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.
AstraZeneca, Sodertalje, Sweden.
A-L
AL
Gustafson
D B
DB
Stedman
J
J
Ball
J M
JM
Hillegass
A
A
Flood
C X
CX
Zhang
J
J
Panzica-Kelly
J
J
Cao
A
A
Coburn
B P
BP
Enright
M B
MB
Tornesi
M
M
Hetheridge
K A
KA
Augustine-Rauch
D000014:Abnormalities, Drug-Induced; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000592:standards*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D023421:Models, Animal; D015203:Reproducibility of Results; D058028:Research Report; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods / Q000592:standards*; D015027:Zebrafish
D013723:Teratogens