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Analysing reproductive toxicity studies using the FeDTex database - does an F2-generation provide an additional benefit?

 
: Schulz, Florian; Lewin, Geertje; Mangelsdorf, Inge; Batke, Monika; Escher, Sylvia

Naunyn-Schmiedebergs archives of pharmacology 387 (2014), Supplement 1, pp.S89, A357
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <80, 2014, Hannover>
English
Journal Article, Conference Paper
Fraunhofer ITEM ()

Abstract
Numerous animal studies are required under the EU program on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). Developmental and reproductive toxicity studies are expected to be the major cost factor and the major consumer of animals. Thus, there is great necessity to develop new alternative testing strategies. One opportunity may be the replacement of the conventional two-generation reproduction toxicity study (OECD 416) by the recently implemented extended one generation reproduction toxicity study (EOGRTS, OECD guideline 443). Existing animal data can be integrated in the process of development by validation of alternative methods.
The Fraunhofer Fertility and Developmental Toxicity in experimental animals database (FeDTex DB) currently covers 269 chemicals with 535 developmental and reproduction toxicity studies conducted in rodents and rabbits during the last three decades. Comparing the generation NOELs of multi-generation reproduction studies, the F1 generation was identified as most responsive. In contrast, the NOEL of the F2 generation was lower than the F1 NOEL only in 10% of the studies. The detailed analysis of the underlying effects in these studies left only 3 studies, where the LOEL of F2 was lower than in F1 or F0. Additionally, the observed F1-effects would clearly have triggered mating of F1 in an EOGRTS design. Thus, the impact of the F2 generation on the study NOEL is low and critical effects would not have been missed following the EOGRTS protocol. Furthermore, an impaired F1-fertility was only observed in 5 studies at the study LOEL. In all these studies, effects on reproductive organs or an impaired fertility were already adequately detected in F0.
In conclusion, studies following the EOGRTS protocol may serve as an alternative in toxicity testing strategies.

: http://publica.fraunhofer.de/documents/N-310695.html