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Development of the larval amphibian growth and development assay: Effects of chronic 4-tert-octylphenol or 17ß-trenbolone exposure in Xenopus laevis from embryo to juvenile
Citation:
Haselman, J., Pat Kosian, Joe Korte, A. Olmstead, T. Iguchi, R. Johnson, AND S. Degitz. Development of the larval amphibian growth and development assay: Effects of chronic 4-tert-octylphenol or 17ß-trenbolone exposure in Xenopus laevis from embryo to juvenile. JOURNAL OF APPLIED TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 36(12):1639-1650, (2016).
Impact/Purpose:
This manuscript will be the first peer-reviewed journal article that presents methods and results from the EDSP Tier II Larval Amphibian Growth and Development Assay. This agency guideline is in the final stages of review within EPA and is currently being reviewed by OECD as a globally harmonized testing method. This test guideline is anticipated to be finalized and implemented in 2015. Should this manuscript be published, it will assuredly be referenced for organism growth rates and various methodological details by public and private laboratories charged with running the assay. In addition, the results presented in this manuscript will serve as precedent for estrogenic and androgenic effects that may be observed from future chemicals tested using the LAGDA under OCSPP/OSCP/EFED oversight.
Description:
The Larval Amphibian Growth and Development Assay (LAGDA) is a Tier II test guideline being developed by the US Environmental Protection Agency under the Endocrine Disruptor Screening Program. The LAGDA was designed to evaluate effects of chronic chemical exposure on growth, thyroid-mediated amphibian metamorphosis and reproductive development. To evaluate the assay’s performance, two model chemicals targeting the hypothalamic-pituitary-gonadal (HPG) axis were tested; a weak estrogen receptor agonist, 4-tert-octylphenol (tOP), and an androgen receptor agonist, 17β-trenbolone (TB). Xenopus laevis embryos were constantly exposed in flow-through conditions to various test concentrations of tOP (nominal: 6.25, 12.5, 25, 50 μg/L) or TB (nominal: 12.5, 25, 50, 100 ng/L) and clean water controls until 8 weeks post-metamorphosis, at which time growth measurements were taken and histopathology assessments were made on 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 at the concentrations tested. Exposure to tOP caused a treatment-related decrease in circulating thyroxine and an increase in thyroid follicular cell hypertrophy and hyperplasia (25, 50 μg/L). Müllerian duct development was clearly affected following exposure to both chemicals; tOP exposure caused dose-dependent maturation of oviducts in both male and female frogs, whereas TB exposure caused accelerated Müllerian duct regression in males and complete regression in >50% of the females in the 100ng/L treatment. Based on these results, the LAGDA performs adequately to evaluate estrogen and androgen agonism and is the first standardized amphibian multiple life-stage chronic toxicity test to date.
