Inter-laboratory assessment of a harmonized zebrafish developmental toxicology assay - progress report on phase I.

Autor: Gustafson AL; AstraZeneca, Sodertalje, Sweden., Stedman DB, Ball J, Hillegass JM, Flood A, Zhang CX, Panzica-Kelly J, Cao J, Coburn A, Enright BP, Tornesi MB, Hetheridge M, Augustine-Rauch KA
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2012 Apr; Vol. 33 (2), pp. 155-64. Date of Electronic Publication: 2011 Dec 21.
DOI: 10.1016/j.reprotox.2011.12.004
Abstrakt: 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.
(Copyright © 2011 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE