This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 681002Keywords
REACH, RDT, LOEL
Objective
The majority of toxic chemicals cause their most sensitive toxicological effects in liver, kidney or the respiratory tract in studies with repeated exposure. Nevertheless, there are compounds that show other types of toxicity. However, even if unaffected at the lowest observed effect level (LOEL), there is a 95% probability that effects on liver or kidney are observed in vivo at the next higher dose. The objective of this case study is to gain knowledge on how toxicological data derived from neuro, lung, liver, or kidney in vitro models can be used to predict the LOEL of test compounds and whether an additional safety factor will be needed.
Testing Strategy
In this case study, compounds that show specific toxicity effects in target organs different from the EU-ToxRisk test method panel have been selected for testing. In this way, knowledge will be gained in how far we can use the results of neuro/lung/liver or kidney models to predict the LOEL of such compounds. This case study applies cross-system testing and a 3-tiered approach: hypothesis generation, test cellular assays, PBPK modeling. Finally, data will be analyzed and the next tests will be refined based on the information gained in the first phase.
Contributors
ITEM, UL, BDS, VU, LUMC, HULAFE, IRFM, CRX, SIMCYP.
