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2013
Journal Article
Titel
FeDTex database - a versatile tool condensing data from developmental and reproductive toxicity studies
Abstract
Studies on developmental and reproductive toxicity are the major cost factor and the major consumer of animals in toxicity testing. Thus, these studies are in contrast to the 3R-principle (Reduction, Refinement and Replacement of animal testing) and there is great necessity to develop new alternative in vitro and in silico methods. Existing animal data can be integrated in this process by identifying critical targets and by validation of alternative methods covering diverse adverse outcome pathways. The Fertility and Developmental Toxicity in experimental animals database (FeDTex DB) developed by Fraunhofer ITEM focusses on developmental and reproductive toxicity studies. Currently, 269 chemicals are covered with 535 studies conducted in rodents and rabbits during the last three decades. FeDTex DB is structured into three major parts: reference, study design and toxicological data. Unique tick-sheets and pick-lists were implemented for a multitude of subcategories to ensure consistent and precise database entries. The study design covers the general study data including test substance, study type, species used including strain, sex and number of animals per dose group, exposure including dosage, route of application and duration and sacrifice. Notably, a documentation of the scope of examination is also integrated in the study design to allow a matching with the toxicological effects. This is important as FeDTex DB contains studies following international guidelines as well as non-guideline studies with varying examinations. (Adverse) effects are assigned to the corresponding generation (i.e. F0, F1, F2 or F3), developmental stage (i.e. prenatal, postnatal or adult), and target/organ. Every single effect is finally characterised by a specific LOEL for the affected sex, examinations without effect result in a related NOEL. In order to determine the added value of the F2 generation in reproductive toxicity studies, NOELs of the F0, F1 and F2 generation have been compared. Further, a considerable chemical overlap with the Fraunhofer Repeated Dose Toxicity Database (RepDose DB) allows combined analysis of reproductive toxicity and repeated dose toxicity data.