title: Inhibition of the thyroid hormone pathway in Xenopus laevis by 2-mercaptobenzothiazole.
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.
authors.affiliation: US 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
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Tietge
authors.forename: Sigmund J
authors.initials: SJ
authors.lastname: Degitz
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Haselman
authors.forename: Brian C
authors.initials: BC
authors.lastname: Butterworth
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Korte
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kosian
authors.forename: Annelie J
authors.initials: AJ
authors.lastname: Lindberg-Livingston
authors.forename: Emily M
authors.initials: EM
authors.lastname: Burgess
authors.forename: Pamela E
authors.initials: PE
authors.lastname: Blackshear
authors.forename: Michael W
authors.initials: MW
authors.lastname: Hornung
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000032:analysis / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D007453:Iodide Peroxidase / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000187:drug effects; D016019:Survival Analysis; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism; D014867:Water / Q000737:chemistry; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*; D014982:Xenopus laevis
chemical_list: D052160:Benzothiazoles; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; D014867:Water; C005563:captax; D007453:Iodide Peroxidase