. They have to show similar chemical properties, structural as well as physico-chemical, and similar toxicological properties, for example, the same apical findings in vivo or even a similar adverse outcome pathway (AOP). The AOP describes the chain of events leading to toxicity of a substance, from the initial event that triggers further key events of increasing complexity which eventually lead to the actual toxic effect relevant for regulatory assessment.
Aiming at animal-free integrated approaches to testing and assessment
The experimental work performed at Fraunhofer ITEM includes testing in precision-cut lung and liver slices. For the lung model, air-liquid exposure is at the focus of interest. By these case studies, the ITEM scientists aim to learn more about the use of NAMs in risk assessment: They are planning to integrate a battery of suitable in-vitro and ex-vivo models into integrated approaches to testing and assessment - IATA in brief.
The ultimate goal of EU-ToxRisk is to deliver testing strategies enabling reliable, animal-free hazard and risk assessment of chemicals.