Thyroid Disruption Research And Regulation: Challenges And Lessons Learned

The endocrine system employs estrogen, androgen, and thyroid hormone pathways to help regulate proper growth and development of an organism. Endocrine disrupting chemicals (EDCs) can mimic or alter endogenous hormone function leading to a variety of adverse health outcomes. Since the 1990s EDC research has revealed widespread exposure across human populations and low dose effects in vivo and in vitro, bringing the class of environmental chemicals to the public's attention. More recently, economic studies show that EDCs cost Europe over $200 billion dollars a year in lost earning potential and health care expenses, especially from neurobehavioral outcomes. Given the complexity of the endocrine system, it may be helpful to focus research and subsequent regulation to specific adverse outcome pathways. In particular, exposure to thyroid disrupting chemicals (TDCs) (e.g perchlorate) is often associated with neurological dysfunction; this may occur through interference with thyroid hormone homeostasis via the hypothalamic-pituitary-thyroid axis. Here we review the state of the science on TDCs, identify key aspects of the adverse outcome pathway, and examine US Environmental Protection Agency efforts specific to thyroid disruption. Furthermore, we draw upon lessons learned from international bodies that have tried to address endocrine disrupting chemicals, including TDCs, in a regulatory framework. We will discuss challenges that may arise in establishing specific human risk assessment approaches for thyroid disruption, and propose next steps in moving towards developing guidance.