Teratogenicity test models

Fujrnaga M et al (1988) Rat whole embryo culture an in vitro model for testing nitrous oxide teratogenicity. Anesthesiology 69 401-404... 

Figure 9-5 The sensitivity of the conceptus to a theoretical teratogen during rat gestation (modified from 161). The most susceptible window is organogenesis with low levels of vulnerability at the time of implantation and the period of functional maturation. Superimposed are the approximations of when the developmental landmarks that are represented in the four in vitro tests occur. The chick embryo neural retina model (CENR) represents events around GD 10-13. The mouse embryonic stem cell test (EST) corresponds roughly to the period of GD 6-10 in the rat, near the peak of sensitivity. Whole embryo culture (WEC) recapitulates the window at the peak of sensitivity, between GD 9-11 or GD 10-12 depending upon the window within which the culture is conducted. Rabbit cultures are also done between GD 10-12. Represented by the single ( ) and double asterisk ( ), respectively, are the initiation and termination of the dosing period in regulatory compliant preclinical embryo/fetal toxicity studies. Thus, the zebrafish is the only model that permits exposure to test article during this important period.

Many possible alternative models have been explored during the last decades (e.g., whole rate embryo culture and primary or permanent embryonic stem cells54). Furthermore, different attempts have been made to develop QSAR approaches for the prediction of teratogenic effects.55-57 Fish embryos also appear to be a promising alternative test system for the reliable and cost-effective identification of potential human teratogenic compounds.58 An experimental advantage is their extracorporal development and the transparency of the eggs of... 

Although animal studies are a required component of drug testing, extrapolation of the results of such testing to humans is not always accmate. One example is thalidomide, which was found to be safe in some animal models but proved to have teratogenic effects in human offspring. ... 

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