Enhancing the predictive validity of Frog Embryo Teratogenesis Assay—Xenopus (FETAX)

Abstract

Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a 4-day, alternative developmental toxicity assay designed to pre-screen chemicals and environmental mixtures. An approach used in the scoring of FETAX results, which focuses on the determination of characteristic abnormalities induced by a given test material, was used to evaluate results from previous validation efforts. Characteristic abnormalities are induced specifically by exposure to a given test material and are determined by the relationship between concentration and the response induced and the change in severity of response. Use of this approach eliminates non-specific effects that alter numerical endpoints, reduces intralaboratory variability, reduces the number of equivocal test results (gray area), helps to determine specific syndromes associated with teratogen exposure and, in some instances, increases the predictability of FETAX. In an effort to evaluate this approach, a 12-compound validation study that produced a relatively high degree of equivocal FETAX results was re-evaluated using the characteristic malformation criteria. Data were evaluated for repeatability, predictability and variability. Results from this study indicated that this scoring approach increased repeatability, test endpoint precision and predictability.

The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARγ in Xenopus tropicalis

“…In the present paper, we employed a modified frog embryo teratogenesis assay Xenopus (FETAX) protocol (Fort and Paul, 2002; Yu et al, 2011) to assess UVI3003-induced malformations in X. tropicalis embryos specific to certain developmental windows of chemical exposure. In a previous study, we found that the well-known agonist of RXR, triphenyltin (TPT), induced stage-specific malformations and phenotypic changes in Xenopus embryos (Yuan et al, 2011).…”

“…Breeding was induced by subcutaneous injection of human chorionic gonadotrophin (hCG) (Zhejiang, China) as described (Yu et al, 2011; Hu et al, 2015a). The exposure experiments were conducted following the Frog Embryo Teratogenesis Assay (FETAX) protocol (Fort and Paul, 2002) with some modifications. Briefly, approximately 12 h after the second injection of hCG, adults were removed from their tanks, and embryos were harvested without removing the jelly coats (Supplementary Fig.…”

Agricultural intensity in ovo affects growth, metamorphic development and sexual differentiation in the Common toad (Bufo bufo)

“…Possible explanations include: non-anthropogenic differences in water quality, maternal transfer of pollutants, distinct genetic groups and epigenetic effects caused by early exposure to pollutants from the ambient aquatic environment. Although conductivity and DO values differed between sites, it has been reported that values of 42-1,790 lS/cm have no effect in FETAX (Fort and Paul 2002), and it seems unlikely that the differences in DO would affect these endpoints. It has also been reported that different races of Rana temporaria display different age and size at metamorphosis in the laboratory, depending on latitude of the parent frogspawn (Laugen et al 2003), although the range of sampling sites in the latter study was 14°N (*1,500 km) compared to 1°N latitude (*160 km) here.…”

In vitro assays for hazard identification of nanoparticles

“…However, because of economic and ethical constrains with in vivo studies, alternatives for in vivo toxicity studies are being developed and validated , Fort et al 2002, Spielmann et al 2006. Due to the complexity of the developmental process, it is a challenge to develop non-animal based methods that cover the whole developmental process .…”

“…To assess possible adverse eff ects of NPs on the developing fetus, in vivo developmental toxicity studies can be performed in for example rats or mice. However, because of economic and ethical constrains with in vivo studies, alternatives for in vivo toxicity studies are being developed and validated , Fort and Paul 2002, Spielmann et al 2006). …”