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Aop: 138

AOP Title

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Organic anion transporter (OAT1) inhibition leading to renal failure and mortality

Short name:

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OAT1 inhibition

Graphical Representation

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Click to download graphical representation template

Authors

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Kellie Fay

Point of Contact

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Kellie Fay   (email point of contact)

Contributors

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  • Kellie Fay

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite 1.29 Under Development


This AOP was last modified on January 27, 2018 15:34

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Revision dates for related pages

Page Revision Date/Time
Inhibition, organic anion transporter 1 (OAT1) September 16, 2017 10:16
Increased, blood uric acid concentration September 16, 2017 10:16
Occurrence, renal proximal tubular necrosis September 16, 2017 10:16
Increased, blood potassium concentration September 16, 2017 10:16
Increased, Mortality May 15, 2017 11:34
Decline, Population December 03, 2016 16:33
Occurrence, tophi (urate) deposition December 03, 2016 16:37
Occurrence, cardiac arrhythmia September 16, 2017 10:17
Increased, Oxidative Stress September 16, 2017 10:16
Inhibition, organic anion transporter 1 (OAT1) leads to Increased, blood uric acid concentration December 03, 2016 16:38
Increased, blood uric acid concentration leads to Occurrence, tophi (urate) deposition December 03, 2016 16:38
Occurrence, tophi (urate) deposition leads to Occurrence, renal proximal tubular necrosis December 03, 2016 16:38
Occurrence, renal proximal tubular necrosis leads to Increased, blood potassium concentration December 03, 2016 16:38
Increased, blood potassium concentration leads to Occurrence, cardiac arrhythmia December 03, 2016 16:38
Occurrence, cardiac arrhythmia leads to Increased, Mortality December 03, 2016 16:38
Occurrence, renal proximal tubular necrosis leads to Increased, blood uric acid concentration December 03, 2016 16:38
Increased, blood uric acid concentration leads to Increased, Oxidative Stress December 03, 2016 16:38
Increased, Oxidative Stress leads to Occurrence, renal proximal tubular necrosis December 03, 2016 16:38

Abstract

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Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 877 Inhibition, organic anion transporter 1 (OAT1) Inhibition, organic anion transporter 1 (OAT1)
2 KE 1096 Increased, blood uric acid concentration Increased, blood uric acid concentration
3 KE 1097 Occurrence, renal proximal tubular necrosis Occurrence, renal proximal tubular necrosis
4 KE 1098 Increased, blood potassium concentration Increased, blood potassium concentration
5 KE 1102 Occurrence, tophi (urate) deposition Occurrence, tophi (urate) deposition
6 KE 1106 Occurrence, cardiac arrhythmia Occurrence, cardiac arrhythmia
7 KE 1088 Increased, Oxidative Stress Increased, Oxidative Stress
8 AO 351 Increased, Mortality Increased, Mortality
9 AO 361 Decline, Population Decline, Population

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Inhibition, organic anion transporter 1 (OAT1) leads to Increased, blood uric acid concentration adjacent High High
Increased, blood uric acid concentration leads to Occurrence, tophi (urate) deposition adjacent High High
Occurrence, renal proximal tubular necrosis leads to Increased, blood potassium concentration adjacent Moderate
Increased, blood potassium concentration leads to Occurrence, cardiac arrhythmia adjacent
Occurrence, cardiac arrhythmia leads to Increased, Mortality adjacent
Occurrence, renal proximal tubular necrosis leads to Increased, blood uric acid concentration adjacent
Occurrence, tophi (urate) deposition leads to Occurrence, renal proximal tubular necrosis non-adjacent Moderate
Increased, blood uric acid concentration leads to Increased, Oxidative Stress non-adjacent
Increased, Oxidative Stress leads to Occurrence, renal proximal tubular necrosis non-adjacent

Network View

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Stressors

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Life Stage Applicability

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Life stage Evidence
Adult High

Taxonomic Applicability

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Term Scientific Term Evidence Link
Gyps coprotheres Gyps coprotheres High NCBI
Gyps fulvus Gyps fulvus NCBI
Gyps bengalensis Gyps bengalensis High NCBI
Gyps africanus Gyps africanus High NCBI
Gyps himalayensis Gyps himalayensis High NCBI
Gallus gallus Gallus gallus High NCBI
Aegypius monachus Aegypius monachus Moderate NCBI
Gyps indicus Gyps indicus High NCBI

Sex Applicability

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Sex Evidence
Male
Female

Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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