EVALUATION OF THE FROG EMBRYO TERATOGENESIS ASSAY - XENOPUS (FETAX) AS A MODEL SYSTEM FOR MIXTURE TOXICITY HAZARD ASSESSMENT

The joint toxic action for several binary mixtures was determined with FETAX (frog embryo tetratogenesis assay: Xenopus) to evaluate the malformation and lethality end points for potential value in mixture toxicity studies. Nine combinations of developmental toxicants were selected for testing at malformation-inducing concentrations, based on presently accepted modes of teratogenesis of each chemical and on the primary types of malformations each had elicited in earlier tests. Two combinations were selected for embryo-lethal end-point testing. Three mixture ratios (3:1, 1:1, 1:3) were tested for each combination, with each combination being tested on three or four separate occasions. Individual tests of each chemical were simultaneously conducted for each combination to serve as positive controls (i.e., 1:0 and 0:1 solutions). Toxic unit analysis was used to determine the type of joint action for each combination. Concentration addition was observed for three combinations in which both chemicals were thought to have the same mode of teratogenesis. The other six combinations, with the chemicals having different modes of action, showed a response-additive joint action. Response addition was also seen for both combinations tested at the embryolethal end point, with an exception for one mixture ratio that was antagonistic. The results indicate FETAX should be useful for mixture toxicity hazard assessment, especially when the malformation end point is considered.