The ChemScreen project to design a pragmatic alternative approachto predict reproductive toxicity of chemicals
| Autor: | Aldert H. Piersma, Eduard Pauné, Inge Mangelsdorf, Bart van der Burg, Michael Schwarz, Daniel R. Dietrich, Eva Bay Wedebye, Joanna Jaworska, E. Dinant Kroese |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Test strategy
Read accross Reproductive toxicity Integration testing Computer science In silico RAPID - Risk Analysis for Products in Development 010501 environmental sciences Animal Testing Alternatives Toxicology Models Biological Risk Assessment 01 natural sciences 03 medical and health sciences In vitro Life ddc:570 Toxicity Tests Endocrine disruptiona Animals Humans Food and Nutrition Computer Simulation Integrated testing Endocrine disruption 030304 developmental biology 0105 earth and related environmental sciences Rapid testing Animal use Toxicology Nutrition 0303 health sciences Reproductive Physiological Phenomena business.industry Androgen Antagonists Estrogens High-Throughput Screening Assays 3. Good health Biotechnology Teratogens Biochemical engineering ELSS - Earth Life and Social Sciences business Healthy Living Mutagens |
| Zdroj: | Reproductive Toxicology, 10 p. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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