Validation of an in vitro human thyroid microtissue model for chemical screening
Current regulatory decision-making for potential thyroid-disrupting chemicals is based on in vivo apical endpoints including alterations in thyroid hormone levels. New approach methodologies (NAMs) to complement or replace traditional in vivo tests are being developed to enable higher-throughput mechanistic understanding of potential endocrine-disrupting chemicals. A key element to the acceptance of NAMs in regulatory contexts is to establish confidence through validation studies that evaluate a NAM’s reliability and relevance for a specific application.
NICEATM is coordinating an interlaboratory validation study of the utility of a thyroid 3D microtissue model for evaluating chemical effects on thyroid hormone synthesis and tissue viability. The lead laboratory is within the EPA Office of Research and Development, with three agrochemical industry and commercial labs participating in the transferability phase. Goals of this effort include (1) development of the study design, (2) test method harmonization and standardization and demonstration of intralaboratory reproducibility, and (3) method transferability, reference chemical testing, and demonstration of interlaboratory reproducibility. Refinement of standard operating procedures, tissue procurement, method standardization in the main laboratory, and an initial assessment of method transferability were completed in 2023. Method transfer and model validation are currently being completed in the additional laboratories, to be followed by method performance evaluation by all laboratories. Results of the study will be described in a study validation report.