Evaluation of Xenopus tropicalis as an Alternative Test Organism for Frog Embryo Teratogenesis Assay—Xenopus (FETAX)

Abstract

As a formal recommendation from an Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) workshop review of the Frog Embryo Teratogenesis Assay—Xenopus (FETAX) developmental toxicity model, the use of Xenopus tropicalis as an alternative test species for this model was evaluated. Three test substances with varying developmental toxicity potentials were evaluated using FETAX modified to accommodate the use of X. tropicalis. Two separate definitive concentration-response tests were performed with isoniazid, methotrexate, and 6-aminonicotinamide. Historical FETAX results with X. laevis were compared to the results from FETAX assays with X. tropicalis. Test with X. tropicalis indicated that each of the compounds possessed teratogenic potential with varying degrees of potency: 6-aminonicotinamide>methotrexate>isoniazid. Based on overt teratogenicity, but not embryo-lethality, results from these studies indicated that these two species responded similarly to the test compounds. Malformation syndromes induced in both species were similar in X. tropicalis and X. laevis. These results suggested that X. tropicalis should be further evaluated as an alternative test organism for the FETAX model.

Key Words: :

• Xenopus tropicalis
• FETAX
• Developmental toxicity
• Isoniazid
• Methotrexate
• 6-Aminonicotinamide