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Technical evaluation and standardization of the human thyroid microtissue assay
Briana Foley1, Kristen Hopperstad1, John Gamble1,2
1Center for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Summary
This study established performance standards for the human thyroid microtissue (hTMT) assay, a new approach method (NAM) using human cells to assess thyroid-disrupting chemicals without animal testing.
Area of Science:
- Toxicology and Environmental Health
- In Vitro Toxicology
- New Approach Methodologies (NAMs)
Background:
- Reducing reliance on animal testing necessitates reliable in vitro and in silico methods for human health risk assessment.
- Organotypic culture models using primary human cells offer human relevance but face challenges in standardization and validation.
- Establishing performance standards is crucial for validating new approach methods (NAMs) without animal data.
Purpose of the Study:
- To define technical parameters for donor procurement, thyrocyte qualification, and performance in the human thyroid microtissue (hTMT) assay.
- To establish benchmark ranges for reference chemical responses within the hTMT assay.
- To ensure human-relevant predictions from in vitro NAMs by addressing inter-individual variability.
Main Methods:
- Characterized thyrocytes from 32 diverse donors for morphological and functional variability.
- Utilized the human thyroid microtissue (hTMT) assay with primary human thyrocytes.
- Profiled reference chemical responses to assess donor-dependent variability.
Main Results:
- Defined data-informed minimum acceptance criteria for donor qualification.
- Established benchmark parameters for method transfer, proficiency testing, and validation.
- Demonstrated the variability of donor-dependent effects in response to reference chemicals.
Conclusions:
- The study provides a framework for standardizing and validating the hTMT assay for thyroid-disrupting chemical assessment.
- Setting performance benchmarks is essential for the reliable application of human cell-based NAMs.
- This work supports the U.S. EPA's goals for reducing, refining, and replacing animal testing.
