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Evaluation of an Adverse Outcome Pathway Network for Thyroid Hormone System Disruption Across Taxonomic Groups
Citation:
Vergauwen, L., J. O'Brien, C. LaLone, Dan Villeneuve, AND D. Knapen. Evaluation of an Adverse Outcome Pathway Network for Thyroid Hormone System Disruption Across Taxonomic Groups. SETAC North America 42nd Annual meeting, Portland, OR, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.17105681
Impact/Purpose:
Presentation to the Society of Environmental Toxicology and Chemistry (SETAC) Meeting November 2021. Endocrine active chemicals are of special concern for chemical hazard evaluation. Screening assays can be used to detect chemical activities that can lead to thyroid disruption, but identifying relevant links to hazard across different taxa and life stages is important for the risk assessment of thyroid axis chemicals. The present work describes a network of adverse outcome pathways (AOP) linking thyroid disrupting biological activities to outcomes of concern and identifies important data gaps and priority areas for additional AOP development. The work will aid program offices like OCSPP in hazard screening and risk assessment of thyroid axis-active chemicals.
Description:
Thyroid hormone system disrupting chemicals (THDCs) are widely regarded as potential threats to human and environmental health. Thus, significant efforts have been made within both the human health and ecotoxicology communities to develop screening assays capable of identifying THDCs and to describe adverse outcome pathways (AOPs) that link thyroid hormone system disruption (THD) to adverse outcomes. In recent years, a small fish-specific, AOP network (AOPN) consisting of 5 AOPs linking the inhibition of enzymes important for the synthesis and activation of thyroid hormones to impaired swim bladder inflation was developed. As an example of how the AOPN can be used to address the current gaps in methods for THDC screening and testing in fish, a suite of assays along the AOPN that can be implemented in a tiered screening and testing approach was identified. When expanding the network to all AOPs for THD that have been endorsed or are under development in fish, mammals and amphibians, a cross-species AOPN for THD emerges. This broader AOPN provides a scientifically plausible and evidence-based foundation for the measurement of endpoints using fish and amphibian assays, as well as in vitro or in chemico assays, to predict outcomes in humans. In the present work, the taxonomic applicability of the AOPN was evaluated. Upon filtering the AOPN based on the currently described taxonomic domain of applicability of the AOPs (i.e., fish, amphibians or mammals), it was found that most AOPs have been developed with a focus on one specific taxon and information on the taxonomic domain of applicability is often missing. Evaluation of which AOPs have already been defined for more than one taxon, which AOPs are taxon-specific and thus irrelevant to other taxa (e.g., swim bladder inflation), and which novel pathways linking molecular initiating events to adverse outcomes (i.e., emergent AOPs) in a particular taxon are potential targets for dedicated AOP development was completed. Based on this evaluation, we identified data gaps and prioritized AOP development efforts. Since developmental neurotoxicity (DNT) is often considered the most important outcome of THD in humans, and no AOPs for DNT in fish and amphibians exist, DNT was highlighted as a priority for cross-species AOP development and a potential route to expedite the use of fish and amphibian assays for predicting effects in humans. The contents of this abstract neither constitute, nor necessarily reflect, US EPA policy.
URLs/Downloads:
DOI: Evaluation of an Adverse Outcome Pathway Network for Thyroid Hormone System Disruption Across Taxonomic Groups
VERGAUWEN-SETAC-PORTLAND_V2.PDF (PDF, NA pp, 2534.605 KB, about PDF)