Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption

Abstract

Thyroid hormone system disrupting compounds are considered potential threats for human and environmental health. Multiple adverse outcome pathways (AOPs) for thyroid hormone system disruption (THSD) are being developed in different taxa. Combining these AOPs results in a cross-species AOP network for THSD which may provide an evidence-based foundation for extrapolating THSD data across vertebrate species and bridging the gap between human and environmental health. This review aimed to advance the description of the taxonomic domain of applicability (tDOA) in the network to improve its utility for cross-species extrapolation. We focused on the molecular initiating events (MIEs) and adverse outcomes (AOs) and evaluated both their plausible domain of applicability (taxa they are likely applicable to) and empirical domain of applicability (where evidence for applicability to various taxa exists) in a THSD context. The evaluation showed that all MIEs in the AOP network are applicable to mammals. With some exceptions, there was evidence of structural conservation across vertebrate taxa and especially for fish and amphibians, and to a lesser extent for birds, empirical evidence was found. Current evidence supports the applicability of impaired neurodevelopment, neurosensory development (e.g., vision) and reproduction across vertebrate taxa. The results of this tDOA evaluation are summarized in a conceptual AOP network that helps prioritize (parts of) AOPs for a more detailed evaluation. In conclusion, this review advances the tDOA description of an existing THSD AOP network and serves as a catalog summarizing plausible and empirical evidence on which future cross-species AOP development and tDOA assessment could build.

Specific effects on the thyroid relevant for performing a dietary cumulative risk assessment of pesticide residues: 2024 update

“…Thus, the eight AOPs on altered amphibian metamorphosis (AOP175, AOP176, AOP188, AOP189, AOP190, AOP191, AOP366, AOP367), the seven AOPs on increased mortality and decreased population growth rate in fish via swim bladder inflation (AOP155, AOP156, AOP157, AOP158, AOP159), altered retinal layer structure (AOP363) or decreased eye size (Microphthalmos) (AOP399), as well as the AOP271 on inhibition of TPO leading to impaired fertility in fish were not considered further. The human relevance of available AOPs may be revised in the future based on the outcome of ongoing research on the evidence‐based applicability of AOPs for HPT axis disruption to other taxonomic groups and cross‐species extrapolations (Haigis et al., 2023 ). In addition, information on MIE, key events (KEs) and AO is not provided for AOP484 (Bisphenol A analogues induce cellular dysfunction in human trophoblast cells in a thyroid hormone receptor‐dependent manner: in silico and in vitro analyses), which is therefore also not included in the list of relevant AOPs for this report.…”

Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps

“…Figure 7 shows that most AOPs together form one large AOP network connecting different areas of endocrine and metabolic disruption. While the THSD AOPN has recently been curated to improve the connectivity among AOPs (Haigis et al, 2023), curation may be needed in other parts of the AOP network to reduce duplication and increase connectivity, e.g., to reflect crosstalk between endocrine axes. In the THSD area of the AOP network, hub key events, mostly representing alterations in hormone levels, can be identified where AOPs with multiple MIEs converge and subsequently diverge towards various AOs.…”

Toxicometabolomics as a tool for next generation environmental risk assessment

“…Furthermore, metabolomics data can be compared across different species and even extrapolated to predict the effects of stressors in other organisms. Cross‐species applicability is essential for the development of AOPs with relevance to multiple species and ecological contexts (Ankley et al., 2010 ; Brockmeier et al., 2017 ; Haigis et al., 2023 ). Metabolomics‐based read‐across and grouping approaches, utilising structural similarity, have been shown to successfully support evidence through reducing uncertainty in the characterisation of the toxicity profile of analogue chemicals (e.g.…”