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2014
Journal Article
Titel
The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals
Titel Supplements
Abstract
Abstract
There is a great need for rapid testing strategies for developmental toxicity testing, avoiding animal use. The ChemScreen project aimed to fill this gap in a pragmatic manner using existing tools and novel ones if needed and place them in an innovative animal free testing strategy. In our approach we combined knowledge on critical processes affected by reproductive toxicants with knowledge on the mechanistic basis of such effects. It uses 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 a mechanistic high throughput methods and lower throughput assays that relate to more apical endpoints in experimental animals (Piersma et al., 2013). Several modules for rapid exposure predictions via diverse exposure routes have been set up. Consideration of the resulting in vivo concentration estimates was shown to greatly improve predictivity of the in vitro tests. As a further step, we have generated examples how to predict reproductive toxicity of chemicals using all available data, including in vitro screening data, and reference data for so-called read-across purposes. We are actively engaged in promoting regulatory acceptance of the tools developed as an essential step towards practical application. With this, a significant saving in animal use and associated costs seems very feasible.