Regulation of thyroid-disrupting chemicals to protect the developing brain

Abstract

Synthetic chemicals with endocrine disrupting properties are pervasive in the environment and are present in the bodies of humans and 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 measuring serum tetraiodothyronine in rats, which may be inadequate to assess TDCs with disparate mechanisms of action and insufficient to evaluate the potential neurotoxicity of TDCs. In this review 2 neurodevelopmental processes that are dependent on TH action are highlighted, neuronal migration and maturation of gamma amino butyric acid-ergic interneurons. We discuss how interruption of these processes by TDCs may contribute to abnormal brain circuitry following developmental TH insufficiency. Finally, we identify issues in evaluating the developmental neurotoxicity of TDCs and the strengths and limitations of current approaches designed to regulate them. It is clear that an enhanced understanding of how THs affect brain development will lead to refined toxicity testing, reducing uncertainty and improving our ability to protect children's health.