The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 2006-2007

Morphologic and genomic approaches to evaluate the zebrafish embryo test as an alternative in vitro screening model system to predict developmental toxicity

Hilda Witters, PhD
VITO - Flemish Institute for Technological Research

Developmental toxicity is a major issue in children's health worldwide. The developing human system is susceptible to many toxicants, and chemical exposure during development may cause lasting metabolic deficits. Such damage can range from subtle to severe, and it may impose substantial burdens on affected individuals, their families, and society. Testing compounds for developmental toxicity endpoints is an important societal and scientific goal.

Zebrafish is an established animal model for many aspects of human development and diseases that will benefit from extended embryological knowledge and genomic research. The first specific aim of the project will be the determination of the developmental time course of early physical malformations and neurobehavioural dysfunctions caused by a selection of candidate compounds in a dose range matter. The second aim will be a detailed investigation of the cellular and molecular mechanisms (fingerprints of genes), contributing to these (d)effects as observed for the most potent compounds.

The overall purpose of this research project is to utilize zebrafish embryos, as a simple and fast high-throughput assay to predict for potential malformations and dysfunctional effects during early development, caused by exposure to different classes of chemicals. This short term zebrafish assay might in the first place replace and reduce the number of mammals currently used for testing of chemicals. And eventually as it does contribute to an improved and cost-efficient test strategy for numerous chemicals, it may lead to reduction or prevention of the majority of induced birth defects.