Citation:

Gilbert, M. Thyroid Disrupting Chemicals Protecting the Developing Rat Brain. Developmental Neurotoxicology Society (DNTS), Charleston, SC, June 24 - 28, 2023.

Impact/Purpose:

The thyroid system provides for a variety of targets sites where environmental chemicals can interfere to either alter production and metabolism of hormone or interfere with thyroid hormone signaling. The EPA has expended considerable resources into the development of highthroughput assays to identify potential thyroid system disruptors (TSDC). A parallel effort to develop Adverse Outcome Pathways to provide a biological framework for interpretation of output of in vitro based screening assays has also been mounted. This presentation will focus of the interface of these areas of research as they pertain to the neurodevelopmental consequences associated with chemical-induced disruption of the thyroid axis.

Description:

Thyroid hormones (TH) 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. Environmental chemicals can interfere with the thyroid system at numerous sites, and these can largely be detected by alterations in circulating TH in the serum. Considerable efforts in the US and abroad have provided a suite of in vitro-based methodologies (NAMs) targeting specific sites within the thyroid system where the chemical may act. The Adverse Outcome Pathway (AOP) framework has been adopted by regulatory agencies as a means to assemble, organize, and integrate all available biological information, including NAMs and traditional in vivo animal studies, to inform chemical regulatory practices. The AOP provides a scientific grounding that links intervening key biological events, can identify knowledge gaps within that biological sequence, and can direct research to specifically address those gaps, ultimately reducing uncertainties in determining chemical risk. However, owing largely to our limited understanding of the relationships between concentrations of TH in serum, target tissues, and the downstream effects on brain development, significant uncertainties exist in translating in vitro NAMs to in vivo effects and in predicting neurodevelopmental outcomes from alterations in serum chemistry. An overview of the NAM strategy for detecting thyroid system-disrupting chemicals, advances identifying brain-based markers of thyroid-dependent neurodevelopmental insult, and new in vivo data on target sites of chemical interference will be presented. Does not reflect US EPA policy.

Record Details: