Preliminary validation of a short-term morphological assay to evaluate adverse effects on amphibian metamorphosis and thyroid function using Xenopus laevis

Short-term static-renewal studies were performed on Xenopus laevis embryos with 16 selected test materials from day 50 (stage 60) to day 64 (stage 66) (14-day test) to evaluate effects on tail resorption and thyroid function. Of the 16 test materials, nine were found to inhibit significantly the rat e of tail resorption, four were found to stimulate metamorphosis and three had no appreciable effect on the rate of metamorphosis. In an effort to det ermine if the morphological effects observed were related to alteration in thyroid activity, measurement of triiodothyronine (T-3) in the test organis ms and coadministration studies using thyroxine (agonist) or propylthiourac il (antagonist) were performed based on the morphological response noted du ring tail resorption. Of the nine compounds found to inhibit the rate of ta il resorption, six were found to reduce the levels of T-3. In each case, th e inhibitory response could be at least partially alleviated by the co-admi nistration of thyroxine, Larvae exposed to the four stimulatory agents had somewhat elevated levels of T-3 and were responsive to propylthiouracil ant agonism, These results suggest that 12 of the 14 compounds tested in this s tudy that altered the rate of tail resorption did so via the thyroid axis. Overall, the X, laevis model appeared to be a suitable system for evaluatin g the impact of environmental agents and chemical products on thyroid funct ion. Copyright (C) 2000 John Wiley & Sons, Ltd.