Biomedical Engineering Reference
In-Depth Information
Chapter
2
Developmental Toxicity
Assessment in Zebrafish
Maryann Haldi
1
, Maegan Harden
1
, Louis D'Amico
1
, Anthony DeLise
2
, and
Wen Lin Seng
1
1
Phylonix, Cambridge, MA, USA
2
Sanofi-Aventis, Bridgewater, NJ, USA
2.1 INTRODUCTION
After the developmental effects of thalidomide were recognized in 1966, the FDA
established protocols to be used for assessing drug effects on reproduction and
development prior to approval for human use (Marathe and Thomas, 1990). In
addition, due to concerns about chemicals in the human food supply, the EPA issued
similar guidelines for pesticides in 1982 and industrial chemicals in 1985. Current
methods for studying developmental toxicity and teratogenicity include in vivo
mammal segment studies, in vitro rodent whole embryo culture test, in vitro cell
culture test, in vitro embryonic stem cell test, and FETAX (frog embryo teratogenesis
assay—Xenopus). The in vitro culture tests have been shown to have limited value
in predicting the effect of drugs on human embryonic and fetal development
(Oberemm, 2000) and the FETAX assay is limited by the animal's partial transparency.
In addition, frogs are insensitive to halogenated aromatic hydrocarbons (Fort
et al., 1988), and responses to toxicant exposure in Xenopus differ from response in
mammals. Although mammalian models remain the gold standard for assessing
developmental toxicity, acceptance of zebrafish as a model for toxicological analysis
is increasing in the US, mirroring widespread use in Europe for environmental
assessment (Parng, 2005; Spitsbergen and Kent, 2003). There is strong rationale for
performing developmental toxicity studies in zebrafish including the following
(Ton et al., 2006): (1) zebrafish is a distinct species, potentially enhancing sensitivity
for identifying compounds that exhibit teratogenicity in vivo, (2) developmental
processes in zebrafish are highly conserved, (3) zebrafish embryos can be cultured
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