title: Thyroid histopathology assessments for the amphibian metamorphosis assay to detect thyroid-active substances.
abstract: 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.
authors.affiliation: Smithsonian National Zoological Park, Conservation and Research Center, Center for Species Survival, Front Royal, VA 22630, USA. grim.christiana@epa.gov, grimc@si.edu
authors.forename: K Christiana
authors.initials: KC
authors.lastname: Grim
authors.forename: Marilyn
authors.initials: M
authors.lastname: Wolfe
authors.forename: Thomas
authors.initials: T
authors.lastname: Braunbeck
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ohta
authors.forename: Osamu
authors.initials: O
authors.lastname: Tooi
authors.forename: Les
authors.initials: L
authors.lastname: Touart
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wolf
authors.forename: Joe
authors.initials: J
authors.lastname: Tietge
mesh_terms: D000818:Animals; D001284:Atrophy; D001681:Biological Assay; D006651:Histocytochemistry; D006965:Hyperplasia / Q000139:chemically induced; D006984:Hypertrophy / Q000139:chemically induced; D007814:Larva / Q000254:growth & development; D008675:Metamorphosis, Biological / Q000187:drug effects*; D010472:Perchlorates / Q000633:toxicity*; D013961:Thyroid Gland / Q000033:anatomy & histology* / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D013974:Thyroxine / Q000378:metabolism / Q000494:pharmacology; D015262:Xenobiotics / Q000633:toxicity*; D014982:Xenopus laevis / Q000254:growth & development*
chemical_list: D010472:Perchlorates; D015262:Xenobiotics; D013974:Thyroxine; C494474:perchlorate