Aop:194

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Status

This is a legacy representation of this AOP. Please see the current version here:

https://aopwiki.org/aops/194


AOP Title

Hepatic nuclear receptor activation leading to altered amphibian metamorphosis
Short name: Hepatic nuclear receptor activation alters metamorphosis

Authors

Jonathan T. Haselman, National Health and Environmental Effects Research Laboratory, US EPA, Duluth, MN, USA <haselman.jon@epa.gov>

Sigmund J. Degitz, National Health and Environmental Effects Research Laboratory, US EPA, Duluth, MN, USA <degitz.sigmund@epa.gov>

Michael W. Hornung, National Health and Environmental Effects Research Laboratory, US EPA, Duluth, MN, USA <hornung.michael@epa.gov>

Status

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Under development: Do not distribute or cite.

This AOP page was last modified on 12/11/2016.

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Abstract

Background (optional)

Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Hepatic nuclear receptor(s), Activation Moderate

Key Events

Event Support for Essentiality
Hepatic thyroid hormone uptake/transport, Increased Moderate
Upregulation of glucuronyltransferase activity, Induction Moderate
Biliary excretion TH glucuronide, Increase Moderate
Thyroxin (T4) in serum, Decreased Strong
Thyroxine (T4) in tissues, Decreased Moderate
Triiodothyronine (T3) in tissues, Decreased Moderate

Adverse Outcome

Adverse Outcome
Amphibian metamorphosis, Altered

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Hepatic nuclear receptor(s), Activation Directly Leads to Hepatic thyroid hormone uptake/transport, Increased Moderate Weak
Hepatic nuclear receptor(s), Activation Directly Leads to Upregulation of glucuronyltransferase activity, Induction Moderate Weak
Hepatic thyroid hormone uptake/transport, Increased Indirectly Leads to Biliary excretion TH glucuronide, Increase Weak Weak

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Life Stage Applicability

Life Stage Evidence Links
development Moderate

Taxonomic Applicability

Name Scientific Name Evidence Links
African clawed frog Xenopus laevis Weak NCBI

Sex Applicability

Sex Evidence Links
Unspecific Moderate

Graphical Representation

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Weight of Evidence Summary

Summary Table
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Quantitative Considerations

Summary Table
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Considerations for Potential Applications of the AOP (optional)

References