New strategies in toxicological risk assessment: how we contribute to the paradigm shift in toxicology

© Photo Fraunhofer ITEM

New strategies and concepts for hazard and risk assessment of chemicals are being developed in different research projects at Fraunhofer ITEM. The focus here is on human-relevant, non-animal methods such as in-vitro tests and in-silico computational tools.

An important starting point for avoiding animal testing in chemical safety assessment is the use of existing data for a group of “similar” substances and the use of read-across.

These approaches have been investigated at Fraunhofer ITEM in several publicly funded projects (e.g. in EU projects such as DETECTIVE within the SEURAT research cluster and the project EU-ToxRisk under the Horizon 2020 program).

The new Horizon 2020 project EU-ToxRisk is focused on systemic toxicity after repeated exposure in four key targets: liver, kidney, lung, and neurotoxicity. Furthermore, a better mechanistic understanding of developmental and reproductive toxicity will be developed. This aim will be achieved by testing four different types of case studies, starting with data-rich read-across (RAX) groups.

Fraunhofer ITEM is contributing to the selection of the RAX groups by analyzing in-vivo data from the Fraunhofer databases RepDose (repeated-dose toxicity) and FeDTeX (reproductive toxicity). The institute will also contribute to physiologically based toxicokinetic (PBTK) models, for example by developing a PBTK database and in-vitro measurement of relevant data. Fraunhofer experts will furthermore explore the integration of data from human precision-cut lung/liver slices (PCLS). PCLS will help to bridge the gap between in-vitro systems and the whole organism (in-vivo studies). Finally, Fraunhofer toxicologists will guide the integration of “novel” data, e.g. fit-for-purpose testing batteries, into a pragmatic risk assessment framework that is in line with regulatory needs.

Further approaches to improving risk assessment strategies include the derivation of time extrapolation factors and enhancement of the TTC concept.