Title
The ChemScreen project to design a pragmatic alternative approachto predict reproductive toxicity of chemicals
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.
Publication year
2015
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.
Subject
Life
RAPID - Risk Analysis for Products in Development
ELSS - Earth, Life and Social Sciences
Food and Nutrition
Toxicology Nutrition
Healthy Living
In vitro
In silico
Integrated testing
Read accross
Reproductive toxicity
Endocrine disruptiona
To reference this document use:
http://resolver.tudelft.nl/uuid:6b53f9d7-807e-4141-8ad8-fa508207cd55
DOI
https://doi.org/10.1016/j.reprotox.2015.01.008
TNO identifier
525836
Source
Reproductive Toxicology
Document type
article