Study on the development of bioassay system for organic halogenated compounds with thyroid-disrupting activity

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In vertebrates, thyroid hormones are essential for post-embryonic development, such as establishing the central nervous system in mammals and metamorphosis in amphibians. The present study focused on the extra-thyroidal processes that environmental chemicals are known to or suspected to target in the thyroid hormone-signaling pathway. We developed three in vitro and one in vivo bioassays, which detect chemicals interfering with thyroid hormone binding to plasma transthyretin (TTR assay), thyroid hormone binding to nuclear receptor (TR assay), induction of thyroid hormone-dependent reporter gene expression (Luc assay, and gene expression during thyroid hormone-induced amphibian metamorphosis (metamorphosis assay). Several organohalogens affect different aspects of the extra-thyroidal thyroid-hormone-signaling pathway but hardly affect thyroid hormone binding to receptors. Amphibian tadpoles are most sensitive to the effects of environmental chemicals during specific thyroid-hormone-related developmental windows. The thyroid hormone-disrupting activity of contaminants in aquatic environments in Japan and Thailand was surveyed by these bioassays. Our assays demonstrated that wastewater treatment effectively removed the TH-disrupting contaminants from wastewater in paper manufacturing plants and sewage-treatment plants. The Luc assay indicated that sewage-treatment plant effluents in Japan contained Ta-like activity whereas that in Thailand contained anti-Ta-like activity. It is likely that the three in vitro bioassays detected the same or different contaminants with TH-disrupting activity in a water sample-dependent manner. Our results indicate that a combination of several in vitro bioassays facilitates the rapid screening of environmental water samples to identify the locations of contaminants with TH-disrupting activity.