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A Risk-based Prioritization Strategy for Thyroid Disruption Under EDSP21
Citation:
Lynn, S., M. Hornung, M. Gilbert, S. Degitz, AND K. Crofton. A Risk-based Prioritization Strategy for Thyroid Disruption Under EDSP21. Presented at Teratology Society Meeting, Bellevue, WA, June 28 - July 02, 2014.
Impact/Purpose:
for presentation at the Teratology Society Meeting, June 28 to July 2, 2014, Bellevue, Washington
Description:
The US Environmental Protection Agency (EPA) established the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances may have an effect in humans or wildlife that disrupt the estrogen, androgen or thyroid axes. The EDSP is now utilizing computational and high throughput screening (HTS) in vitro assays to more efficiently and rapidly assess chem icals for prioritizat ion of endocrine disruption testing. Of the II Tier I assays, only three inform on potential thyroid disruption with limited endpoints and these are in vivo assays which are expensive and time-consuming. Recent comprehensive and systematic literature reviews of the thyroid pathway have identified a number of potential target sites that could serve as Molecular Initiat ing Events (MfEs) for potential thyroid disrupting chemicals. MIEs for thyroid disruption span the pathway starting with production and release of thyrotropin-releasing hormone (TRH) in the hypothalamus and going to transcriptional and cellular responses of thyroid receptor (TR) activation. Literature search resu lts were combined with data from assays currently in EPA's ToxCast and the US Tox21 programs to: 1) support nominations for HTS assay development which would increase coverage of thyroid MIEs; and 2) generate a prioritized list of chemicals that in combination with exposure estimates, would yield a risk-based chemical prioritization leading to endocrine testing for thyroid disruption. The end goal is to develop computationally predictive models using results of HTS assays that inform on numerous MIEs in order to provide comprehensive coverage of relevant biological targets of the thyroid system .