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
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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