ArticleEnvironmental toxicology and chemistry2021
The Extended Amphibian Metamorphosis Assay: A Thyroid-Specific and Less Animal-Intensive Alternative to the Larval Amphibian Growth and Development Assay.
Article in Environmental toxicology and chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- The assessment for potential thyroid-mediated endocrine disruption in amphibians: Clarification on the use of new methods and on the interpretation of changes in thyroid histology.EFSA journal. European Food Safety Authority · 2025Article
- Peer review of the pesticide risk assessment of the active substance phenmedipham.EFSA journal. European Food Safety Authority · 2025Review
- Unveiling the Endocrine-Disrupting Potential of Plant-Derived Compounds: An Ecotoxicological Review.Toxins · 2025Review
- Amphibian studies to investigate the endocrine-disrupting properties of chemicals through the thyroid modality: a comparison of their statistical power.Environmental toxicology and chemistry · 2025Article
- Peer review of the pesticide risk assessment of the active substance flufenacet.EFSA journal. European Food Safety Authority · 2024Review
- Endocrine disruption in teleosts and amphibians is mediated by anthropogenic and natural environmental factors: implications for risk assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Statement concerning the testing strategy and timelines proposed by the applicant for the assessment of the endocrine disruption properties of acibenzolar-S-methyl in the context of the review of the approval of the active substance.EFSA journal. European Food Safety Authority · 2023Article
- Environmental endocrine disruptors and amphibian immunity: A bridge between the thyroid hormone axis and T cell development.Developmental and comparative immunology · 2023Article
- Normal Table of Xenopus development: a new graphical resource.Development (Cambridge, England) · 2022Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amphibian metamorphosis assay (AMA; US Environmental Protection Agency [USEPA] test guideline 890.1100 and Organisation for Economic Co-Operation and Development test guideline 231) has been used for more than a decade to assess the potential thyroid-mediated endocrine activity of chemicals. In 2013, in the context of the Endocrine Disruptor Screening Program of the USEPA, a Scientific Advisory Panel reviewed the results from 18 studies and recommended changes to the AMA test guideline, including a modification to a fixed-stage design rather than a fixed-time (i.e., 21-d) design. We describe an extended test design for the AMA (or EAMA) that includes thyroid histopathology and time to metamorphosis (Nieuwkoop-Faber [NF] stage 62), to address both the issues with the fixed-time design and the specific question of thyroid-mediated adversity in a shorter assay than the larval amphibian growth and development assay (LAGDA; Organisation for Economic Co-Operation and Development test guideline 241), using fewer animals and resources. A demonstration study was conducted with the EAMA (up to NF stage 58) using sodium perchlorate. Data analyses and interpretation of the fixed-stage design of the EAMA are more straightforward than the fixed-time design because the fixed-stage design avoids confounded morphometric measurements and thyroid histopathology caused by varying developmental stages at test termination. It also results in greater statistical power to detect metamorphic delays than the fixed-time design. By preferentially extending the AMA to NF stage 62, suitable data can be produced to evaluate thyroid-mediated adversity and preclude the need to perform a LAGDA for thyroid mode of action analysis. The LAGDA remains of further interest should investigations of longer term effects related to sexual development modulated though the hypothalamus-pituitary-gonadal axis be necessary. However, reproduction assessment or life cycle testing is currently not addressed in the LAGDA study design. This is better addressed by higher tier studies in fish, which should then include specific thyroid-related endpoints. Environ Toxicol Chem 2021;40:2135-2144. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
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