The Doerenkamp-Zbinden Chair

 Starting in July 2008, the Doerenkamp-Zbinden Chair Group was installed, which was placed within the Division of Toxicology at the Institute for Risk Assessment Sciences at UtrechtUniversity. At this Division of Toxicology research is mainly focused on understanding the toxicity of foreign compounds. During the last decades this work is nearly completely carried out on in vitro alternatives. The Chair Group now consists of me as the chair holder, a junior researcher, five PhD students and two technicians.

The vision: The work in the group is focusing on the need to improve the toxicological risk assessment process, thereby acknowledging the need to reduce and replace the use of animal-based models. This requires a shift in the paradigm of toxicity testing from a system that is based on determining apical endpoints (clinical, clinical-chemical and histopathological parameters) in animal studies towards the interpretation of mechanisms of toxicity linked to changes in biological pathways in cellular systems. Using these data as the basis for a quantitative extrapolation from in vitro dose metrics to in vivo exposure scenarios in a transparent, robust and reliable system will then give improved predictions of toxicological risk. When cellular systems derived from human tissues are employed, thus avoiding the problems with interspecies extrapolations, such systems can be better used for predicting human health risks.

The mission: The chair group’ work will focus on the construction of strategies that aim at: development, implementation and acceptance of non-animal methods in toxicological risk assessment. Emphasis is on those parts of the risk assessment where many animals are being used for regulatory purposes, with special attention for diminishing the need to use companion animals.

Ongoing projects:

1. Improving quantitative in vitro-in vivo extrapolation by using alternative dose metrics in vitro
2. The role of facilitated transport by serum protein in in vitro intrinsic clearance
3. The development of in vitro assays to test for sex steroid hormone production interference
4. The development of in vitro models to study the hypothalamus pituitary gonadal (HPG) axis
5. An in vitro model to study the regulation of alkaline phosphatase induction in the liver
6. The effect of the displacement of chemicals from serum constituents on in vitro mixture toxicity
7. Data on in vitro metabolism and mechanisms of action in combination with kinetic modeling: integrating in risk assessment
8. Profiling the toxicity of new drugs: a non animal-based approach integrating toxico-dynamics and biokinetics
9. Factors stimulating or obstructing the acceptance and implementation of the 3rs in the regulatory process.