The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Abstract for TestSmart--A Humane and Efficient Approach to Screening Information Data Sets (SIDS) Data

Getting the most out of FETAX Developmental Toxicology Data

Jack Bantle
Oklahoma State University

The Frog Embryo Teratogenesis Assay (FETAX) is useful as a high throughput developmental toxicity screening assay. Endpoints are mortality, malformation, Teratogenic Index (TI=96-h LC50/96-h EC50 (malformation)) and growth inhibition as determined by the Minimum Concentration that Inhibits Growth (MCIG). Decision criteria for teratogenicity includes the extent the TI exceeds 1.5, an MCIG that is less than 30% of the 96-h LC50 and the severity of malformations caused. FETAX has been validated with 242 different chemicals, 63 of which have been tested with an metabolic activation system (MAS) comprised of Aroclor 1254-induced rat liver microsomes. Results indicate a FETAX predictive accuracy of >83% for tests not employing MAS and >88% accuracy for tests using MAS. This was for tests where rat or mouse data was available. In another study sixteen chemicals were tested in FETAX and in a side by side rat segment II study. In only one case, did FETAX not accurately predict teratogenicity. An ICCVAM committee is considering FETAX for adoption as a developmental toxicity screening test. The test currently meets most ICCVAM requirements. For even higher throughput screening FETAX can be further modified such that five chemicals can be tested instead on just one and a similar savings in terms of the numbers of animals used as well. This results in a considerable cost savings. Structure activity relationships can be drawn for chemicals in a similar chemical series. FETAX can be used to confirm these models and thereby reduce the amount and cost of testing. FETAX can be performed for $3,000 per test of five chemicals in this model with MAS. This can be done with GLP compliance. With ICCVAM acceptance, FETAX can serve to reduce the dependency on mammalian testing.