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

Bart van der Burg, Eva Bay Wedebye, Daniel R. Dietrich, Joanna Jaworska, Inge Mangelsdorf, Eduard Paune, Michael Schwarz, Aldert H. Piersma, E. Dinant Kroese

Research output: Contribution to journalJournal articleResearchpeer-review

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 preferably using validated existing tools and place them in an innovative alternative testing strategy. In our approach we combined knowledge on critical processes affected by reproductive toxicants with knowledge on the mechanistic basis of such effects. We used in silico methods for prescreening chemicals for relevant toxic effects aiming at reduced testing needs. For those chemicals that need testing we have set up an in vitro screening panel that includes mechanistic high throughput methods and lower throughput assays that measure more integrative endpoints. In silico pharmacokinetic modules were developed for rapid exposure predictions via diverse exposure routes. These modules to match in vitro and in vivo exposure levels greatly improved predictivity of the in vitro tests. As a further step, we have generated examples how to predict reproductive toxicity of chemicals using available data. We have executed formal validations of panel constituents and also used more innovative manners to validate the test panel using mechanistic approaches. We are actively engaged in promoting regulatory acceptance of the tools developed as an essential step towards practical application, including case studies for read-across purposes. With this approach, a significant saving in animal use and associated costs seemi very feasible. (C) 2015 Elsevier Inc. All rights reserved.
Original languageEnglish
JournalReproductive Toxicology
Volume55
Issue numberSI
Pages (from-to)114-123
Number of pages10
ISSN0890-6238
DOIs
Publication statusPublished - 2015

Keywords

  • In vitro
  • Insilico
  • Integrated testing
  • Read accross
  • Reproductive toxicity
  • Endocrine disruption

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