Friday, October 6, 2023
Adverse Outcome Pathways For Thyroid Disruption: Filling The Gaps From In Vitro Screens To Developmental Neurotoxicity In A Mammalian System
Mary Gilbert
Senior Investigator
United States Environmental Protection Agency | US EPA ยท Center for Public Health and Environmental Assessment
The complexity of the thyroid hormone signaling pathways present a myriad of targets for interference by environmental chemicals. Because thyroid hormones are essential for normal brain development, there is a significant public health need to protect the developing brain of the fetus, newborn, and young child from thyroid system-disrupting chemicals (TSDC). This concern has led to the development of a suite of in vitro-based methodologies (NAMs) targeting specific sites within the thyroid system where chemicals may act. Currently, regulatory decisions for TSDC are largely based on alterations in circulating levels of thyroid hormone in rodent studies, but translation from NAM outputs to serum hormones is lacking. So too is our understanding of the relationships between concentrations of TH in serum, target tissues, and the downstream effects on brain development. This presentation will provide an overview of current approaches to identify and characterize TSDCs for informed regulatory decision making. It will focus ongoing research efforts to unravel how TSDC interfere with thyroid signaling at the molecular, structural, and functional level using a case study with the drinking water contaminant perchlorate. Does not reflect US EPA policy.