Related Experiment Video
Updated: May 16, 2026
In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Inhibition of the thyroid hormone pathway in Xenopus laevis by 2-mercaptobenzothiazole
Joseph E Tietge1, Sigmund J Degitz, Jonathan T Haselman
1US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, Duluth, MN 55804, United States. tietge.joe@epa.gov
Abstract:
Determining the effects of chemicals on the thyroid system is an important aspect of evaluating chemical safety from an endocrine disrupter perspective. Since there are numerous chemicals to test and limited resources, prioritizing chemicals for subsequent in vivo testing is critical. 2-Mercaptobenzothiazole (MBT), a high production volume chemical, was tested and shown to inhibit thyroid peroxidase (TPO) enzyme activity in vitro, a key enzyme necessary for the synthesis of thyroid hormone. To determine the thyroid disrupting activity of MBT in vivo, Xenopus laevis larvae were exposed using 7- and 21-day protocols. The 7-day protocol used 18-357 μg/L MBT concentrations and evaluated: metamorphic development, thyroid histology, circulating T4, circulating thyroid stimulating hormone, thyroidal sodium-iodide symporter gene expression, and thyroidal T4, T3, and related iodo-amino acids. The 21-day protocol used 23-435 μg/L MBT concentrations and evaluated metamorphic development and thyroid histology. Both protocols demonstrated that MBT is a thyroid disrupting chemical at the lowest concentrations tested. These studies complement the in vitro study used to identify MBT as a high priority for in vivo testing, supporting the utility/predictive potential of a tiered approach to testing chemicals for TPO activity inhibition. The 7-day study, with more comprehensive, sensitive, and diagnostic endpoints, provides information at intermediate biological levels that enables linking various endpoints in a robust and integrated pathway for thyroid hormone disruption associated with TPO inhibition.
Insights
2-Mercaptobenzothiazole (MBT) disrupts the thyroid system by inhibiting thyroid peroxidase (TPO) enzyme activity. This chemical safety evaluation in Xenopus laevis larvae confirms MBT as a thyroid disruptor, supporting tiered testing approaches.
Area of Science:
- Endocrinology
- Environmental Toxicology
- Chemical Safety Assessment
Background:
- Evaluating chemical safety requires understanding endocrine-disrupting effects on the thyroid system.
- Prioritizing high-production volume chemicals for in vivo testing is crucial due to limited resources.
- 2-Mercaptobenzothiazole (MBT) was identified as a potential thyroid disruptor due to in vitro inhibition of thyroid peroxidase (TPO).
Purpose of the Study:
- To determine the in vivo thyroid-disrupting activity of 2-Mercaptobenzothiazole (MBT).
- To validate the predictive potential of in vitro thyroid peroxidase (TPO) inhibition assays for in vivo chemical safety assessments.
- To establish a tiered approach for prioritizing chemicals for endocrine disruption testing.
Main Methods:
- Xenopus laevis larvae were exposed to MBT using 7-day and 21-day protocols with varying concentrations.
- Endpoints evaluated included metamorphic development, thyroid histology, circulating thyroid hormones (T4, T3), and thyroidal gene expression (sodium-iodide symporter).
- The 7-day protocol provided comprehensive data on intermediate biological levels, linking various endpoints in a thyroid hormone disruption pathway.
Main Results:
- Both 7-day and 21-day exposure protocols demonstrated that MBT is a thyroid-disrupting chemical at the lowest tested concentrations.
- MBT exposure led to significant effects on thyroid hormone synthesis and regulation.
- The 7-day study successfully linked molecular and physiological endpoints, supporting a pathway for MBT-induced thyroid disruption via TPO inhibition.
Conclusions:
- 2-Mercaptobenzothiazole (MBT) is confirmed as an in vivo thyroid-disrupting chemical.
- The findings support the utility of in vitro TPO inhibition assays for prioritizing chemicals for further testing.
- A tiered testing strategy, integrating in vitro and in vivo data, is effective for evaluating chemical safety and endocrine disruption potential.
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