Aop:128

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AOP Title

Kidney dysfunction by decreased thyroid hormone
Short name: Kidney dysfunction

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OECD Project 1.40: The AOP for Kidney dysfunction by decreased thyroid hormone

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

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Abstract

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Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Thyroid hormone synthesis, Decreased Strong

Key Events

Event Support for Essentiality
Thyroxine (T4) in serum, Decreased Strong
Glomerular filtration, Decreased Weak
Renal plasma flow, Decreased Weak
Sodium reabsorption, Decreased Weak
Serum creatinine, Increased Strong
Cystic dilatation (renal tubule), Occurrence Weak
Cytoplasmic vacuolization (podocyte), Occurrence Weak
Cytoplasmic vacuolization (Renal tubule), Occurrence Weak
Renal ability to dilute urine, Decreased Weak

Adverse Outcome

Adverse Outcome
Kidney toxicity, Occurrence

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Thyroid hormone synthesis, Decreased Directly Leads to Thyroxine (T4) in serum, Decreased Strong
Thyroid hormone synthesis, Decreased Directly Leads to Serum creatinine, Increased Strong
Thyroxine (T4) in serum, Decreased Directly Leads to Cytoplasmic vacuolization (Renal tubule), Occurrence Weak
Thyroxine (T4) in serum, Decreased Directly Leads to Cystic dilatation (renal tubule), Occurrence Weak
Serum creatinine, Increased Directly Leads to Cytoplasmic vacuolization (Renal tubule), Occurrence Weak
Serum creatinine, Increased Directly Leads to Cystic dilatation (renal tubule), Occurrence Weak
Thyroxine (T4) in serum, Decreased Directly Leads to Cytoplasmic vacuolization (podocyte), Occurrence Weak
Serum creatinine, Increased Directly Leads to Cytoplasmic vacuolization (podocyte), Occurrence Weak
Cytoplasmic vacuolization (Renal tubule), Occurrence Indirectly Leads to Glomerular filtration, Decreased Weak
Cytoplasmic vacuolization (Renal tubule), Occurrence Indirectly Leads to Renal plasma flow, Decreased Weak
Cytoplasmic vacuolization (Renal tubule), Occurrence Indirectly Leads to Sodium reabsorption, Decreased Weak
Cytoplasmic vacuolization (Renal tubule), Occurrence Indirectly Leads to Renal ability to dilute urine, Decreased Weak
Cystic dilatation (renal tubule), Occurrence Indirectly Leads to Glomerular filtration, Decreased Weak
Cystic dilatation (renal tubule), Occurrence Indirectly Leads to Renal plasma flow, Decreased Weak
Cystic dilatation (renal tubule), Occurrence Indirectly Leads to Sodium reabsorption, Decreased Weak
Cystic dilatation (renal tubule), Occurrence Indirectly Leads to Renal ability to dilute urine, Decreased Weak
Cytoplasmic vacuolization (podocyte), Occurrence Indirectly Leads to Glomerular filtration, Decreased Weak
Cytoplasmic vacuolization (podocyte), Occurrence Indirectly Leads to Renal plasma flow, Decreased Weak
Cytoplasmic vacuolization (podocyte), Occurrence Indirectly Leads to Sodium reabsorption, Decreased Weak
Cytoplasmic vacuolization (podocyte), Occurrence Indirectly Leads to Renal ability to dilute urine, Decreased Weak
Glomerular filtration, Decreased Directly Leads to Kidney toxicity, Occurrence Strong
Renal plasma flow, Decreased Directly Leads to Kidney toxicity, Occurrence Strong
Sodium reabsorption, Decreased Directly Leads to Kidney toxicity, Occurrence Strong
Renal ability to dilute urine, Decreased Directly Leads to Kidney toxicity, Occurrence Strong

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Life Stage Applicability

Life Stage Evidence Links
1 to < 3 months Strong
Adults Strong

Taxonomic Applicability

Name Scientific Name Evidence Links
Sprague-Dawley Strong
Homo sapiens Homo sapiens NCBI

Sex Applicability

Sex Evidence Links
Male Strong
Unspecific Strong

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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

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Quantitative Considerations

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

References