A research opportunity is available at the Environmental Protection Agency (EPA), Office of Research and Development (ORD), Center for Computational Toxicology and Exposure (CCTE), Great Lakes Toxicology & Ecology Division (GLTED) located in Duluth, Minnesota.
Research Project: The US EPA is mandated to address the endocrine disrupting potential of thousands of chemicals. For the majority of these chemicals there is a lack of information regarding whether they have the potential to cause adverse effects from impacts on thyroid hormone status. Understanding the important targets within the network of processes involved in maintaining normal functioning thyroid hormone levels, and what approaches to best assess activity at those targets are critical to developing a comprehensive approach to evaluating thyroid hormone disrupting potential of large numbers of chemicals.
Recently, a number of thyroid-related in vitro high-throughput screening (HTS) assays have been developed to broaden assay coverage for molecular targets potentially leading to thyroid disruption and were implemented to screen US EPA’s ToxCast Phase 1, 2 and E1K libraries. This battery of thyroid-related in vitro HTS assays can be employed to rapidly assess potential chemical toxicity toward these targets. However, this screening approach leaves uncertainties regarding the meaning of in vitro activity data as it relates to in vivo outcomes. Part of this research effort aims to develop a translational process that integrates relevant information, models, and data streams to provide richer context to in vitro results related to thyroid disruption. To that end, targeted in vivo testing will be performed using a model amphibian species (Xenopus sp.) routinely used for testing thyroid disrupting chemicals, to understand whether, and how, in vitro activity of chemicals translates to in vivo outcomes. Additionally, this research will employ existing computational tools such as the octanol-water partition coefficient (logKow) and quantitative structure-activity relationships (QSAR) models to provide deeper interpretation of in vitro data and further prioritize chemicals most likely to impact thyroid function in aquatic systems. The translational principles demonstrated will have much broader applicability across ToxCast HTS assays and aquatic vertebrates. This research will provide translational context necessary for ecological risk assessment and deliver timely information relative to PFAS thyroid toxicity. Coordinated efforts will be undertaken in the mammalian model in parallel to these efforts to bolster cross-species concordance of modes of action and adverse outcome pathways (AOPs) related to thyroid disruption.
Deadline: June 1, 2021