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AOP: 365
Title
Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning
Short name
Graphical Representation
Point of Contact
Contributors
- Lucia Vergauwen
- Lisa Gölz
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
---|---|---|---|---|
1.35 | Under Development |
This AOP was last modified on July 01, 2025 11:47
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Thyroperoxidase, Inhibition | November 04, 2022 09:24 |
Thyroid hormone synthesis, Decreased | November 04, 2022 09:25 |
Thyroxine (T4) in serum, Decreased | October 10, 2022 08:52 |
Decreased, Triiodothyronine (T3) | October 07, 2022 08:26 |
Altered, Photoreceptor patterning | June 16, 2021 06:56 |
Increased Mortality | July 08, 2022 07:32 |
Decrease, Population growth rate | January 03, 2023 09:09 |
Altered, Visual function | July 08, 2022 07:30 |
Thyroperoxidase, Inhibition leads to TH synthesis, Decreased | November 04, 2022 09:27 |
TH synthesis, Decreased leads to T4 in serum, Decreased | October 10, 2022 08:56 |
T4 in serum, Decreased leads to Decreased, Triiodothyronine (T3) | October 10, 2022 09:02 |
Decreased, Triiodothyronine (T3) leads to Altered, Photoreceptor patterning | October 17, 2021 16:34 |
Altered, Photoreceptor patterning leads to Altered, Visual function | June 16, 2021 07:24 |
Altered, Visual function leads to Increased Mortality | July 08, 2022 08:26 |
Increased Mortality leads to Decrease, Population growth rate | July 08, 2022 08:29 |
Abstract
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 279 | Thyroperoxidase, Inhibition | Thyroperoxidase, Inhibition |
KE | 277 | Thyroid hormone synthesis, Decreased | TH synthesis, Decreased |
KE | 281 | Thyroxine (T4) in serum, Decreased | T4 in serum, Decreased |
KE | 1003 | Decreased, Triiodothyronine (T3) | Decreased, Triiodothyronine (T3) |
KE | 1640 | Altered, Photoreceptor patterning | Altered, Photoreceptor patterning |
KE | 1643 | Altered, Visual function | Altered, Visual function |
AO | 351 | Increased Mortality | Increased Mortality |
AO | 360 | Decrease, Population growth rate | Decrease, Population growth rate |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
Taxonomic domain of applicability
According to the evaluation of the empirical taxonomic domain of applicability (tDOA) of an adverse outcome pathway network for thyroid hormone system disruption (THSD) by Haigis et al., 2023, the level of confidence for a linkage between TPO inhibition and reduced thyroid hormone (TH) levels as well as for a linkage between THSD and altered visual function in general, was considered high for mammals and fish and moderate for amphibians. In addition, the level of confidence was considered moderate for birds for a linkage between THSD and altered visual function. This was supported by structural protein conservation analysis by Lalone et al., 2018 and Haigis et al., 2023. Structural protein conservation of mammalian, fish, amphibian, reptilian and avian TPO was found compared to the human (Homo sapiens) protein target using the U.S. Environmental Protection Agency’s Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS v6.0; seqapass.epa.gov/seqapass/) tool, while acknowledging the potential existence of interspecies differences in conservation. No empirical evidence linking TPO inhibition to THSD was found for reptiles and birds. Furthermore, no empirical evidence linking THSD to altered visual function was found for reptiles, but this taxon is considered part of the plausible tDOA based on the evaluation by Haigis et al., 2023. Scientific inference and the consideration of structural/functional conservation of organs, systems and pathways indicate that altered visual function can plausibly be measured and is plausibly linked to THSD.
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
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Quantitative Understanding
Considerations for Potential Applications of the AOP (optional)
References
Haigis A-C., Vergauwen L., LaLone C.A., Villeneuve D.L., O'Brien J.M., Knapen D. (2023). Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption. Toxicol Sci. 195, 1-27.
Lalone, C. A., Villeneuve, D. L., Doering, J. A., Blackwell, B. R., Transue, T. R., Simmons, C. W., Swintek, J., Degitz, S. J., Williams, A. J., and Ankley, G. T. (2018). Evidence for cross species extrapolation of mammalian-based high-throughput screening assay results. Environ. Sci. Technol. 52, 13960–13971