The selection of appropriate compounds is one of the most important steps
when planning and designing a database. A small group of nominated experts
from the participating companies carefully selected 14 proprietary and 2 reference substances as test compounds. These compounds were known to cause toxicities to liver and/or kidney in the rat after subchronic administration. In addition, appropriate doses for each of the selected compounds were selected.
During the first 18 months of the project, in-vivo studies in male rats were performed using a harmonized experimental protocol. Briefly, each test compound was tested at two dose levels and groups of 5 rats were sacrificed after single (day 2) and after repeated administration on day 4 and day 15. At each time point of necropsy a time matched control group was sacrificed as well.
Classical toxicological parameters were monitored, e.g. determination of serum and urine parameters (e.g. transaminases, bilirubin etc.), haematological parameters and histopathology of liver and kidney and other potential target organs. In addition, samples were collected for toxicogenomics (tissue from liver and kidney, whole blood), proteomics (tissue from liver and kidney, serum, urine) and metabonomics (serum and urine).
Study Design and Investigations
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Toxicity of Compounds and Study Design
(192KB)