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Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a 4-day, alternative developmental toxicity assay designed to pre-screen chemicals and environmental mixtures. An approach used in the scoring of FETAX results, which focuses on the determination of characteristic abnormalities induced by a given test material, was used to evaluate results from previous validation efforts. Characteristic abnormalities are induced specifically by exposure to a given test material and are determined by the relationship between concentration and the response induced and the change in severity of response. Use of this approach eliminates non-specific effects that alter numerical endpoints, reduces intralaboratory variability, reduces the number of equivocal test results (gray area), helps to determine specific syndromes associated with teratogen exposure and, in some instances, increases the predictability of FETAX. In an effort to evaluate this approach, a 12-compound validation study that produced a relatively high degree of equivocal FETAX results was re-evaluated using the characteristic malformation criteria. Data were evaluated for repeatability, predictability and variability. Results from this study indicated that this scoring approach increased repeatability, test endpoint precision and predictability.

In an effort to assess potential ecological hazards to amphibian species in selected regions within New Hampshire, the traditional Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 14-/21 day tail resorption thyroid disruption assay and >30 day limb development tests were conducted with representative surface water and sediment samples. Two separate sets of samples collected from five sites were evaluated. The primary objectives of the study were to determine if samples were capable of inducing early embryo-larval maldevelopment, to determine if maldevelopment included limb defects, to determine if thyroxine co-administration altered the rates of limb malformation and to evaluate the impact of the samples on growth rates, developmental progress and metamorphic climax. Results from these studies suggested that pond water and sediment extract samples, but not whole sediment samples, from B2, FW, LP and W ponds were capable of inducing abnormal early embryo-larval development. In addition, water samples from B2 and W ponds induced significant abnormal hindlimb development. Some abnormal forelimb development was noted in the tail resorption studies, but not to the same extent as the hindlimbs. Each of the water samples induced appreciable developmental delay, including the paired reference site B1, which could be reversed by the addition of exogenous thyroxine.

The developmental toxicities of five test compounds including carbon tetrachloride, urethane, phenacetin, parathion, and chloroform, were evaluated using Frog Embryo Teratogenesis Assay--Xenopus (FETAX), with minor modification. Post-isolation mixtures of differently-induced rat liver microsomes (phenobarbital- (PB), beta-naphthoflavone- (beta-NF), and isoniazid- (INH)-induced preparations) were co-cultured directly with X. laevis embryos. Results from these studies suggest that the Aroclor 1254-induced MAS could effectively be replaced by a mixed lot of PB-, beta-NF-, and INH-induced rat liver microsomes. Each of the test materials were found to be developmentally toxic when bioactivated by the mixed MAS.

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