Cefic-lri Programme | European Chemical Industry Council

HBM3: Data on in vitro metabolism and mechanisms of action in combination with kinetic modelling: integrating in risk assessment

Principal Investigator

Dr. Bas Blaauboer
PO Box 80.177
3508 TD Utrecht
The Netherlands
Tel: +31 30 2535330
Fax: +31 30 2535077

Collaborators

Dr. Harvey J Clewell, Dr. Cecila Tan, Dr. Melvin Andersen – The Hamner Institute for Health Sciences, USA

Description

The objectives of this project are the further development of strategies making use of the integration of different areas of knowledge on the chemistry and the biological activity of compounds, and their use in the interpretation of biomonitoring data.

These integrated approaches will include:

– the chemical structure and its relevance for the biological activity ((Q)SARs);
– the mechanisms of toxic action for chemicals;
– estimates of the exposure towards these chemicals;
– internal exposure in in vivo situations, as modelled by in silico (PBBK) kinetic models

An essential element in this project is the use of in vitro data on metabolism, in vitro data on the toxicodynamics and the use of these data in physiologically-based kinetic and dynamic modelling. This would enable a quantification of the risk of exposure to compounds.

Related Publications

Research project summary:

Data on in vitro metabolism and mechanisms of action in combination with kinetic modeling: integrating in risk assessment by M. Dingemans, B. Blaauboer, A. Efremenko, M. Yoon, J.L. Campbell,  H.J. Clewell, E. Rorije, J. Bessems, M. Schriks and W. Brands

Presentation:

Integration of metabolic fate, health effects and biokinetics predictions in an in silico-in vitro-in vivo approach in a tiered testing strategy by Bas J. Blaauboer

Posters:

Integrating In Vitro Kinetic and Toxicity Data in Quantifying In Vivo Risk of Exposure to Compounds by Elton Zvinavashea, Jerry Campbell Jr,Harvey Clewell III, Melvin Andersen and Bas Blaauboer

Inclusion of metabolism in toxicity predictions comparing in silico with in vivo by Milou M.L. Dingemans, Alina Efremenko, Emiel Rorije, Jos Bessems, Harvey Clewell and Bas J. Blaauboer

Timeline: April 2008 > March 2010

LRI funding: €399,676

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