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The Larval Amphibian Growth and Development Assay (LAGDA) is a globally harmonized test guideline developed by the U.S. Environmental Protection Agency in collaboration with Japan's Ministry of the Environment. The LAGDA was designed to evaluate apical effects of chronic chemical exposure on growth, thyroid-mediated amphibian metamorphosis and reproductive development. During the validation phase, two well-characterized endocrine-disrupting chemicals were tested to evaluate the performance of the initial assay design: xenoestrogen 4-tert-octylphenol (tOP) and xenoandrogen 17-trenbolone (TB). Xenopus laevis embryos were exposed, in flow-through conditions, to tOP (nominal concentrations: 0.0, 6.25, 12.5, 25 and 50 mu gl(-1)) or TB (nominal concentrations: 0.0, 12.5, 25, 50 and 100ngl(-1)) until 8weeks post-metamorphosis, at which time growth measurements were taken, and histopathology assessments were made of the gonads, reproductive ducts, liver and kidneys. There were no effects on growth in either study and no signs of overt toxicity, sex reversal or gonad dysgenesis. Exposure to tOP caused a treatment-related decrease in circulating thyroxine and an increase in thyroid follicular cell hypertrophy and hyperplasia (25 and 50 mu gl(-1)) during metamorphosis. Mullerian duct development was affected after exposure to both chemicals; tOP exposure caused dose-dependent maturation of oviducts in both male and female frogs, whereas TB exposure caused accelerated Mullerian duct regression in males and complete regression in >50% of the females in the 100ngl(-1) treatment. Based on these results, the LAGDA performed adequately to evaluate apical effects of chronic exposure to two endocrine-active compounds and is the first standardized amphibian multiple life stage toxicity test to date. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

The Larval Amphibian Growth and Development Assay (LAGDA) is a globally harmonized test guideline designed to evaluate apical effects of chronic chemical exposure with emphasis on endocrine disruption. Xenoestrogen, 4-tert-octylphenol, and xenoandrogen, 17-trenbolone, were tested to evaluate the performance of the assay. Chemical-specific effects on thyroid homeostasis and reproductive development were identified. Notably, Mullerian duct development was the most sensitive endpoint affected by both chemicals. The LAGDA performed adequately to evaluate apical effects of chronic exposure to two endocrine-active compounds.