Interlaboratory Validation of an Exogenous Metabolic Activation System for FETAX

Frog Embryo Teratogenesis Assay: Xenopus (FETAX) is a 96-h, whole-embryo bioassay designed to detect potential developmental toxicants. The primary goal of this research is to improve the predictability and increase the overall utility of FETAX as a screen for developmental toxicants that pose a hazard to human health. Since Xenopus laevis embryos lack mixed-fliriction oxidase metabolism (cytochrome P-450) prior to 96 hours of development, the first specific aim is to explore the use of phenobarbital, b-naphthoflavone, and isoniazid-induced rat liver microsomes as an exogenous metabolic activation system. This particular inducing system would supplant the presently used Aroclor 1254 system which has recently proven to be somewhat unreliable and needs to be replaced based on long-term considerations. Post-isolation mixtures of these microsomes would represent a broader spectrum of P-450 isozymes, and thus, bioactivate/inactivate a wider range of compounds. The second specific objective is to demonstrate the utility of FETAX as an alternative test for rapidly identifying developmental toxicants. The FETAX test may be easily commercialized and used by most environmental and biomedical testing laboratories across the U.S. Industries producing drugs and chemicals can quickly screen their products for developmental toxicity and save considerable arnounts of time and money once this test has been validated. Use of FETAX will enable the U.S. Army to evaluate potential developmental toxicity hazards both in the field and work place in a rapid, cost-effective manner.