Frog Embryo Teratogenesis Assay-Xenopus (FETAX): Use in Alternative Preclinical Safety Assessment

The primary objective of this protocol is to provide alternative developmental toxicity data using the frog embryo teratogenesis assay-Xenopus (FETAX) model for preclinical safety assessment. FETAX is most useful in the prioritization of developmental toxicity hazard for sets of discovery-level compounds. Assessment of teratogenic potential is based on teratogenic indices (TI), which measure the teratogenic potential of a given test material. The relative hazard ranking is based on a set of weighted endpoints that include developmental toxicity potency, teratogenic potential, and growth inhibition. Because of the importance of potency and teratogenic potential in determining relative hazard, these endpoints are weighted 2×. Growth inhibition is weighted 1×. These data determine a generic ranking. The generic hazard rank is based on numerical endpoint data derived from an assessment of potency, teratogenic potential as determined by the TI value, and concentration at which growth inhibition is detected when expressed as a proportion of the 4-d LC50 value. With the generic rank, the lower the generic hazard ranking the greater the developmental toxicity hazard relative to the other materials evaluated. However, the relative severity of the malformation syndromes induced is not incorporated into the generic ranking process. An objective evaluation of the severity of the deformities induced is an important process in the evaluation of FETAX results; therefore, a final definitive ranking process is used. A final definitive ranking is determined using the generic rank and the severity of the malformations induced (weighted 5×).