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

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.