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

Utility of Xenopus Data from FETAX Assay for Prediction of Fish Acute Toxicity (or Fish Reproductive/Larval Toxicity)

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. During organogenesis, cytochrome P-450 activity is very low. Uptake of contaminants can vary but not as much as in adults. When FETAX results for a specific array of contaminants are compared with similar results from a fathead minnow embryo-larval assay using the same exposure and environmental conditions (5 day exposure, FETAX solution and 24 degrees centigrade) very similar results are obtained. For three of the six chemicals tested, FETAX was more sensitive than the minnow assay, while the minnow assay was more sensitive than FETAX in the other three assays. Sensitivity differences were usually less than five fold and never more than 10 fold. More importantly, the judgement of which chemical is teratogenic was the same in all cases. This determination is independent of the concentration required to cause effects. Thus, FETAX can serve as an effective developmental toxicity screening assay for developmental toxicants that pose a hazard to aquatic vertebrates. The ability of FETAX to predict adult toxicity in aquatic vertebrates was considered. Unfortunately, FETAX was validated with mostly pharmaceuticals, while adult fish toxicity studies have been conducted with insecticides, herbicides and fungicides. Thus it is unknown whether FETAX can serve in this role. It should be remembered that developmental toxicity can not be predicted by adult studies. Thus, reproductive and developmental toxicity studies need to be performed along with other studies to ensure chemical safety.