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The ChemScreen project to design a pragmatic alternative approachto predict reproductive toxicity of chemicals

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Author: Van der Burg, B. · Wedebye, E.B. · Dietrich, D.R. · Jaworska, J. · Mangelsdorf, I. · Paune, E. · Schwarz, M. · Piersma, A.H. · Kroese, E.D.
Type:article
Date:2015
Source:Reproductive Toxicology, 10 p.
Identifier: 525836
doi: doi:10.1016/j.reprotox.2015.01.008
Keywords: Toxicology Nutrition · In vitro · In silico · Integrated testing · Read accross · Reproductive toxicity · Endocrine disruptiona · Food and Nutrition · Healthy Living · Life · RAPID - Risk Analysis for Products in Development · ELSS - Earth, Life and Social Sciences

Abstract

There is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use.The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner prefer-ably using validated existing tools and place them in an innovative alternative testing strategy. In ourapproach we combined knowledge on critical processes affected by reproductive toxicants with knowl-edge on the mechanistic basis of such effects. We used in silico methods for prescreening chemicalsfor relevant toxic effects aiming at reduced testing needs. For those chemicals that need testing wehave set up an in vitro screening panel that includes mechanistic high throughput methods and lowerthroughput assays that measure more integrative endpoints. In silico pharmacokinetic modules weredeveloped for rapid exposure predictions via diverse exposure routes. These modules to match in vitroand in vivo exposure levels greatly improved predictivity of the in vitro tests. As a further step, we havegenerated examples how to predict reproductive toxicity of chemicals using available data. We haveexecuted formal validations of panel constituents and also used more innovative manners to validatethe test panel using mechanistic approaches. We are actively engaged in promoting regulatory accep-tance of the tools developed as an essential step towards practical application, including case studies forread-across purposes. With this approach, a significant saving in animal use and associated costs seemsvery feasible.