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Lecture in “Toxicity testing in the 21st century: A vision and a strategy”
January 2009

Daniel Krewski, PhD, MHA
NSERC Chair in Risk Science
Professor and Director
McLaughlin Centre for Population
Health Risk Assessment
University of Ottawa
Room 320, One Stewart Street
Ottawa, Ontario CANADA K1N 6N5
Tel: 613-562-5381/Fax: 613-562-5380


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There are three main element of the NRC Vision for Toxicity Testing;   Chemical characterization, toxicity testing, and dose response and extrapolation modeling.  At each step, population based data and human exposure information are considered, as is the question of what data are needed for decision-making.

Chemical characterization includes physical and chemical properties of substances including possible breakdown products and metabolites, how the substances are used, and their concentrations are in the environment.  Compiling of this data will allow for development of computational modeling and the predictive properties of different substances depending on their physical and chemical nature. 
A central element of the vision is that toxicity testing will move away from in vivo apical  end points in animal models, to in vitro perturbations of toxicity pathways in human cells and cell line assays.  High throughput testing will allow for numerous chemicals alone and in combination, in a range of dose from very high to very low, to be tested in a timely and cost-efficient manner. 

The final element of the vision is the dose-response and extrapolation modeling component which will be used to integrate and interpret the toxicity testing data.  Pharmacokinetics models will determine which toxicity pathways in which tissues have been perturbed and the combination of these models should be able to identify biomarkers that indicate a biological change or susceptibility that needs to be investigated.



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