Estimating the Maximum Tolerated Concentration for Amphibian Metamorphosis Assays

Estimating the Maximum Tolerated Concentration for Amphibian Metamorphosis Assays

Under current European Union regulations, all biocides and plant protection products must be evaluated for potential endocrine disrupting (ED) effects, specifically for estrogen, androgen, thyroid, or steroidogenic (EATS) modalities. The amphibian metamorphosis assay (AMA) is an in vivo assay with Xenopus laevis larvae used to screen for potential impacts on hypothalamus-pituitary-thyroid (HPT) signaling. The AMA is considered a level 3 Organisation for Economic Cooperation and Development (OECD) evaluation method in the OECD conceptual framework for the assessment of ED capabilities and utilized to evaluate the potential for a compound to interact with the HPT axis. Such compounds may have acute/chronic fish data available from previous registration requirements, but there is rarely amphibian toxicity data. This lack of available amphibian toxicity data poses a challenge when selecting appropriate levels for ED testing, as the goal of ED testing is to test to levels high enough to investigate potential EATS activity without inducing overt toxicity, a level referred to as the maximum tolerated concentration (MTC).

Current guidance in OECD 231 suggests using 1/3 the LC50 value as a method for estimating the MTC; however, this method may not always be appropriate. The objective of this project was to provide guidance regarding the use of existing fish toxicity data for the selection of levels for the AMA; thus, reducing uncertainty around the identification of the MTC for testing and reducing the number of organisms needed for range-finding studies. To achieve this goal, data from the ECOTOX database, the Office of Pesticide Programs, and the Screening Results and Data Evaluation Records for EDSP Tier I Chemicals was compared to evaluate how available acute/chronic fish data relates to the estimated MTC for AMAs.

This meta-analysis will provide guidance for study directors and study monitors selecting levels for AMA testing; as well as potentially reducing the number of organisms needed during range- finding studies for some well-described compounds.

Dr. Julie Krzykwa will present this research at the SETAC North America 42nd Annual Meeting, November 14-18, 2021.

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Julie Krzykwa SETAC 2021 Estimating the Maximum Tolerated Concentration AMA
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