Advancing the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) towards a sensitive screening assay.

Within Europe, alternative methods for toxicity assessment of xenobiotics become very important. Several pharmaceutical, agrochemical and cosmetic companies are currently using the zebrafish embryo as an alternative for animal testing to screen new compounds for developmental toxicity. However, false negative and false positive results are reported in the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) for known mammalian teratogens and non-teratogens, respectively. For safety, false negative results are more critical, as teratogens may be missed. This project aims to further refine the ZEDTA in order to increase the sensitivity of the assay and as such better predict birth defects caused by using drugs during the 1st trimester of pregnancy. In order to achieve this goal, first the number of evaluated morphological endpoints will be extended by including skeletal staining in the ZEDTA. Second, due to the intrinsically low biotransformation capacity of zebrafish embryos, a metabolic activation system will be developed in order to expose the zebrafish embryos not only to the parent compound but also to its potential teratogenic metabolite(s). Finally, additional morphological endpoints will be programmed in image analysis software that will be combined with an automated handling and imaging system. As such, this project will increase the sensitivity and throughput of the ZEDTA, resulting in better, faster and laboratory animal-free screening of teratogenic drugs.

Keywords:ZEBRAFISH, EMBRYOLOGY, IN VITRO

Disciplines:In vitro testing, Non-clinical studies, Embryology

Project type:Collaboration project