Letter to the Editor

Comment on ‘Use of an in vitro–in silico testing strategy to predict inter-species and inter-ethnic human differences in liver toxicity of the pyrrolizidine alkaloids lasiocarpine and riddelliine’ by Ning et al., Arch Toxicol doi:
  • H. Mielke
  • F. PartoschEmail author
  • U. Gundert-Remy
Letter to the Editor, News and Views

In vitro methods are increasingly used to characterize pharmacological and toxicological properties of substances. However, in vitro data can provide concentration–effect relationships, but no dose–effect relationship which is necessary for risk and safety assessment. In vitro obtained data can be used applying physiologically based pharmacokinetic (PBPK) modeling, to allow for ‘reverse dosimetry’ or quantitative in vitro–in vivo extrapolation ((Q)IVIVE) by which the concentration into effect relationship is converted into a dose–effect relationship (Bessems et al. 2014). When performing the in vitro studies, the concentration in the medium and in the cells should be measured to know the concentration in the target for toxicity (Kramer et al. 2015). Recently, we have shown that protein binding is an important element to be considered for the (Q)IVIVE and that the extrapolation might be hampered if the concentration in the cultivated cells is not known (Mielke et al. 2017; Algharably...



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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Federal Institute for Risk AssessmentBerlinGermany
  2. 2.Institute for Occupational, Social and Environmental MedicineGeorg-August-University GöttingenGöttingenGermany
  3. 3.Institute of Clinical Pharmacology and ToxicologyCharité Universitätsmedizin BerlinBerlinGermany

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