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Assessing the Predictive Value of Thyroid In Vitro Screening Assays Through Comparisons to Observed Impacts In Vivo
Citation:
Eytcheson, S., J. Olker, K. Paul-Friedman, M. Hornung, AND S. Degitz. Assessing the Predictive Value of Thyroid In Vitro Screening Assays Through Comparisons to Observed Impacts In Vivo. SETAC North America, Louisville, KY, November 12 - 16, 2023. https://doi.org/10.23645/epacomptox.25114523
Impact/Purpose:
In vivo testing lacks the capacity to screen thousands of chemicals for endocrine disruption. In vitro high-throughput screening assays have been developed to rapidly screen larger chemical libraries. This abstract describes an analysis of whether the currently available thyroid related in vitro high-throughput assays provide sufficient lines of evidence to predict in vivo impacts. Limitations of the currently available assays were identified, and some suggestions for improvement were discussed. This work is applicable to those interested in rapid identification of chemicals with the potential to disrupt the thyroid system or in alternatives to animal testing.
Description:
Product description/abstract: Rusty will copy/paste this in from your abstract/paper. The U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) was developed to investigate the potential for chemicals to interact with the vertebrate endocrine system and to characterize adverse effects resulting from these interactions. Since inception of the program, new approach methodologies (NAMs), such as in vitro high-throughput screening (HTS) and in silico modeling, have become available. One challenge of HTS is translating activity in vitro to predict an adverse effect in vivo. The objective of this work was to analyze whether the current suite of thyroid relevant HTS assays provides sufficient lines of evidence supporting action on receptors and proteins in the thyroid axis. The fifty-two chemicals screened in EDSP Tier 1 assays were selected for this analysis. The in vitro data used in this evaluation were mined from the in vitro assay database (invitroDB version 3.4), and the in vivo data were pulled from the weight of evidence evaluations prepared by the EDSP and from a literature review. Decision trees were made to classify chemicals as active in vivo only, in vitro only, in vivo and in vitro, or inactive to surmise concordance between in vitro and in vivo activity. With this framework, concordance between in vitro activity and in vivo impacts ranged from ~60-80%. Limitations of thyroid HTS were identified including the lack of assays for some known molecular initiating events within the thyroid system (e.g., serum binding proteins), limited availability of orthogonal or confirmatory assays, and lack of a set of reference chemicals. Addressing these limitations would enhance the predictive value of HTS assays and improve our understanding of how well thyroid activity in vitro predicts to in vivo effects of chemicals for which in vivo data are unavailable. The contents of this abstract neither constitute, nor necessarily reflect, US EPA policy.
URLs/Downloads:
DOI: Assessing the Predictive Value of Thyroid In Vitro Screening Assays Through Comparisons to Observed Impacts In Vivo
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