WP5: Improving in vitro/in vivo correlations – Absorption, Distribution, Excretion

 

Results WP5 pdf 105kB, download the entire summary.

 

In WP5 the focus was to investigate the influence of ADE (administration, distribution and elimination) on the kinetics of chemicals using modeling and in vitro testing, with the aim to identify factors that influence the correlation between in vitro toxicity (concentration) and in vivo toxicity (dosage) and to develop an algorithm that accounts for this. 

 

Important factors to be considered have been:
1. The degree and rate of absorption after oral uptake
2. The distribution over the different organs and tissues
3. The elimination of compounds
4. The determination of the concentration of the compound in the in vitro system

 

To address the points mentioned above the following methodologies have been used:

• Neural network models for oral and blood brain barrier (BBB) passage
• In vitro measurements of BBB passage
• In vitro measurements for determination of oral absorption
• In vitro biokinetics: evaluation of free concentration of a chemical
• Physiologically-based kinetic modeling

 

In summary, the accumulative results from WP5 show the importance of an analysis of the kinetic factors that influence the relationship between in vitro derived cytotoxicity data and in vivo acute toxicity parameters. This ranges from – on the one hand – a better understanding and interpreting of in vitro data by taking into account the in vitro biokinetics, to – on the other hand – determining (in vitro or in silico) parameters that determine the actual concentrations to which cells and tissues are exposed in the in vivo situation.

 

Read more in the entire summery above.