Regulation of Thyroid Disrupting Chemicals to Protect the Developing Brain

Manmade chemicals with endocrine disrupting properties are pervasive in the environment and are present in the bodies of humans and in wildlife. As thyroid hormones (THs) control normal brain development, and maternal hypothyroxinemia is associated with neurological impairments in children, chemicals that interfere with TH signaling are of considerable concern for children's health. However, identifying thyroid disrupting chemicals (TDCs) in vivo is largely based on serum tetraiodothyronine (T4) measures in rats, which may be inadequate to assess TDCs with disparate mechanisms of action. Neither are detection of serum hormone deficits alone sufficient to evaluate the potential neurotoxicity of TDCs. In this review we describe two neurodevelopmental processes that are dependent on TH action, neuronal migration and maturation of GABAergic interneurons. We discuss how interruption of these processes may contribute to abnormal brain circuitry following developmental TH insufficiency, and thus may also be affected by TDCs. Finally, we outline existing issues in evaluating the developmental neurotoxicity TDCs in rodent models, and the strengths and limitations of current approaches to their regulation. Given the state of the science, it is clear that an enhanced understanding of how THs affect brain development will lead to refined toxicity testing, reducing uncertainty and improve our ability to protect children's health.