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Thyroid Histopathology Assessments for the Amphibian Metamorphosis Assay to Detect Thyroid-active Substances

¹ Smithsonian National Zoological Park, Conservation and Research Center, Center for Species Survival, Front Royal, VA U.S.A. and U.S. Environmental Protection Agency, Office of Science Coordination and Policy, Washington, DC U.S.A
² Experimental Pathology Laboratories, Inc., Sterling, Virgina U.S.A
³ Aquatic Ecology and Toxicology Group, Department of Zoology, University of Heidelberg, Germany
⁴ Division of Bio-Environmental Science, Department of Bio-Environmental Science, Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, Aichi, Japan
⁵ Laboratory of Experimental Animals, Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Koyama, Japan
⁶ Institute of Environmental Ecology, IDEA Consultants, Inc., Shizuoka, Japan
⁷ U.S. Environmental Protection Agency, Office of Science Coordination and Policy, Washington, DC U.S.A
⁸ National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina and Duluth, Minnesota, U.S.A

Correspondence: Dr. K. Christiana Grim, Smithsonian National Zoological Park, Conservation Research Center, Center for Species Survival, 1500 Remount Road, Front Royal, VA 22630, U.S.A.; U.S. Environmental Protection Agency, Office of Science Coordination Policy, 1200 Pennsylvania Ave., NW, Ariel Rios (7203M), Washington, DC 20460, U.S.A.; e-mail addresses:grim.christiana{at}epa.gov,grimc{at}si.edu.

In support of an Organization for Economic Cooperation and Development (OECD) Amphibian Metamorphosis Assay (AMA) Test Guideline for the detection of substances that interact with the hypothalamic-pituitary-thyroid axis, a document was developed that provides a standardized approach for evaluating the histology/histopathology of thyroid glands in metamorphosing Xenopus laevis tadpoles. Here, a consolidated description of histology evaluation practices, core diagnostic criteria and severity grading schemes for the AMA, an atlas of the normal architecture of amphibian thyroid glands over the course of metamorphosis, and the core diagnostic criteria with examples of severity grades is provided. Core diagnostic criteria include thyroid gland hypertrophy/atrophy, follicular cell hypertrophy, and follicular cell hyperplasia. The severity grading scheme is semiquantitative and employs a four-grade approach describing ranges of variation within assigned ordinal classes: not remarkable, mild, moderate, and severe. The purpose of this severity grading approach is to provide an efficient, semi-objective tool for comparing changes (compound-related effects) among animals, treatment groups, and studies. Proposed descriptions of lesions for scoring the four core criteria are also given.

Key Words: amphibia • metamorphosis • thyroid • histopathology • histology • Xenopus laevis

Abbreviations: AMA, amphibian metamorphosis assay; • EAS, endocrine active substances; • H&E, hematoxylin and eosin; • HPT, hypothalamic-pituitary-thyroid; • N&F, Nieuwkoop and Faber; • OECD, Organization for Economic Cooperation and Development; • TSH, thyroid stimulating hormone.

This version was published on June 1, 2009

Toxicologic Pathology, Vol. 37, No. 4, 415-424 (2009)
DOI: 10.1177/0192623309335063


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