Toxicological Risk Assessment: changing the strategy from animal...


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Title Toxicological Risk Assessment: changing the strategy from animal experimentation to the integrated use of in vitro and other non-animal data and in silico modelling techniques.
Period 09 / 2008 - unknown
Status Current
Research number OND1334362
Data Supplier ZonMw Projectenbank


This project aims at obtaining an overview of the possibilities and bottlenecks of implementing new strategies in toxicological risk assessment of chemicals, which are much less relying on animal studies and are based on the integration of knowledge on a chemical s structural properties in relation to biological activities; on toxicity profiles obtained in in vitro experiments; on in silico models for determining the biokinetic behaviour of the compound and of its toxicodynamics. The overview will be obtained by using our national and international network of experts in this area, literature searches, and a working conference.The project should ultimately lead to a better and faster implementation of these strategies in the regulatory toxicity field.
The area of toxicological risk assessment is still heavily dependent on regulations that prescribe the use of animal models. Apart from the obvious ethical reservations, there are also scientific objections towards this animal use. These objections are mainly related to the high degree of uncertainty in the present regulatory procedures and result from the necessary extrapolation to the human exposure situation. Over the last decades methods have been developed that allow a more scientific approach towards risk assessment. These methods include the optimisation of in vitro methods for studying the toxic mechanisms, the use of human in vitro preparations, the use of QSARs, and the use of computer-based (in silico) biokinetic and toxicodynamic models.This development has resulted in proposals to drastically change the basis for toxicological risk assessment. Strategies are proposed, whereby the integration of different areas of knowledge will be appied, including: QSARs, mechanisms of toxic action (determined in in vitro methods), internal exposure (modelled by in silico (PBBK) models).This project will be surveying the state of the art of the integrated approach in toxicological risk assessment, identify the research needs for those elements in the strategies that are seen as limitations, map the area for those fields where possibilities for implementing the approaches already exist, and identify ways in which new strategies can be implemented more efficiently.

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Project leader Prof.dr. B.J. Blaauboer


D22700 Toxicology (plants, invertebrates)

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