Inter-laboratory assessment of a harmonized zebrafish developmental toxicology assay – Progress report on phase I

This report provides a progress update of a consortium effort to develop a harmonized zebrafish developmental toxicity assay. Twenty non-proprietary compounds (10 animal teratogens and 10 animal non-teratogens) were evaluated blinded in 4 laboratories. Zebrafish embryos from pond-derived and cultivated strain wild types were exposed to the test compounds for 5 days and subsequently evaluated for lethality and morphological changes. Each of the testing laboratories achieved similar overall concordance to the animal data (60–70%). Subsequent optimization procedures to improve the overall concordance focused on compound formulation and test concentration adjustments, chorion permeation and number of replicates. These optimized procedures were integrated into a revised protocol and all compounds were retested in one lab using embryos from pond-derived zebrafish and achieved 85% total concordance. To further assess assay performance, a study of additional compounds is currently in progress at two laboratories using embryos from pond-derived and cultivated-strain wild type zebrafish.

► An update on an ongoing consortium effort with an aim to develop a harmonized zebrafish developmental toxicity assay is given.
► 10 teratogens and 10 non teratogens were evaluated blinded in 4 laboratories.
► Laboratories achieved similar overall concordance (60–70% to animal data) despite the use of different zebrafish strains.
► Following integration of optimized procedures into the protocol, retesting of compounds in one lab achieved 85% concordance.
► To further assess performance, 40 proprietary compounds are in evaluation at 2 laboratories.