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

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

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

Dateien

Dietrich_0-291169.pdfGröße: 311 KBDownloads: 798

Datum

2015

Autor:innen

van der Burg, Bart

Wedebye, Eva Bay

Dietrich, Daniel R.

Jaworska, Joanna

Mangelsdorf, Inge

Paune, Eduard

Schwarz, Michael

Piersma, Aldert H.

Kroese, E. Dinant

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Reproductive Toxicology. 2015, 55, pp. 114-123. ISSN 0890-6238. eISSN 1873-1708. Available under: doi: 10.1016/j.reprotox.2015.01.008

Zusammenfassung

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 seems very feasible.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

In vitro; In silico; Integrated testing; Read accross; Reproductive toxicity; Endocrine disruption

Zitieren

ISO 690

VAN DER BURG, Bart, Eva Bay WEDEBYE, Daniel R. DIETRICH, Joanna JAWORSKA, Inge MANGELSDORF, Eduard PAUNE, Michael SCHWARZ, Aldert H. PIERSMA, E. Dinant KROESE, 2015. The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals. In: Reproductive Toxicology. 2015, 55, pp. 114-123. ISSN 0890-6238. eISSN 1873-1708. Available under: doi: 10.1016/j.reprotox.2015.01.008

BibTex

@article{vanderBurg2015-08-01ChemS-31181,
  year={2015},
  doi={10.1016/j.reprotox.2015.01.008},
  title={The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals},
  volume={55},
  issn={0890-6238},
  journal={Reproductive Toxicology},
  pages={114--123},
  author={van der Burg, Bart and Wedebye, Eva Bay and Dietrich, Daniel R. and Jaworska, Joanna and Mangelsdorf, Inge and Paune, Eduard and Schwarz, Michael and Piersma, Aldert H. and Kroese, E. Dinant}
}

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Universitätsbibliographie

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